Author: "Pascale Loiseau" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Pascale Loiseau"' showing total 126 results

Start Over Author "Pascale Loiseau"

126 results on '"Pascale Loiseau"'

1. HLA-DRB1*11 is a strong risk factor for acquired thrombotic thrombocytopenic purpura in children

Author: Bérangère S. Joly, Pascale Loiseau, Michael Darmon, Thierry Leblanc, Hervé Chambost, Fanny Fouyssac, Vincent Guigonis, Jérôme Harambat, Alain Stepanian, Paul Coppo, and Agnès Veyradier
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2020
Full Text: View/download PDF

2. The ADAMTS131239–1253 peptide is a dominant HLA-DR1-restricted CD4+ T-cell epitope

Author: Laurent Gilardin, Sandrine Delignat, Ivan Peyron, Mathieu Ing, Yu-Chun Lone, Bagirath Gangadharan, Baptiste Michard, Yousra Kherabi, Meenu Sharma, Anastas Pashov, Jean-Baptiste Latouche, Mohamad Hamieh, Olivier Toutirais, Pascale Loiseau, Lionel Galicier, Agnès Veyradier, Srini Kaveri, Bernard Maillère, Paul Coppo, and Sébastien Lacroix-Desmazes
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Acquired thrombotic thrombocytopenic purpura is a rare and severe disease characterized by auto-antibodies directed against “A Disintegrin And Metalloproteinase with Thrombospondin type 1 repeats, 13th member" (ADAMTS13), a plasma protein involved in hemostasis. Involvement of CD4+ T cells in the pathogenesis of the disease is suggested by the IgG isotype of the antibodies. However, the nature of the CD4+ T-cell epitopes remains poorly characterized. Here, we determined the HLA-DR-restricted CD4+ T-cell epitopes of ADAMTS13. Candidate T-cell epitopes were predicted in silico and binding affinities were confirmed in competitive enzyme-linked immunosorbent assays. ADAMTS13-reactive CD4+ T-cell hybridomas were generated following immunization of HLA-DR1 transgenic mice (Sure-L1 strain) and used to screen the candidate epitopes. We identified the ADAMTS131239–1253 peptide as the single immunodominant HLA-DR1-restricted CD4+ T-cell epitope. This peptide is located in the CUB2 domain of ADAMTS13. It was processed by dendritic cells, stimulated CD4+ T cells from Sure-L1 mice and was recognized by CD4+ T cells from an HLA-DR1-positive patient with acute thrombotic thrombocytopenic purpura. Interestingly, the ADAMTS131239–1253 peptide demonstrated promiscuity towards HLA-DR11 and HLA-DR15. Our work paves the way towards the characterization of the ADAMTS13-specific CD4+ T-cell response in patients with thrombotic thrombocytopenic purpura using ADAMTS131239–1253-loaded HLA-DR tetramers.
Published: 2017
Full Text: View/download PDF

3. Donor-specific Anti-HLA antibodies in allogeneic hematopoietic stem cell transplantation

Author: Sarah Morin-Zorman, Pascale Loiseau, Jean-Luc Taupin, and Sophie Caillat-Zucman
Subjects: HLA Antigens, allogeneic hematopoietic stem cell transplantation, donor-specific antibodies, Graft failure, Single antigen flow bead assay, Immunologic diseases. Allergy, RC581-607
Abstract: Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT) is a curative treatment for a wide variety of hematological diseases. In 30% of the cases, a geno-identical donor is available. Any other situation displays some level of Human Leukocyte Antigen (HLA) incompatibility between donor and recipient. Deleterious effects of anti-HLA immunization have long been recognized in solid organ transplant recipients. More recently, anti-HLA immunization was shown to increase the risk of Primary Graft Failure (PGF), a severe complication of AHSCT that occurs in 3 to 4% of matched unrelated donor transplantation and up to 15% in cord blood transplantation and T-cell depleted haplo-identical stem cell transplantation. Rates of PGF in patients with DSA were reported to be between 24 to 83% with the highest rates in haplo-identical and cord blood transplantation recipients. This led to the recommendation of anti-HLA antibody screening to detect Donor Specific Antibodies (DSA) in recipients prior to AHSCT. In this review, we highlight the role of anti-HLA antibodies in AHSCT and the mechanisms that may lead to PGF in patients with DSA, and discuss current issues in the field.
Published: 2016
Full Text: View/download PDF

4. Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party

Author: Raynier Devillier, Jean-Hugues Dalle, Austin Kulasekararaj, Maud D’aveni, Laurence Clément, Alicja Chybicka, Stéphane Vigouroux, Patrice Chevallier, Mickey Koh, Yves Bertrand, Mauricette Michallet, Marco Zecca, Ibrahim Yakoub-Agha, Jean-Yves Cahn, Per Ljungman, Marc Bernard, Pascale Loiseau, Valérie Dubois, Sébastien Maury, Gérard Socié, Carlo Dufour, and Regis Peffault de Latour
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P
Published: 2016
Full Text: View/download PDF

5. Natural killer cell licensing after double cord blood transplantation is driven by the self-HLA class I molecules from the dominant cord blood

Author: Nicolas Guillaume, Pascale Loiseau, Katia Gagne, Hélène Moins-Teissserenc, Jean-Michel Cayuela, Guylaine Henry, Marie Robin, Régis Peffault de Latour, Eliane Gluckman, Gérard Socié, Christelle Retiere, Nicolas Dulphy, and Antoine Toubert
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2016
Full Text: View/download PDF

6. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors.

Author: Suella Martino, Mathieu Jamme, Christophe Deligny, Marc Busson, Pascale Loiseau, Elie Azoulay, Lionel Galicier, Frédéric Pène, François Provôt, Antoine Dossier, Samir Saheb, Agnès Veyradier, Paul Coppo, and French Reference Center for Thrombotic Microangiopathies
Subjects: Medicine, Science
Abstract: Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population.
Published: 2016
Full Text: View/download PDF

7. Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease

Author: Isabelle Laverdière, Chantal Guillemette, Ryad Tamouza, Pascale Loiseau, Regis Peffault de Latour, Marie Robin, Félix Couture, Alain Filion, Marc Lalancette, Alan Tourancheau, Dominique Charron, Gérard Socié, and Éric Lévesque
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-versus-host disease prevalence. Indeed, an increased risk of acute graft-versus-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (hazard ratio=3.04; P=0.002), nuclear factor of activated T cells (cytoplasmic 1) (hazard ratio=2.69; P=0.004), adenosine triphosphate-binding cassette sub-family C2 (hazard ratio=3.53; P=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (hazard ratio=3.67; P=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-versus-host disease (hazard ratio=0.32–0.41; P=0.0009–0.008), those of nuclear factor of activated T cells (cytoplasmic 2) are found to increase such risk (hazard ratio=3.85; P=0.0004). None of the tested single nucleotide polymorphisms was associated with the occurrence of chronic graft-versus-host disease. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential role of germline biomarkers in predicting acute graft-versus-host disease. Further investigations are warranted to improve our understanding of these relationships to personalize immunosuppressive therapy and optimize outcomes.
Published: 2015
Full Text: View/download PDF

8. Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation

Author: Vissal David Kheav, Marc Busson, Catherine Scieux, Régis Peffault de Latour, Guitta Maki, Philippe Haas, Marie-Christine Mazeron, Maryvonnick Carmagnat, Emeline Masson, Aliénor Xhaard, Marie Robin, Patricia Ribaud, Nicolas Dulphy, Pascale Loiseau, Dominique Charron, Gérard Socié, Antoine Toubert, and Hélène Moins-Teisserenc
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Natural killer cells are the first lymphocyte subset to reconstitute, and play a major role in early immunity after allogeneic hematopoietic stem cell transplantation. Cells expressing the activating receptor NKG2C seem crucial in the resolution of cytomegalovirus episodes, even in the absence of T cells. We prospectively investigated natural killer-cell reconstitution in a cohort of 439 adult recipients who underwent non-T-cell-depleted allogeneic hematopoietic stem cell transplantation between 2005 and 2012. Freshly collected blood samples were analyzed 3, 6, 12 and 24 months after transplantation. Data were studied with respect to conditioning regimen, source of stem cells, underlying disease, occurrence of graft-versus-host disease, and profiles of cytomegalovirus reactivation. In multivariate analysis we found that the absolute numbers of CD56bright natural killer cells at month 3 were significantly higher after myeloablative conditioning than after reduced intensity conditioning. Acute graft-versus-host disease impaired reconstitution of total and CD56dim natural killer cells at month 3. In contrast, high natural killer cell count at month 3 was associated with a lower incidence of chronic graft-versus-host disease, independently of a previous episode of acute graft-versus-host disease and stem cell source. NKG2C+CD56dim and total natural killer cell counts at month 3 were lower in patients with reactivation of cytomegalovirus between month 0 and month 3, but expanded greatly afterwards. These cells were also less numerous in patients who experienced later cytomegalovirus reactivation between month 3 and month 6. Our results advocate a direct role of NKG2C-expressing natural killer cells in the early control of cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.
Published: 2014
Full Text: View/download PDF

9. Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Société Francophone d’Histocompatibilité et d’Immunogénétique (SFHI) and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) analysis

Author: Annalisa Ruggeri, Vanderson Rocha, Emeline Masson, Myriam Labopin, Renato Cunha, Lena Absi, Ali Boudifa, Brigitte Coeffic, Anne Devys, Muriel De Matteis, Valérie Dubois, Daniel Hanau, Françoise Hau, Isabelle Jollet, Dominique Masson, Beatrice Pedron, Pascale Perrier, Christophe Picard, Annie Ramouneau-Pigot, Fernanda Volt, Dominique Charron, Eliane Gluckman, and Pascale Loiseau
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: Graft failure is a major complication after unrelated cord blood transplantation. Presence of HLA-antibodies before cord blood transplantation may impact graft failure. To analyze the effect of anti-HLA antibodies on unrelated cord blood transplantation outcomes, we analyzed 294 unrelated cord blood transplant recipients after reduced intensity conditioning regimen. The majority of the patients (82%) were transplanted for malignancies, 60% with double-unrelated cord blood transplant, 63% were HLA mismatched. Retrospectively, pre-unrelated cord blood transplant serum was tested for HLA-Ab using Luminex™ platform. Results were interpreted as mean fluorescence intensity (MFI) against donor-specific mismatch. Among 62 recipients (23%) who had anti-HLA antibodies before unrelated cord blood transplant, 14 patients had donor specific anti-HLA antibodies (DSA) (7 were donor-specific anti-HLA antibodies for single unrelated cord blood transplant and 7 for double unrelated cord blood transplant). Donor specific anti-HLA antibodies threshold ranged from 1620–17629 of mean fluorescence intensity (MFI). Cumulative incidence of Day-60 neutrophil engraftment was 76%: 44% for recipients with donor specific anti-HLA antibodies and 81% in those without donor specific anti-HLA antibodies (P=0.006). The cumulative incidence of 1-year transplant related mortality was 46% in patients with donor specific anti-HLA antibodies and 32% in those without antibodies (P=0.06). The presence of donor specific anti-HLA antibodies was associated with a trend for decreased survival rate (42% vs. 29%; P=0.07). Donor specific anti-HLA antibody in recipients of unrelated cord blood transplant is associated with graft failure and decreased survival. Patient’s screening for donor specific anti-HLA antibodies before unrelated cord blood transplantation is recommended before choosing an HLA mismatched cord blood unit. Whenever possible it is important to avoid selecting a unit for which the patient has donor specific anti-HLA antibodies.
Published: 2013
Full Text: View/download PDF

10. A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.

Author: Didier Payen, Anne-Claire Lukaszewicz, Matthieu Legrand, Etienne Gayat, Valérie Faivre, Bruno Megarbane, Elie Azoulay, Fabienne Fieux, Dominique Charron, Pascale Loiseau, and Marc Busson
Subjects: Medicine, Science
Abstract: BackgroundTo investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis.Methodology/principal findingsProspective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to "no AKI" and mild AKI (pConclusionsAKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.
Published: 2012
Full Text: View/download PDF

11. Phenotype frequencies of autosomal minor histocompatibility antigens display significant differences among populations.

Author: Eric Spierings, Matthijs Hendriks, Léna Absi, Angelica Canossi, Sonal Chhaya, John Crowley, Harry Dolstra, Jean-François Eliaou, Tom Ellis, Jürgen Enczmann, Maria E Fasano, Thibaut Gervais, Clara Gorodezky, Brigitte Kircher, David Laurin, Mary S Leffell, Pascale Loiseau, Mari Malkki, Miroslaw Markiewicz, Miryam Martinetti, Etsuko Maruya, Narinder Mehra, Fatma Oguz, Machteld Oudshoorn, Noemi Pereira, Rajni Rani, Ruhena Sergeant, Jackie Thomson, Thuong Hien Tran, Hannu Turpeinen, Kuo-Liang Yang, Renata Zunec, Mary Carrington, Peter de Knijff, and Els Goulmy
Subjects: Genetics, QH426-470
Abstract: Minor histocompatibility (H) antigens are allogeneic target molecules having significant roles in alloimmune responses after human leukocyte antigen-matched solid organ and stem cell transplantation (SCT). Minor H antigens are instrumental in the processes of transplant rejection, graft-versus-host disease, and in the curative graft-versus-tumor effect of SCT. The latter characteristic enabled the current application of selected minor H antigens in clinical immunotherapeutic SCT protocols. No information exists on the global phenotypic distribution of the currently identified minor H antigens. Therefore, an estimation of their overall impact in human leukocyte antigen-matched solid organ and SCT in the major ethnic populations is still lacking. For the first time, a worldwide phenotype frequency analysis of ten autosomal minor H antigens was executed by 31 laboratories and comprised 2,685 randomly selected individuals from six major ethnic populations. Significant differences in minor H antigen frequencies were observed between the ethnic populations, some of which appeared to be geographically correlated.
Published: 2007
Full Text: View/download PDF

12. HLA-matched unrelated donors for patients with sickle cell disease: results of international donor searches

Author: Neifi Hassan Saloum Degaide, Margareth Torres, Danielli C. M. Oliveira, Eliane Gluckman, Simone Kashima, Ana Cristina Silva Pinto, Graziana Maria Scigliuolo, Ryad Tamouza, Annalisa Ruggeri, Vanderson Rocha, Juliana Fernandes Cardoso, Barbara Cappelli, Pascale Loiseau, Hendrik Veelken, Evandra Strazza Rodrigues, Hanadi Elayoubi, Chantal Kenzey, Alina Ferster, Belinda Pinto Simões, Karina Tozatto-Maio, and Fernanda Volt
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Hematopoietic stem cell transplantation, Anemia, Sickle Cell, Human leukocyte antigen, Ethnic origin, Disease, 03 medical and health sciences, 0302 clinical medicine, HLA Antigens, Internal medicine, medicine, Humans, Registries, Sibling, Allele, Unrelated donor search, Transplantation, business.industry, Histocompatibility Testing, Sickle cell disease, Haplotype, Hematology, medicine.disease, Transplantation d'organes, Tissue Donors, HLA, Hemoglobinopathy, 030220 oncology & carcinogenesis, Stem cell donor registry, Unrelated Donors, business, Brazil, Hématologie, 030215 immunology
Abstract: Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Hematopoietic stem cell transplantation (HCT) is the sole curative therapy for SCD, but few patients will have a matched sibling donor. Patients with SCD are mostly of African origin and thus are less likely to find a matched unrelated donor in international registries. Using HaploStats, we estimated HLA haplotypes for 185 patients with SCD (116 from a Brazilian center and 69 from European Society for Blood and Marrow Transplantation [EBMT] centers) and classified the ethnic origin of haplotypes. Then we assessed the probability of finding an HLA-matched unrelated adult donor (MUD), considering loci A, B, and DRB1 (6/6), in international registries. Most haplotypes were African, but Brazilians showed a greater ethnic admixture than EBMT patients. Nevertheless, the chance of finding at least one 6/6 potential allelic donor was 47% for both groups. Most potential allelic donors were from the US National Marrow Donor Program registry and from the Brazilian REDOME donor registry. Although the probability of finding a donor is higher than previously reported, strategies are needed to improve ethnic diversity in registries. Moreover, predicting the likelihood of having an MUD might influence SCD management., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2020

13. HLA-DRB1*11 is a strong risk factor for acquired thrombotic thrombocytopenic purpura in children

Author: Alain Stepanian, Agnès Veyradier, Paul Coppo, Michael Darmon, Hervé Chambost, Jérôme Harambat, Bérangère S. Joly, Fanny Fouyssac, Vincent Guigonis, Pascale Loiseau, Thierry Leblanc, Service d’Hématologie Biologique [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Biologique [Hôpital Robert Debré, Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Pédiatrie médicale [CHU Limoges], CHU Limoges, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), AP-HP - Hôpital Antoine Béclère [Clamart], Programme Hospitalier Recherche Clinique AOM 05012CSL-Behring AP-HP-2017-47-26, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and Lucas, Nelly
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Thrombotic thrombocytopenic purpura, ADAMTS13 Protein, Human leukocyte antigen, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Von Willebrand factor, Risk Factors, medicine, HLA-DQ beta-Chains, Humans, Risk factor, Child, Letters to the Editor, HLA-DRB1, ComputingMilieux_MISCELLANEOUS, Acquired Thrombotic Thrombocytopenic Purpura, Purpura, Thrombotic Thrombocytopenic, biology, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, medicine.disease, ADAMTS13, 3. Good health, Immunology, biology.protein, business, HLA-DRB1 Chains, 030215 immunology
Abstract: International audience
Published: 2020
Full Text: View/download PDF

14. Codage HLA dans ProMISe : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Cécile Veron, Anne Kennel, Maguy Pereira, Ibrahim Yakoub-Agha, Catherine Faucher, Pascale Loiseau, and Nicole Raus
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Bone marrow transplantation, Marrow transplantation, business.industry, Hematology, General Medicine, Human leukocyte antigen, Transplantation, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, Radiology, Nuclear Medicine and imaging, Stem cell, business, 030215 immunology
Abstract: As part of the 7th Annual francophone workshop series on the harmonization of clinical practices in allogeneic stem cell transplantation held in Lille in September 2016, our workgroup discussed how transplant centers might follow a collective approach to coding data. This was done mainly by analyzing the study results found in the literature that do not provide clear answers. In addition, we discuss practical ways of coding for both donor and recipient HLA typing in the European bone marrow transplantation database called ProMISe which is managed by the European Society for Blood and Marrow Transplantation (EBMT).
Published: 2017
Full Text: View/download PDF

15. [Haploidentical hematopoietic stem cell transplant: How to choose the best donor? Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]

Author: Bénédicte Bruno, C. Giannoli, Valérie Dubois, Stéphanie Nguyen, Pascale Loiseau, Raynier Devillier, Paul-Olivier Rouzaire, Patrice Chevallier, Ibrahim Yakoub-Agha, Kahina Amokrane, Mhamed Harif, Gwendaline Guidicelli, Florent Delbos, Yves Beguin, Pauline Varlet, CCSD, Accord Elsevier, Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie, Université de Liège, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], Etablissement Français du Sang [Nantes], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etablissement français du sang- Rhône-Alpes [Lyon], Service d'immunologie et d'immunogénétique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux], Immunogénétique humaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Lille (CHU de Lille), Department of Microbiology and Immunology, East Carolina University [Greenville] (ECU), and University of North Carolina System (UNC)-University of North Carolina System (UNC)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Myeloid, Haploidentical transplantation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Human leukocyte antigen, Hematopoietic stem cell transplantation, DSA, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Donor choice, medicine, Radiology, Nuclear Medicine and imaging, Greffe haplo-identique, 10. No inequality, Gynecology, business.industry, Hematology, General Medicine, medicine.disease, 3. Good health, Lymphoma, [SDV] Life Sciences [q-bio], Specific antibody, 030104 developmental biology, medicine.anatomical_structure, Oncology, Bone transplantation, 030220 oncology & carcinogenesis, Choix du donneur, Bone marrow, Stem cell, business
Abstract: International audience; Haploidentical hematopoietic stem cell transplantation has been growing steadily since 2012. The SFGM-TC has twice published guidelines concerning T-cell repleted haploidentical grafts with high dose cyclophosphamide post-transplantation. The 2013 workshop recommended using the non-myeloablative Baltimore protocol with bone marrow and developed prospective protocols to evaluate these transplantations. The 2015 workshop reported improved results of reduced conditioning regimens in Hodgkin's lymphoma and intensive conditioning in myeloid hemopathies, and a similar outcome with 10/10 HLA matched donor with the same disease-risk score thus raising the question of the qualifier "alternative" for haploidentical transplants. The current work concerns the criteria for selecting the donor. The main criterion remains the absence of anti-HLA antibodies directed against the donor present in the recipient sera (DSA - Donor Specific Antibodies). In case of DSA and in the absence of an alternative donor, desensitization protocols exist. The other criteria are impossible to prioritize: age, sex, CMV, and blood type. The degree of relatedness and the number of HLA incompatibilities do not seem to be a criterion of choice. The 'ideal' donor would be a young man, CMV-matched, without major ABO incompatibility with a marrow transplant. There is insufficient data for the KIR-ligand and NIMA/NIPA mismatch. Peripheral stem cell grafts appear to yield more acute GVHD than bone marrow grafts after intensive conditioning, but with comparable survival rates. Based on the literature review, the comparison of haploidentical with unrelated donors encourages inclusion in existing national protocols randomizing these different donors.
Published: 2020
Full Text: View/download PDF

16. Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus host disease in conjunction with the CMV status

Author: Philippe Moreau, Machteld Oudshoorn, Catherine Paillard, Valérie Dubois, Raphael Carapito, Irina Kotova, Antoine Toubert, Ismail Aouadi, Perrine Spinnhirny, Eric Spierings, A. Parissiadis, Ibrahim Yakoub-Agha, Mauricette Michallet, Myriam Labalette, Seiamak Bahram, Régis Peffault de Latour, Jürgen Kuball, Mohamad Mohty, Christophe Picard, Bronno van der Holt, Didier Blaise, Ryad Tamouza, Myriam Maumy-Bertrand, Frédéric Bertrand, Pascale Loiseau, Véronique Rolli, Jan J. Cornelissen, Aurore Morlon, Anne Cesbron, Gérard Socié, Yasuo Morishima, Peter A. von dem Borne, Frans H.J. Claas, Cécile Macquin, Angélique Pichot, Bruno Lioure, Dominique Charron, Katia Gagne, Equipe Plate-forme GENOMAX (Inserm U1109), Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA)-Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), INSERM Franco-Japanese Nextgen HLA Laboratory [Strasbourg] (FJ-HLA), Laboratoire International Associé (LIA), INSERM Franco-Japanese Nextgen HLA Laboratory[Nagano], Pôle de Biologie - Laboratoire d’Immunologie [Nouvel Hôpital Civil, Strasbourg] (Plateau Technique de Biologie), Nouvel Hôpital Civil - NHC [Strasbourg], BIOMICA SA [Strasbourg], Etablissement Français du Sang [Nantes], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Europdonor operated by Matchis Foundation [Leiden], Leiden University Medical Center (LUMC), Erasmus MC Cancer Institute, Rotterdam, Laboratoire d'Immunologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University Medical Center [Utrecht], Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Ecotaxie, microenvironnement et développement lymphocytaire (EMily (UMR_S_1160 / U1160)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Hôtel-Dieu [Paris], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre & marie Curie, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Aichi Cancer Center Research Institute, This work was supported by grants from the Agence Nationale de la Recherche (ANR) (ANR-11-LABX-0070_TRANSPLANTEX), and the INSERM (UMR_S 1109), the Institut Universitaire de France (IUF), all to SB, from the University of Strasbourg (IDEX UNISTRA) to CP and SB, from the European regional development fund (European Union) INTERREG V program (project n°3.2 TRIDIAG) to RC and SB, and from MSD-Avenir grant AUTOGEN to SB., We would like to thank Prof. Robert Zeiser (University of Freiburg/Germany) for critical reading of this manuscript. We thank Martin Verniquet for critical review of statistical analyses. We would also like to thank Nicole Raus (SFGM-TC, Lyon, France) for retrieving the clinical data from the ProMISe database., Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Hospitalo-Universitaire OMICARE-Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Universiteit Leiden, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hematology, Erasmus MC other, and Bernardo, Elizabeth
Subjects: medicine.medical_specialty, Congenital cytomegalovirus infection, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Typing, Amino Acids, Retrospective Studies, Transplantation, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Hematopoietic Stem Cell Transplantation, Hematology, medicine.disease, 3. Good health, Graft-versus-host disease, 030220 oncology & carcinogenesis, Cytomegalovirus Infections, business, 030215 immunology
Abstract: International audience; Graft-versus-host disease (GVHD) and cytomegalovirus (CMV)-related complications are leading causes of mortality after unrelated-donor hematopoietic cell transplantation (UD-HCT). The non-conventional MHC class I gene MICB, alike MICA, encodes a stress-induced polymorphic NKG2D ligand. However, unlike MICA, MICB interacts with the CMV-encoded UL16, which sequestrates MICB intracellularly, leading to immune evasion. Here, we retrospectively analyzed the impact of mismatches in MICB amino acid position 98 (MICB98), a key polymorphic residue involved in UL16 binding, in 943 UD-HCT pairs who were allele-matched at HLA-A, -B, -C, -DRB1, -DQB1 and MICA loci. HLA-DP typing was further available. MICB98 mismatches were significantly associated with an increased incidence of acute (grade II-IV: HR, 1.20; 95% CI, 1.15 to 1.24; P < 0.001; grade III-IV: HR, 2.28; 95% CI, 1.56 to 3.34; P < 0.001) and chronic GVHD (HR, 1.21; 95% CI, 1.10 to 1.33; P < 0.001). MICB98 matching significantly reduced the effect of CMV status on overall mortality from a hazard ratio of 1.77 to 1.16. MICB98 mismatches showed a GVHD-independent association with a higher incidence of CMV infection/reactivation (HR, 1.84; 95% CI, 1.34 to 2.51; P < 0.001). Hence selecting a MICB98-matched donor significantly reduces the GVHD incidence and lowers the impact of CMV status on overall survival.
Published: 2020
Full Text: View/download PDF

17. Polymorphisme des gènes HLA et KIR et l’impact sur le devenir de la greffe et le choix du donneur non apparenté de cellules souche hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author: Pauline Varlet, Florent Delbos, Anne Brignier, Ibrahim Yakoub-Agha, Valérie Dubois, Vincent Elsermans, Christophe Picard, Katia Gagne, Anne Kennel, Béatrice Pédron, Anne Cesbron, Aurélie Ravinet, Pascale Loiseau, Sociétés, Acteurs, Gouvernement en Europe (SAGE), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne (PRISME-GSPE), Centre National de la Recherche Scientifique (CNRS), Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Service Immunologie Biologique [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Etablissement Français du Sang [Nantes], Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Recherche en Communications et en Cybernétique de Nantes (IRCCyN), Mines Nantes (Mines Nantes)-École Centrale de Nantes (ECN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS), Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne ( PRISME-GSPE ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'hématologie ( ERL 8254 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut de Recherche en Communications et en Cybernétique de Nantes ( IRCCyN ), Mines Nantes ( Mines Nantes ) -École Centrale de Nantes ( ECN ) -Ecole Polytechnique de l'Université de Nantes ( Polytech Nantes ), Université de Nantes ( UN ) -Université de Nantes ( UN ) -PRES Université Nantes Angers Le Mans ( UNAM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Mines Nantes (Mines Nantes)-École Centrale de Nantes (ECN)-Ecole Polytechnique de l'Université de Nantes (Polytech Nantes)
Subjects: Cancer Research, medicine.medical_specialty, Bone marrow transplantation, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Unrelated Donor, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Radiology, Nuclear Medicine and imaging, ComputingMilieux_MISCELLANEOUS, Gynecology, [ SDV ] Life Sciences [q-bio], business.industry, French, Hematology, General Medicine, language.human_language, 3. Good health, Clinical Practice, Transplantation, Oncology, 030220 oncology & carcinogenesis, language, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030215 immunology
Abstract: In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country with the purpose of offering careful analysis of published studies on clinical practice issues that remain to be disputed. This article addresses the impact of HLA and KIR gene polymorphism on the outcome of the transplantation in order to optimize unrelated donor selection.
Published: 2016
Full Text: View/download PDF

18. Recovery of central memory and naive peripheral T cells in Follicular Lymphoma patients receiving rituximab-chemotherapy based regimen

Author: Nathalie Josseaume, P. Brice, Sandy Amorim, Quentin Riller, Benoit Milcent, Sophie Sibéril, Florent Petitprez, Jean-Luc Teillaud, Catherine Thieblemont, Antoine Toubert, Pascale Loiseau, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), NF-kappaB, Différenciation et Cancer (OncokappaB - EA 7324), Université Paris Descartes - Paris 5 (UPD5), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Dieu-Nosjean, Marie-Caroline, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Teillaud, Jean-Luc, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Follicular lymphoma, lcsh:Medicine, CD38, Lymphocyte Activation, 0302 clinical medicine, Immunophenotyping, immune system diseases, T-Lymphocyte Subsets, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, lcsh:Science, Lymphoma, Follicular, Immunity, Cellular, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Treatment Outcome, Vincristine, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Female, Immunotherapy, medicine.drug, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Adaptive immunity, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, TIGIT, medicine, Humans, Lymphocyte Count, Cyclophosphamide, Aged, Neoplasm Staging, business.industry, lcsh:R, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, 030104 developmental biology, Doxorubicin, Cancer research, Prednisone, lcsh:Q, Neoplasm Grading, business, Immunologic Memory, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers
Abstract: International audience; Preclinical models and clinical studies have shown that anti-CD20-based treatment has multifaceted consequences on t-cell immunity. We have performed a prospective study of peripheral t-cell compartment in FL patients, all exhibiting high tumor burden and receiving rituximab-chemotherapy-based regimen (R-CHOP). Before treatment, FL patients harbor low amounts of peripheral naive T cells, but high levels of CD4 + t eM , CD4 + t reg and CD8 + t eMRA subsets and significant amounts of CD38 + HLA-DR + activated T cells. A portion of these activated/differentiated T cells also expressed PD-1 and/or TIGIT immune checkpoints. Hierarchical clustering of phenotyping data revealed that 5/8 patients with only a partial response to R-cHop induction therapy or with disease progression segregate into a group exhibiting a highly activated/differentiated T cell profile and a markedly low proportion of naive T cells before treatment. Rituximab-based therapy induced a shift of CD4 + and CD8 + t cells toward a central memory phenotype and of CD8 + T cells to a naive phenotype. In parallel, a decrease in the number of peripheral T cells expressing both PD-1 and TIGIT was detected. These observations suggest that the standard rituximab-based therapy partially reverts the profound alterations observed in t-cell subsets in FL patients, and that blood T-cell phenotyping could provide a better understanding of the mechanisms of rituximab-based treatment. Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL). Its clinical course is highly variable and survival medians are 7-15 years depending on the studies. Follicular lymphoma management is characterized by a risk-adapted therapy based on the stage of the disease and the symptoms of the patients. For high tumor burden patients, treatment options could be either rituximab plus cyclophosphamide, vincristine and prednisone with (R-CHOP) or without (R-CVP) doxorubicin or other anthracyclines, or rituxi-mab plus fludarabine for patients not eligible for anthracyclines, or rituximab plus bendamustine. Experimental therapies as well as allogeneic stem cell transplantation are rather considered for relapsed and more refractory disease 1. The addition of the anti-CD20 monoclonal antibody (mAb) rituximab to chemotherapy has resulted in a higher rate of complete remission and improved survival 2. In addition, rituximab as maintenance therapy
Published: 2019
Full Text: View/download PDF

19. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Author: Christophe Picard, Cécile Macquin, Sergi Querol, Catherine Paillard, Katharina Fleischhauer, Gaëlle Giacometti, Bronno van der Holt, Ibrahim Yakoub-Agha, Wassila Ilias, Anne Cesbron, Myriam Labopin, Masao Ota, Jorge Sierra, Fabio Ciceri, Dominique Charron, Ryad Tamouza, Régis Peffault de Latour, Xavier Lafarge, Katia Gagne, Seiamak Bahram, Myriam Maumy-Bertrand, Meiggie Untrau, Pascale Loiseau, Raphael Carapito, Jürgen Kuball, Bruno Lioure, Frans H.J. Claas, Noel Milpied, Antoine Toubert, Jan J. Cornelissen, Irina Kotova, Philippe Moreau, Eric Spierings, Mauricette Michallet, Arnon Nagler, Annette Schmitt-Graeff, Angélique Pichot, Petya Apostolova, Mohamad Mohty, Aurore Morlon, Myriam Labalette, Nicolas Jung, Didier Blaise, Yoshihiko Katsuyama, Hidetoshi Inoko, A. Parissiadis, Frédéric Bertrand, Marius Kwemou, Sandra Michel, Machteld Oudshoorn, Gérard Socié, Robert Zeiser, Peter A. von dem Borne, Valérie Dubois, Luca Vago, Carapito, Raphael, Jung, Nicola, Kwemou, Mariu, Untrau, Meiggie, Michel, Sandra, Pichot, Angélique, Giacometti, Gaëlle, Macquin, Cécile, Ilias, Wassila, Morlon, Aurore, Kotova, Irina, Apostolova, Petya, Schmitt Graeff, Annette, Cesbron, Anne, Gagne, Katia, Oudshoorn, Machteld, Van Der Holt, Bronno, Labalette, Myriam, Spierings, Eric, Picard, Christophe, Loiseau, Pascale, Tamouza, Ryad, Toubert, Antoine, Parissiadis, Anne, Dubois, Valérie, Lafarge, Xavier, Maumy Bertrand, Myriam, Bertrand, Frédéric, Vago, Luca, Ciceri, Fabio, Paillard, Catherine, Querol, Sergi, Sierra, Jorge, Fleischhauer, Katharina, Nagler, Arnon, Labopin, Myriam, Inoko, Hidetoshi, Von Dem Borne, Peter A., Kuball, Jürgen, Ota, Masao, Katsuyama, Yoshihiko, Michallet, Mauricette, Lioure, Bruno, De Latour, Régis Peffault, Blaise, Didier, Cornelissen, Jan J., Yakoub Agha, Ibrahim, Claas, Fran, Moreau, Philippe, Milpied, Noël, Charron, Dominique, Mohty, Mohamad, Zeiser, Robert, Socié, Gérard, Bahram, Seiamak, inconnu, Inconnu, Institut de Recherche Mathématique Avancée (IRMA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), laboratoire d'Etudes et de recherches en Statistiques et Développement (LERSTAD), Université Gaston Bergé Sénégal, Laboratoire d'Acoustique Environnementale (IFSTTAR/AME/LAE), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-Université de Lyon-PRES Université Nantes Angers Le Mans (UNAM), Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Etablissement Français du Sang [Nantes], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Service de pneumologie [Rennes] = Pneumology [Rennes], CHU Pontchaillou [Rennes], Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Sociétés, Acteurs, Gouvernement en Europe (SAGE), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne (PRISME-GSPE), Centre National de la Recherche Scientifique (CNRS), Centre de Transfusion Sanguine Aquitaine-Limousin (CTS AQUITAINE-LIMOUSIN), Centre de Transfusion Sanguine, Ospedale San Raffaele, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Barcelona Cord Blood Bank, Agrosystèmes tropicaux (ASTRO), Institut National de la Recherche Agronomique (INRA), Chaim Sheba Medical Center [Ramat Gan, Israel], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Université Paris Diderot - Paris 7 (UPD7), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Immunohematology and Blood Transfusion, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'Investigations Biomédicales-Hématologie, Oncologie et Greffes (CIB-HOG), Hôpital St Louis, Assistance Publique des Hôpitaux de Paris (AP-HP), Centre d'Investigations Biomédicales-Hématologie, Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), ALWP-EBMT & Département d'hématologie et de thérapie cellulaire [AP-HP Hôpital Saint-Antoine], AP-HP - Hôpital Saint-Antoine, Hematology, Institut de Recherche Mathématique Avancée ( IRMA ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Mathématiques et Modélisation d'Evry ( LaMME ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -ENSIIE-Centre National de la Recherche Scientifique ( CNRS ), laboratoire d'Etudes et de recherches en Statistiques et Développement ( LERSTAD ), Laboratoire d'Acoustique Environnementale ( IFSTTAR/AME/LAE ), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux ( IFSTTAR ) -Université de Lyon-PRES Université Nantes Angers Le Mans ( UNAM ), Laboratoire d'Histoire des Sciences et de Philosophie - Archives Henri Poincaré ( LHSP ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Physique des interactions ioniques et moléculaires ( PIIM ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Functional Genomics and Cancer, Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes], Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Alloimmunité-Autoimmunité-Transplantation ( A2T ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Sociétés, Acteurs, Gouvernement en Europe ( SAGE ), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne ( PRISME-GSPE ), Centre National de la Recherche Scientifique ( CNRS ), Centre de Transfusion Sanguine Aquitaine-Limousin ( CTS AQUITAINE-LIMOUSIN ), Géographie de l'environnement ( GEODE ), Centre National de la Recherche Scientifique ( CNRS ) -Université Toulouse - Jean Jaurès ( UT2J ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Agrosystèmes tropicaux ( ASTRO ), Institut National de la Recherche Agronomique ( INRA ), Hospices Civils de Lyon ( HCL ), IFR Saint-Louis, institut d'hématologie ( ISLIH ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC University medical Centre / Daniel den Hoed Cancer centre, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Laboratoire de Mathématiques et Modélisation d'Evry, PRES Université Nantes Angers Le Mans (UNAM)-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-ENSIIE-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medizin, Graft vs Host Disease, Hematopoietic stem cell transplantation, Biochemistry, Linkage Disequilibrium, immune system diseases, HLA Antigens, Cytotoxic T cell, Child, ComputingMilieux_MISCELLANEOUS, HLA-DQB1, biology, Histocompatibility Testing, Incidence, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Allografts, 3. Good health, surgical procedures, operative, NK Cell Lectin-Like Receptor Subfamily K, Child, Preschool, Acute Disease, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, Adolescent, Immunology, Human leukocyte antigen, 03 medical and health sciences, MHC class I, medicine, Journal Article, Humans, Aged, Retrospective Studies, Transplantation, [ SDV ] Life Sciences [q-bio], Histocompatibility Antigens Class I, Infant, Newborn, Infant, Cell Biology, medicine.disease, Histocompatibility, stomatognathic diseases, 030104 developmental biology, Graft-versus-host disease, Chronic Disease, biology.protein
Abstract: Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B. Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA. MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice.
Published: 2016
Full Text: View/download PDF

20. Impact of the source of hematopoietic stem cell in unrelated transplants: Comparison between 10/10, 9/10-HLA matched donors and cord blood

Author: Clémence Granier, Régis Peffault de Latour, Gérard Socié, Pascale Loiseau, Jérôme Larghero, Lucie Biard, Emeline Masson, Dominique Charron, Nathalie Dhedin, Marie Robin, Etienne Lengliné, Aliénor Xhaard, Nicolas Boissel, Patricia Ribaud, and Raphaël Porcher
Subjects: Oncology, medicine.medical_specialty, Multivariate analysis, business.industry, Hematopoietic stem cell, Hematology, Human leukocyte antigen, Disease, UCB transplantation, medicine.anatomical_structure, Cord blood, Internal medicine, Immunology, medicine, Cumulative incidence, Serostatus, business
Abstract: In absence of available matched-related or unrelated donor (MUD), mismatched unrelated donors (MMUD) and unrelated cord blood (UCB) are both considered to be suitable donors, with similar post-transplant overall survival. In most of these retrospective comparisons, HLA typing of adult donors was performed at eight loci. The aim of this study was to compare the outcome of patients transplanted from UCB (N = 64) with those transplanted from 9/10-HLA MMUD (N = 84) or 10/10-HLA MUD (N = 196). In multivariate analysis, UCB was associated with less Grade II–IV acute GVHD in comparison with MUD (aHR 1.97, 95% CI 1.19–3.27, P = 0.009) and MMUD transplants (aHR 1.79, 95% CI 1.02–3.15, P = 0.042), while the cumulative incidence of chronic GVHD was not significantly different between the three groups. Overall survival (OS), non-relapse mortality, and relapse were not different between MMUD and UCB transplantation, whereas OS was impaired after UCB in comparison with MUD (aHR 0.65, 95% CI 0.43–0.99, P = 0.043). Factors also impacting OS were the donor/recipient CMV serostatus (Donor−/Recipient+ aHR 1.76, 95% CI 1.23–2.52, P = 0.002 compared with D−/R−), the donor/recipient gender combination (Female/Male versus other combinations aHR 1.57, 95% CI 1.11–2.22, P = 0.012) and disease risk (aHR 1.58, 95% CI 1.05–2.38, P = 0.027 for high vs. low risk disease). Our data confirm that UCB and 9/10-HLA MMUD are both relevant alternative options when no 10/10-HLA donor is available. Donor/recipient gender combination and CMV serostatus had a significant impact on survival and may be taken into account, along with donor type, in the setting of MMUD and UCB transplants. Am. J. Hematol. 90:897–903, 2015. © 2015 Wiley Periodicals, Inc.
Published: 2015
Full Text: View/download PDF

21. HLA-DRB3/4/5 mismatches are associated with increased risk of acute GVHD in 10/10 matched unrelated donor hematopoietic cell transplantation

Author: Virginie Moalic, A. Parissiadis, Mauricette Michallet, Matthieu Filloux, Florent Delbos, Marie-Thérèse Rubio, Edouard Forcade, Patrice Chevallier, A. Dormoy, Xavier Lafarge, Virginie Renac, Anne Cesbron, Béatrice Pédron, Christophe Picard, Pascale Loiseau, Abdelali Boudifa, Kahina Amokrane, Federico Garnier, F Quainon, Dominique Masson, Peter van Endert, Françoise Hau, M Fort, Raphaël Porcher, Ibrahim Yakoub-Agha, Valérie Dubois, Isabelle Jollet, Julie Bonneau, Etienne Daguindau, Natacha Maillard, Gérard Socié, Anne Kennel, Jacques-Olivier Bay, Anne Devys, Erwann Quelvennec, Régis Peffault de Latour, Stéphanie Ducreux, Myriam Labalette, Claude-Eric Bulabois, Muriel De Matteis, Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de neurophysiologie clinique (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Etablissement français du sang [Angers], Laboratoire de Génétique Moléculaire et d'Histocompatibilité [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Etablissement français du sang - Normandie (EFS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'histocompatibilité et d'immunogénétique [Angers], Université d'Angers (UA), Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biologie Médicale [Rennes], Etablissement français du sang [Rennes] (EFS Bretagne), Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), CHU Toulouse [Toulouse], Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Centre hospitalier universitaire de Nantes (CHU Nantes), Etablissement Français du Sang [Nantes], CHU Clermont-Ferrand, Etablissement français du sang [Clermont-Ferrand] (EFS), Agence de la biomédecine [Saint-Denis la Plaine], Hopital Saint-Louis [AP-HP] (AP-HP), Immunogénétique humaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté]), CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Subjects: Oncology, medicine.medical_specialty, Hematopoietic cell, business.industry, [SDV]Life Sciences [q-bio], Hazard ratio, Hematology, Disease, Matched Unrelated Donor, 3. Good health, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Increased risk, Unrelated Donor, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, 030215 immunology, HLA-DRB3
Abstract: International audience; Matching for HLA‐A, ‐B, ‐C, and ‐DRB1 loci (8/8 match) is currently the gold standard for unrelated donor hematopoietic cell transplantation (HCT). In Europe, patients are also matched at the HLA‐DQB1 loci (10/10 match). However, there is increasing evidence that matching at HLA‐DRB3/4/5 loci may help to lower transplant‐related morbidity and mortality. We therefore investigated the impact of HLA‐DRB3/4/5 mismatches on outcomes in 1975 patients who received a first 10/10 matched unrelated donor (MUD) HCT in France from 2000 to 2012 for a hematological malignancy. High‐resolution typing was performed at HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1, ‐DPB1, and ‐DRB3/4/5 loci for all donor/recipient pairs. Compared with DRB3/4/5‐matched pairs, patients who received a MUD HCT from a DRB3/4/5 mismatched donor had a significantly increased risk of grade II‐IV acute graft‐versus‐host disease (aGVHD) (Adjusted Hazard Ratio (HR) 1.43 (1.07 to 1.90)) associated with lower graft‐versus‐host disease‐free and relapse‐free survival (GRFS) (Adjusted HR 1.20 (1.02 to 1.42)). Conversely, we observed no differences in terms of chronic GVHD, nonrelapse mortality, relapse and overall survival. However, we believe that patients stand to benefit from DRB3/4/5 loci being considered for unrelated donor selection to improve GRFS and then quality of life after unrelated HCT.
Published: 2018
Full Text: View/download PDF

22. [HLA coding in ProMISe: Guidelines from the Francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC)]

Author: Nicole, Raus, Catherine, Faucher, Anne, Kennel, Maguy, Pereira, Cécile, Veron, Ibrahim, Yakoub-Agha, and Pascale, Loiseau
Subjects: Databases, Factual, HLA Antigens, Histocompatibility Testing, Cell- and Tissue-Based Therapy, Humans, France, Alleles, Societies, Medical, Bone Marrow Transplantation
Abstract: As part of the 7th Annual francophone workshop series on the harmonization of clinical practices in allogeneic stem cell transplantation held in Lille in September 2016, our workgroup discussed how transplant centers might follow a collective approach to coding data. This was done mainly by analyzing the study results found in the literature that do not provide clear answers. In addition, we discuss practical ways of coding for both donor and recipient HLA typing in the European bone marrow transplantation database called ProMISe which is managed by the European Society for Blood and Marrow Transplantation (EBMT).
Published: 2017

23. Human Leukocyte Antigen Matched Unrelated Donors for Patients with Sickle Cell Disease According to Geographic Origin: Results of International Donor Searches

Author: Belinda Pinto Simões, Chantal Kenzey, Eliane Gluckman, Pascale Loiseau, Fernanda Volt, Graziana Maria Scigliuolo, Vanderson Rocha, Evandra Strazza Rodrigues, Hanadi Elayoubi, Renato Cunha, Barbara Cappelli, Ana Cristina Silva Pinto, Annalisa Ruggeri, Karina Tozatto-Maio, Alina Ferster, Juliana Fernandes Cardoso, Neifi Hassan Saloum Degaide, Hendrik Veelken, Danielli C. M. Oliveira, Ryad Tamouza, Margareth Afonso Torres, and Simone Kashima
Subjects: business.industry, medicine.medical_treatment, Immunology, Cell, Cell Biology, Hematology, Hematopoietic stem cell transplantation, Disease, Human leukocyte antigen, medicine.disease, Biochemistry, Sickle cell anemia, medicine.anatomical_structure, Geographic origin, HLA-A2 Antigen, medicine, Stem cell donor, business
Abstract: Background: Hematopoietic stem cell transplantation (HSCT), the only available curative therapy for sickle cell disease (SCD), remains hampered by the lack of histocompatible stem cell donors. Most patients will not have a suitable human leukocyte antigen(HLA) matched sibling donor. In addition, SCD affects ethnic groups that are underrepresented in stem cell donor registries worldwide. Objective: to assess the probability of having a potential allelic HLA matched unrelated donor(MUD) for HLA-A,B and DRB1 loci (6/6) in international donor registries for patients with SCD. Methods: 185 patients with SCD were included, 116 from Brazil, of whom 23 underwent HSCT, and 69 patients who underwent HSCT in centers reporting to the European Society for Blood and Marrow Transplantation (EBMT). All patients had HLA typing available at intermediate or high resolution. For intermediate resolution, using the National Marrow Donor Program (NMDP) code, we assigned alleles based on allele frequencies.We performed HLA haplotype estimation using the HaploStats website, which describes HLA haplotype frequency from the NMDP registry for the following ethnic groups: Caucasian, African-American, Asian, Hispanic and Native American. Because Hispanic is not a primary ethnicity, we did not consider this group in our analyses. Based on haplotype frequency of each ethnic group, we defined the most likely ethnicity for each estimated haplotype; those with frequency >1:1000 in all ethnic groups were named common. Unrelated donor search was done using the World Marrow Donor Association (WMDA) algorithm, which is based on haplotype matching. A potential allelic donor was defined as a full match high resolution 6/6 donor. Because it is described that testing at least 5 potential allelic donors simultaneously increases the chances of having a real donor, we assessed the probability of finding at least 1 and at least 5 potential allelic donors. Patients who received HSCT from MUD were excluded from donor searches (n=10).Comparisons of probabilities of having potential allelic donors between Brazilian and EBMT cohorts were performed by chi-square. Results: In the Brazilian cohort, from 181 HLA haplotypes, 45% were classified as African-American, 18% common, 12% Caucasian, 9% Amerindian and 16% could not be classified. In the EBMT cohort, from 116 HLA haplotypes, 70% were classified as African-American, 8% common, 6% Caucasian, 3% Amerindian and 13% were not classified. Although Brazilians showed greater genetic admixture, chances of finding at least one potential allelic MUD were 47% in both groups (p-value not significant) and chances of having at least 5 potential allelic MUD were 24% for Brazilians and 15% for EBMT (p-value not significant). Overall, most potential allelic MUD were found in the NMDP registry, followed by the Brazilian registry (REDOME) and by the German registry (ZKMD); for the Brazilian cohort, most potential allelic MUD were found in REDOME. Discussion: Migration from Africa to Brazil started at the colonial period, and interethnic admixture have been occurring since then, explaining the higher diversity observed in the Brazilian cohort. Despite differences in ethnic composition, chances of having at least one potential allelic MUD are identical, probably because carrying at least one African or Amerindian haplotype decreases the chances of a full HLA matching. Although we demonstrated higher probabilities of finding a potential allelic MUD in SCD than previous studies, the chances are still low, therefore further strategies are required to increase donor representativeness for SCD. In this setting, alternative sources, such as haploidentical HSCT and cord blood, should be considered. Also, our study might help to predict the probabilities of finding a MUD for patients with SCD. This is important because given that HSCT in SCD has better results if performed at earlier age, knowing which patients are less likely to find a MUD might influence therapy management. Disclosures No relevant conflicts of interest to declare.
Published: 2019
Full Text: View/download PDF

24. HLA phenotypes of candidates for HSCT: comparing transplanted versus non-transplanted candidates, resulting in the predictive estimation of the probability to find a 10/10 HLA matched donor

Author: M. L. Balère, C. Faucher, Evelyne Marry, A. Dormoy, Pierre-Antoine Gourraud, F. Garnier, and Pascale Loiseau
Subjects: Receiver operating characteristic, Immunology, Haplotype, Locus (genetics), General Medicine, Human leukocyte antigen, Biology, Biochemistry, Phenotype, Unrelated Donor, Sample size determination, Genetics, Immunology and Allergy, Allele
Abstract: In order to study the impact of human leucocyte antigen (HLA) polymorphism distribution in identifying a matched haematopoietic stem cells unrelated donor (UD), we performed a multi-centric retrospective analysis with the aim of comparing the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 phenotypes of 2126 patients (772 patients for whom a donor search failed to identify a matched UD, and 1354 patients who received a 10/10 allele level matched UD). Our results showed that rare HLA-C is often responsible for difficulty in identifying a donor. This locus may add a degree of complexity to a supposed ‘frequent’ HLA-A HLA-B and HLA-DRB1 phenotype, turning this phenotype into a less frequent one. For example, 32.5% of the phenotypes in the non-transplanted patients could not be explained by any of the pairs of known HLA-A, HLA-B, HLA-C and HLA-DRB1 haplotypes while this percentage dropped to less than 2% if combinations of only HLA-A, HLA-B and HLA-DRB1 haplotypes were considered. Such situations can be anticipated by computing an index, based on HLA haplotype frequency, the average registry sample size (ARS). ARS is defined as the inverse of the phenotype frequency computed using all corresponding pairs of haplotype frequencies. ARS confirmed that the most significant difference between transplanted and non-transplanted patients was correlated with the introduction of the locus HLA-C in the analysis (median: 8.3e + 4 vs 3.1e + 6, P
Published: 2013
Full Text: View/download PDF

25. Corrigendum: Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

Author: Hocine R. Hocine, Luis R. Borlado, Jérôme Giustiniani, Noemie Dam, Reem Al-Daccak, Itziar Palacios, Pascale Loiseau, Nabila Jabrane-Ferrat, Hicham El Costa, Armand Bensussan, Caroline Suberbielle, and Dominique Charron
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Article, Antibodies, 03 medical and health sciences, HLA Antigens, Internal medicine, medicine, Humans, Progenitor cell, Typographical error, Sensitization, Multidisciplinary, business.industry, Histocompatibility Testing, Myocardium, Stem Cells, Derived stem, Corrigenda, Spelling, Immunity, Humoral, body regions, 030104 developmental biology, medicine.anatomical_structure, business, Stem Cell Transplantation
Abstract: Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are currently under clinical investigation for cardiac repair. While cellular immune response against allogeneic hCPC could be part of their beneficial-paracrine effects, their humoral immune response remains largely unexplored. Donor-specific HLA antibodies (DSA-HLA-I/DSA-HLA-II), primary elements of antibody-mediated allograft injury, might present an unidentified risk to allogeneic hCPC therapy. Here we established that the binding strength of anti-HLA monoclonal antibodies delineates hCPC proneness to antibody-mediated injury. In vitro modeling of clinical setting demonstrated that specific DSA-HLA-I of high/intermediate binding strength are harmful for hCPC whereas DSA-HLA-II are benign. Furthermore, the Luminex-based solid-phase assays are suitable to predict the DSA-HLA risk to therapeutic hCPC. Our data indicate that screening patient sera for the presence of HLA antibodies is important to provide an immune-educated choice of allogeneic therapeutic cells, minimize the risk of precipitous elimination and promote the allogeneic reparative effects.
Published: 2017

26. Donor Specific Antibodies are not only directed against HLA-DR: Minding your Ps and Qs

Author: Pascale Loiseau, Jean-Luc Taupin, Julien Lion, Amy Cross, Denis Glotz, Dominique Charron, Nuala Mooney, Immunogénétique humaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital d'Instruction des Armées du Val de Grâce, and Service de Santé des Armées
Subjects: 0301 basic medicine, Graft Rejection, HLA-DP Antigens, [SDV]Life Sciences [q-bio], Immunology, HLA-DP, Human leukocyte antigen, Histocompatibility Testing, 030230 surgery, Biology, Isoantibodies, 03 medical and health sciences, Epitopes, 0302 clinical medicine, Antigen, Transplantation Immunology, HLA-DQ Antigens, HLA-DQ, HLA-DR, Immunology and Allergy, Humans, ComputingMilieux_MISCELLANEOUS, HLA-DQ Antigen, Graft Survival, Antibody-Dependent Cell Cytotoxicity, Hematopoietic Stem Cell Transplantation, General Medicine, HLA-DR Antigens, Kidney Transplantation, 3. Good health, Immunity, Humoral, body regions, 030104 developmental biology, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: During solid organ transplantation, interactions between recipient and donor immune cells occur chiefly in the allograft microvasculature. All three HLA class II antigens, DR, DP and DQ, have been detected on renal EC with a markedly increased expression of HLA class II observed in renal allografts undergoing rejection. Recent studies of donor-specific antibodies (DSA) have exposed the prevalence of de novo DSA directed against HLA-DQ, as well as a strong association between these antibodies and allograft damage. The HLA-DQ molecule can be distinguished from the other class II antigens by its transcription, expression and peptide repertoire. The distinct intragraft expression and immunogenicity of HLA-DQ may contribute to the incidence of HLA-DQ DSA, as well as directing the DSA-mediated damage. The possibility of HLA class II antigen-specific signaling in EC may reveal different mechanisms of allograft damage that act in tandem with complement-dependent injury. This review addresses the features of the HLA-DQ heterodimer that may underlie the high incidence of HLA-DQ directed DSA and their association with allograft damage. We also consider existing data in hematopoietic stem cell transplantation concerning HLA directed DSA.
Published: 2016
Full Text: View/download PDF

27. [Polymorphism in HLA and KIR genes and the impact on hematopoietic stem cell transplantation outcomes and unrelated donor selection: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]

Author: Valérie, Dubois, Anne, Brignier, Vincent, Elsermans, Katia, Gagne, Anne, Kennel, Béatrice, Pedron, Christophe, Picard, Aurélie, Ravinet, Pauline, Varlet, Anne, Cesbron, Florent, Delbos, Ibrahim, Yakoub-Agha, and Pascale, Loiseau
Subjects: Polymorphism, Genetic, Treatment Outcome, Genotype, Receptors, KIR, Histocompatibility, Histocompatibility Antigens, Hematopoietic Stem Cell Transplantation, Humans, France, Alleles, Societies, Medical, Donor Selection
Abstract: In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country with the purpose of offering careful analysis of published studies on clinical practice issues that remain to be disputed. This article addresses the impact of HLA and KIR gene polymorphism on the outcome of the transplantation in order to optimize unrelated donor selection.
Published: 2016

28. Impact of KIR/HLA genetic combinations on double umbilical cord blood transplantation outcomes. Results of a French multicentric retrospective study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and the Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI)

Author: F Quainon, Evelyne Marry, C Retière, J.-F. Eliaou, A. Parissiadis, O Avinens, A Boudifa, Dominique Masson, N Legrand, Nicole Raus, Ibrahim Yakoub-Agha, A Batho, P Rettman, Florent Delbos, David Senitzer, Anne Kennel, A. Dormoy, Xavier Lafarge, Anne Devys, L. Absi, I Theodorou, M de Matteis, Anne Cesbron, M Drouet, Pascale Loiseau, Florent Malard, M Fort, Katia Gagne, Christophe Picard, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ArcelorMittal Maizières Research SA, ArcelorMittal, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Etablissement Français du Sang Nouvelle Aquitaine [Bordeaux] (EFS Bordeaux Nouvelle Aquitaine), Etablissement français du sang [Nice] (EFS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Etablissement français du sang [Clermont-Ferrand] (EFS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etablissement français du sang [Caen], Ambiances, Architectures, Urbanités (AAU ), École Centrale de Nantes (ECN)-École nationale supérieure d'architecture de Nantes (ENSA Nantes)-École nationale supérieure d'architecture de Grenoble (ENSAG)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, City of Hope National Medical Center, Registre France Greffe de Moelle [Saint-Denis La Plaine] (RFGM), Agence de la biomédecine [Saint-Denis la Plaine], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Etablissement Français du Sang [Nantes], Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Arcelor Research S.A, Arcelor, Laboratoire d'Immunologie, CHU Saint-Eloi, Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Etablissement français du sang [Besançon] ( EFS ), Centre de Transfusion Sanguine Aquitaine-Limousin ( CTS AQUITAINE-LIMOUSIN ), Centre de Transfusion Sanguine, Etablissement français du sang [Nice] ( EFS ), Laboratoire Paul Painlevé - UMR 8524 ( LPP ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Groupe Immunité des Muqueuses et Agents Pathogènes ( GIMAP ), Université Jean Monnet [Saint-Étienne] ( UJM ), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Ambiances architecturales et urbaines ( AAU ), Ministère de la Culture et de la Communication ( MCC ) -École nationale supérieure d'architecture de Grenoble ( ENSAG ) -École nationale supérieure d'architecture de Nantes ( ENSA Nantes ) -École Centrale de Nantes ( ECN ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'allergologie, Centre Hospitalier Universitaire d'Angers, Registre France Greffe de Moelle [Saint-Denis La Plaine] ( RFGM ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Biologie des Organismes et Ecosystèmes Aquatiques ( BOREA ), Université des Antilles ( UA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de Recherche pour le Développement ( IRD ) -Muséum National d'Histoire Naturelle ( MNHN ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire Paul Painlevé - UMR 8524 (LPP), Université Jean Monnet [Saint-Étienne] (UJM), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, École nationale supérieure d'architecture de Nantes (ENSA Nantes)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Grenoble (ENSAG)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Nantes (ECN), Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Human leukocyte antigen, 03 medical and health sciences, 0302 clinical medicine, Receptors, KIR, HLA Antigens, Transplantation Immunology, Humans, Medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Progenitor cell, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Gynecology, Transplantation, [ SDV ] Life Sciences [q-bio], business.industry, Umbilical Cord Blood Transplantation, French, Retrospective cohort study, Hematology, medicine.disease, humanities, language.human_language, 3. Good health, Treatment Outcome, 030104 developmental biology, Graft-versus-host disease, Immunology, language, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cord Blood Stem Cell Transplantation, France, Stem cell, business, 030215 immunology
Abstract: Impact of KIR/HLA genetic combinations on double umbilical cord blood transplantation outcomes. Results of a French multicentric retrospective study on behalf of the Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) and the Societe Francophone d’Histocompatibilite et d’Immunogenetique (SFHI)
Published: 2016
Full Text: View/download PDF

29. Black Patients of African Descent and HLA-DRB1*15:03 Frequency Overrepresented in Epidermolysis Bullosa Acquisita

Author: C. Zumelzu, Antoine Petit, Marc Busson, F. Aucouturier, Serge Doan, M. Heller, Valérie Pendaries, Dominique Charron, Christelle Le Roux-Villet, Marie-Dominique Brette, Liliane Laroche, Catherine Prost-Squarcioni, Frédéric Caux, N. Lièvre, Francis Pascal, and Pascale Loiseau
Subjects: Adult, Male, Epidermolysis bullosa acquisita, medicine.medical_specialty, Adolescent, Population, Black People, Dermatology, Human leukocyte antigen, Epidermolysis Bullosa Acquisita, Biochemistry, White People, Young Adult, Gene Frequency, parasitic diseases, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Young adult, Child, education, Molecular Biology, Allele frequency, HLA-DRB1, Retrospective Studies, education.field_of_study, business.industry, Incidence (epidemiology), Cell Biology, Middle Aged, medicine.disease, Surgery, Child, Preschool, Female, business, HLA-DRB1 Chains
Abstract: Epidermolysis bullosa acquisita (EBA) is a rare autoimmune bullous disease (AIBD). However, higher EBA incidence and predisposing genetic factor(s) involving an HLA haplotype have been suspected in some populations. This retrospective study assessed the overrepresentation of black patients with EBA, its link with HLA- DRB1*15:03 , and their clinical and immunological characteristics. Between 2005 and 2009, 7/13 (54%) EBA and 6/183 (3%) other-AIBD patients seen consecutively in our department were black ( P =10 −6 ); moreover 7/13 (54%) black patients and 6/183 (3%) white patients had EBA ( P =10 −6 ). In addition, between 1983 and 2005, 12 black patients had EBA. Finally, among the 19 black EBA patients, most of them had very atypical clinical presentations, 9 were natives of sub-Saharan Africa, 1 from Reunion Island, 7 from the West Indies, and 2 were of mixed ancestry. HLA- DRB1*15:03 allelic frequencies were 50% for African patients, significantly higher than the control population ( P −3 ), and 21% for the West Indians (nonsignificant). High EBA frequencies have already been reported in American blacks significantly associated with the HLA- DR2 . In conclusion, black-skinned patients developing EBA seem to have a genetic predisposition, and EBA should be suspected systematically for every AIBD seen in this population.
Published: 2011
Full Text: View/download PDF

30. Pharmacogenetics of Toxicity, Plasma Trough Concentration and Treatment Outcome with Nevirapine-Containing Regimen in Anti-Retroviral-Naïve HIV-Infected Adults: An Exploratory Study of the TRIANON ANRS 081 Trial

Author: Claire Gozalo, Jean-Michel Molina, Céline Verstuyft, Odile Launay, Pascale Loiseau, Laurence Gérard, Gilles Peytavin, Laurence Morand-Joubert, Laurent Becquemont, Pierre Dellamonica, and Jean-Pierre Aboulker
Subjects: Pharmacology, education.field_of_study, Nevirapine, business.industry, Population, General Medicine, Toxicology, Regimen, Toxicity, Medicine, Trough level, Trough Concentration, business, education, Viral load, Pharmacogenetics, medicine.drug
Abstract: The aim of this exploratory study was to investigate in a homogeneous population of anti-retroviral naive HIV-1-infected adults, the relationships between genetic polymorphisms involved in nevirapine metabolism [CYP2B6 516G>T, 785A>G and 1459C>T; CYP3A5 6986A>G (CYP3A5*3)], transport (ABCB1 2677G>T/A and 3435C>T), and antigen recognition (HLA-DRB1*0101), and the hepatic and/or cutaneous toxicity occurring within the first 8 or 72 weeks of treatment, plasma trough concentrations (C(trough) ) at week 8 and immuno-virological response to nevirapine at week 24. Associations between genetic polymorphisms and toxicity, C(trough) and response to nevirapine were performed in a population of 72 HIV-1 positive and nevirapine-treated patients followed during 72 weeks, as part of the previous study called: ANRS081 'Trianon' trial. Among the 18 patients who developed toxicity events during the 72 weeks of the study, 12 patients exhibited early toxicity before week 8. No significant association could be evidenced between any of the analysed single nucleotide polymorphisms (SNPs) and nevirapine early or global toxicity, pharmacokinetics and immuno-virological responses even though a possible association between CYP2B6 516G>T and 1459C>T and the trough level of nevirapine was suggested.
Published: 2011
Full Text: View/download PDF

31. Analysis of the HLA population data (AHPD) submitted to the 15th International Histocompatibility/Immunogenetics Workshop by using the Gene[rate] computer tools accommodating ambiguous data (AHPD project report)

Author: J. Rousseau, Soraya Benhamamouch, Derek Middleton, M. Rahal, Maria Eugenia Riccio, Lucie Richard, Alicia Sanchez-Mazas, Angelica Canossi, Karima Fadhlaoui-Zid, Mirko Spiroski, D. Piancatelli, Fabien Ries, Pascale Loiseau, Mathias Currat, Da Di, Jose Manuel Nunes, A. J. Almada, G. Sulcebe, D. C. M. de Oliveira, Stéphane Buhler, Barbara Nelly Kervaire, Gottfried Fischer, Matilde Romero, O. Benitez, C. Papasteriades, and Jean-Marie Tiercy
Subjects: Immunology, Population, Population genetics, Human leukocyte antigen, Biology, Biochemistry, Génétique humaine, 03 medical and health sciences, 0302 clinical medicine, Genetic drift, Resampling, Genetics, Immunology and Allergy, education, Allele frequency, ddc:599.9, 030304 developmental biology, 0303 health sciences, education.field_of_study, General Medicine, Histocompatibility, HLA, Transplantation, Biostatistique, Evolutionary biology, 030215 immunology
Abstract: During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy–Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1–7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies.
Published: 2010
Full Text: View/download PDF

32. KIR-ligand incompatibility in the graft-versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia

Author: Vanderson Rocha, Yves Beguin, Eliane Gluckman, R. Willemze, F. Garnier, Gérard Socié, Cristina Navarrete, Christelle Ferra, Gérard Michel, Irina Ionescu, Gesine Kögler, Karim Boudjedir, Lucilla Lecchi, Luis Madero, Bernard Rio, Pascale Loiseau, Myriam Labopin, Timothy Devos, Marc Renaud, Joan Garcia, Guillermo Sanz, Anne Sirvent, C. A. Rodrigues, M. Mohty, and A. L. Herr
Subjects: Male, Herpesvirus 4, Human, Cancer Research, medicine.medical_treatment, Hematopoietic stem cell transplantation, Gastroenterology, KIR-ligand, Receptors, KIR, HLA Antigens, Child, Acute leukemia, Leukemia, Incidence, Remission Induction, Myeloid leukemia, Hematology, Middle Aged, Killer Cells, Natural, Treatment Outcome, Oncology, Child, Preschool, Histocompatibility, Cord blood, Acute Disease, cord blood, Female, Cord Blood Stem Cell Transplantation, Adult, medicine.medical_specialty, Adolescent, Graft vs Leukemia Effect, Article, Young Adult, Internal medicine, medicine, Humans, Transplantation, Homologous, Aged, Retrospective Studies, Umbilical Cord Blood Transplantation, business.industry, Infant, medicine.disease, Transplantation, Immunology, Virus Activation, business, transplantation
Abstract: Donor killer cell immunoglobulin-like receptor (KIR)-ligand incompatibility is associated with decreased relapse incidence (RI) and improved leukemia-free survival (LFS) after haploidentical and HLA-mismatched unrelated hematopoietic stem cell transplantation. We assessed outcomes of 218 patients with acute myeloid leukemia (AML n=94) or acute lymphoblastic leukemia (n=124) in complete remission (CR) who had received a single-unit unrelated cord blood transplant (UCBT) from a KIR-ligand-compatible or -incompatible donor. Grafts were HLA-A, -B or -DRB1 matched (n=21) or mismatched (n=197). Patients and donors were categorized according to their degree of KIR-ligand compatibility in the graft-versus-host direction by determining whether or not they expressed HLA-C group 1 or 2, HLA-Bw4 or HLA-A3/-A11. Both HLA-C/-B KIR-ligand- and HLA-A-A3/-A11 KIR-ligand-incompatible UCBT showed a trend to improved LFS (P=0.09 and P=0.13, respectively). Sixty-nine donor–patient pairs were HLA-A, -B or -C KIR-ligand incompatible and 149 compatible. KIR-ligand-incompatible UCBT showed improved LFS (hazards ratio=2.05, P=0.0016) and overall survival (OS) (hazards ratio=2.0, P=0.004) and decreased RI (hazards ratio=0.53, P=0.05). These results were more evident for AML transplant recipients (2-year LFS and RI with or without KIR-ligand incompatibility 73 versus 38% (P=0.012), and 5 versus 36% (P=0.005), respectively). UCBT for acute leukemia in CR from KIR-ligand-incompatible donors is associated with decreased RI and improved LFS and OS. Supplementary information The online version of this article (doi:10.1038/leu.2008.365) contains supplementary material, which is available to authorized users.
Published: 2009
Full Text: View/download PDF

33. Evidence for a new HLA class II determinant present on cells from HLA-DR1 and/or -DR4 individuals

Author: C. Mallet, M. Colombani, Laurent Degos, Jacques Colombani, Pascale Loiseau, D. Alcalay, Corinne Douay, and Virginia Lepage
Subjects: Adult, Male, musculoskeletal diseases, Hla class ii, HLA-DR1, Immunology, Population, Biochemistry, Parental cell, Epitope, Epitopes, Isoantibodies, immune system diseases, HLA-DR4 Antigen, Genetics, Humans, Immunology and Allergy, Child, skin and connective tissue diseases, education, education.field_of_study, biology, HLA-DR1 Antigen, Histocompatibility Antigens Class II, General Medicine, Mutant cell, On cells, biology.protein, Female, Antibody
Abstract: Evidence for a new HLA class II specificity is presented. It is recognized by LE serum, which reacts with most DR1 and/or DR4 individuals (r = 0.86). Its frequency in the French population is 0.33. Absorption-elution experiments showed that the serum reactivity was not due to a mixture of anti-DR1 and anti-DR4 antibodies, but to a single antibody population which could be absorbed on and eluted from both DR1(+) or DR4(+) cells. LE specificity seemed to be expressed on DR but not on DQ molecules since the serum reacted with and could be absorbed by DR+,DQw- cells; it did not react with a DR-,DQw+ mutant cell, but did react with the DR+,DQw+ parental cell. The relationship between LE specificity and MC1 and Te23 specificities remains to be determined.
Published: 2008
Full Text: View/download PDF

34. Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI

Author: Thomas Cluzeau, Isabelle Jollet, R Peffault de La Tour, Jean-Luc Taupin, Béatrice Pédron, Pascale Loiseau, Françoise Hau, Myriam Labalette, Pascal Perrier, Vincent Dubois, Damien Masson, M Fort, K Dessaux, Christophe Picard, Florent Delbos, Matthieu Filloux, Dominique Charron, Nicole Raus, Anne Devys, F Quainon, M de Matteis, Virginie Renac, Jason Lambert, L. Absi, P Van Endert, Brigitte Mercier, A Ramounau-Pigot, Service d'hématologie adulte [Hôpital de Saint Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Etablissement français du sang, Auvergne-Loire [Saint-Etienne] (EFS), Etablissement Français du Sang, Etablissement Français du Sang (EFS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Etablissement Français du Sang [Pays de la Loire] (EFS - Site de Nantes), Hôpital Hôtel-Dieu [Nantes] (Centre Hospitalier Universitaire de Nantes), Etablissement français du sang [Nice] (EFS), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Etablissement Français du Sang Rhone-Alpes Auvergne, Etablissement français du sang [Rouen], Etablissement français du sang [Poitiers] (EFS), Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service Immunologie Biologique [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement français du sang [Clermont-Ferrand] (EFS), Laboratoire de Biologie Médicale [Rennes], Etablissement français du sang [Rennes] (EFS Bretagne), Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Recherche de Chimie Paris (IRCP), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Université Nice Sophia Antipolis (... - 2019) (UNS), CHU Saint Louis [APHP], Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri-Mondor, Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Laboratoire de Recherche en Informatique ( LRI ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Département Imagerie et Simulation pour le Contrôle ( DISC ), Laboratoire d'Intégration des Systèmes et des Technologies ( LIST ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Groupe Immunité des Muqueuses et Agents Pathogènes ( GIMAP ), Université Jean Monnet [Saint-Étienne] ( UJM ), Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Paul Painlevé - UMR 8524 ( LPP ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Etablissement français du sang [Nice] ( EFS ), Politique, Religion, Institutions et Sociétés : Mutations Européennes - Groupe de Sociologie Politique Européenne ( PRISME-GSPE ), Centre National de la Recherche Scientifique ( CNRS ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Etablissement français du sang [Poitiers] ( EFS ), Laboratoire d'Immunologie ( EA 2686 ), EFS Rhône-Alpes, EFS, Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Etablissement français du sang [Clermont-Ferrand] ( EFS ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Institut de Recherche pour le Développement - IRD, Institut de Recherche de Chimie Paris ( IRCP ), and Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP )
Subjects: Oncology, Adult, Graft Rejection, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Transplantation Immunology, Internal medicine, Neoplasms, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Risk factor, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, Univariate analysis, [ SDV ] Life Sciences [q-bio], business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, 3. Good health, Histocompatibility, Survival Rate, Graft-versus-host disease, Treatment Outcome, surgical procedures, operative, 030220 oncology & carcinogenesis, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Unrelated Donors, 030215 immunology
Abstract: International audience; Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already beenpublished. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006–2012).Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the FrenchSociety for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading toa low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignantdiseases remained significant risk factors (P = 0.04 and Po0.0001, respectively). In multivariate analysis, only status of disease was asignificant risk factor (Po0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/orHLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their rolewas more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio = 0.57[0.32–1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.
Published: 2016
Full Text: View/download PDF

35. Natural killer cell licensing after double cord blood transplantation is driven by the self-HLA class I molecules from the dominant cord blood

Author: Hélène Moins-Teisserenc, Antoine Toubert, Jean-Michel Cayuela, Katia Gagne, Pascale Loiseau, Nicolas Dulphy, Eliane Gluckman, Nicolas Guillaume, Régis Peffault de Latour, Guylaine Henry, Gérard Socié, Christelle Retière, Marie Robin, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Eurocord [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Dulphy, Nicolas, Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, chemical and pharmacologic phenomena, Cord Blood Stem Cell Transplantation, Immunogenetics, Human leukocyte antigen, HLA-C Antigens, Biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Natural killer cell, 03 medical and health sciences, medicine, Humans, Receptor, Online Only Articles, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Cord blood transplantation, ComputingMilieux_MISCELLANEOUS, 4. Education, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Natural killer T cell, Allografts, Hematologic Diseases, Killer Cells, Natural, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Cord blood, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Immunology, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract: Natural killer (NK) cells gain functionality through an educational process (“licensing”) that depends on killer immunoglobulin-like receptor (KIR) recognition of self-HLA class I molecules. In allogenic double umbilical cord blood stem cell transplantation (2CBT), the respective roles of the
Published: 2016
Full Text: View/download PDF

36. A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritis

Author: Xavier Mariette, Hartmut Kupper, Pascale Loiseau, Céline Verstuyft, Emmanuelle Comets, Laurent Becquemont, Ryad Tamouza, Philippe Ravaud, Corinne Miceli-Richard, Dominique Charron, Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation Biologique (CIB), Immunogénétique humaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Abbott GmbH & Co. KG, Comets, Emmanuelle, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Male, rheumatoid arthritis, haplotype, MESH: Antirheumatic Agents, Arthritis, Gastroenterology, MESH: Antibodies, Monoclonal, Arthritis, Rheumatoid, MESH: Genotype, 0302 clinical medicine, immune system diseases, adalimumab, Immunopathology, genetic polymorphism, Immunology and Allergy, MESH: Treatment Outcome, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Aged, MESH: Arthritis, Rheumatoid, 0303 health sciences, MESH: Middle Aged, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Polymorphism, Single Nucleotide, Antibodies, Monoclonal, Middle Aged, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Treatment Outcome, MESH: Methotrexate, Antirheumatic Agents, Rheumatoid arthritis, Drug Therapy, Combination, Female, TNF-alpha, medicine.drug, Adult, musculoskeletal diseases, medicine.medical_specialty, Genotype, Immunology, Antibodies, Monoclonal, Humanized, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, Adalimumab, Humans, Aged, 030304 developmental biology, 030203 arthritis & rheumatology, Autoimmune disease, MESH: Humans, Tumor Necrosis Factor-alpha, business.industry, Haplotype, MESH: Adult, HLA-DR Antigens, MESH: Haplotypes, MESH: HLA-DR Antigens, medicine.disease, MESH: Male, MESH: Drug Therapy, Combination, Methotrexate, Haplotypes, MESH: Tumor Necrosis Factor-alpha, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, MESH: Female, HLA-DRB1 Chains
Abstract: Objective:To determine whether tumour necrosis factor (TNF) gene polymorphisms and/or the shared epitope are genetic predictors of the response to adalimumab (ADA) in rheumatoid arthritis (RA).Methods:This ancillary study to the Research in Active Rheumatoid Arthritis (ReAct) Phase IIIb study included a large cohort of Caucasian patients with RA from France (n = 388) treated with ADA plus methotrexate (MTX) (n = 182), ADA plus any other DMARD (n = 98) or ADA alone (n = 108). The primary outcome was ACR50 at 12 weeks. Patients underwent genotyping for HLA-DRB1 and three TNF gene polymorphisms (–238A/G,–308A/G and–857C/T). Extended haplotypes involving HLA-DRB1 and TNF loci were reconstructed using the PHASE program.Results:A total of 151 patients (40%) had an ACR50 response at week 12. Neither the number of HLA-DRB1 shared epitope copies nor presence of the three TNF polymorphisms tested separately was significantly associated with ACR50 response at week 12. However, haplotype reconstruction of the TNF locus revealed that the GGC haplotype (–238G/–308G/–857C) in a homozygous form (i.e. present in more than half of the patients) was significantly associated with a lower ACR50 response to ADA at 12 weeks (34% vs. 50% in patients without the haplotype) (p = 0.003; pa = 0.015). This effect was more important in the subgroup of patients concomitantly treated with MTX.Conclusion:This large pharmacogenetic study provides preliminary data indicating that a single TNF locus haplotype (–238G/–308G/–857C), present on both chromosomes is associated with a lower response to ADA, mainly in patients treated with ADA and MTX.
Published: 2007
Full Text: View/download PDF

37. HLA Association with Hematopoietic Stem Cell Transplantation Outcome: The Number of Mismatches at HLA-A, -B, -C, -DRB1, or -DQB1 Is Strongly Associated with Overall Survival

Author: Valérie Dubois, Evelyne Marry, A. Dormoy, Virginia Lepage, Monique Bois, Marc Busson, Pascale Perrier, Jean-Pierre Jouet, Pascale Loiseau, L. Gebuhrer, Marie-Lorraine Balere, Denis Reviron, Didier Blaise, Dominique Masson, Ryad Tamouza, Dominique Charron, Agnès Moine, Katia Gagne, Jean-Denis Bignon, Colette Raffoux, Antoine Toubert, L. Absi, Zina Chir, and Isabelle Jollet
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Adolescent, Bone marrow transplantation, Survival, medicine.medical_treatment, GVHD, Graft vs Host Disease, Histocompatibility Testing, Human leukocyte antigen, Hematopoietic stem cell transplantation, Risk Assessment, Cohort Studies, HLA Antigens, Recurrence, immune system diseases, Internal medicine, medicine, Humans, Relapse, Child, Survival analysis, Proportional Hazards Models, Retrospective Studies, Transplantation, Proportional hazards model, business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, Infant, Hematology, Middle Aged, Survival Analysis, Confidence interval, HLA-A, KIR, HLA, Child, Preschool, Immunology, Female, business
Abstract: HLA matching between the donor and recipient improves the success of unrelated hematopoietic stem cell transplantation (HSCT). Because many patients in need of an unrelated transplant have only donors with mismatch, information is needed to evaluate the limits of HLA mismatching. We examined the association of survival, acute graft-versus-host disease (aGVHD) and relapse with HLA-A, -B, -C, -DRB, -DQB1, and -DPB1 mismatching in 334 patients coming from 12 French transplant centers and who received a non-T cell-depleted bone marrow graft from an unrelated donor. All patients were prepared with the use of myeloablative conditioning regimens. Our analyses demonstrate negative effects of HLA mismatching for either HLA-A, -B, -C, -DRB1, or -DQB1 loci on survival. Multivariate Cox analyses showed that a single mismatch was associated with a significant decrement in survival (P = .046, hazard ratio [HR] = 1.41, confidence interval [CI] 95% 1.1-1.98). The presence of multiple mismatches was worse for survival (P = .003, HR = 1.91, CI 95% 1.26-2.91) and severe aGVHD (grade III-IV) (P = .002, HR = 2.51, CI95% 1.41-4.46). The cumulative incidences of aGVHD and relapse in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with 2, 1, or 0 DPB1 incompatibilities were 63%, 50%, and 51%, and 12%, 27%, and 20%, respectively, but these differences were not statistically significant. Similar differences of aGVHD and relapse, but not statistically significant, were observed in those HLA-A, -B, -C, -DRB1, and -DQB1 identical pairs with DPB1 disparities classified into permissive or nonpermissive mismatches according to Zino’s classification based on a hierarchy of the immunogenicity of the HLA-DP molecules. “Missing killer cell immunoglobulin-like receptor (KIR) ligand” evaluated on the presence of HLA-C1, -C2, and Bw4 groups in the recipients was not associated with aGVHD, survival, and relapse in this cohort of non-T cell-depleted HSCT.
Published: 2007
Full Text: View/download PDF

38. Use of Single-Antigen Flow Beads Assays to Assess Anti-HLA Donor-Specific Antibody Strength

Author: Sophie Caillat-Zucman, Jonathan Visentin, Vissal-David Kheav, Pascale Loiseau, Jean-Luc Taupin, and Kahina Amokhrane
Subjects: Graft Rejection, Male, Transplantation Conditioning, medicine.medical_treatment, Histocompatibility Testing, Hematopoietic stem cell transplantation, Human leukocyte antigen, 030230 surgery, Isoantibodies, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA Antigens, Medicine, Humans, Transplantation, Graft rejection, business.industry, Donor specific antibodies, Graft Survival, Hematopoietic Stem Cell Transplantation, Hematology, Immunology, Female, business, 030215 immunology
Published: 2015

39. The ADAMTS13

Author: Laurent, Gilardin, Sandrine, Delignat, Ivan, Peyron, Mathieu, Ing, Yu-Chun, Lone, Bagirath, Gangadharan, Baptiste, Michard, Yousra, Kherabi, Meenu, Sharma, Anastas, Pashov, Jean-Baptiste, Latouche, Mohamad, Hamieh, Olivier, Toutirais, Pascale, Loiseau, Lionel, Galicier, Agnès, Veyradier, Srini, Kaveri, Bernard, Maillère, Paul, Coppo, and Sébastien, Lacroix-Desmazes
Subjects: CD4-Positive T-Lymphocytes, Purpura, Thrombotic Thrombocytopenic, Immunodominant Epitopes, Coagulation & Its Disorders, HLA-DR1 Antigen, ADAMTS13 Protein, Antigen-Presenting Cells, Epitopes, T-Lymphocyte, Mice, Transgenic, Peptide Fragments, Article, Mice, hemic and lymphatic diseases, Immunoglobulin G, Animals, Humans, Immunization, Amino Acid Sequence, Alleles, Protein Binding
Abstract: Acquired thrombotic thrombocytopenic purpura is a rare and severe disease characterized by auto-antibodies directed against “A Disintegrin And Metalloproteinase with Thrombospondin type 1 repeats, 13th member" (ADAMTS13), a plasma protein involved in hemostasis. Involvement of CD4+ T cells in the pathogenesis of the disease is suggested by the IgG isotype of the antibodies. However, the nature of the CD4+ T-cell epitopes remains poorly characterized. Here, we determined the HLA-DR-restricted CD4+ T-cell epitopes of ADAMTS13. Candidate T-cell epitopes were predicted in silico and binding affinities were confirmed in competitive enzyme-linked immunosorbent assays. ADAMTS13-reactive CD4+ T-cell hybridomas were generated following immunization of HLA-DR1 transgenic mice (Sure-L1 strain) and used to screen the candidate epitopes. We identified the ADAMTS131239–1253 peptide as the single immunodominant HLA-DR1-restricted CD4+ T-cell epitope. This peptide is located in the CUB2 domain of ADAMTS13. It was processed by dendritic cells, stimulated CD4+ T cells from Sure-L1 mice and was recognized by CD4+ T cells from an HLA-DR1-positive patient with acute thrombotic thrombocytopenic purpura. Interestingly, the ADAMTS131239–1253 peptide demonstrated promiscuity towards HLA-DR11 and HLA-DR15. Our work paves the way towards the characterization of the ADAMTS13-specific CD4+ T-cell response in patients with thrombotic thrombocytopenic purpura using ADAMTS131239–1253-loaded HLA-DR tetramers.
Published: 2015

40. Genetic factors in pemphigus

Author: Mondher Zitouni, François Tron, Pascale Loiseau, Laurent Drouot, S. Makni, Mourad Ben Ayed, Pascal Joly, Hugo Mouquet, Hatem Masmoudi, Danièle Gilbert, and Dominique Charron
Subjects: Male, Candidate gene, Quantitative Trait Loci, Immunology, Human leukocyte antigen, Biology, Desmoglein, MHC Class II Gene, HLA Antigens, medicine, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Alleles, Pemphigus foliaceus, Genetics, integumentary system, Desmoglein 1, Pemphigus vulgaris, Histocompatibility Antigens Class II, medicine.disease, Cytoskeletal Proteins, Pemphigus, Desmoplakins, Female, Desmogleins
Abstract: Epidemiological studies performed in different ethnic populations and family studies, notably based on a partial phenotype of the autoimmune process, indicate that genetic factors are involved in the occurrence of pemphigus. However, the precise heritability remains uncertain in the absence of twin concordance rate studies. Among the different strategies available to identify genetic factors participating in autoimmune disease susceptibility, only population studies based on case-control design have been performed in pemphigus. These studies consistently showed that MHC locus, in particular HLA class II alleles, are associated with pemphigus vulgaris and pemphigus foliaceus. Other genes of the MHC locus may also participate in disease susceptibility as shown by studies using microsatellite markers across different regions of the MHC. It is likely that other non-MHC genes are involved in the pathogenesis of pemphigus. In particular, involvement of a polymorphic variant of desmoglein 1 gene was shown to be associated with pemphigus foliaceus and to interact in an epistatic manner with MHC class II genes to contribute to the autoimmune process. Other candidate genes to which a role can be assigned in the disease pathogenesis should be considered to design case-control or family-based association studies. Genome scan studies which require a large number of multiplex families to reach statistical power, should also be considered in the endemic form of pemphigus foliaceus because of the high number of familial cases.
Published: 2005
Full Text: View/download PDF

41. In primary Sjögren's syndrome, HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response

Author: Jean Sibilia, Jacques-Eric Gottenberg, Virginia Lepage, Dominique Charron, Julien Cohen-Solal, Marc Busson, Pascale Loiseau, and Xavier Mariette
Subjects: musculoskeletal diseases, Biologic marker, Autoimmune disease, business.industry, Immunology, Autoantibody, Human leukocyte antigen, Neutropenia, medicine.disease, stomatognathic diseases, Rheumatology, Immunopathology, medicine, Genetic predisposition, Immunology and Allergy, Rheumatoid factor, Pharmacology (medical), business
Abstract: Objective To reevaluate, in a large series of patients with Sjogren's syndrome (SS) recruited from 2 French centers, the question of whether HLA is associated with SS itself or with a pattern of secretion of autoantibodies. Methods One hundred forty-nine white patients fulfilling the American-European Consensus Group criteria for SS were divided into 3 subgroups, according to their anti-Ro/SSA and anti-La/SSB status, as follows: group 1 (n = 53), no antibody; group 2 (n = 46), anti-SSA only; group 3 (n = 50), both anti-SSA and anti-SSB. Patients were compared with 222 unrelated healthy subjects representative of the white population in France. Results Comparisons between the 149 SS patients and 222 controls confirmed the association of SS with DRB1*03 (the frequency was 25% in patients versus 10% in controls) and DQB1*02 (32% versus 22%). The association between HLA and SS was restricted to patients with anti-SSA and/or anti-SSB; no association with HLA was observed in patients in group 1 (no antibody). The frequency of HLA–DRB1*15 was highest in group 2 (24%), compared with 11% in group 1 and 11% in controls, whereas the frequency of HLA–DRB1*03 was highest in group 3 (44%), compared with 12% in group 1, 19% in group 2, and 10% in controls. Group 2 and group 3 had more clinical and biologic markers of activity than did group 1 but were not clinically different. HLA alleles were not associated with clinical features of the disease, and were associated with only some biologic features: rheumatoid factor positivity, increased serum IgG, and thrombocytopenia were associated with HLA–DRB1*03, and neutropenia was associated with DQB1*01. Conclusion HLA class II markers confer genetic susceptibility to Sjogren's syndrome. The association between HLA and SS is restricted to patients with anti-SSA and/or anti-SSB antibodies; HLA is not associated with SS in patients without these autoantibodies. The absence of a difference in disease severity between groups 2 and 3, as well as the restricted association of HLA–DRB1*03 in group 3, strongly suggest that HLA alleles predispose to autoantibody secretion, without being associated with clinical outcome. HLA class II phenotype might support epitope spreading: HLA–DR15 favors anti-SSA synthesis, whereas HLA–DR3 is associated with both anti-SSA and anti-SSB production.
Published: 2003
Full Text: View/download PDF

42. Paraneoplastic pemphigus is associated with the DRB1*03 allele

Author: Virginia Lepage, Philippe Martel, Philippe Courville, Danièle Gilbert, Béatrice Flageul, François Tron, Dominique Charron, Hugo Mouquet, Pascal Joly, Pascale Loiseau, Philippe Musette, and Marc Busson
Subjects: education.field_of_study, integumentary system, Paraneoplastic Syndromes, Immunology, Pemphigus vulgaris, Autoantibody, HLA-DR Antigens, Biology, medicine.disease, Desmoglein, Pemphigus, Paraneoplastic pemphigus, Haplotypes, immune system diseases, Desmoglein 1, Desmoglein 3, medicine, Humans, Immunology and Allergy, skin and connective tissue diseases, education, Pemphigus foliaceus, HLA-DRB1 Chains
Abstract: Pemphigus is a group of autoimmune blistering diseases caused by autoantibodies directed against keratinocyte adhesion molecules. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF), in which autoantibodies bind, respectively, to desmoglein 3 and desmoglein 1, are strongly associated with HLA-class II DR4 and DR14 alleles. In paraneoplastic pemphigus (PNP), a rare variant associated with neoplasia, autoantibodies target proteins of the plakin family in addition to desmogleins 1 and 3. The presence of anti-desmoglein antibodies in all types of pemphigus raises the question of common molecular mechanisms of susceptibility, particularly similar MHC-class II allele associations, in the different forms of the disease. HLA-DRB1 typing was performed in 13 PNP patients and results were compared to those obtained from 84 healthy controls, 37 PV and 31 PF patients. Our data demonstrate a significant association of PNP with HLA-DRB1*03 allele which was found in 61.5% of the patients, whereas DRB1*04 and DRB1*14 appear not to be involved in PNP susceptibility. Therefore, the HLA-genetic background of PNP differs from that of other types of pemphigus, which suggests that distinct mechanism(s) initiate(s) the immunological response in this form of pemphigus.
Published: 2003
Full Text: View/download PDF

43. Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease

Author: Marie Robin, Chantal Guillemette, Félix Couture, Alan Tourancheau, Régis Peffault de Latour, Isabelle Laverdière, Éric Lévesque, Gérard Socié, Ryad Tamouza, Marc Lalancette, Alain Filion, Pascale Loiseau, and Dominique Charron
Subjects: Adult, Male, Candidate gene, Canada, medicine.medical_treatment, Graft vs Host Disease, Single-nucleotide polymorphism, Hematopoietic stem cell transplantation, Biology, Pharmacology, Polymorphism, Single Nucleotide, Cohort Studies, Young Adult, medicine, Biomarkers, Tumor, Humans, Neoplasm Staging, Incidence, Hazard ratio, Hematopoietic Stem Cell Transplantation, Immunosuppression, Hematology, Articles, Middle Aged, Prognosis, Adenosine, Transplantation, Survival Rate, Methotrexate, Pharmacogenetics, Hematologic Neoplasms, Acute Disease, Chronic Disease, Cyclosporine, Female, Immunosuppressive Agents, medicine.drug, Follow-Up Studies
Abstract: Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-versus-host disease prevalence. Indeed, an increased risk of acute graft-versus-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (hazard ratio=3.04; P=0.002), nuclear factor of activated T cells (cytoplasmic 1) (hazard ratio=2.69; P=0.004), adenosine triphosphate-binding cassette sub-family C2 (hazard ratio=3.53; P=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (hazard ratio=3.67; P=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-versus-host disease (hazard ratio=0.32–0.41; P=0.0009–0.008), those of nuclear factor of activated T cells (cytoplasmic 2) are found to increase such risk (hazard ratio=3.85; P=0.0004). None of the tested single nucleotide polymorphisms was associated with the occurrence of chronic graft-versus-host disease. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential role of germline biomarkers in predicting acute graft-versus-host disease. Further investigations are warranted to improve our understanding of these relationships to personalize immunosuppressive therapy and optimize outcomes.
Published: 2015

44. List of Contributors

Author: Julia Bosch, Shijie Cai, Lee Carpenter, Keith M. Channon, Dominique Charron, Theofanis K. Chatzistamatiou, Audrey Cras, Robert Danby, Francesco Dazzi, Amalia Dinou, Dominique Farge, Lydia Foeken, Antonio Galleu, Marietta Giannakou, Vasiliki Gkioka, Aspasia Goula, Gregory Katz, Cheen P. Khoo, Gesine Kögler, George Koutitsas, Joanne Kurtzberg, Paul Leeson, Stefanie Liedtke, Pascale Loiseau, Daniel Markeson, Elena Markogianni, Emeline Masson, Efstathios Michalopoulos, Anna Rita Migliaccio, Maria Mitrossili, Cristina Navarrete, Laura Newton, Yannis Nikolados, Amanda L. Olson, Paul J. Orchard, Daniela Orsini, Andreas Papassavas, Thalia Papayannopoulou, George Pierrakos, Sergio Querol, Teja Falk Radke, Paolo Rebulla, Vanderson Rocha, Marcos Sarris, Aurore Saudemont, Andromachi Scaradavou, Markella Serafetinidi, Elizabeth J. Shpall, Angela R. Smith, Sotiris Soulis, Stamatia Sourri, Catherine Stavropoulos-Giokas, Jessica M. Sun, LingYun Sun, Antoine Toubert, Dandan Wang, Suzanne M. Watt, Youyi Zhang, and Yong Zhao
Published: 2015
Full Text: View/download PDF

45. HLA and Immunogenetics in Cord Blood Transplantation

Author: Dominique Charron, Pascale Loiseau, and Emeline Masson
Subjects: biology, business.industry, medicine.medical_treatment, Context (language use), Human leukocyte antigen, Immunogenetics, Hematopoietic stem cell transplantation, Major histocompatibility complex, Transplantation, Cord blood, Immunology, biology.protein, Medicine, Antibody, business
Abstract: Human leukocyte antigen (HLA) and non-HLA immunogenetic factors impact the outcome of hematopoietic stem cell transplantation (HSCT). While in early studies of cord blood transplantation (CBT) the major histocompatibility complex immunogenetic barrier was considered less important in some cases than in HSCT from unrelated donors, and preference was given to the number of cells infused as a success criteria, the most recent data emphasize the critical role for HLA matching. This affects the choice of strategy for immunogenetic typing for cord blood banking. Other immunogenetic systems may be of interest in the context of CBT and warrant further investigation. Finally the role of antibodies is also discussed as well as the overall immunogenetic assessment (HLA and beyond HLA). It will provide a tailored and personalized choice of the best donor for each individual patient.
Published: 2015
Full Text: View/download PDF

46. Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study

Author: Dominique Masson, Virginie Renac, Christophe Picard, I Theodorou, M de Matteis, J.-F. Eliaou, Ibrahim Yakoub-Agha, F Quainon, Evelyne Marry, Isabelle Jollet, B. Coeffic, A. Dormoy, Daniel Hanau, Béatrice Pédron, Françoise Hau, Pascale Perrier, Pascale Loiseau, V Moalic, Florent Delbos, Anne Cesbron, Valérie Dubois, M Fort, Françoise Dufossé, Nicole Raus, A Batho, Xavier Lafarge, Katia Gagne, L. Absi, Sophie Caillat-Zucman, Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Labex_Transplantex (Labex_Transplantex), Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang- Rhône-Alpes [Lyon], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Etablissement français du sang [Besançon] (EFS), Etablissement français du sang [Poitiers] (EFS), Laboratoire de Biologie Médicale [Rennes], Etablissement français du sang [Rennes] (EFS Bretagne), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Centre de Transfusion Sanguine Aquitaine-Limousin (CTS AQUITAINE-LIMOUSIN), Centre de Transfusion Sanguine, Laboratoire d'Analyses de Biologie Médicale (LABM), Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS Alsace, Etablissement français du sang [Clermont-Ferrand] (EFS), Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etablissement français du sang [Angers], Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Génétique Moléculaire et d'Histocompatibilité [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Etablissement français du sang [Nice] (EFS), Immunologie cellulaire et tissulaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang [Rouen], Etablissement français du sang [Caen], Service Immunologie Biologique [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Registre France Greffe de Moelle [Saint-Denis La Plaine] (RFGM), Agence de la biomédecine [Saint-Denis la Plaine], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service greffe de moelle osseuse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Etablissement Français du Sang [Nantes], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Jean Monnet [Saint-Étienne] (UJM), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], CHU Toulouse [Toulouse], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Labex_Transplantex ( Labex_Transplantex ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Etablissement français du sang [Besançon] ( EFS ), Etablissement français du sang [Poitiers] ( EFS ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Etablissement français du sang - Auvergne-Rhône-Alpes ( EFS ), Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Centre de Transfusion Sanguine Aquitaine-Limousin ( CTS AQUITAINE-LIMOUSIN ), Laboratoire d'Analyses de Biologie Médicale ( LABM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -EFS Alsace, Etablissement français du sang [Clermont-Ferrand] ( EFS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Groupe Immunité des Muqueuses et Agents Pathogènes ( GIMAP ), Université Jean Monnet [Saint-Étienne] ( UJM ), Laboratoire d'Immunologie, CHU Saint-Eloi, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Etablissement français du sang [Nice] ( EFS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Registre France Greffe de Moelle [Saint-Denis La Plaine] ( RFGM ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Graft vs Host Disease, Human leukocyte antigen, Hematopoietic stem cell transplantation, Internal medicine, medicine, Humans, Child, HLA-DP beta-Chains, Aged, Transplantation, [ SDV ] Life Sciences [q-bio], HLA-DPB1, business.industry, Hematopoietic Stem Cell Transplantation, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, Allografts, Confidence interval, 3. Good health, Graft-versus-host disease, surgical procedures, operative, Host vs Graft Reaction, Relative risk, Child, Preschool, Hematologic Neoplasms, Immunology, Female, HLA-DPB1 disparity, France, business, Unrelated Donors, Algorithms
Abstract: International audience; We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.Bone Marrow Transplantation advance online publication, 3 November 2014; doi:10.1038/bmt.2014.253.
Published: 2015
Full Text: View/download PDF

47. HLA study in anti-complement factor H antibody-associated atypical hemolytic uremic syndrome

Author: Shambhuprasad Kotresh Togarsimalemath, Pilar Sánchez-Corral, Marie-Agnès Dragon-Durey, Zoltán Prohászka, Ágnes Szilágyi, Margarita López-Trascasa, Pascale Loiseau, Kevin J. Marchbank, Shweta Tyagi, Marie Senant, Elisabetta Valoti, Timothy H.J. Goodship, Mamta Puruswani, Santiago Rodríguez de Córdoba, Manish Mourya, Uma Kanga, and Arvind Bagga
Subjects: biology, business.industry, Immunology, Atypical hemolytic uremic syndrome, Anti complement, biology.protein, Medicine, Human leukocyte antigen, Antibody, business, medicine.disease, Molecular Biology
Published: 2017
Full Text: View/download PDF

48. BOTH GENETIC AND CLINICAL FACTORS PREDICT THE DEVELOPMENT OF GRAFT-VERSUS-HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Author: Pascale Loiseau, Eliane Gluckman, Marc Busson, Gérard Socié, Anne Janin, Dominique Charron, and Ryad Tamouza
Subjects: Adult, Male, Aging, Adolescent, medicine.medical_treatment, Graft vs Host Disease, Disease, Hematopoietic stem cell transplantation, Biology, Recurrence, Risk Factors, Minor histocompatibility antigen, medicine, Humans, Transplantation, Homologous, Child, Transplantation, Polymorphism, Genetic, HLA-A Antigens, Hematopoietic Stem Cell Transplantation, Middle Aged, Prognosis, medicine.disease, Tissue Donors, Histocompatibility, Graft-versus-host disease, Child, Preschool, Relative risk, Immunology, Cytokines, Female, Gene polymorphism
Abstract: BACKGROUND Graft-versus-host disease is the main complication of hematopoietic stem cell transplantation. Recently, pro- and anti-inflammatory cytokines and mismatches of minor histocompatibility antigens between HLA-identical sibling donor/recipient pairs have been implicated in the development of acute graft-versus-host disease. It is not known, however, whether these factors are independent of other clinically recognized risk factors such as age and disease stage. METHODS In this study, we searched for risk factors of acute graft-versus-host disease using multivariate Cox regression analysis in 100 consecutive patients who underwent allogeneic stem cell transplantation from an HLA-identical sibling donor. Eight polymorphisms from five different cytokine genes were studied (tumor necrosis factor alpha, tumor necrosis factor beta, interleukin (IL) 6, IL-10, and interferon gamma). Mismatches for the minor histocompatibility antigen HA-1 were searched in HLA-A*0201 individuals. In addition to these new risk factors, patient, donor, disease, and transplant risk factors were analyzed by multivariate analysis using the Cox proportional hazards model. RESULTS Acute graft-versus-host disease was independently associated with IL-10 gene polymorphisms both from the recipient (relative risk=7.9, P
Published: 2001
Full Text: View/download PDF

49. HLA Class II Polymorphism Contributes to Specify Desmoglein Derived Peptides in Pemphigus Vulgaris and Pemphigus Foliaceus

Author: Dominique Charron, Catherine Prost, Pascale Loiseau, Marc Busson, Jean-Claude Roujeau, Laurence Lecleach, Sylvie Bastuji-Garin, and Virginia Lepage
Subjects: Male, musculoskeletal diseases, Genes, MHC Class II, Molecular Sequence Data, Immunology, Human leukocyte antigen, Biology, Autoantigens, Desmoglein, Antigen, immune system diseases, HLA-DQ Antigens, medicine, HLA-DQ beta-Chains, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Amino Acid Sequence, Prospective Studies, skin and connective tissue diseases, Alleles, Pemphigus foliaceus, Polymorphism, Genetic, Desmoglein 1, Pemphigus vulgaris, Autoantibody, Desmosomes, HLA-DR Antigens, Middle Aged, Cadherins, medicine.disease, Cytoskeletal Proteins, Pemphigus, Desmoplakins, Female, Desmogleins, Peptides, HLA-DRB1 Chains, Protein Binding
Abstract: Susceptibility to Pemphigus, an autoimmune disease of the skin, has been previously linked to DRB1*0402, 1401/04 and DQB1*0503 in pemphigus vulgaris (PV), to DRB1*0102, 0404, 1402/06 in endemic pemphigus foliaceus in Brazil and to DRB1*04 in Italian patients suffering from pemphigus foliaceus (PF). The disease is caused by autoantibodies against desmoglein (Dsg1 in PF, Dsg3 in PV). Molecular typing of 57 French patients suffering from PV (37) and from PF (20) confirmed previous results concerning PV and showed that DRB1*0102 and 0404 are susceptible molecules to PF in France. We have analysed the characteristics of the 'pockets' of the susceptibility-associated molecules to PV and PF and we showed that (i) in PV, two kinds of Dsg3 derived peptides may be presented by HLA-DR according to HLA polymorphism (DRB1*0402 or DRB1*14/0406), (ii) the same Dsg1 peptides may be presented by DRB1*0102, DQB1*0404 or DRB1*14 in PF, (iii) the DRB1*14/0406 PV-related molecules may be able to present Dsg1 and Dsg3 peptides thereby providing an explanation for the cases of PV with combined responses to Dsg1 and to Dsg3 which are typified by a muco-cutaneous clinical phenotype.
Published: 2000
Full Text: View/download PDF

50. Matching of MHC Class I Chain-Related Genes a and B Is Associated with Reduced Incidence of Severe Acute Graft-Versus-Host Disease after Unrelated Hematopoietic Stem Cell Transplantation

Author: Myriam Labopin, Nicole Raus, Régis Peffault de Latour, Mohamad Mohty, Katharina Fleischhauer, Gérard Socié, Daniel Hanau, Nicolas Jung, Ibrahim Yakoub-Agha, Xavier Lafarge, Miriam Hoffmann, Raphael Carapito, Jordi Sierra, Philippe Moreau, Anne Cesbron, Masao Ota, Seiamak Bahram, Arnon Nagler, A. Parissiadis, Mauricette Michallet, Ryad Tamouza, Franz Claas, Gaëlle Giacometti, Myriam Labalette, Ronnie van der Holt, Pascale Loiseau, Fabio Ciceri, Didier Blaise, Eric Spierings, Meiggie Untrau, Valérie Dubois, Catherine Paillard, Luca Vago, Noel Milpied, Antoine Toubert, Hidetoshi Inoko, Sergio Querol, Christophe Picard, Angélique Pichot, Dominique Charron, Sandra Michel, Katia Gagne, Bruno Lioure, Machteld Oudshoorn, Carapito, R, Jung, N, Untrau, M, Michel, S, Pichot, A, Giacometti, G, Cesbron, A, Gagne, K, Oudshoorn, M, Van der Holt, R, Labalette, M, Spierings, E, Picard, C, Loiseau, P, Tamouza, R, Toubert, A, Hanau, D, Parissiadis, A, Dubois, V, Raus, N, Lafarge, X, Vago, L, Ciceri, F, Paillard, C, Querol, S, Sierra, J, Fleischhauer, K, Nagler, A, Hoffmann, M, Milpied, N, Michallet, M, Lioure, B, de Latour, Rp, Labopin, M, Inoko, H, Claas, F, Blaise, D, Yakoub-Agha, I, Moreau, P, Charron, D, Ota, M, Mohty, M, Socie, G, Bahram, S, Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_treatment, Immunology, Medizin, Hematopoietic stem cell transplantation, Human leukocyte antigen, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, medicine, Minor histocompatibility antigen, Cumulative incidence, 030304 developmental biology, 0303 health sciences, Univariate analysis, business.industry, Donor selection, Cell Biology, Hematology, 3. Good health, Transplantation, surgical procedures, operative, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, CD8, 030215 immunology
Abstract: Background: Graft-versus-host disease (GVHD) is a major cause of mortality after unrelated hematopoietic stem cell transplantations (HSCT). Despite the development of modern immunosuppressive strategies, a nearly perfectly controlled compatibility of the classical HLA genes (HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1) and availability of numerous so-called minor histocompatibility antigens (e.g. HY or HA-1), its incidence remains largely unexplained to date. MIC genes (MHC class I chain-related) - a distinct lineage of MHC class I genes – are promising candidates to explain, at least partially, the incidence of GVHD in HLA-matched transplantations. MICA and MICB are highly polymorphic (100 alleles for MICA and 40 for MICB) and encode functional cell-surface glycoproteins up-regulated by cell stress. They interact with NKG2D, an activating receptor expressed on the surface of cytotoxic αβ CD8+ and γδ T lymphocytes and natural killer cells. MIC genes are already known to have a HLA-independent effect on solid graft outcomes and may play a similar role in HSCT by triggering GVHD. Objective: The objective of the present study was to determine the impact of donor/patient matching at the MICA and MICB loci on the incidence of GVHD in patients undergoing unrelated HSCT. Methods: We retrospectively analyzed a multicenter cohort of 1072 unrelated transplantations performed between 1996 and 2013. All donor-recipient pairs were fully typed at high resolution for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 and were matched for ten of ten HLA alleles (HLA 10/10 matched). High resolution genotyping of MICA and MICB was performed by sequenced-based typing in order to define matching grades between donors and patients. The endpoints of the study were acute and chronic GVHD. Apart from HLA-DPB1 matching, statistical models were adjusted for major clinical variables which have been shown to be associated with outcome (patient’s age, patient’s and donor’s sex, patient’s and donor’s serological status for cytomegalovirus, year of transplantation, time to transplantation, transplantation center, source of stem cells, conditioning regimen, GVHD prophylaxis, treatment with anti-thymocyte globulin, disease category and severity at transplantation). Results: Of the 1072 transplantations, 134 (12.5 %) and 380 (35.4 %) were mismatched at the MICA and MICB locus, respectively. Both MICA and MICB mismatches were significantly associated with an increased incidence of severe acute GVHD (grades III-IV) in univariate and multivariate models (multivariate model: HR = 2.32, 95 % CI = 1.84-2.92; p=0.0003 for MICA and HR = 1.49, 95 % CI = 1.24-1.79; p=0.03 for MICB). At day 100 post-HSCT severe acute GVHD incidences in mismatched vs. matched transplantations were 19.62 % vs. 15.08 % and 20.00 % vs. 14.84 % for MICA and MICB, respectively (Figure 1). Chronic GVHD was associated with MICA and MICB mismatches in univariate analysis (HR = 1.55, 95 % CI = 1.27-1.89; p=0.029 for MICA and HR=1.38, 95 % CI = 1.19-1.62; p=0.03 for MICB), but showed only a trend for association in multivariate models. Figure 1 Estimated cumulative incidence curves of grades III–IV acute GVHD according to MICA (panel A) and MICB (panel B) matching status. The solid and dashed lines represent MIC matched and mismatched grafts, respectively. The Fine and Gray model was used with relapse and death considered as competing risks. Figure 1. Estimated cumulative incidence curves of grades III–IV acute GVHD according to MICA (panel A) and MICB (panel B) matching status. The solid and dashed lines represent MIC matched and mismatched grafts, respectively. The Fine and Gray model was used with relapse and death considered as competing risks. Conclusion: To date this is the largest reported MICA and MICB sequence analysis whether in HSCT or solid organ transplantation. Inclusion of MICA and MICB typing in the donor selection process may be a practical clinical strategy for lowering the risks of severe acute GVHD after unrelated HSCT. Disclosures No relevant conflicts of interest to declare.
Published: 2014
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

126 results on '"Pascale Loiseau"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources