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1. Anti-dsDNA IgE: a potential non-invasive test for prediction of lupus nephritis relapse

Author

Karine Baumstarck, Noémie Jourde-Chiche, Eric Daugas, Marie Himbert, Léa Chapart, and Nicolas Charles

Subjects
Medicine
Abstract

Objectives Discontinuation or continuation of maintenance immunosuppressive therapy (MIST) after a severe lupus nephritis (LN) requires measuring the risk of relapse but reliable clinical and biological markers are lacking. The WIN-IgE study assesses the value of serum anti-dsDNA IgE autoantibodies as a biomarker for the prediction of relapse in severe LN.Methods WIN-IgE is an ancillary study of the WIN-Lupus study (NCT01284725), a prospective controlled clinical trial which evaluated the discontinuation of MIST after 2–3 years in class III or IV±V LN with active lesions. WIN-IgE included all patients with available serum collected at randomisation for continuation or discontinuation of MIST. In these sera, anti-dsDNA antibodies, IgE and IgG, were quantified by ELISA and compared between patients who experienced LN relapse and those who did not during the 24 months of follow-up.Results 52 patients were included, 25 in the MIST continuation group and 27 in the MIST discontinuation group, 12 experienced a biopsy-proven relapse of LN. Initial anti-dsDNA IgE antibodies levels were higher in patients with subsequent LN relapse. Anti-dsDNA IgG was not associated with relapse. Survival without LN relapse was lower in patients with anti-dsDNA IgE levels above vs below a threshold of 1.9 arbitrary units (p=0.019), particularly in the subgroup of patients randomised to discontinue MIST (p=0.002). In all patients, anti-dsDNA IgE above 1.9 arbitrary units had a positive predictive value of 0.8 for severe LN relapse.Conclusions These results suggest blood anti-dsDNA IgE as a non-invasive predictive marker of LN relapse.

Published
2024
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2. Presence of specific SARS-COV2 antibodies in hemodialysis patients and their caregivers after the first wave of COVID-19

Author

Thomas Robert, Guillaume Lano, Noémie Resseguier, Mickaël Bobot, Dammar Bouchouareb, Stéphane Burtey, Xavier de Lamballerie, Jean Dhorne, Bertrand Dussol, Ariane Duval, Julien Faraut, Toscane Fourié, Philippe Giaime, Mourad Hallah, Dominique Jaubert, Océane Jéhel, Tristan Legris, Stéphane Liotatis, Valérie Moal, Laetitia Ninove, Nathalie Pedinielli, Marion Pelletier, Manon Romeu-Giannoli, Mariela Saba, Marion Sallée, Laurent Samson, Adriana Saveanu, Violaine Scarfoglière, Pascale Sebahoun, Romain Vial, Clarissa Von Kotze, Philippe Brunet, Gaëtan Lebrun, Stanislas Bataille, and Noémie Jourde-Chiche

Subjects
Medicine, Science
Abstract

Abstract Hemodialysis (HD) patients are at risk for severe COVID-19 and cannot comply with social distancing. SARS-COV2 seroprevalence in French patients and caregivers after the first wave of COVID-19 is unknown. SeroCOVIDial is a prospective study conducted between June and December 2020. SARS-COV2 seroprevalence was evaluated by a rapid serological test (BIOSYNEX) in HD patients and caregivers, and the presence or not of anti-SARS-COV2 neutralizing or non-neutralizing antibodies in patients was also determined by ELISA and seroneutralization. In June 2020, 451 HD patients and 238 caregivers were included. Overall SARS-COV2 seroprevalence was 8.4% (patients) and 6.7% (caregivers), and was 87.1% (patients) and 90.0% (caregivers) in participants with a previously documented SARS-COV2 infection. Overall seroprevalence reached 13.8% (patients) and 12.6% (caregivers) following the second epidemic wave. During the follow-up, 38 (8.4%) patients died (9 of COVID-19). Among the 44 (10.6%) patients who became infected, only two were seropositive at M0. The levels of anti-SARS-COV2 antibodies decreased over time in patients and caregivers. The BIOSYNEX test showed 82.9% sensitivity and 97.7% specificity. Prevalence of anti-SARS-COV2 antibodies was low in HD patients and caregivers after the first epidemic wave but rose after the second wave. A rapid serological test showed good performances and could be useful for future monitoring of anti-SARS-COV2 antibodies.

Published
2022
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3. Biopsy-proven kidney involvement in hypocomplementemic urticarial vasculitis

Author

Alice Corthier, Marie Jachiet, Daniel Bertin, Aude Servais, Christelle Barbet, Adrien Bigot, Marie-Sylvie Doutre, Didier Bessis, Ancuta Bouffandeau, Olivier Moranne, Pierre-André Jarrot, Nathalie Bardin, Benjamin Terrier, Stephane Burtey, Xavier Puéchal, Laurent Daniel, and Noémie Jourde-Chiche

Subjects
Hypocomplementemic urticarial vasculitis, McDuffie syndrome, Glomerulonephritis, Renal vasculitis, Renal biopsy, Anti-C1q antibody, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Hypocomplementemic urticarial vasculitis (HUV) is a rare systemic vasculitis. We aimed to describe the kidney involvement of HUV in a multicenter national cohort with an extended follow-up. Methods All patients with HUV (international Schwartz criteria) with a biopsy-proven kidney involvement, identified through a survey of the French Vasculitis Study Group (FVSG), were included. A systematic literature review on kidney involvement of HUV was performed. Results Twelve patients were included, among whom 8 had positive anti-C1q antibodies. All presented with proteinuria, from mild to nephrotic, and 8 displayed acute kidney injury (AKI), requiring temporary haemodialysis in 2. Kidney biopsy showed membrano-proliferative glomerulonephritis (MPGN) in 8 patients, pauci-immune crescentic GN or necrotizing vasculitis in 3 patients (with a mild to severe interstitial inflammation), and an isolated interstitial nephritis in 1 patient. C1q deposits were observed in the glomeruli (n = 6), tubules (n = 4) or renal arterioles (n = 3) of 8 patients. All patients received corticosteroids, and 9 were also treated with immunosuppressants or apheresis. After a mean follow-up of 8.9 years, 6 patients had a preserved renal function, but 2 patients had developed stage 3–4 chronic kidney disease (CKD) and 4 patients had reached end-stage kidney disease (ESKD), among whom 1 had received a kidney transplant. Conclusion Renal involvement of HUV can be responsible for severe AKI, CKD and ESRD. It is not always associated with circulating anti-C1q antibodies. Kidney biopsy shows mostly MPGN or crescentic GN, with frequent C1q deposits in the glomeruli, tubules or arterioles.

Published
2022
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4. Kidney biopsy in very elderly patients: indications, therapeutic impact and complications

Author

Mathilde Fedi, Mickaël Bobot, Julia Torrents, Pierre Gobert, Éric Magnant, Yannick Knefati, David Verhelst, Gaëtan Lebrun, Valérie Masson, Philippe Giaime, Julien Santini, Stanislas Bataille, Philippe Brunet, Bertrand Dussol, Stéphane Burtey, Julien Mancini, Laurent Daniel, and Noémie Jourde-Chiche

Subjects
Kidney biopsy, Elderly patient, Advanced age, Acute kidney injury, Nephrotic syndrome, Glomerulonephritis, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Few data is available on the risk/benefit balance of native kidney biopsy (KB) in very elderly patients. Methods Multicenter retrospective cohort study in the Aix-Marseille area: the results of KB and medical charts of all patients over 85 years biopsied between January 2010 and December 2018 were reviewed. Results 104 patients were included. Median age was 87 years. Indications for KB were: acute kidney injury (AKI) in 69.2% of patients, nephrotic syndrome (NS) with AKI in 13.5%, NS without AKI in 12.5%, and proteinuria in 4.8%. Median serum creatinine was 262 μmol/L, 21% of patients required dialysis at the time of KB. Significant bleeding occurred in 7 (6.7%) patients, requiring blood cell transfusion in 4 (3.8%), and radiological embolization in 1 (1%). The most frequent pathological diagnoses were: non-diabetic glomerular diseases (29.8%, including pauci-immune crescentic glomerulonephritis in 9.6%), hypertensive nephropathy (27.9%), acute interstitial nephritis (16.3%), renal involvement of hematological malignancy (8.7%), and acute tubular necrosis (6.7%). After KB, 51 (49%) patients received a specific treatment: corticosteroids (41.3%), cyclophosphamide (6.7%), rituximab (6.7%), bortezomib (3.8%), other chemotherapies (3.8%). Median overall survival was 31 months. Conclusions KB can reveal a diagnosis with therapeutic impact even in very elderly patients. Severe bleeding was not frequent in this cohort, but KB may have not been performed in more vulnerable patients.

Published
2021
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5. Comparative study of granulomatosis with polyangiitis subsets according to ANCA status: data from the French Vasculitis Study Group Registry

Author

Eric Hachulla, Luc Mouthon, Michele Iudici, Pascal Cohen, François Maurier, Benjamin Terrier, Bernard Bonnotte, Loic Guillevin, Claire de Moreuil, Alexandre Karras, Achille Aouba, Christian Pagnoux, Xavier Puechal, Mohamed Hamidou, Thomas Quemeneur, Jean-François Viallard, OLIVIER AUMAITRE, Alain Le Quellec, Noémie Jourde-Chiche, François Lifermann, Pascal Godmer, Chahera Khouatra, Claire Blanchard-Delaunay, Marc Ruivard, and Thomas Le Gallou

Subjects
Medicine
Published
2022
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6. Hydroxychloroquine levels in patients with systemic lupus erythematosus: whole blood is preferable but serum levels also detect non-adherence

Author

Benoit Blanchet, Moez Jallouli, Marie Allard, Pascale Ghillani-Dalbin, Lionel Galicier, Olivier Aumaître, François Chasset, Véronique Le Guern, Frédéric Lioté, Amar Smail, Nicolas Limal, Laurent Perard, Hélène Desmurs-Clavel, Du Le Thi Huong, Bouchra Asli, Jean-Emmanuel Kahn, Laurent Sailler, Félix Ackermann, Thomas Papo, Karim Sacré, Olivier Fain, Jérôme Stirnemann, Patrice Cacoub, Gaelle Leroux, Judith Cohen-Bittan, Jérémie Sellam, Xavier Mariette, Claire Goulvestre, Jean Sébastien Hulot, Zahir Amoura, Michel Vidal, Jean-Charles Piette, on behalf of the PLUS Group, Noémie Jourde-Chiche, and Nathalie Costedoat-Chalumeau

Subjects
Hydroxychloroquine, Systemic lupus erythematosus, Serum, Drug monitoring, Adherence, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Hydroxychloroquine (HCQ) levels can be measured in both serum and whole blood. No cut-off point for non-adherence has been established in serum nor have these methods ever been compared. The aims of this study were to compare these two approaches and determine if serum HCQ cut-off points can be established to identify non-adherent patients. Methods HCQ levels were measured in serum and whole blood from 573 patients with systemic lupus erythematosus (SLE). The risk factors for active SLE (SLEDAI score > 4) were identified by multiple logistic regression. Serum HCQ levels were measured in 68 additional patients known to be non-adherent, i.e. with whole-blood HCQ

Published
2020
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7. Parvovirus B19 infection and kidney injury: report of 4 cases and analysis of immunization and viremia in an adult cohort of 100 patients undergoing a kidney biopsy

Author

Maëlis Kauffmann, Mickaël Bobot, Laurent Daniel, Julia Torrents, Yannick Knefati, Olivier Moranne, Stéphane Burtey, Christine Zandotti, and Noémie Jourde-Chiche

Subjects
Parvovirus B19, Glomerulonephritis, Thrombotic microangiopathy, Primary infection, Prevalence, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background The seroprevalence of human Parvovirus B19 (PVB19) is 70–85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy. Methods Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017–2018. Results The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis. Conclusion PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.

Published
2020
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9. First phenotypic description of a female patient with c.610 T > C variant of GLA: a renal-predominant presentation of Fabry disease

Author

Sophie Greillier, Laurent Daniel, Catherine Caillaud, Bertrand Dussol, Guy Touchard, Jean-Michel Goujon, Noémie Jourde-Chiche, and Mickaël Bobot

Subjects
Fabry disease, Female, Phenotype, GLA variant, lysoGb3, Renal involvement, Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Fabry disease (FD) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase activity leading to intracellular glycosphingolipid accumulation. Multiple variants have been reported in the GLA gene coding for alpha-galactosidase, and the question of the pathogenicity of rare variants needs to be addressed, especially in patients with mild phenotypes. Case presentation The patient, a 37-year-old female, presented with a persistent proteinuria after an otherwise uncomplicated first pregnancy. Renal biopsy showed both mild mesangial IgA deposits, and a striking vacuolization of podocytes and tubular cells consistent with Fabry disease. On electron microscopy, discrete but characteristic pseudo-myelinic lamellar inclusions were observed in the podocytes’ lysosomes. A more detailed physical examination revealed an angiokeratoma, and medical history ancient acroparesthesia. There was no cardiac or cerebral involvement of Fabry disease on magnetic resonance imaging. While blood enzymatic activity of alpha-ga lactosidase was normal in this patient, lysoGb3 was elevated (3 N), and a rare heterozygous variant called c.610 T > C was documented in GLA gene. The patient was treated with an ACE inhibitor, with a rapid decrease in proteinuria. After a 5-year follow-up, her renal function has remained normal, with mild proteinuria, and normal cardiac echography. Conclusions We report and phenotypically describe the first case of a Fabry disease female patient carrying the GLA c.610 T > C variant associated with a renal-predominant clinical presentation.

Published
2020
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10. Sequential development of ANCA‐associated vasculitis and anti‐GBM disease: A report of two cases

Author

Camille Le Moine, Noémie Jourde‐Chiche, Delphine Kemlin, Benjamin Terrier, and Frédéric Vandergheynst

Subjects
ANCA‐associated vasculitis, anti‐GBM disease, glomerulonephritis, myeloperoxidase, Medicine, Medicine (General), R5-920
Abstract

Abstract In case of AAV with kidney involvement, physicians should explore anti‐GBM antibodies and be aware of the possible sequential development of AAV, especially with MPO‐ANCA, and anti‐GBM glomerulonephritis. This sequential disease history is associated with a poor renal outcome, highlighting the need for urgent diagnosis and management.

Published
2021
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11. Prognostic Factors in Anti-glomerular Basement Membrane Disease: A Multicenter Study of 119 Patients

Author

Cindy Marques, Julien Carvelli, Lucie Biard, Stanislas Faguer, François Provôt, Marie Matignon, Jean-Jacques Boffa, Emmanuelle Plaisier, Alexandre Hertig, Maxime Touzot, Olivier Moranne, Xavier Belenfant, Djillali Annane, Thomas Quéméneur, Jacques Cadranel, Hassan Izzedine, Nicolas Bréchot, Patrice Cacoub, Alexis Piedrafita, Noémie Jourde-Chiche, and David Saadoun

Subjects
anti-glomerular basement membrane disease, Goodpasture's disease, glomerulonephritis, vasculitis, outcome, mortality, Immunologic diseases. Allergy, RC581-607
Abstract

We report the overall and renal outcome in a French nationwide multicenter cohort of 119 patients with anti-glomerular basement membrane (anti-GBM) disease. Sixty-four patients (54%) had an exclusive renal involvement, 7 (6%) an isolated alveolar hemorrhage and 48 (40%) a combined renal and pulmonary involvement. Initial renal replacement therapy (RRT) was required in 78% of patients; 82% received plasmapheresis, 82% cyclophosphamide, and 9% rituximab. ANCA positive (28%) patients were older (70 vs. 47 years, p < 0.0001), less frequently smokers (26 vs. 54%, p = 0.03), and had less pulmonary involvement than ANCA- patients. The 5 years overall survival was 92%. Risk factors of death (n = 11, 9.2%) were age at onset [HR 4.10 per decade (1.89–8.88) p = 0.003], hypertension [HR 19.9 (2.52–157 0.2) p = 0.005], dyslipidemia [HR 11.1 (2.72–45) p = 0.0008], and need for mechanical ventilation [HR 5.20 (1.02–26.4) p = 0.047]. The use of plasmapheresis was associated with better survival [HR 0.29 (0.08–0.98) p = 0.046]. At 3 months, 55 (46%) patients had end-stage renal disease (ESRD) vs. 37 (31%) ESRD-free and 27 (23%) unevaluable with follow-up < 3 months. ESRD patients were older, more frequently female and had a higher serum creatinine level at presentation than those without ESRD. ESRD-free survival was evaluated in patients alive without ESRD at 3 months (n = 37) using a landmark approach. In conclusion, this large French nationwide study identifies prognosis factors of renal and overall survival in anti-GBM patients.

Published
2019
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12. Anti-PLA2R1 Antibodies Containing Sera Induce In Vitro Cytotoxicity Mediated by Complement Activation

Author

Maël Lateb, Hajar Ouahmi, Christine Payré, Vesna Brglez, Kevin Zorzi, Guillaume Dolla, Mohamad Zaidan, Sonia Boyer-Suavet, Bertrand Knebelmann, Thomas Crépin, Cécile Courivaud, Noémie Jourde-Chiche, Vincent Esnault, Gérard Lambeau, and Barbara Seitz-Polski

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy (MN). However, the pathogenic role of anti-PLA2R1 autoantibodies is unclear. Our aim was to evaluate the in vitro cytotoxicity of anti-PLA2R1 antibodies mediated by complement. Forty-eight patients with PLA2R1-related MN from the prospective cohort SOURIS were included. Anti-PLA2R1 titer, epitope profile, and anti-PLA2R1 IgG subclasses were characterized by ELISA. Cell cytotoxicity was evaluated by immunofluorescence in HEK293 cells overexpressing PLA2R1 incubated with patient or healthy donor sera in the presence or absence of rabbit complement or complement inhibitors. Mean cytotoxicity of anti-PLA2R1 sera for HEK293 cells overexpressing PLA2R1 was 2±2%, which increased to 24±6% after addition of rabbit complement (p

Published
2019
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13. D25V apolipoprotein C-III variant causes dominant hereditary systemic amyloidosis and confers cardiovascular protective lipoprotein profile

Author

Sophie Valleix, Guglielmo Verona, Noémie Jourde-Chiche, Brigitte Nédelec, P. Patrizia Mangione, Frank Bridoux, Alain Mangé, Ahmet Dogan, Jean-Michel Goujon, Marie Lhomme, Carolane Dauteuille, Michèle Chabert, Riccardo Porcari, Christopher A. Waudby, Annalisa Relini, Philippa J. Talmud, Oleg Kovrov, Gunilla Olivecrona, Monica Stoppini, John Christodoulou, Philip N. Hawkins, Gilles Grateau, Marc Delpech, Anatol Kontush, Julian D. Gillmore, Athina D. Kalopissis, and Vittorio Bellotti

Subjects
Science
Abstract

Decrease in Apolipoprotein C-III (ApoC-III) yields a cardioprotective lipoprotein profile. Here, Valleix et al.reveal a novel ApoC-III variant conferring low plasma ApoC-III concentration and cardioprotection despite renal insufficiency, and, unexpectedly, causing dominant hereditary systemic amyloidosis due to its fibrillogenic nature.

Published
2016
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14. Both Monoclonal and Polyclonal Immunoglobulin Contingents Mediate Complement Activation in Monoclonal Gammopathy Associated-C3 Glomerulopathy

Author

Sophie Chauvet, Lubka T. Roumenina, Pierre Aucouturier, Maria-Chiara Marinozzi, Marie-Agnès Dragon-Durey, Alexandre Karras, Yahsou Delmas, Moglie Le Quintrec, Dominique Guerrot, Noémie Jourde-Chiche, David Ribes, Pierre Ronco, Frank Bridoux, and Véronique Fremeaux-Bacchi

Subjects
complement, alternative pathway activation, C3 glomerulopathies, monoclonal gammopathy, autoantibodies, Immunologic diseases. Allergy, RC581-607
Abstract

C3 glomerulopathy (C3G) results from acquired or genetic abnormalities in the complement alternative pathway (AP). C3G with monoclonal immunoglobulin (MIg-C3G) was recently included in the spectrum of “monoclonal gammopathy of renal significance.” However, mechanisms of complement dysregulation in MIg-C3G are not described and the pathogenic effect of the monoclonal immunoglobulin is not understood. The purpose of this study was to investigate the mechanisms of complement dysregulation in a cohort of 41 patients with MIg-C3G. Low C3 level and elevated sC5b-9, both biomarkers of C3 and C5 convertase activation, were present in 44 and 78% of patients, respectively. Rare pathogenic variants were identified in 2/28 (7%) tested patients suggesting that the disease is acquired in a large majority of patients. Anti-complement auto-antibodies were found in 20/41 (49%) patients, including anti-FH (17%), anti-CR1 (27%), anti-FI (5%) auto-antibodies, and C3 Nephritic Factor (7%) and were polyclonal in 77% of patients. Using cofactor assay, the regulation of the AP was altered in presence of purified IgG from 3/9 and 4/7 patients with anti-FH or anti-CR1 antibodies respectively. By using fluid and solid phase AP activation, we showed that total purified IgG of 22/34 (65%) MIg-C3G patients were able to enhance C3 convertase activity. In five documented cases, we showed that the C3 convertase enhancement was mostly due to the monoclonal immunoglobulin, thus paving the way for a new mechanism of complement dysregulation in C3G. All together the results highlight the contribution of both polyclonal and monoclonal Ig in MIg-C3G. They provide direct insights to treatment approaches and opened up a potential way to a personalized therapeutic strategy based on chemotherapy adapted to the B cell clone or immunosuppressive therapy.

Published
2018
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15. Brincidofovir Use after Foscarnet Crystal Nephropathy in a Kidney Transplant Recipient with Multiresistant Cytomegalovirus Infection

Author

Romain Vial, Christine Zandotti, Sophie Alain, Alexandre Decourt, Noémie Jourde-Chiche, Raj Purgus, Charleric Bornet, Laurent Daniel, Valérie Moal, and Tristan Legris

Subjects
Surgery, RD1-811
Abstract

Background. Cytomegalovirus (CMV) antiviral drug resistance constitutes an increasing challenge in transplantation. Foscarnet is usually proposed when resistance for ganciclovir is suspected, but its use is limited by its nephrotoxicity. Case Presentation. We report a case of multiresistant CMV disease in a kidney transplant recipient. Foscarnet was prescribed after ganciclovir treatment failure in a patient with two mutations in the UL97 viral gene. Foscarnet induced biopsy-proven kidney crystal precipitation that resulted in severe acute transplant failure and nephrotic syndrome. Despite a large decrease in immunosuppression, CMV disease was not controlled and a salvage therapy with Brincidofovir (BCV), which is an oral lipid conjugate of cidofovir with limited nephrotoxicity, was attempted. Clinical and virological remission was observed after a 21-day course of BCV, despite mild and reversible liver toxicity. However, a new relapse could not be effectively cured by BCV due to a new mutation in the UL54 gene, which is known to confer resistance to cidofovir. A new course of foscarnet finally resulted in prolonged CMV remission. Herein, we present a review of foscarnet nephropathy cases in solid-organ transplanted patients. Conclusions. This unique case highlights the potential benefit of BCV use during resistant CMV infection, although mutations in the UL54 gene may limit its therapeutic efficacy. These findings need to be confirmed in clinical trials.

Published
2017
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16. Endothelial Toxicity of High Glucose and its by-Products in Diabetic Kidney Disease

Author

Laetitia Dou and Noémie Jourde-Chiche

Subjects
ages, diabetic kidney disease, endothelial dysfunction, glucose, polyols, Medicine
Abstract

Alterations of renal endothelial cells play a crucial role in the initiation and progression of diabetic kidney disease. High glucose per se, as well as glucose by-products, induce endothelial dysfunction in both large vessels and the microvasculature. Toxic glucose by-products include advanced glycation end products (AGEs), a group of modified proteins and/or lipids that become glycated after exposure to sugars, and glucose metabolites produced via the polyol pathway. These glucose-related endothelio-toxins notably induce an alteration of the glomerular filtration barrier by increasing the permeability of glomerular endothelial cells, altering endothelial glycocalyx, and finally, inducing endothelial cell apoptosis. The glomerular endothelial dysfunction results in albuminuria. In addition, high glucose and by-products impair the endothelial repair capacities by reducing the number and function of endothelial progenitor cells. In this review, we summarize the mechanisms of renal endothelial toxicity of high glucose/glucose by-products, which encompass changes in synthesis of growth factors like TGF-β and VEGF, induction of oxidative stress and inflammation, and reduction of NO bioavailability. We finally present potential therapies to reduce endothelial dysfunction in diabetic kidney disease.

Published
2019
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17. Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus.

Author

Maëlle Plawecki, Elise Lheritier, Giovanna Clavarino, Noémie Jourde-Chiche, Saber Ouili, Stéphane Paul, Evelyne Gout, Françoise Sarrot-Reynauld, Nathalie Bardin, Pierre-Yves Boëlle, Laurent Chiche, Laurence Bouillet, Nicole M Thielens, Jean-Yves Cesbron, and Chantal Dumestre-Pérard

Subjects
Medicine, Science
Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection. Samples from healthy controls (n = 48) were matched with SLE sera. Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 56 of 165 (34%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (r = 0.38, p

Published
2016
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18. Original Approach for Automated Quantification of Antinuclear Autoantibodies by Indirect Immunofluorescence

Author

Daniel Bertin, Noémie Jourde-Chiche, Pierre Bongrand, and Nathalie Bardin

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Introduction. Indirect immunofluorescence (IIF) is the gold standard method for the detection of antinuclear antibodies (ANA) which are essential markers for the diagnosis of systemic autoimmune rheumatic diseases. For the discrimination of positive and negative samples, we propose here an original approach named Immunofluorescence for Computed Antinuclear antibody Rational Evaluation (ICARE) based on the calculation of a fluorescence index (FI). Methods. We made comparison between FI and visual evaluations on 237 consecutive samples and on a cohort of 25 patients with SLE. Results. We obtained very good technical performance of FI (95% sensitivity, 98% specificity, and a kappa of 0.92), even in a subgroup of weakly positive samples. A significant correlation between quantification of FI and IIF ANA titers was found (Spearman's ρ=0.80, P

Published
2013
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19. Pregnancy outcomes in women with primary Sjögren's syndrome: an analysis of data from the multicentre, prospective, GR2 study

Author

Grégoire Martin de Frémont, Nathalie Costedoat-Chalumeau, Estibaliz Lazaro, Rakiba Belkhir, Gaëlle Guettrot-Imbert, Nathalie Morel, Gaétane Nocturne, Anna Molto, Tiphaine Goulenok, Elisabeth Diot, Laurent Perard, Nicole Ferreira-Maldent, Maelle Le Besnerais, Nicolas Limal, Nihal Martis, Noémie Abisror, Odile Debouverie, Christophe Richez, Vincent Sobanski, François Maurier, Gaëtan Sauvetre, Hervé Levesque, Marie-Agnès Timsit, Nathalie Tieulié, Pauline Orquevaux, Boris Bienvenu, Matthieu Mahevas, Thomas Papo, Céline Lartigau-Roussin, Elodie Chauvet, Emilie Berthoux, Françoise Sarrot-Reynauld, Loïc Raffray, Marion Couderc, Nicolas Martin Silva, Noémie Jourde-Chiche, Nicolas Belhomme, Thierry Thomas, Vincent Poindron, Viviane Queyrel-Moranne, Juliette Delforge, Camille Le Ray, Emmanuelle Pannier, Xavier Mariette, Véronique Le Guern, Raphaèle Seror, Alexandra AUDEMARD-VERGER, Emmanuel AZZI, Béatrice BANNEVILLE, Antoine BAUDET, Constance BEAUDOUIN BAZIRE, Cristina BELIZNA, Alexandre Belot, Ygal BENHAMOU, Alice Berezné, Fanny BERNARD-GUERVILLY, Sabine BERTHIER, Holy BEZANAHARY, Lisa BIALE, Adrien BIGOT, Claire BLANCHARD-DELAUNAY, Anne CALAS, Julien CAMPAGNE, Pascal CATHEBRAS, Claire CAZALETS, Benjamin CHAIGNE, Olivia CHANDESRIS, Jérémy CHATELAIS, Emmanuel CHATELUS, Fleur COHEN, Bernard Combe, Céline COMPARON, Pascal COQUERELLE, Louise DAMIAN, Eric DAUGAS, Mathilde DE MENTHON, Claire DE MOREUIL, Estelle DELATTRE, Azeddine DELLAL, Catherine Deneux-Tharaux, Amélie DENIS, Camille DEPROUW, Emmanuelle DERNIS, Alban DEROUX, Sandra DESOUCHES, Philippe Dieudé, Guillaume DIREZ, Maxime Dougados, Marine DRIESSEN, Aurélie DU THANH, Laetitia DUNOGEANT, Cécile DURANT, Cécile-Audrey DUREL, Isabelle DURIEU, Florence EBOUE, Elisabeth Elefant, Olivier FAIN, Bruno FAUTREL, René-Marc FLIPO, Aline FRAZIER, Antoine FROISSART, Sophie GEORGIN-LAVIALLE, Elisabeth GERVAIS, Bertrand GODEAU, François Goffinet, Anne GOMPEL, Laure GOSSEC, Philippe GOUPILLE, Claire GRANGE, Constance GUILLAUD-DANIS, Eric HACHULLA, Sabine HOEFSLOOT, Aurélie HUMMEL, Patrick JEGO, Stéphanie JOBARD, Laurence JOSSELIN-MAHR, Marc LAMBERT, Vincent LANGLOIS, Delphine LARIVIERE, Claire LARROCHE, Augustin LATOURTE, Christian LAVIGNE, Thomas LE GALLOU, Gaëlle LEROUX, Jean Guillaume LETAROUILLY, Frédéric LIOTÉ, Laurence Loeuillet, Jonathan London, Valentine Loustau, Pierre LOZAC'H, Emmanuel MAHEU, Hélène MAILLARD, Hubert MAROTTE, Agathe MASSEAU, Arsène MEKINIAN, Sara Melboucy Belkhir, Corinne Miceli-Richard, Martin MICHAUD, Marc MICHEL, Olivier MORANNE, Chafika MORATI-HAFSAOUI, Guillaume MOULIS, Luc MOUTHON, Barbara NICOLAS, Jacky Nizard, Jérémy ORA, Rodérau OUTH, Elisabeth PASQUIER, Jean-Loup PENNAFORTE, Antoinette PERLAT, Hélène PETIT-BAUER, Evangeline PILLEBOUT, Jean-Maxime PIOT, Agnès PORTIER, Olivier Pourrat, Xavier PUECHAL, Gregory PUGNET, Manon REDONDIN, Alexis REGENT, Mélanie RORIZ, Laurent SAILLER, Léa SAVEY, Marc SCHERLINGER, Nicolas SCHLEINITZ, Jérémie Sellam, Loïc Sentilhes, Aude SERVAIS, Perrine SMETS, Christelle SORDET, Martin SOUBRIER, Katia STANKOVIC-STOJANOVIC, Geoffrey URBANSKI, Véronique VEIT, Emmanuelle WEBER, and Cécile YELNIK

Subjects
Rheumatology, Immunology, Immunology and Allergy
Published
2023

20. Categorization of patients with systemic lupus erythematosus using disease activity, patient-reported outcomes, and transcriptomic signatures

Author

Elisabeth Jouve, Noémie Jourde-Chiche, Laurent Chiche, and Robin Arcani

Subjects
Transcriptome, Disease activity, Text mining, Categorization, Rheumatology, business.industry, Medicine, General Medicine, business, Bioinformatics
Abstract

Objective Patients with systemic lupus erythematosus (SLE) display symptoms that are not always related to disease activity and may distort clinical trial results. Recently, a clinical categorization based on the presence of type 1 (inflammatory manifestations) and/or type 2 (widespread pain, fatigue, depression) symptoms has been proposed in SLE. Our aim was to develop a type 2 score derived from the Short-Form health survey (SF-36) to categorize SLE patients and to compare immunological and transcriptomic profiles between groups. Methods Seventeen items from the SF-36 were selected to build a type 2 score for 50 SLE patients (100 visits; LUPUCE cohort) and the SLEDAI was used to define type 1 symptoms. Patients were categorized in four groups: minimal (no symptoms), type 1, type 2 and mixed (both type 1 and type 2 symptoms). Clinical, immunological and transcriptomic profiles were compared between the groups. Results Type 2 scores ranged from 0 to 31, with a cut-off value of 14 (75th percentile). The sample categorization was: minimal in 39%, type 1 in 37%, type 2 in 9% and mixed in 15%. Type 2 patients were older than minimal patients and had a longer disease duration than type 1 and mixed patients. Immunological data and modular interferon signatures did not differ between the groups. Conclusion Patients with SLE can be categorized into four clinical groups using the SLEDAI score and our SF-36-derived type 2 score. This categorization is non-redundant with immunological or transcriptomic profiles and could prove useful to stratify patients in clinical trials.

Published
2023

21. Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study

Author

Anne Murarasu, Gaëlle Guettrot-Imbert, Véronique Le Guern, Cécile Yelnik, Viviane Queyrel, Nicolas Schleinitz, Nicole Ferreira-Maldent, Elisabeth Diot, Geoffrey Urbanski, Emmanuelle Pannier, Estibaliz Lazaro, Odile Souchaud-Debouverie, Pauline Orquevaux, Nicolas Belhomme, Nathalie Morel, Elodie Chauvet, François Maurier, Maëlle Le Besnerais, Noemie Abisror, Tiphaine Goulenok, Françoise Sarrot-Reynauld, Alban Deroux, Elisabeth Pasquier, Claire de Moreuil, Holy Bezanahary, Laurent Pérard, Nicolas Limal, Vincent Langlois, Anne Calas, Bertrand Godeau, Christian Lavigne, Eric Hachulla, Fleur Cohen, Ygal Benhamou, Loïc Raffray, Mathilde de Menthon, Nathalie Tieulié, Vincent Poindron, Luc Mouthon, Maddalena Larosa, Elisabeth Eléfant, Loic Sentilhes, Anna Molto, Catherine Deneux-Tharaux, Nathalie Costedoat-Chalumeau, Emmanuel Azzi, Béatrice Banneville, Antoine Baudet, Constance Beaudouin-Bazire, Cristina Belizna, Rakiba Belkhir, Alice Berezne, Emilie Berthoux, Sabine Berthier, Lisa Biale, Boris Bienvenu, Claire Blanchard-Delaunay, Pascal Cathebras, Claire Cazalets, Benjamin Chaigne, Olivia Chandesris, Jérémy Chatelais, Emmanuel Chatelus, Pascal Coquerelle, Marion Couderc, Juliette Delforge, Amélie Denis, Sandra Desouches, Philippe Dieudé, Guillaume Direz, Marine Driessen, Aurélie Du Thanh, Laetitia Dunogeant, Cécile Durant, Isabelle Durieu, Marc Fabre, Olivier Fain, René-Marc Flipo, Aline Frazier, Antoine Froissart, Sophie Georgin-Lavialle, Elisabeth Gervais, Anne Gompel, Laure Gossec, Phillipe Goupille, Claire Grange, Constance Guillaud-Danis, Aurélie Hummel, Moez Jallouli, Patrick Jego, Stéphane Jobard, Laurence Josselin-Mahr, Noémie Jourde-Chiche, Anne-Sophie Korganow, Marc Lambert, Delphine Lariviere, Claire Larroche, Céline Lartigau-Roussin, Augustin Latourte, Thomas Le Gallou, Gaëlle Leroux, Hervé Levesque, Frédéric Lioté, Jonathan London, Valentine Loustau, Emmanuel Maheu, Matthieu Mahevas, Hélène Maillard, Xavier Mariette, Hubert Marotte, Nicolas Martin-Silva, Nihal Martis, Agathe Masseau, Arsène Mekinian, Sara Melboucy-Belkhir, Martin Michaud, Marc Michel, Chafika Morati-Hafsaoui, Jacky Nizard, Jérémy Ora, Jean-Loup Pennaforte, Antoinette Perlat, Hélène Petit Bauer, Evangeline Pillebout, Jean-Maxime Piot, Agnès Portier, Gregory Pugnet, Manon Redondin, Alexis Regent, Christophe Richez, Mélanie Roriz, Laurent Sailler, Gaëtan Sauvêtre, Léa Savey, Vincent Sobanski, Christelle Sordet, Martin Soubrier, Katia Stankovic Stojanovic, Thierry Thomas, Marie-Agnès Timsit, and Vassilis Tsatsaris

Subjects
Rheumatology, Immunology, Immunology and Allergy
Published
2022

23. The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies

Author

Friederike Petzold, Katy Billot, Xiaoyi Chen, Charline Henry, Emilie Filhol, Yoann Martin, Marina Avramescu, Maxime Douillet, Vincent Morinière, Pauline Krug, Cécile Jeanpierre, Kalman Tory, Olivia Boyer, Anita Burgun, Aude Servais, Remi Salomon, Alexandre Benmerah, Laurence Heidet, Nicolas Garcelon, Corinne Antignac, Mohamad Zaidan, Sophie Saunier, Tania Attié-Bitach, Valerie Comier-Daire, Jean-Michel Rozet, Yaacov Frishberg, Brigitte Llanas, Michel Broyer, Nabil Mohsin, Marie-Alice Macher, Nicole Philip, Véronique Baudouin, Damian Brackman, Chantal Loirat, Marina Charbit, Maud Dehennault, Claude Guyot, Pierre Bataille, Mariet Elting, Georges Deschenes, Andrea Gropman, Geneviève Guest, Marie-France Gagnadoux, Philippe Nicoud, Pierre Cochat, Bruno Ranchin, Albert Bensman, Anne-Marie Guerrot, Bertrand Knebelmann, Ilmay Bilge, Danièle Bruno, Stéphane Burtey, Caroline Rousset Rouvière, Valérie Caudwell, Denis Morin, Hélène Dollfus, Anne Maisin, Christian Hamel, Eric Bieth, Sophie Gie, Judith Goodship, Gwenaelle Roussey, Hermine La Selve, Hubert Nivet, Lucie Bessenay, Mathilde Caillez, Jean Bernard Palcoux, Stéphane Benoît, Philippe Dubot, Marc Fila, Fabienne Giuliano, Daouya Iftene, Michele Kessler, Theresa Kwon, Anine Lahoche, Audrey Laurent, Anne-Laure Leclerc, David Milford, Thomas Neuhaus, Sylvie Odent, Philippe Eckart, Dominique Chauveau, Patrick Niaudet, Horacio Repetto, Sophie Taque, Alexandra Bruel, Alexandra Noel-Botte, Emma Allain Launay, Lisa Allard, Dany Anlicheau, Anne-Laure Adra, Arnaud Garnier, Arvind Nagra, Remy Baatard, Justine Bacchetta, Banu Sadikoglu, Christine Barnerias, Anne Barthelemy, Lina Basel, Nader Bassilios, Hedi Ben Maiz, Fatma Ben Moussa, Faïza Benmati, Romain Berthaud, Aurélia Bertholet, Dominique Blanchier, Jean Jacques Boffa, Karim Bouchireb, Ihab Bouhabel, Zakaria Boukerroucha, Guylhène Bourdat-Michel, Odile Boute, Karine Brochard, Roseline Caumes, Siham Chafai Elalaoui, Bernard Chamontin, Marie Caroline Chastang, Christine Pietrement, Christine Richer, Christophe Legendre, Karin Dahan, Fabienne Dalla-Vale, Damien Thibaudin, Maxime Dauvergne, Salandre Davourie, Martin Debeukelaer, Jean Daniel Delbet, Constantinos Deltas, Denis Graber, Nadège Devillars, Boucar Diouf, Martine Doco Fenzy, Jean-Luc André, Dominique Joly, Alan Fryer, Laetitia Albano, Elisabeth Cassuto, Aline Pincon, Ana Medeira, Annabelle Chaussenot, Anne Mensire-Marinier, Francois Bouissou, Stephane Decramer, Armand Bottani, Aurélie Hummel, Alexandre Karras, Avi Katz, Christine Azema, Bénédicte Janbon, Bernard Roussel, Claude Bonniol, Christiophe Mariat, Gérard Champion, Deborah Chantreuil, Nicolas Chassaing, Christiane Mousson, Christine Baudeau, Delphine Hafdar Cuntz, Cyril Mignot, Laurene Dehoux, Didier Lacombe, Thierry Hannedouche, Elodie Mérieau, Emmanuelle Charlin, Eric Gauthier, Florent Plasse, Stanislas Faguer, Fanny Lebas, Florence Demurger, Francesco Emma, François Cartault, Geneviève Dumont, Nathalie Godefroid, Vincent Guigonis, Sophie Hillaire, Jaap Groothoff, Jan Dudley, Noémie Jourde-Chiche, Khalil El Karoui, Saoussen Krid, Krier Coudert, Larbi Bencheick, Laurent Yver, Marie-Pierre Lavocat, Le Monies De Sagazan, Valerie Leroy, Lise Thibaudin, Liz Ingulli, Lorraine Gwanmesia, Lydie Burglen, Marie-Hélène Saïd-Menthon, Marta Carrera, Mathilde Nizon, Catherine Melander, Michel Foulard, Monique Blayo, Jacques Prinseau, Nadine Jay, Nathalie Brun, Nicolas Camille, François Nobili, Olivier Devuyst, Ouafa Ben Brahim, Paloma Parvex, Laurence Perrin Sabourin, Philippe Blanc, Philippe Vanhille, Pierre Galichon, Sophie Pierrepont, Vincent Planquois, Gwenaelle Poussard, Claire Pouteil Noble, Radia Allal, Raphaelle Bernard, Raynaud Mounet, Rémi Cahen, Renaud Touraine, Claire Rigothier, Amélie Ryckewaert, Mathieu Sacquepee, Salima El Chehadeh, Charlotte Samaille, Shuman Haq, Ari Simckes, Stéphanie Lanoiselée, Stephanie Tellier, Jean-François Subra, Sylvie Cloarec, Julie Tenenbam, Thomas Lamy, Valérie Drouin Garraud, Huguette Valette, Vanina Meyssonnier, Rosa Vargas-Poussou, Yves Snajer, Sandrine Durault, Emmanuelle Plaisier, Etienne Berard, Fadi Fakhouri, Ferielle Louillet, Paul Finielz, Michel Fischbach, Bernard Foliguet, Hélène Francois-Pradier, Florentine Garaix, Marion Gerard, Gianfranco Rizzoni, Brigitte Gilbert, Denis Glotz, Astrid Godron Dubrasquet, Jean-Pierre Grünfeld, Guillaume Bollee, Michelle Hall, Sverker Hansson, Damien Haye, Hélène Taffin, Friedhelm Hildebrandt, Maryvonne Hourmand, Hümya Kayserili, Ivan Tack, Marie Line Jacquemont, Jennifer Fabre-Teste, Cliff Kashtan, Kkoen Van Hoeck, Alexandre Klein, Yannick Knefati, Nine Knoers, Martin Konrad, Alain Lachaux, Isabelle Landru, Gilbert Landthaler, Philippe Lang, Patrick Le Pogamp, Tristan Legris, Catherine Didailler, Thierry Lobbedez, Loïc de Parscau, Lucile Pinson, Hervé Maheut, Marc Duval-Arnould, Marlène Rio, Marie-Claire Gubler, Pierre Merville, Guillaume Mestrallet, Maite Meunier, Karine Moreau, Jérôme Harambat, Graeme Morgan, Georges Mourad, Niksic Stuber, Odile Boespflug-Tanguy, Olivier Dunand, Olivier Niel, Nacera Ouali, Paolo Malvezzi, Pauline Abou Jaoude, Solenne Pelletier, Julie Peltier, M.B. Petersen, Philippe Michel, Philippe Rémy, Jean-Baptiste Philit, Valérie Pichault, Thierry Billette de Villemeur, Bernard Boudailliez, Bruno Leheup, Claire Dossier, Djamal-Dine Djeddi, Yves Berland, Bruno Hurault de Ligny, Susan Rigden, Christophe Robino, Annick Rossi, Sabine Sarnacki, Messaoud Saidani, Albane Brodin Sartorius, Elise Schäfer, Sztriha Laszlo, Marie-Christine Thouret, Angélique Thuillier-Lecouf, Howard Trachtman, Claire Trivin, Michel Tsimaratos, Rita Van Damme-Lombaerts, Marjolaine Willems, Michel Youssef, Ariane Zaloszyc, Alexis Zawodnik, and Marie-Julia Ziliotis

Subjects
Nephrology
Abstract

Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.

Published
2023

24. Beyond the kidney biopsy: genomic approach to undetermined kidney diseases

Author

Thomas Robert, Laure Raymond, Marine Dancer, Julia Torrents, Noémie Jourde-Chiche, Stéphane Burtey, Christophe Béroud, and Laurent Mesnard

Subjects
Transplantation, Nephrology
Abstract

Background and objectives According to data from large national registries, almost 20 to 25% of patients with end-stage kidney disease have an undetermined kidney disease (UKD). Recent data have shown that monogenic disease-causing variants are under-diagnosed. We performed exome sequencing (ES) on UKD patients in our center to improve the diagnosis rate. Design, setting, participants, and measurements ES was proposed in routine practice for patients with UKD including kidney biopsy from January 2019 to December 2021. Mutations were detected using a targeted bioinformatic customized kidney gene panel (675 genes). The pathogenicity was assessed using American College of Medical Genetics guidelines. Results We included 230 adult patients, median age 47.5 years. Consanguinity was reported by 25 patients. A family history of kidney disease was documented in 115 patients (50%). Kidney biopsies were either inconclusive in 69 patients (30.1%) or impossible in 71 (30.9%). We detected 28 monogenic renal disorders in 75 (32.6%) patients. Collagenopathies was the most common genetic kidney diagnosis (46.7%), with COL4A3 and COL4A4 accounting for 80% of these diagnoses. Tubulopathies (16%) and ciliopathies (14.7%) yielded respectively the second and third genetic kidney diagnosis category and UMOD-associated nephropathy as the main genetic findings for tubulopathies (7/11). Ten of the 22 patients having ES ‘first’ eventually received a positive diagnosis, thereby avoiding 11 biopsies. Among the 44 patients with glomerular, tubulo-interstitial or vascular nephropathy, 13 (29.5%) were phenocopies. The diagnostic yield of ES was higher in female patients (p = 0.02) and in patients with a family history of kidney disease (p Conclusion Genetic diagnosis has provided new clinical insights by clarifying or reclassifying kidney disease etiology in over a third of UKD patients. Exome ‘first’ may have a significant positive diagnostic yield, thus avoiding invasive kidney biopsy; moreover, the diagnostic yield remains elevated even when biopsy is impossible or inconclusive. ES provides a clinical benefit for routine nephrological healthcare in patients with UKD.

Published
2023

25. Early proximal tubular injury in COVID-19 related ARDS: the URICOV study

Author

Mickaël Bobot, Xavier Heim, Howard Max, José Boucraut, Pierre Simeone, Claire Stein, Lionel Velly, Nicolas Bruder, Jean-Marie Forel, Sami Hraiech, Christophe Guervilly, Julien Carvelli, Marc Gainnier, Jean-Louis Mège, Sophie Chopinet, Noémie Jourde-Chiche, Laurent Papazian, and Stéphane Burtey

Abstract

Background: During COVID-19, renal impairment is the most frequent after lung impairment and is associated with a poor prognosis particularly in intensive care unit (ICU). In this work we aimed to assess the existence and incidence of early renal dysfunction and its prognostic value in patients with COVID-19-related acute respiratory distress syndrome (ARDS) and to compare them with patients with non-COVID-19-related ARDS. Methods: This prospective multicenter study was conducted in 3 ICUs. Patients aged 18 years and older with invasive mechanical ventilation for ARDS were enrolled. Precise evaluation of renal dysfunction markers including urinary proteins electrophoresis (UPE) and quantification, was performed within 24 hours after mechanical ventilation onset. Results: From March 2020 to December 2021, 135 patients in ICU for ARDS were enrolled: 100 COVID-19 ARDS and 35 non-COVID-19 ARDS. UPE found more tubular dysfunction in COVID-19 patients (68% vs. 21.4%, pvs. 11.2%, p=0.0003). COVID-19 patients significantly displayed early urinary leakage of tubular proteins like beta-2-microglobulin and free-light chains, tended to display more frequently acute kidney injury (AKI) (51.0% vs 34.3%, p=0.088), and had longer mechanical ventilation (20 vs. 9 days, pvs. 15 days, p95%CI [1.003-1.025], p=0.011). Conclusion: Patients admitted to the ICU for COVID-19-related ARDS display a proximal tubular dysfunction, prior to the onset of AKI, which predicts AKI. Proximal tubular damage seems an important mechanism of COVID-19-induced nephropathy. Analysis of urinary proteins is a reliable and non-invasive tool to assess proximal tubular dysfunction in the ICU. Trial Registration: Registered retrospectively with www.clinicaltrials.gov (NCT05699889) 26 January 2023.

Published
2023

27. Aortitis is an under-recognized manifestation of antiphospholipid syndrome: A case report and literature review

Author

Thomas Escoda, Julia George, Pierre-André Jarrot, Rodolphe Jean, Karin Mazodier, Frederick Sanderson, Pascale Poullin, Ludivine Saby, Noémie Jourde-Chiche, Gilles Kaplanski, and Laurent Chiche

Subjects
Adult, Aortitis, Rheumatology, Pregnancy, immune system diseases, Microcirculation, Antibodies, Antiphospholipid, Humans, Lupus Erythematosus, Systemic, Female, Thrombosis, Antiphospholipid Syndrome, skin and connective tissue diseases
Abstract

Aortitis is a classic manifestation of large vessel vasculitis. Antiphospholipid syndrome (APS), sometimes known as Hughes syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent venous or arterial thrombosis. Patients with APS may also suffer from various underlying diseases, most frequently systemic lupus erythematosus (SLE). Catastrophic antiphospholipid syndrome (CAPS) is a rare but serious complication of APS characterized by failure of several organs due to diffuse microcirculatory thrombi. Its main manifestations involve the kidneys, lungs, heart and central nervous system, and require early diagnosis and rapid therapeutic management. While APS can affect virtually any blood vessel, aortitis is not a known symptom of APS. We report the case of a 36-year-old patient with APS and SLE who presented with CAPS during pregnancy, with no concomitant SLE flare. The first manifestation of CAPS was aortitis, preceding renal, cardiac and haematological manifestations. The outcome was favourable with combined treatment including corticosteroids, anticoagulants, plasma exchange and rituximab. We then carried out a literature search for papers describing the presence of aortitis in APS and/or SLE. In the cases of aortic involvement identified in the literature, including another case of CAPS, the occurrence of aortitis in SLE, often associated with the presence of antiphospholipid antibodies/APS, suggests that aortitis should be considered as an under-recognized manifestation and potential non-criterion feature of APS.

Published
2022

28. Disease Activity and Adverse Events in Patients with ANCA-Associated Vasculitides Undergoing Long-Term Dialysis

Author

Thomas Quemeneur, Cécile Couchoud, Xavier Puéchal, Philippe Brunet, Grégoire Couvrat-Desvergnes, Stéphane Burtey, Frédéric Lavainne, Maëlis Kauffmann, Mickaël Bobot, Noémie Jourde-Chiche, Stanislas Faguer, Benjamin Terrier, Thomas Robert, Alexandre Karras, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), 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), Institut Polytechnique de Paris (IP Paris), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Polyclinique de l’Atlantique, Partenaires INRAE, Centre atlantique, Nantes, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence Maladies Systémiques et Autoimmunes Rares, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre hospitalier [Valenciennes, Nord], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and Agence de la biomédecine [Saint-Denis la Plaine]

Subjects
Male, Epidemiology, medicine.medical_treatment, Microscopic Polyangiitis, Critical Care and Intensive Care Medicine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Recurrence, Cause of Death, Neoplasms, Medicine, Registries, infections, end stage kidney diseasechronic dialysis, Aged, 80 and over, relapse, immunosuppression, ANCA, Incidence, cardiovascular, Incidence (epidemiology), Remission Induction, Immunosuppression, Middle Aged, Progression-Free Survival, Survival Rate, Editorial, Cardiovascular Diseases, Nephrology, Cohort, Female, France, Microscopic polyangiitis, Vasculitis, Immunosuppressive Agents, medicine.medical_specialty, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil Cytoplasmic, Renal Dialysis, Internal medicine, Humans, Renal Insufficiency, Chronic, Dialysis, Aged, Retrospective Studies, Transplantation, business.industry, Granulomatosis with Polyangiitis, Original Articles, medicine.disease, Kidney Transplantation, business, disease activity, Follow-Up Studies
Abstract

International audience; Background and objectives Kidney impairment of ANCA-associated vasculitides can lead to kidney failure. Patients with kidney failure may suffer from vasculitis relapses but are also at high risk of infections and cardiovascular events, which questions the maintenance of immunosuppressive therapy. Design, setting, participants, & measurements Patients with ANCA-associated vasculitides initiating long-term dialysis between 2008 and 2012 in France registered in the national Renal Epidemiology and Information Network registry and paired with the National Health System database were included. We analyzed the proportion of patients in remission off immunosuppression over time and overall and event-free survival on dialysis (considering transplantation as a competing risk). We compared the incidence of vasculitis relapses, serious infections, cardiovascular events, and cancers before and after dialysis initiation. Results In total, 229 patients were included: 142 with granulomatous polyangiitis and 87 with microscopic polyangiitis. Mean follow-up after dialysis initiation was 4.6±2.7 years; 82 patients received a kidney transplant. The proportion of patients in remission off immunosuppression increased from 23% at dialysis initiation to 62% after 5 years. Overall survival rates on dialysis were 86%, 69%, and 62% at 1, 3, and 5 years, respectively. Main causes of death were infections (35%) and cardiovascular events (26%) but not vasculitis flares (6%). The incidence of vasculitis relapses decreased from 57 to seven episodes per 100 person-years before and after dialysis initiation ( P =0.05). Overall, during follow-up, 45% of patients experienced a serious infection and 45% had a cardiovascular event, whereas 13% experienced a vasculitis relapse. Conclusions The proportion of patients with ANCA-associated vasculitis in remission off immunosuppression increases with time spent on dialysis. In this cohort, patients were far less likely to relapse from their vasculitis than to display serious infectious or cardiovascular events. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_11_08_CJN03190321.mp3

Published
2021

29. Importance of temporality and context in relation to life habit restrictions among patients with systemic lupus erythematosus: A psychosocial qualitative study

Author

Marie-Anastasie Aim, Viviane Queyrel, Nathalie Tieulié, Laurent Chiche, Julien Faraut, Cécile Manet, Nicolas Schleinitz, Jean-Robert Harlé, Noémie Jourde-Chiche, Lionel Dany, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and 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)

Subjects
Adult, Male, social participation, [SDV]Life Sciences [q-bio], life habits, qualitative interviews, Habits, systemic lupus erythematosus, Rheumatology, Quality of Life, Humans, Lupus Erythematosus, Systemic, Female, Interpersonal Relations, stigmamasking strategies, Qualitative Research
Abstract

Objective Life habits (LH) encompass an individual’s engagement in daily activities such as nutrition, fitness, personal care, communication, housing, and mobility, along with his/her social role (responsibility, interpersonal relationships, community life, education, employment, and recreation). This qualitative study explores the nature and context of LH restrictions in systemic lupus erythematosus (SLE) individuals across their SLE journey. Methods Narrative interviews were conducted with adult SLE patients. Interview transcripts were subjected to a thematic content analysis, using the Disability Creation Process model as a framework. Results Forty participants were interviewed. Three major themes were highlighted: (1) Temporality, capabilities, and environmental contexts: although all participants experienced LH restrictions at some point, the expression of these limitations depended on the individual’s and SLE disease characteristics as well as on temporal (time of life and lupus course) and environmental (material, social, and societal) contexts. (2) Identity issues, illness stigma, and (fear of) discriminations: LH were discussed through the lens of participants’ social roles and identities. While illness stigma can influence social relations, it is also expressed at a societal level. (3) Masking and minimizing strategies: due to illness stigma and fear of discrimination, participants developed strategies to manage their relationships, including masking and minimization. Their use was both advantageous and disadvantageous regarding LH. Conclusions For individuals with SLE, LH restrictions must be considered as an ongoing process that takes place within specific contexts. Our findings provide many opportunities for interventions that can benefit patients and their families, as well as healthcare providers.

Published
2022

30. Urinary soluble CD163: a non-invasive biomarker to monitor lupus nephritis

Author

Eya Toumi, Noémie Jourde-Chiche, Maxence Tailliar, Soraya Mezouar, Afaf Bouamri, Daniel Bertin, Muriel Militello, Guillaume Penaranda, Anne Plauzolles, Philippe Halfon, Jean-Louis Mege, and Nathalie Bardin

Abstract

Due to the role of macrophages in glomerular inflammation, macrophage surface molecules such as CD163 and CD11b represent attractive biomarkers for monitoring Lupus Nephritis (LN). We hypothesize that their urinary levels may reflect kidney disease activity. Here, we first analyzed the levels of urinary soluble CD163 (U-sCD163) and CD11b (U-sCD11b) in a cohort of 40 patients with LN including 23 with active disease. U-sCD163 levels were significantly elevated in active LN and correlated with the renal activity score, in contrast to U-sCD11b. Then, we developed the pristane induced LN mouse model to analyze, in a longitudinal way, the evolution of U-sCD163 levels according to the glomerular inflammation progression and response to treatment. We showed an increase of U-sCD163 levels associated with glomerular immune-complex deposits on mouse kidney biopsies at an early stage of the disease and a correlation with inflammatory markers including interferon-α, C-reactive protein and tumor necrosis factor-α. In addition, we showed that U-sCD163 levels decreased following efficient hydroxychloroquine treatment. Altogether our results led us to conclude that U-sCD163 represent a non-invasive biomarker for LN reflecting glomerular inflammation. Although prospective study in patients with LN, active or not, are necessary, U-sCD163 could be proposed to monitor response to treatment.

Published
2022

31. Erratum à : Diagnostic performance of pulmonary ultrasonography and a clinical score for the evaluation of fluid overload in haemodialysis patients [Nephrol. & Therap. 17 (1) (2021) 42–49]

Author

Mickaël Bobot, Laurent Zieleskiewicz, Noémie Jourde-Chiche, Clarissa Von Kotze, Manon Ebersolt, Bertrand Dussol, Marion Sallée, Sophie Chopinet, Yvon Berland, Philippe Brunet, Thomas Robert, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and 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)

Subjects
Nephrology, [SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

32. Complex relationships between inflammatory manifestations/type 1 and type 2 symptoms in systemic lupus erythematosus: A narrative literature review

Author

Thomas Escoda, Noémie Jourde-Chiche, Brigitte Granel, Divi Cornec, and Laurent Chiche

Subjects
Rheumatology
Abstract

Objective Recent studies have highlighted that systemic lupus erythematosus (SLE) is characterized by different types of symptoms: type 1 symptoms related to inflammation and disease activity and type 2 symptoms such as fatigue, anxiety-depression, and pain. Our aim was to investigate the relation between type 1 and type 2 symptoms, and their impact on health-related quality of life (HRQoL) in SLE. Methods A literature review was conducted about disease activity/type1 and type 2 symptoms. Articles in English published after 2000 were located on Medline via Pubmed. The articles chosen evaluated at least one type 2 symptom or HRQoL using a validated scale in adult patients. Results Overall, 182 articles were analyzed and 115 were retained including 21 randomized, controlled trials and corresponding to 36 831 patients. We found that in SLE, inflammatory activity/type 1 symptoms were mostly uncorrelated with type 2 symptoms and/or HRQoL. Several studies even showing an inverse relationship. No or weak correlation was observed in 85, 3% (92, 6%), 76, 7% (74, 4%) and 37, 5% (73, 1%) of studies (patients) for fatigue, anxiety-depression, and pain, respectively. For HRQoL, no or weak correlation was observed in 77, 5% of studies (88% of patients). Conclusion Type 2 symptoms are poorly correlated with inflammatory activity/type 1 symptoms in SLE. Possible explanations and implications for clinical care and therapeutic evaluation are discussed.

Published
2023

33. Diagnostic performance of pulmonary ultrasonography and a clinical score for the evaluation of fluid overload in haemodialysis patients

Author

Thomas Robert, Bertrand Dussol, Laurent Zieleskiewicz, Sophie Chopinet, Clarissa Von Kotze, Mickaël Bobot, Manon Ebersolt, Noémie Jourde-Chiche, Marion Sallée, Yvon Berland, Philippe Brunet, 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), Aix-Marseille Université - École de médecine (AMU SMPM MED), Aix-Marseille Université - Faculté des sciences médicales et paramédicales (AMU SMPM), Aix Marseille Université (AMU)-Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), CCSD, Accord Elsevier, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Assistance Publique - Hôpitaux de Marseille (APHM), Assistance Publique - Hôpitaux de Marseille (APHM), and Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)

Subjects
medicine.medical_specialty, Water-Electrolyte Imbalance, 030232 urology & nephrology, Physical examination, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Internal medicine, medicine, Humans, Chronic hemodialysis, Lung, Daily routine, Ultrasonography, Hydration status, Lung ultrasound, medicine.diagnostic_test, business.industry, Ultrasound, Reflux, Gold standard (test), [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Haemodialysis, Echocardiography, Nephrology, Fluid overload, Cardiology, business
Abstract

International audience; Introduction. - There is no feasible benchmark in daily routine to estimate the hydration status of haemodialysis patients, which is essential to their management. Objective. - We performed a study in haemodialysis patients to assess the diagnostic performance of pulmonary ultrasound and clinical examination for the evaluation of fluid overload using transthoracic echocardiography as a gold standard.Methods. - Thirty-one patients receiving chronic haemodialysis patients were included. Evaluation of hydration status was assessed weekly before haemodialysis sessions using clinical and Echo Comet Score from pulmonary ultrasound and transthoracic echocardiography (reference method).Results. - Five patients had a transthoracic echocardiography overload. Compared with transthoracic echocardiography, the diagnostic performance of the clinical overload score has a sensitivity of 100%, a specificity of 77%, a positive predictive value of 50% and a negative predictive value of 100% with a k of 0.79. Only orthopnoea (P = 0.008), jugular turgor (P = 0.005) and hepatic-jugular reflux (P = 0.008) were significantly associated with transthoracic echocardiography overload diagnosis. The diagnostic performance of Echo Comet Score by pulmonary ultrasound has a sensitivity of 80%, a specificity of 58%, a positive predictive value of 26% and a negative predictive value of 94%. Ten patients (32.3%) had an increase of extravascular pulmonary water without evidence of transthoracic echocardiography or clinical overload.Conclusions. - Our clinical score has a convincing diagnostic performance compared to transthoracic echocardiography and could be easily used in daily clinical routine to adjust dry weight. The evaluation of the overload using pulmonary ultrasound seems poorly correlated with the overload evaluated by transthoracic echocardiography. Extravascular pulmonary water undetected by clinical examination and transthoracic echocardiography remains a parameter that requires further investigation. (C) 2020 Societe francophone de nephrologie, dialyse et transplantation.

Published
2021

34. Kidney Biopsy in Type 2 Diabetes: A Multicenter Cross-Sectional Study

Author

Laurent Daniel, François Vrtovsnik, Jonathan Maurice Chemouny, Elsa Ferriere, Cécile Vigneau, Jean-Michel Halimi, Noémie Jourde-Chiche, Valentin Maisons, Christophe Barba, Nathalie Rioux-Leclercq, Dominique Joly, Aurélie Sannier, Mickaël Bobot, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP], CHU Pontchaillou [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Male, medicine.medical_specialty, Time Factors, [SDV]Life Sciences [q-bio], Biopsy, Kidney biopsy, 030232 urology & nephrology, Renal function, Diabetic nephropathy, Type 2 diabetes, 030204 cardiovascular system & hematology, Kidney, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Hypertensive Nephropathy, medicine, Humans, Diabetic kidney disease, Aged, Hematuria, Retrospective Studies, Proteinuria, business.industry, Patient Selection, Middle Aged, medicine.disease, 3. Good health, Hypertensive kidney disease, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Nephrology, Female, Kidney Diseases, medicine.symptom, business, Nephrotic syndrome, Glomerular Filtration Rate
Abstract

Introduction: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. Methods: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients’ records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. Results: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1–4 respectively. Conversely, no patient who underwent KB for indications 5–7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio

Published
2021

35. Localized versus systemic granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry

Author

Claire de Moreuil, Olivier Aumaître, Pascal Godmer, Alexis Régent, François Maurier, Christian Pagnoux, Luc Mouthon, Bernard Bonnotte, Xavier Puéchal, Michele Iudici, Chahéra Khouatra, Noémie Jourde-Chiche, Marc Ruivard, François Lifermann, Benjamin Terrier, Claire Blanchard-Delaunay, Antoine Néel, Eric Hachulla, Pascal Cohen, Delphine S. Courvoisier, Thomas Le Gallou, Jean-François Viallard, Alain Le Quellec, Achille Aouba, Loïc Guillevin, Thomas Quemeneur, Alexandre Karras, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), and 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)

Subjects
Vasculitis, medicine.medical_specialty, Cyclophosphamide, Subglottic stenosis, [SDV]Life Sciences [q-bio], Context (language use), macromolecular substances, vasculitis, Antibodies, Antineutrophil Cytoplasmic, stomatognathic system, Rheumatology, Recurrence, Internal medicine, medicine, Humans, Pharmacology (medical), Registries, Sinusitis, Retrospective Studies, ddc:616, Lung, granulomatosis with polyangiitis, business.industry, medicine.disease, Otitis, medicine.anatomical_structure, Granulomatosis with polyangiitis, medicine.symptom, business, ANCA-associated vasculitis, medicine.drug
Abstract

Objective To describe the main features at diagnosis and evolution over time of patients with localized granulomatosis with polyangiitis (L-GPA) compared with those of systemic GPA (S-GPA). Methods EULAR definitions of L-GPA, i.e. upper and/or lower respiratory tract involvement, and S-GPA were applied to patients from the French Vasculitis Study Group Registry. L-GPA and S-GPA patients’ characteristics at diagnosis and long-term outcomes were analysed and compared. Results Among the 795 Registry patients, 79 (10%) had L-GPA. Their main clinical manifestations were rhinitis, lung nodules, sinusitis and otitis. L-GPA vs S-GPA patients at diagnosis, respectively, were younger, more frequently had saddle nose deformity or subglottic stenosis and were less often PR3-ANCA–positive. L-GPA vs S-GPA induction therapy less frequently included CYC but more often a combination of MTX and glucocorticoids; 64% of MTX-treated patients experienced disease progression within 18 months post-diagnosis. L- and S-GPA patients’ estimated relapse-free–survival probabilities, relapse rates and refractory disease rates at each time point were comparable, but L-GPA patients had more frequent ENT and lung relapses, and higher overall survival rates (P Conclusions The relapse risks of L-GPA and S-GPA were similar, but relapse patterns differed and L-GPA overall survival rate was higher. About one-quarter of L-GPA patients developed S-GPA over time, but without end-stage organ involvement.

Published
2022

36. Monoallelic pathogenic ALG5 variants cause atypical polycystic kidney disease and interstitial fibrosis

Author

Hugo Lemoine, Loann Raud, François Foulquier, John A. Sayer, Baptiste Lambert, Eric Olinger, Siriane Lefèvre, Bertrand Knebelmann, Peter C. Harris, Pascal Trouvé, Aurore Desprès, Gabrielle Duneau, Marie Matignon, Anais Poyet, Noémie Jourde-Chiche, Dominique Guerrot, Sandrine Lemoine, Guillaume Seret, Miguel Barroso-Gil, Coralie Bingham, Rodney Gilbert, Yannick Le Meur, Marie-Pierre Audrézet, Emilie Cornec-Le Gall, CarMeN, laboratoire, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Newcastle University [Newcastle], CH de Lorient, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Mayo Clinic [Rochester], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Association des Urémiques de Bretagne [Lorient] (AUB), Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Association Régionale d'Aide aux Urémiques du Centre Ouest [Bourges] (ARAUCO), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Association ECHO [Expansion des Centres d’Hémodialyse de l’Ouest], Royal Devon and Exeter NHS Foundation Trust [UK], University of Southampton, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor [Créteil]

Subjects
N-linked glycosylation, Cysts, [SDV]Life Sciences [q-bio], Kidney, Polycystic Kidney, Autosomal Dominant, Fibrosis, Article, autosomal dominant tubulo-interstitial kidney disease, renal insufficiency, [SDV] Life Sciences [q-bio], autosomal-dominant polycystic kidney disease, ALG5, Mutation, Exome Sequencing, Genetics, Humans, Genetics (clinical)
Abstract

International audience; Disorders of the autosomal dominant polycystic kidney disease (ADPKD) spectrum are characterized by the development of kidney cysts and progressive kidney function decline. PKD1 and PKD2, encoding polycystin (PC)1 and 2, are the two major genes associated with ADPKD; other genes include IFT140, GANAB, DNAJB11, and ALG9. Genetic testing remains inconclusive in ∼7% of the families. We performed whole-exome sequencing in a large multiplex genetically unresolved (GUR) family affected by ADPKD-like symptoms and identified a monoallelic frameshift variant (c.703\₇04delCA) in ALG5. ALG5 encodes an endoplasmic-reticulum-resident enzyme required for addition of glucose molecules to the assembling N-glycan precursors. To identify additional families, we screened a cohort of 1,213 families with ADPKD-like and/or autosomal-dominant tubulointerstitial kidney diseases (ADTKD), GUR (n = 137) or naive to genetic testing (n = 1,076), by targeted massively parallel sequencing, and we accessed Genomics England 100,000 Genomes Project data. Four additional families with pathogenic variants in ALG5 were identified. Clinical presentation was consistent in the 23 affected members, with non-enlarged cystic kidneys and few or no liver cysts; 8 subjects reached end-stage kidney disease from 62 to 91 years of age. We demonstrate that ALG5 haploinsufficiency is sufficient to alter the synthesis of the N-glycan chain in renal epithelial cells. We also show that ALG5 is required for PC1 maturation and membrane and ciliary localization and that heterozygous loss of ALG5 affects PC1 maturation. Overall, our results indicate that monoallelic variants of ALG5 lead to a disorder of the ADPKD-spectrum characterized by multiple small kidney cysts, progressive interstitial fibrosis, and kidney function decline.

Published
2022

37. Comparative study of granulomatosis with polyangiitis subsets according to ANCA status: data from the French Vasculitis Study Group Registry

Author

Xavier Puéchal, Michele Iudici, Christian Pagnoux, Pascal Cohen, Mohamed Hamidou, Achille Aouba, François Lifermann, Marc Ruivard, Olivier Aumaître, Bernard Bonnotte, Francois Maurier, Thomas Le Gallou, Eric Hachulla, Alexandre Karras, Chahéra Khouatra, Noémie Jourde-Chiche, Jean-François Viallard, Claire Blanchard-Delaunay, Pascal Godmer, Alain Le Quellec, Thomas Quéméneur, Claire de Moreuil, Luc Mouthon, Benjamin Terrier, Loïc Guillevin, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Geneva University Hospitals and Geneva University, University of Toronto, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], and CHU Pontchaillou [Rennes]

Subjects
Male, granulomatosis with polyangiitis, Myeloblastin, [SDV]Life Sciences [q-bio], Immunology, autoimmunity, urologic and male genital diseases, Antibodies, Antineutrophil Cytoplasmic, respiratory tract diseases, Rheumatology, immune system diseases, Humans, Immunology and Allergy, Female, autoimmune diseases, Registries, cardiovascular diseases, systemic vasculitis, skin and connective tissue diseases, Retrospective Studies
Abstract

ObjectiveTo investigate whether antineutrophil cytoplasm antibody (ANCA)-negative and myeloperoxidase (MPO)-ANCA–positive granulomatosis with polyangiitis (GPA) differ from proteinase-3 (PR3)-ANCA–positive GPA.MethodsDiagnostic characteristics and outcomes of newly diagnosed French Vasculitis Study Group Registry patients with ANCA-negative, MPO-ANCA–positive or PR3-ANCA–positive GPA satisfying American College of Rheumatology criteria and/or Chapel Hill Conference Consensus Nomenclature were compared.ResultsAmong 727 GPA, 62 (8.5%) were ANCA-negative, 119 (16.4%) MPO-ANCA–positive and 546 (75.1%) PR3-ANCA–positive. ANCA-negative patients had significantly (pConclusionsBased on this large cohort, ANCA-negative versus ANCA-positive patients more frequently had limited disease but similar RFS and OS. MPO-ANCA–positive patients had similar RFS but lower OS due to their older age. PR3-ANCA–positive GPA patients’ RFS was lower than those of the two other subsets combined but that difference did not persist when comparing only PR3 versus MPO-ANCA–positive patients.

Published
2022

38. Reducing the initial number of rituximab maintenance-therapy infusions for ANCA-associated vasculitides: randomized-trial post-hoc analysis

Author

Olivier Aumaître, Xavier Puéchal, Grégory Pugnet, Pascal Godmer, François Maurier, P. Gobert, Stanislas Faguer, Mohamed Hamidou, François Lifermann, Sophie Rivière, Luc Mouthon, Noémie Jourde-Chiche, Bernard Bonnotte, Benjamin Terrier, Christian Agard, Nadine Meaux-Ruault, Loïc Guillevin, Agnès Dechartres, Antoine Huart, Nicolas Martin-Silva, Jean Sibilia, Alexandre Karras, Pierre Charles, Maxime Samson, Marie Matignon, Pascal Cohen, Jean-François Viallard, and Catherine Hanrotel-Saliou

Subjects
medicine.medical_specialty, Randomization, Antigens, CD19, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Gastroenterology, Disease-Free Survival, Drug Administration Schedule, Antibodies, Antineutrophil Cytoplasmic, Maintenance Chemotherapy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Maintenance therapy, Randomized controlled trial, law, Internal medicine, Post-hoc analysis, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Survival rate, 030203 arthritis & rheumatology, business.industry, medicine.disease, Antirheumatic Agents, Rituximab, Microscopic polyangiitis, Granulomatosis with polyangiitis, business, medicine.drug
Abstract

ObjectiveThe randomized, controlled MAINRITSAN2 trial was designed to compare the capacity of an individually tailored therapy [randomization day 0 (D0)], with reinfusion only when CD19+ lymphocytes or ANCA had reappeared, or if the latter’s titre rose markedly, with that of five fixed-schedule 500-mg rituximab infusions [D0 + D14, then months (M) 6, 12 and 18] to maintain ANCA-associated vasculitis (AAV) remissions. Relapse rates did not differ at M28. This ancillary study was undertaken to evaluate the effect of omitting the D14 rituximab infusion on AAV relapse rates at M12.MethodsMAINRITSAN2 trial data were subjected to post-hoc analyses of M3, M6, M9 and M12 relapse-free survival rates in each arm as primary end points. Exploratory subgroup analyses were run according to CYC or rituximab induction and newly diagnosed or relapsing AAV.ResultsAt M3, M6, M9 and M12, respectively, among the 161 patients included, 79/80 (98.8%), 76/80 (95%), 74/80 (92.5%) and 73/80 (91.3%) from D0, and 80/81 (98.8%), 78/81 (96.3%), 76/81 (93.8%) and 76/81 (93.8%) from D0+D14 groups were alive and relapse-free. No between-group differences were observed. Results were not affected by CYC or rituximab induction, or newly diagnosed or relapsing AAV.ConclusionsWe were not able to detect a difference between the relapse-free survival rates for up to M12 for the D0 and D0+D14 rituximab-infusion groups, which could suggest that omitting the D14 rituximab remission-maintenance dose did not modify the short-term relapse-free rate. Nevertheless, results at M12 may also have been influenced by the rituximab-infusion strategies for both groups.

Published
2020

39. Kidney involvement in hereditary transthyretin amyloidosis: a cohort study of 103 patients

Author

Justine Solignac, Emilien Delmont, Etienne Fortanier, Shahram Attarian, Julien Mancini, Laurent Daniel, Ioana Ion, Jean-Etienne Ricci, Thomas Robert, Gilbert Habib, Olivier Moranne, Noémie Jourde-Chiche, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), 'Cancer, Biomedicine & Society' group (SESSTIM - U1252 INSERM - AMU - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut Desbrest de santé publique (IDESP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
Proteinuria, [SDV.GEN]Life Sciences [q-bio]/Genetics, Transplantation, Nephrology, Chronic kidney disease, Hereditary transthyretin amyloidosis, ATTR, Kidney amyloidosis
Abstract

Background Hereditary transthyretin amyloidosis (ATTRv) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has not been systematically studied, particularly in non-V30M mutations, and is not well known to nephrologists. Methods We conducted a retrospective study describing the kidney phenotype of all prevalent patients with ATTR mutations, with neurological or cardiac involvement or presymptomatic carriers, followed up in two university hospitals from the South of France between June 2011 and June 2021. Results A total of 103 patients were included, among whom 79 were symptomatic and 24 were presymptomatic carriers. Patients carried 21 different ATTR mutations and 54% carried the V30M mutation. After a mean follow-up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD) and 20.3% had a urinary protein:creatinine ratio ≥0.5 g/g. None of the presymptomatic carriers had CKD or proteinuria. In a multivariate analysis, late onset of symptoms (after 60 years), the V122I mutation and proteinuria were significantly associated with CKD. The median CKD-free survival in symptomatic patients was estimated at 81.0 years (interquartile range 77.1–84.9). It did not differ between V30M and non-V30M patients, but was lower in patients with the V122I mutation. The average age of the onset of CKD was 69.3 ± 13.0 years. In one 38-year-old V30M female who presented a kidney-predominant phenotype, treatment with patisiran resulted in remission of the nephrotic syndrome. Conclusion CKD affects almost one-third of patients with symptomatic ATTRv. The role of ATTRv per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies.

Published
2022

40. Anti-PLA2R1 Antibodies Containing Sera Induce In Vitro Cytotoxicity Mediated by Complement Activation

Author

Kévin Zorzi, Vincent L.M. Esnault, Gérard Lambeau, Cécile Courivaud, Barbara Seitz-Polski, Noémie Jourde-Chiche, Thomas Crepin, Guillaume Dolla, Christine Payré, Hajar Ouahmi, M. Lateb, Mohamad Zaidan, Bertrand Knebelmann, Vesna Brglez, Sonia Boyer-Suavet, Institut de pharmacologie moléculaire et cellulaire (IPMC), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Département de Néphrologie - Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Centre Hospitalier Universitaire de Nice (CHU Nice), Néphrologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de Néphrologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), 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 de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital l'Archet, Fondation pour la Recherche Médicale (FRMING20140129210, SPF20150934219, FDT201805005509, and DEQ20180339193), and the Fondation du Rein (award and grant FdR 2018/FRM/G.L), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), ANR-17-CE17-0012,MNaims,Dissection moléculaire de la glomérulonéphrite extramembraneuse liée à PLA2R1: vers l'identification de nouveaux biomarqueurs cliniques(2017), HAL AMU, Administrateur, Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID, Dissection moléculaire de la glomérulonéphrite extramembraneuse liée à PLA2R1: vers l'identification de nouveaux biomarqueurs cliniques - - MNaims2017 - ANR-17-CE17-0012 - AAPG2017 - VALID, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
Cytotoxicity, Immunologic, Male, 0301 basic medicine, PROGNOSIS, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Autoantigens, Glomerulonephritis, Membranous, Immunoglobulin G, Epitope, Cohort Studies, Epitopes, Complement inhibitor, 0302 clinical medicine, SUBCLASS, BINDING, Immunology and Allergy, Prospective Studies, Cytotoxicity, Complement Activation, biology, Podocytes, Chemistry, General Medicine, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Titer, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Rabbits, Antibody, Rituximab, Research Article, lcsh:Immunologic diseases. Allergy, DOMAIN-CONTAINING 7A, IGG4, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, Article Subject, Cell Survival, Immunology, GLOMERULAR-DISEASES, PHOSPHOLIPASE-A2 RECEPTOR AUTOANTIBODIES, 03 medical and health sciences, GLOMERULONEPHRITIS, Animals, Humans, Aged, Autoantibodies, Receptors, Phospholipase A2, Complement System Proteins, Molecular biology, Complement system, HEK293 Cells, 030104 developmental biology, MEMBRANOUS NEPHROPATHY, biology.protein, Alternative complement pathway, lcsh:RC581-607
Abstract

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy (MN). However, the pathogenic role of anti-PLA2R1 autoantibodies is unclear. Our aim was to evaluate the in vitro cytotoxicity of anti-PLA2R1 antibodies mediated by complement. Forty-eight patients with PLA2R1-related MN from the prospective cohort SOURIS were included. Anti-PLA2R1 titer, epitope profile, and anti-PLA2R1 IgG subclasses were characterized by ELISA. Cell cytotoxicity was evaluated by immunofluorescence in HEK293 cells overexpressing PLA2R1 incubated with patient or healthy donor sera in the presence or absence of rabbit complement or complement inhibitors. Mean cytotoxicity of anti-PLA2R1 sera for HEK293 cells overexpressing PLA2R1 was 2±2%, which increased to 24±6% after addition of rabbit complement (p<0.001) (n=48). GVB-EDTA, which inhibits all complement activation pathways, completely blocked cell cytotoxicity, whereas Mg-EGTA, which only inhibits the classical and lectin pathways, highly decreased suggesting a limited role of the alternative pathway. A higher diversity of IgG subclasses beyond IgG4 and high titer of total IgG anti-PLA2R1 were associated with increased cytotoxicity (p=0.01 and p=0.03 respectively). In a cohort of 37 patients treated with rituximab, high level of complement-mediated cytotoxicity was associated with less and delayed remission at month 6 after rituximab therapy (5/12 vs. 20/25 (p=0.03) in 8.5 months±4.4 vs. 4.8±4.0 (p=0.02)). Kaplan-Meier analysis demonstrated that high level of cytotoxicity (≥40%) (p=0.005), epitope spreading (defined by immunization beyond the immunodominant CysR domain) (p=0.002), and high titer of anti-PLA2R1 total IgG (p=0.01) were factors of poor renal prognosis. Anti-PLA2R1 antibodies containing sera can induce in vitro cytotoxicity mediated by complement activation, and the level of cytotoxicity increases with the diversity and the titer of anti-PLA2R1 IgG subclasses. These patients with high level of complement-mediated cytotoxicity could benefit from adjuvant therapy using complement inhibitor associated with rituximab to induce earlier remission and less podocyte injury.

Published
2019

41. Bartonella and Coxiella infections presenting as systemic vasculitis: case series and review of literature

Author

Christophe Rodriguez, Olivier Fain, Alexandre Cez, Noémie Jourde-Chiche, Maxime Beydon, Benjamin Terrier, Xavier Puéchal, Cédric Rafat, Carole Philipponnet, Dan Levy, Antoine Dossier, Nicolas Dupin, Alexandre Karras, Inès Aureau, Loïc Guillevin, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de médecine interne [CHU Saint-Antoine], 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), CHU Clermont-Ferrand, AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Strasbourg, and Centre hospitalier de Pau

Subjects
Bartonella, Vasculitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, 030204 cardiovascular system & hematology, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, 0302 clinical medicine, Glomerulonephritis, Coxiella, Rheumatology, Bartonella Infections, hemic and lymphatic diseases, medicine, Rheumatoid factor, Endocarditis, Humans, Pharmacology (medical), cardiovascular diseases, Cryoglobulinemic vasculitis, Retrospective Studies, 030203 arthritis & rheumatology, Infectious disease, biology, business.industry, ANCA, medicine.disease, biology.organism_classification, bacterial infections and mycoses, Cryoglobulinemia, 3. Good health, Immunology, bacteria, business, Bartonella Infection, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Systemic vasculitis
Abstract

Objectives Coxiella and Bartonella spp. display particular tropism for endothelial or endocardial tissues and an abnormal host response to infections with induced autoimmunity. We aimed, through a case series combined with a comprehensive literature review, to outline characteristics of Coxiella and Bartonella infections presenting as systemic vasculitis. Methods We retrospectively included cases of definite Coxiella and Bartonella infections presenting with vasculitis features and performed a comprehensive literature review. Results Six cases of Bartonella infections were added to 18 cases from literature review. Causative pathogens were mainly B. henselae. Bartonella infection mimicked ANCA-associated vasculitis in 83% with PR3-ANCA and presented as cryoglobulinaemic vasculitis in 8%. GN was present in 92%, and 88% had endocarditis. Complement fractions were low in 82% and rheumatoid factor positive in 85%. Kidney biopsies showed cell proliferation, mostly crescentic, with pauci-immune GN in 29%. Outcome was favourable, with the use of antibiotics alone in one-third. Five cases of Coxiella infections were added to 16 from literature review. Sixteen had small-vessel vasculitides, mainly cryoglobulinaemia vasculitis in 75%. One patient had polyarteritis nodosa-like vasculitis and four large-vessel vasculitis. Outcome was good except for one death. A highly sensitive next generation sequencing analysis on three Coxiella- and two Bartonella-related vasculitides biopsies did not find any bacterial DNA. Conclusion Coxiella and Bartonella are both able to induce vasculitis but display distinct vasculitis features. Bartonella mimics PR3-ANCA-associated vasculitis in the setting of endocarditis, whereas Coxiella may induce vasculitis involving all vessel sizes.

Published
2021

42. Impact of aging on phenotype and prognosis in IgA vasculitis

Author

Stanislas Faguer, Noémie Le Gouellec, François Maurier, Bertrand Lioger, Patrice Cacoub, Noémie Jourde-Chiche, Sébastien Sanges, Christian Lavigne, Benjamin Terrier, Julie Goutte, Geoffrey Urbanski, Zahir Amoura, Aurélie Hummel, Evangeline Pillebout, Sophie Deriaz, Loic Raffray, Alban Deroux, Alexandra Audemard-Verger, Elisabeth Diot, Guillaume Moulis, Nicole Feirreira-Maldent, Johan Chanal, François Maillot, A. Baldolli, Loïc Guillevin, Jean-François Augusto, Eric Thervet, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier [Valenciennes, Nord], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), 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), LUNAM Université [Nantes Angers Le Mans], Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), PRES Université Nantes Angers Le Mans (UNAM), 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 Universitaire de La Réunion (CHU La Réunion), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service Néphrologie et transplantation rénale Adultes [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Groupe de recherche clinique Biomarqueurs d’urgence et de réanimation (GRC 14 - BIOSFAST), Sorbonne Université (SU), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Ambroise Paré [AP-HP], Service de médecine interne et gérontologie clinique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Vasculaire [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Plateforme Histologie, Immunomarquage et Microdissection laser [Institut Cochin] (HistIM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Immunoglobulin A, Adult, Male, Vasculitis, medicine.medical_specialty, Aging, Henoch-Schonlein purpura, Disease, 03 medical and health sciences, IgA vasculitis, 0302 clinical medicine, Rheumatology, Internal medicine, medicine, Humans, Pharmacology (medical), Aged, Retrospective Studies, 030203 arthritis & rheumatology, biology, business.industry, Age Factors, Retrospective cohort study, Middle Aged, medicine.disease, renal involvement, Purpura, 030104 developmental biology, Phenotype, Quartile, age, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biology.protein, outcome, Kidney Failure, Chronic, Female, prognosis, medicine.symptom, business, Henoch–Schönlein purpura
Abstract

Objectives Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV. Methods We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: Results Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P 6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1–38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age. Conclusion Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.

Published
2021

43. Renal and vascular outcomes in patients with isolated antiphospholipid syndrome nephropathy

Author

Clémentine Rousselin, Zahir Amoura, Stanislas Faguer, Pierre Bataille, Jean-Jacques Boffa, Guillaume Canaud, Dominique Guerrot, Noémie Jourde-Chiche for the GCLR, Alexandre Karras, Eric Auxenfants, Agnès Chapelet, Marc Lambert, Hélène Behal, Dominique Nochy, Duong Van Huyen Jean-Paul, Isabelle Brocheriou for the CFPR, Viviane Gnemmi, and Thomas Quemeneur

Subjects
Adult, Lupus Coagulation Inhibitor, Immunology, Antibodies, Antiphospholipid, Humans, Kidney Failure, Chronic, Immunology and Allergy, Female, Kidney Diseases, Antiphospholipid Syndrome, Kidney
Abstract

Antiphospholipid syndrome (APS) nephropathy (APSN) is a rare pattern with specific features resulting from microvascular lesions. The prognosis of APSN, outside of lupus nephritis, is unknown. The aim of this study was to describe the renal, vascular and overall outcomes of patients with APSN.Retrospective multicenter study of patients with antiphospholipid antibodies (aPL) associated with histological APSN lesions and no other nephropathy, identified through a national call for medical records. End-stage renal disease (ESRD)-free survival, thrombosis recurrence-free survival and overall survival were assessed.Thirty patients were included (19 women) with a median age of 40 years (34-52 years). Fifteen patients had APS, 26/28 had lupus anticoagulant, and 15/26 had triple positivity for aPL. Median eGFR was 50 (31-60) mL/min/1.73 mThe renal prognosis of isolated APSN is poor. The severe fibrotic lesions observed are suggestive of late diagnosis.

Published
2022

45. Unsupervised clustering analysis of data from an online community to identify lupus patient profiles with regards to treatment preferences

Author

Julien Mancini, Laurent Chiche, Damien Testa, Lise Radoszycki, Noémie Jourde-Chiche, Pasquale Varriale, Carenity [Paris] (Else Care), 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Européen [Fondation Ambroise Paré - Marseille], Service Biostatistique et Technologies de l’Information et de la Communication [AP-HM Hôpital de la Timone] (BioSTIC), and Malbec, Odile

Subjects
Adult, Male, medicine.medical_specialty, treatment preferences, [SDV]Life Sciences [q-bio], online community, Affect (psychology), Medication Adherence, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Therapeutic Adherence, Rheumatology, systemic lupus erythematosus, Surveys and Questionnaires, medicine, Cluster Analysis, Humans, Lupus Erythematosus, Systemic, 030212 general & internal medicine, Intensive care medicine, Aged, 030203 arthritis & rheumatology, Autoimmune disease, Clinical Trials as Topic, Internet, Systemic lupus erythematosus, business.industry, Social Support, Patient Preference, lupus, Middle Aged, medicine.disease, Online community, [SDV] Life Sciences [q-bio], Pharmaceutical Preparations, therapeutic adherence, Female, France, Unsupervised clustering, business, Attitude to Health, Social Media
Abstract

Objective Lupus is a chronic complex autoimmune disease. Non-adherence to treatment can affect patient outcomes. Considering patients’ preferences into medical decisions may increase acceptance to their medication. The PREFERLUP study used unsupervised clustering analysis to identify profiles of patients with similar treatment preferences in an online community of French lupus patients. Methods An online survey was conducted in adult lupus patients from the Carenity community between August 2018 and April 2019. Multiple Correspondence Analysis (MCA) was used with three unsupervised clustering methods (hierarchical, kmeans and partitioning around medoids). Several indicators (measure of connectivity, Dunn index and Silhouette width) were used to select the best clustering algorithm and choose the number of clusters. Results The 268 participants were mostly female (96%), with a mean age of 44.3 years 83% fulfilled the American College of Rheumatology (ACR) self-reported diagnostic criteria for systemic lupus erythematosus. Overall, the preferred route of administration was oral (62%) and the most important feature of an ideal drug was a low risk of side-effects (32%). Hierarchical clustering identified three clusters. Cluster 1 (59%) comprised patients with few comorbidities and a poor ability to identify oncoming flares; 84% of these patients desired oral treatments with limited side-effects. Cluster 2 (13%) comprised younger patients, who had already participated in a clinical trial, were willing to use implants and valued the compatibility of treatments with pregnancy. Cluster 3 (28%) comprised patients with a longer lupus duration, poorer control of the disease and more comorbidities; these patients mainly valued implants and injections and expected a reduction of corticosteroid intake. Conclusions Different profiles of lupus patients were identified according to their drug preferences. These clusters could help physicians tailor their therapeutic proposals to take into account individual patient preferences, which could have a positive impact on treatment acceptance and then adherence. The study highlights the value of data acquired directly from patient communities.

Published
2021

46. Eculizumab in gemcitabine-induced thrombotic microangiopathy: experience of the French thrombotic microangiopathies reference centre

Author

Claire Pouteil-Noble, Steven Grangé, Claire Presne, Ygal Benhamou, Agnès Veyradier, Paul Coppo, Arnaud François, Véronique Frémeaux-Bacchi, Dominique Guerrot, Noémie Jourde Chiche, François Provôt, Jean-Philippe Coindre, Maximilien Grall, Alexandre Karras, Florence Daviet, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Amiens-Picardie, Centre Hospitalier Le Mans (CH Le Mans), Hospices Civils de Lyon (HCL), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), and Gestionnaire, HAL Sorbonne Université 5

Subjects
Male, Nephrology, Blood transfusion, medicine.medical_treatment, 030204 cardiovascular system & hematology, Kidney Function Tests, urologic and male genital diseases, Deoxycytidine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Medicine, Coagulation, thrombotic disorders and therapies, Cancer and thrombosis, Gemcitabineinduced thrombotic microangiopathy, Remission Induction, Acute kidney injury, Acute Kidney Injury, Middle Aged, Eculizumab, Gemcitabine-induced thrombotic microangiopathy, Haemolysis, 3. Good health, Renal Replacement Therapy, Treatment Outcome, Cancer and thrombosis, 030220 oncology & carcinogenesis, Female, France, medicine.drug, Antimetabolites, Antineoplastic, medicine.medical_specialty, Thrombotic microangiopathy, Urology, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Internal medicine, Humans, Blood Transfusion, Renal replacement therapy, thrombotic disorders and therapies, Coagulation, Thrombotic Microangiopathies, business.industry, Research, Recovery of Function, medicine.disease, Gemcitabine, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Diseases of the genitourinary system. Urology, Complement Inactivating Agents, RC870-923, business, Packed red blood cells
Abstract

Background Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). Methods This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016. Results Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4–44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2–22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0–10) before treatment vs 0 (range 0–1) after one injection, P 2 respectively in the eculizumab group and in the control group. Conclusions These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.

Published
2021

47. Results from a nationwide retrospective cohort measure the impact of C3 and soluble C5b-9 levels on kidney outcomes in C3 glomerulopathy

Author

Sophie Chauvet, Jill J. Hauer, Florent Petitprez, Marion Rabant, Paula Vieira Martins, Véronique Baudouin, Yahsou Delmas, Noémie Jourde-Chiche, Alexandre Cez, David Ribes, Sylvie Cloarec, Aude Servais, Mohamad Zaidan, Eric Daugas, Michel Delahousse, Alain Wynckel, Amélie Ryckewaert, Anne Laure Sellier-Leclerc, Olivia Boyer, Eric Thervet, Alexandre Karras, Richard J.H. Smith, and Véronique Frémeaux-Bacchi

Subjects
Adult, Complement C3 Nephritic Factor, Rare Diseases, Nephrology, Glomerulonephritis, Membranoproliferative, Kidney Glomerulus, Humans, Kidney Diseases, Complement C3, Complement Membrane Attack Complex, Child, Biomarkers, Retrospective Studies
Abstract

C3 glomerulopathy (C3G) is a rare complement-mediated disease. Specific treatments are not yet available and factors predictive of kidney survival such as age, kidney function and proteinuria are not specific to C3G. The prognostic value of biomarkers of complement activation, which are pathognomonic of the diseases, remains unknown. In a large cohort of 165 patients from the French National registry, we retrospectively assess the prognostic value of C3, soluble C5b-9 (sC5b-9), C3 nephritic factor, and rare disease-predicting variants in complement genes in predicting clinical outcome of patients. By multivariate analysis age (adult onset), reduced kidney function (defined by estimated glomerular filtration rate under 60ml/min) and presence of rare disease-predicting variants in complement genes predicted risk of progression to kidney failure. Moreover, by multivariate analysis, normal C3/high sC5b-9 levels or low C3/normal sC5b-9 levels remained independently associated with a worse kidney prognosis, with the relative risk 3.7- and 8-times higher, respectively. Subgroup analysis indicated that the complement biomarker profiles independently correlated to kidney prognosis in patients with adult but not pediatric onset. In this subgroup, we showed that profiles of biomarkers C3 and/or sC5b-9 correlated with intra glomerular inflammation and may explain kidney outcomes. In children, only the presence of rare disease-predicting variants correlated with kidney survival. Thus, in an adult population, we propose a three-point C3G prognostic score based on biomarker profiles at risk, estimated glomerular filtration rate at presentation and genetic findings, which may help stratify adult patients into subgroups that require close monitoring and more aggressive therapy.

Published
2021

48. Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data

Author

Chloe I Bloom, Jacques Banchereau, Mohamed Alfaki, J. Theodore Phillips, Asuncion Mejias, Octavio Ramilo, Karolina Palucka, Laurent Chiche, Farrah Kheradmand, Noémie Jourde-Chiche, Matthew C. Altman, Fleur Mougin, Davide Bedognetti, Marc Lipman, Christine M. Graham, Nicole Baldwin, Mathieu Garand, Patricia Thebault, Scott R. Presnell, Basirudeen Syed Ahamed Kabeer, Darawan Rinchai, Goran B. Klintmalm, Matthew Berry, Ganjana Lertmemongkolchai, Prasong Khaenam, Robert J. Wilkinson, Rodolphe Thiébaut, Damien Chaussabel, Virginia Pascual, Aaron Ayllon-Benitez, Anne O'Garra, Mohammed Toufiq, Elizabeth Whalen, Wellcome Trust, National Institutes of Health, Benaroya Research Institute [Seattle] (BRI), University of Washington [Seattle], Sidra Medicine [Doha, Qatar], Baylor Institute for Immunology Research (BIIR), 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), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Hôpital Européen [Fondation Ambroise Paré - Marseille], 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), The Francis Crick Institute [London], Imperial College London, Royal Cornwall Hospital, University of Cape Town, University College of London [London] (UCL), Khon Kaen University [Thailand] (KKU), Baylor College of Medicine (BCM), Baylor University, Ohio State University [Columbus] (OSU), Jackson Laboratory, Weill Cornell Medicine [New York], Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Weill Cornell Medicine [Cornell University], Cornell University [New York], United States Department of Health & Human Services National Institutes of Health (NIH) - USAU01AI082110Wellcome Trust European Commission 03135Francis Crick Institute from the Wellcome Trust FC10218Cancer Research UK FC10218United States Department of Health & Human Services National Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID)AI067854UK Research & Innovation (UKRI) FC10218United States Department of Health & Human Services National Institutes of Health (NIH) - USA U01AI115940, and European Project: 104803,WT::(2014)

Subjects
0301 basic medicine, Computer science, Systems biology, [SDV]Life Sciences [q-bio], Science, Gene regulatory network, General Physics and Astronomy, Translational immunology, Computational biology, General Biochemistry, Genetics and Molecular Biology, Plot (graphics), Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Profiling (information science), Cluster Analysis, Humans, Gene Regulatory Networks, Data mining, Multidisciplinary, Bacteria, Repertoire, Gene Expression Profiling, Fingerprint (computing), fungi, food and beverages, Computational Biology, General Chemistry, Visualization, 030104 developmental biology, Blood, 030220 oncology & carcinogenesis, Blood Chemical Analysis
Abstract

As the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via: https://drinchai.shinyapps.io/BloodGen3Module/., The blood transcriptome of human subjects can be profiled on an almost routine basis in translational research settings. Here the authors show that a fixed and well-characterized repertoire of transcriptional modules can be employed as a reusable framework for the analysis, visualization and interpretation of such data

Published
2021

49. Sequential development of ANCA‐associated vasculitis and anti‐GBM disease: A report of two cases

Author

Frederic Vandergheynst, Noémie Jourde-Chiche, Delphine Kemlin, Benjamin Terrier, and Camille Le Moine

Subjects
Medicine (General), viruses, Case Report, ANCA-Associated Vasculitis, Disease, urologic and male genital diseases, R5-920, anti‐GBM disease, medicine, Kidney, biology, business.industry, urogenital system, ANCA‐associated vasculitis, Anti-GBM Disease, Glomerulonephritis, General Medicine, medicine.disease, myeloperoxidase, medicine.anatomical_structure, Myeloperoxidase, Immunology, biology.protein, Medicine, Antibody, business, glomerulonephritis
Abstract

In case of AAV with kidney involvement, physicians should explore anti‐GBM antibodies and be aware of the possible sequential development of AAV, especially with MPO‐ANCA, and anti‐GBM glomerulonephritis. This sequential disease history is associated with a poor renal outcome, highlighting the need for urgent diagnosis and management.

Published
2021

50. Prise en charge néphrologique des patients hémophiles A : difficultés diagnostiques et thérapeutiques illustrées par le cas de 2 patients

Author

Nicolas Delmotte, Antoine Lanot, Clarissa Von Kotze, Noémie Jourde-Chiche, David Verhelst, Danielle Botta, P. Henri, Mathilde Fedi, Léa Pietri, Philippe Brunet, Céline Falaise, Hervé Chambost, Thomas Robert, CCSD, Accord Elsevier, Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance Publique - Hôpitaux de Marseille (APHM), Pharmacie, Hôpital Nord, Service d'Hépato-gastroentérologie, Centre Hospitalier Henri Duffaut (Avignon), Aix Marseille Université (AMU), Institut National de la Recherche Agronomique (INRA), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Nephrology, medicine.medical_specialty, Pediatrics, Hémodialyse, Risque hémorragique, medicine.medical_treatment, Peritoneal dialysis, Population, 030232 urology & nephrology, Hemophilia A, Hemorrhagic disorder, 03 medical and health sciences, 0302 clinical medicine, Chronic kidney disease, Internal medicine, Hémophilie A, Medicine, Renal replacement therapy, education, Hemorrhagic risk, Dialysis, Transplantation, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Biopsie rénale, Dialyse péritonéale, medicine.disease, 3. Good health, Hemodialysis, Maladie rénale chronique, Renal biopsy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract

International audience; Hemophilia A is an X-linked genetic hemorrhagic disorder characterized by a factor VIII deficiency. The availability of secured substitution products has led to a dramatic improvement of life expectancy in hemophiliac patients. Nowadays, adult hemophiliac patients may develop Chronic Kidney Disease (CKD) resulting from age-related comorbidities (hypertension, obesity, diabetes). In addition, the high prevalence of viral infections in this population exposes patients to an increased risk of CKD. The risk of hemorrhage in hemophiliac patients is a challenge for their clinical management, both for diagnostic procedures (kidney biopsy in particular) and for renal replacement therapy (dialysis or renal transplantation) when it is needed. This work provides an update of the literature data concerning the management of hemophiliac patients in nephrology, illustrated by the cases of two patients.

Published
2019

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