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1. CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME AND POSTERIOR OCULAR INVOLVEMENT

Author: Véronique Le Guern, Cécile Yelnik, Bertrand Godeau, Hanane Mehawej, Clémence Bonnet, Mathilde Roumier, Marc Lambert, Julien Haroche, Nathalie Morel, Ygal Benhamou, Laurent Perard, Antoine P. Brézin, Nicolas Maillard, Bahram Bodaghi, Jean-Charles Piette, and Nathalie Costedoat-Chalumeau
Subjects: Adult, Male, medicine.medical_specialty, Visual acuity, Adolescent, Fundus Oculi, Vision Disorders, Visual Acuity, Age at diagnosis, Catastrophic antiphospholipid syndrome, Severity of Illness Index, Young Adult, Ophthalmology, Humans, Medicine, Fluorescein Angiography, Aged, Retrospective Studies, Retinal Vascular Occlusion, business.industry, Retinal vasculitis, General Medicine, Middle Aged, Antiphospholipid Syndrome, medicine.disease, Posterior segment of eyeball, Female, medicine.symptom, business, Vasculitis, Tomography, Optical Coherence, Retinopathy
Abstract: PURPOSE To describe the posterior ophthalmic manifestations of catastrophic antiphospholipid syndrome. METHODS Retrospective case series of patients presenting with catastrophic antiphospholipid syndrome and posterior segment ocular manifestations. The main outcomes were the type of posterior segment manifestations at catastrophic antiphospholipid syndrome diagnosis, specifically retinal vascular occlusion, vasculitis, or choroidopathy, and the final best-corrected visual acuity. RESULTS This study included 23 patients (11 cases treated by the authors and 12 published case reports); 21 (91%) of them female. Their median age at diagnosis was 28 years (range, 16-79 years). Ophthalmologic manifestations were usually bilateral (n = 19, 83%) and involved vascular occlusive retinopathy (n = 17, 74%), choroidopathy (n = 11, 48%), or retinal vasculitis (n = 1, 4%). Final best-corrected visual acuity was not significantly worse than the best-corrected visual acuity at diagnosis (P = 0.16). Retinal vascular occlusions were associated with poorer final visual acuity than choroidopathy (P = 0.002). After a median follow-up of 14 months (range, 2-132 months), nearly half the patients (n = 11, 48%) had permanent vision loss including best-corrected visual acuity of
Published: 2021

2. Histiocytosis and the nervous system: from diagnosis to targeted therapies

Author: Jean-François Emile, Fleur Cohen Aubart, Eli L. Diamond, Julien Haroche, Zahir Amoura, Benjamin H. Durham, Ahmed Idbaih, Omar Abdel-Wahab, Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], Hôpital Ambroise Paré [AP-HP], Memorial Sloane Kettering Cancer Center [New York], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurologie [CHU Pitié-Salpêtrière], and IFR70-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Central Nervous System, Cancer Research, Pathology, medicine.medical_specialty, Erdheim-Chester Disease, [SDV]Life Sciences [q-bio], Reviews, Disease, 03 medical and health sciences, 0302 clinical medicine, Rosai-Dorfman-Destombes disease, Langerhans cell histiocytosis, medicine, AcademicSubjects/MED00300, Humans, Rosai–Dorfman disease, Histiocyte, business.industry, CD68, MAPK pathway, medicine.disease, Prognosis, 3. Good health, Histiocytosis, Histiocytosis, Langerhans-Cell, Oncology, 030220 oncology & carcinogenesis, Histiocytoses, Erdheim–Chester disease, AcademicSubjects/MED00310, Neurology (clinical), Histiocytosis, Sinus, business, 030215 immunology
Abstract: Histiocytoses are heterogeneous hematopoietic diseases characterized by the accumulation of CD68(+) cells with various admixed inflammatory infiltrates. The identification of the pivotal role of the mitogen-activated protein kinase (MAPK) pathway has opened new avenues of research and therapeutic approaches. We review the neurologic manifestations of 3 histiocytic disorders with frequent involvement of the brain and spine: Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman-Destombes disease (RDD). Central nervous system (CNS) manifestations occur in 10%-25% of LCH cases, with both tumorous or neurodegenerative forms. These subtypes differ by clinical and radiological presentation, pathogenesis, and prognosis. Tumorous or degenerative neurologic involvement occurs in 30%-40% of ECD patients and affects the hypothalamic-pituitary axis, meninges, and brain parenchyma. RDD lesions are typically tumorous with meningeal or parenchymal masses with strong contrast enhancement. Unlike LCH and ECD, neurodegenerative lesions or syndromes have not been described with RDD. Familiarity with principles of evaluation and treatment both shared among and distinct to each of these 3 diseases is critical for effective management. Refractory or disabling neurohistiocytic involvement should prompt the consideration for use of targeted kinase inhibitor therapies.
Published: 2021

3. Long-term efficacy and safety outcomes of lenalidomide for cutaneous lupus erythematosus: A multicenter retrospective observational study of 40 patients

Author: Nathalie Costedoat-Chalumeau, Olivier Fain, Camille Francès, Zahir Amoura, Fleur Cohen-Aubart, Tullia de Risi-Pugliese, Laurent Arnaud, Patricia Senet, Annick Barbaud, François Chasset, Alexis Mathian, Véronique Le Guern, Arsène Mekinian, Miguel Hie, Jean-Benoît Monfort, Raphael Aitmehdi, Micheline Pha, and Julien Haroche
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, MEDLINE, Dermatology, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Lupus Erythematosus, Cutaneous, medicine, Humans, Immunologic Factors, Lenalidomide, Aged, Retrospective Studies, 030304 developmental biology, 0303 health sciences, business.industry, Retrospective cohort study, Middle Aged, Term (time), Treatment Outcome, Cutaneous Lupus Erythematosus, Female, Dermatologic Agents, business, medicine.drug
Published: 2021

4. Vascularites cérébrales associées aux infections

Author: Sandrine Deltour, Franck Bielle, F. Cohen Aubart, Frédéric Clarençon, Raphael Lhote, Julien Haroche, Eric Caumes, Dimitri Psimaras, Damien Galanaud, A. Lampros, Zahir Amoura, and Matthieu Peyre
Subjects: 0301 basic medicine, Hepatitis B virus, business.industry, 030106 microbiology, Mucormycosis, Gastroenterology, Varicella zoster virus, Context (language use), medicine.disease_cause, medicine.disease, Aspergillosis, 03 medical and health sciences, 0302 clinical medicine, Immunology, Internal Medicine, medicine, business, Vasculitis, Meningitis, 030217 neurology & neurosurgery, Cerebral vasculitis
Abstract: Infections are a frequent cause of cerebral vasculitis, important to diagnose because a specific treatment may be required. Infection-associated vasculitis can be caused by angiotropic pathogens (varicella zoster virus, syphilis, aspergillus). They can be associated with subarachnoidal meningitis (tuberculosis, pyogenic meningitis, cysticercosis). They can appear contiguously to sinuses or orbital infection (aspergillosis, mucormycosis). Finally, they also may be due to an immune mechanism in the context of chronic infections (hepatitis B virus, hepatitis C virus, human immunodeficiency virus). Cerebral vasculitis are severe conditions and their prognosis is directly linked to early recognition and diagnosis. Infectious causes must therefore be systematically considered ahead of cerebral vasculitis, and the appropriate investigations must be determined according to the patient's clinical context. We propose here an update on the infectious causes of cerebral vasculitis, their diagnosis modalities, and therapeutic options.
Published: 2021

5. Coronavirus Disease 2019 Acute Myocarditis and Multisystem Inflammatory Syndrome in Adult Intensive and Cardiac Care Units

Author: Alban Redheuil, Alexis Mathian, Nicolas Bréchot, Juliette Chommeloux, Fleur Cohen-Aubart, Marc Pineton de Chambrun, Sonia Burrel, Gilles Montalescot, Matthieu Schmidt, Johanne Silvain, Pascal Leprince, Mathieu Kerneis, Miguel Hie, Zahir Amoura, Charles-Edouard Luyt, Guillaume Hékimian, Guillaume Lebreton, Michel Zeitouni, Alain Combes, Julien Haroche, and Stéphane Marot
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Abdominal pain, Myocarditis, biology, business.industry, medicine.medical_treatment, Acute kidney injury, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, medicine.disease, Chest pain, Troponin, Systemic inflammatory response syndrome, 03 medical and health sciences, Diarrhea, 0302 clinical medicine, Internal medicine, Extracorporeal membrane oxygenation, biology.protein, Medicine, 030212 general & internal medicine, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Published: 2021

6. Patients with both Langerhans cell histiocytosis and Crohn’s disease highlight a common role of interleukin‐23

Author: Martin Jädersten, Egle Kvedaraite, Jan-Inge Henter, Natalia Mouratidou, Jenée Mitchell, George Kannourakis, Fleur Cohen-Aubart, Yenan T. Bryceson, Magda Lourda, Selma Olsson Åkefeldt, Maja Ideström, George Z. Rassidakis, Tatiana von Bahr Greenwood, Julien Haroche, HongYa Han, Bianca Tesi, Mattias Svensson, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC Pitié BT, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Immunology, Disease, Interleukin-23, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Langerhans cell histiocytosis, 030225 pediatrics, Interleukin 23, Humans, Medicine, In patient, 030212 general & internal medicine, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Crohn's disease, business.industry, Interleukin, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Regular Article, General Medicine, medicine.disease, 3. Good health, interleukin‐23, Histiocytosis, Langerhans-Cell, Pediatrics, Perinatology and Child Health, Regular Articles & Brief Reports, business
Abstract: International audience; Aim: To present the first case series of patients with Langerhans cell histiocytosis (LCH) also affected by Crohn's disease (CD), both of which are granulomatous diseases, and in LCH investigate the role of interleukin (IL)-23, which is a well-described disease mediator in CD.Methods: A case series of three patients with LCH and CD were described; a cohort of LCH patients (n = 55) as well as controls (n = 55) were analysed for circulating IL-23 levels; and the relation between the percentage of LCH cells in lesions and circulating IL-23 levels was analysed in seven LCH patients.Results: Differential diagnostic challenges for these two granulomatous diseases were highlighted in the case series, and it took up to 3 years to diagnose CD. Elevated IL-23 levels were found in LCH patients. The amount of lesional LCH cells correlated with the levels of circulating IL-23.Conclusion: Both CD and LCH should be considered in patients with inflammatory gastrointestinal involvement. The IL-23 pathway is a common immunological trait between these two granulomatous diseases.
Published: 2020

7. ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

Author: Oussama Abla, Stephen Peeke, Irem Eldem, Marianne D. van de Wetering, Jennifer Picarsic, Kseniya Petrova-Drus, Robert B. Lorsbach, Jan A M van Laar, Paul Geraeds Kemps, Sylvie Fraitag, Sébastien Héritier, Kristian T. Schafernak, Amy A. Swanson, Eli L. Diamond, Raf Sciot, Karen Ernestus, Mariko Suchi, Nabeel R. Yaseen, Sanda Alexandrescu, Laura Sophia Hiemcke-Jiwa, Matthew Collin, Ingrid S Tam, Sabrina Rossi, Benjamin H. Durham, F J Sherida H Woei-A-Jin, James A. Whitlock, Brianna Empringham, Laura Munoz-Arcos, Falko Fend, Olga Gryniewicz-Kwiatkowska, Majid Madni, Verena Wiegering, Kerry Turner, Dina El Demellawy, Gianpiero Tamburrini, Aditya Raghunathan, Lucas R. Massoth, Carel J. M. van Noesel, Robert Möhle, Cor van den Bos, Jacinthe Bonneau-Lagacherie, Somak Roy, Pasquale M Barbaro, Andreas Beilken, Stefania Gaspari, Jean-François Emile, David D. Grier, Claire Lamaison, Kee Kiat Yeo, Jean Donadieu, Jon M Brandt, Laure Farnault, Friedrich Feuerhake, Marie-Laure Jullie, Uta Flucke, Pancras C.W. Hogendoorn, Astrid G. S. van Halteren, Antje Bornemann, Bryan A. Sisk, Tina Méry, Joanna Weinstein, Ashish R Kumar, Robert M. Verdijk, V. Baykov, Alysa A Poulin, Mandy M Atkinson, VG Potapenko, Vaish Sridhar, Julien Haroche, Zofia Hélias-Rodzewicz, Shipra Garg, Susan Picton, Michael M. Henry, Jackie Allotey, Daniel Leino, Nishant Tiwari, Martin Ebinger, Jason L Hornick, Bożenna Dembowska-Bagińska, Marco Gessi, Dmitry A Evseev, Paediatric Oncology, CCA - Cancer biology and immunology, Pathology, CCA - Cancer Treatment and Quality of Life, Leiden University Medical Center (LUMC), Universiteit Leiden, Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Ambroise Paré [AP-HP], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pontchaillou [Rennes], CHU Marseille, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], National Institutes of Health, NIH, National Cancer Institute, NCI: P30 CA008748, R37 CA259260-01, Cincinnati Children's Hospital Medical Center, University of Saskatchewan, Leids Universitair Medisch Centrum, LUMC, Institut National Du Cancer, INCa: PRT-K19-143, P.G.K. received a grant from Leiden University Medical Center. A.G.S.v.H. is supported by Stichting 1000 kaarsjes voor Juultje. E.L.D. is supported by the National Institutes of Health/National Cancer Institute Core Grant (P30 CA008748), National Cancer Institute (R37 CA259260-01), the Frame Fund, Applebaum Foundation, and Joy Family West Foundation. J.-F.E. is supported by the Programme de Recherche Translationnelle sur le Cancer from the French National Cancer Institute (PRT-K19-143)., and The authors acknowledge the International Rare Histiocytic Disorders Registry (IRHDR, ClinicalTrial.gov number NCT02285582), which included some patients described in this study. The authors thank Chris Woods (Lead Analyst, Imaging Informatics) and the Research Pathology Laboratory at Cincinnati Children's Hospital Medical Center, John DeCoteau (molecular pathologist) at University of Saskatchewan, Sven van Kempen (senior laboratory technician) and Lennart Kester (clinical molecular biologist in pathology in training) at Princess M?xima Center for Pediatric Oncology, and Demi van Egmond (laboratory technician), Tom van Wezel (clinical molecular biologist in pathology), and Arjen Cleven (pathologist) at Leiden University Medical Center for technical assistance. The authors thank Els Wauters (pulmonologist and respiratory oncologist) at University Hospitals Leuven, Andreas Rosenwald (pathologist) at the Institute of Pathology of the University of W?rzburg, and Bipin Mathew (pathologist) at Leeds Teaching Hospitals for clinical care and/or diagnostics of patients described in this study. The authors thank Les Laboratoires Servier for allowing the use of their medical illustrations (Servier Medical Art, https://smart.servier.com) in the visual abstract. Figure 6 was created with BioRender.com. P.G.K. received a grant from Leiden University Medical Center. A.G.S.v.H. is supported by Stichting 1000 kaarsjes voor Juultje. E.L.D. is supported by the National Institutes of Health/National Cancer Institute Core Grant (P30 CA008748), National Cancer Institute (R37 CA259260-01), the Frame Fund, Applebaum Foundation, and Joy Family West Foundation. J.-F.E. is supported by the Programme de Recherche Translationnelle sur le Cancer from the French National Cancer Institute (PRT-K19-143).
Subjects: Adult, Histiocytic Disorders, Malignant, Male, Pathology, medicine.medical_specialty, Adolescent, Oncogene Proteins, Fusion, [SDV]Life Sciences [q-bio], BLOOD COMMENTARY, Immunology, Disease, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Biochemistry, Young Adult, hemic and lymphatic diseases, medicine, Humans, Anaplastic Lymphoma Kinase, Child, Protein Kinase Inhibitors, Histiocyte, Retrospective Studies, business.industry, Infant, Histology, Cell Biology, Hematology, medicine.disease, Phenotype, Histiocytosis, Histiocytic neoplasm, Child, Preschool, Female, Nervous System Diseases, business
Abstract: Contains fulltext : 249882.pdf (Publisher’s version ) (Closed access) ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.
Published: 2022

8. Erdheim–Chester disease: a rapidly evolving disease model

Author: Matthias Papo, Valerio Maniscalco, Frédéric Charlotte, Augusto Vaglio, Francesco Pegoraro, and Julien Haroche
Subjects: 0301 basic medicine, MAPK/ERK pathway, Cancer Research, Interleukin 1 family, business.industry, Interstitial lung disease, Hematology, Disease, medicine.disease, Bioinformatics, Retroperitoneal fibrosis, Pathogenesis, 03 medical and health sciences, Histiocytosis, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Erdheim–Chester disease, medicine, medicine.symptom, business
Abstract: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis with a putative neoplastic and inflammatory nature. The disease is driven by mutations in proto-oncogenes such as BRAF and MEK, while immune-mediated mechanisms contribute to disease development and progression. The clinical presentation of ECD is highly heterogeneous, ranging from smouldering unifocal forms to multiorgan life-threatening disease. Almost any organ can be involved, but the most common lesions include long-bone involvement, retroperitoneal fibrosis, interstitial lung disease, pericardial and myocardial infiltration, CNS, retro-orbital, and large-vessel involvement. These manifestations may mimic those of neoplastic and systemic immune-mediated diseases. Overlap with these conditions represents an emerging challenge for the clinician. A variety of treatments are efficacious for ECD, targeting both the MAPK-pathway and the immune-mediated pathomechanisms. The traditional approach is based on immunomodulatory agents (interferon-α), but recent alternatives-including anti-cytokine therapies (IL1- and TNFα-blockers) and immunosuppressants (mTOR-inhibitors)-showed promising results. However, since the detection of MAPK pathway activation in most patients and the dramatic efficacy of BRAF and MEK inhibitors, these targeted treatments represent the first-line approach in patients with severe disease forms. High rates of radiologic responses do not often mean clinical remission, especially for CNS involvement, which often results in chronic disability. This review will outline the main clinical features of ECD, with emphasis on the emerging challenges in pathogenesis and management, and on the role of recent targeted approaches.
Published: 2020

9. Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era

Author: Xin Xin Cao, Benjamin H. Durham, Paul C. Hendrie, Aaron M. Goodman, Jennifer Picarsic, Eric D. Jacobsen, Juvianee Estrada-Veras, Andre Abdo, Michael Girschikofsky, Matthew Collin, Kenneth L. McClain, Mineo Kurokawa, Ronald S. Go, Augusto Vaglio, Mark L. Heaney, Kazuhiro Toyama, Lorenzo Dagna, Julien Haroche, Oshrat Hershkovitz-Rokah, Eli L. Diamond, Ofer Shpilberg, Roei D Mazor, Filip Janku, Fleur Cohen-Aubart, Gaurav Goyal, Goyal, G., Heaney, M. L., Collin, M., Cohen-Aubart, F., Vaglio, A., Durham, B. H., Hershkovitz-Rokah, O., Girschikofsky, M., Jacobsen, E. D., Toyama, K., Goodman, A. M., Hendrie, P., Cao, X. -X., Estrada-Veras, J. I., Shpilberg, O., Abdo, A., Kurokawa, M., Dagna, L., Mcclain, K. L., Mazor, R. D., Picarsic, J., Janku, F., Go, R. S., Haroche, J., and Diamond, E. L.
Subjects: Male, Proto-Oncogene Proteins B-raf, Erdheim-Chester Disease, medicine.medical_specialty, genetic structures, MAP Kinase Signaling System, medicine.medical_treatment, Immunology, MEDLINE, Disease, Biochemistry, Targeted therapy, Pericarditis, Fibrosis, medicine, Humans, Molecular Targeted Therapy, Vemurafenib, Clinical Trials as Topic, business.industry, Cell Biology, Hematology, Prognosis, medicine.disease, Dermatology, Histiocytosis, Langerhans-Cell, Histiocytosis, Mutation, Erdheim–Chester disease, Female, business, medicine.drug
Abstract: Erdheim-Chester disease (ECD) is a rare histiocytosis that was recently recognized as a neoplastic disorder owing to the discovery of recurrent activating MAPK (RAS-RAF-MEK-ERK) pathway mutations. Typical findings of ECD include central diabetes insipidus, restrictive pericarditis, perinephric fibrosis, and sclerotic bone lesions. The histopathologic diagnosis of ECD is often challenging due to nonspecific inflammatory and fibrotic findings on histopathologic review of tissue specimens. Additionally, the association of ECD with unusual tissue tropism and an insidious onset often results in diagnostic errors and delays. Most patients with ECD require treatment, except for a minority of patients with minimally symptomatic single-organ disease. The first ECD consensus guidelines were published in 2014 on behalf of the physicians and researchers within the Erdheim-Chester Disease Global Alliance. With the recent molecular discoveries and the approval of the first targeted therapy (vemurafenib) for BRAF-V600–mutant ECD, there is a need for updated clinical practice guidelines to optimize the diagnosis and treatment of this disease. This document presents consensus recommendations that resulted from the International Medical Symposia on ECD in 2017 and 2019. Herein, we include the guidelines for the clinical, laboratory, histologic, and radiographic evaluation of ECD patients along with treatment recommendations based on our clinical experience and review of literature in the molecular era.
Published: 2020

10. Erdheim-Chester disease

Author: Julien Haroche, Zahir Amoura, and Laurent Arnaud
Subjects: Proto-Oncogene Proteins B-raf, Erdheim-Chester Disease, Pathology, medicine.medical_specialty, Myeloid, genetic structures, Immunology, MAP Kinase Kinase 1, Alpha interferon, Disease, Biochemistry, Rheumatology, Animals, Humans, Medicine, Histiocyte, Myeloproliferative Disorders, business.industry, CD68, Myelodysplastic syndromes, Interferon-alpha, Cell Biology, Hematology, Prognosis, medicine.disease, Dermatology, Radiography, Histiocytosis, Leukemia, medicine.anatomical_structure, Leukemia, Myeloid, Myelodysplastic Syndromes, Histiocytoses, Mutation, Erdheim–Chester disease, business
Abstract: Erdheim-Chester disease (ECD) is characterized by the infiltration of tissues by foamy CD68+CD1a− histiocytes, with 1500 known cases since 1930. Mutations activating the MAPK pathway are found in more than 80% of patients with ECD, mainly the BRAFV600E activating mutation in 57% to 70% of cases, followed by MAP2K1 in close to 20%. The discovery of BRAF mutations and of other MAP kinase pathway alterations, as well as the co-occurrence of ECD with LCH in 15% of patients with ECD, led to the 2016 revision of the classification of histiocytoses in which LCH and ECD belong to the “L” group. Both conditions are considered inflammatory myeloid neoplasms. Ten percent of ECD cases are associated with myeloproliferative neoplasms and/or myelodysplastic syndromes. Some of the most striking signs of ECD are the long bone involvement (80%-95%), as well as the hairy kidney appearance on computed tomography scan (63%), the coated aorta (40%), and the right atrium pseudo-tumoral infiltration (36%). Central nervous system involvement is a strong prognostic factor and independent predictor of death. Interferon-α seems to be the best initial treatment of ECD. Since 2012, more than 200 patients worldwide with multisystem or refractory ECD have benefitted from highly effective therapy with BRAF and MEK inhibitors. Targeted therapies have an overall, robust, and reproducible efficacy in ECD, with no acquired resistance to date, but their use may be best reserved for the most severe manifestations of the disease, as they may be associated with serious adverse effects and as-yet-unknown long-term consequences.
Published: 2020

11. Analysis of risk factors for complications and adverse obstetrical outcomes in women with Takayasu arteritis: a French retrospective study and literature review

Author: François Maurier, Patrice Cacoub, Robin Dhote, Bertrand Godeau, Luc Mouthon, Jean Gabriel Fuzibet, L Swiader, Loïc Guillevin, P. Belenotti, Marc Lambert, Catherine Veyssier-Belot, Antoine Néel, Smail Amar, Murielle Rondeau, Alain Fur, F. Renou, Eric Hachulla, Arsène Mekinian, C. Chapelon, Frederic Vandergheynst, Olivier Fain, Françoise Sarrot-Reynault, Marc André, Bruno Devaux, Véronique Le Guern, Jean Baptiste Gauthier, Julien Haroche, Nathalie Costedoat-Chalumeau, Noémie Abisror, Constance Lahuna, Pascal Cathébras, Nihal Martis, Nathalie Morel, Olivier Pourrat, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: medicine.medical_specialty, HELLP syndrome, Birth weight, Pregnancy Complications, Cardiovascular, Intrauterine growth restriction, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Pregnancy, medicine, Humans, 030212 general & internal medicine, Child, Retrospective Studies, Outcome, 030203 arthritis & rheumatology, business.industry, Obstetrics, Infant, Newborn, Pregnancy Outcome, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Retrospective cohort study, General Medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Risk factors, Gestation, Female, business, Vasculitis, Live birth, Takayasu arteritis
Abstract: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed.All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015.The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study.This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.
Published: 2020

12. Long‐term efficacy and safety of 2CdA (cladribine) in extra‐pulmonary adult‐onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review

Author: Claire Dromer, Antoine Néel, Hélène Maillard, Denis Jullien, Anne-Maelle Fontenoy, Carla Araujo, Gwenaël Lorillon, Fleur Cohen-Aubart, Mohamed Hamidou, Loïc Guillevin, Mathilde de Menthon, Benoit Tessoulin, Abdellatif Tazi, Mathieu Artifoni, Jean Donadieu, Julien Haroche, Jean-Emmanuel Kahn, Olivier Hermine, and Thierry Généreau
Subjects: Adult, Male, medicine.medical_specialty, Neutropenia, Antimetabolites, medicine.medical_treatment, Kaplan-Meier Estimate, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Langerhans cell histiocytosis, Sepsis, Internal medicine, medicine, Humans, Age of Onset, Cladribine, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Chemotherapy, Dose-Response Relationship, Drug, Cumulative dose, business.industry, Remission Induction, Hematology, Middle Aged, medicine.disease, Vinblastine, Histiocytosis, Langerhans-Cell, Histiocytosis, Virus Diseases, 030220 oncology & carcinogenesis, Cytarabine, Female, France, business, Immunosuppressive Agents, 030215 immunology, medicine.drug
Abstract: Langerhans cell histiocytosis (LCH) is a rare protean disease that usually affects children. Few data are available for management of adult-onset cases. A complete picture of the efficacy and safety of 2CdA (2-chlorodeoxyadenosine, cladribine) is lacking. We report a retrospective multicentre study of 23 adult LCH (a-LCH) patients who received single-agent 2CdA and a systematic literature review. All had previously received systemic therapy (vinblastine, n = 19). Response to 2CdA was evaluable in 22 cases. Overall response rate (ORR) was 91%. Complete response (CR) occurred in 11 cases (50%). Nine patients (39%) developed grade 3-4 neutropenia and/or severe infection. A literature review yielded 48 additional cases. A pooled analysis confirmed our findings (ORR: 88%, CR: 49%). CRs were rare with cumulative dose
Published: 2020

13. Lung Involvement in Destombes-Rosai-Dorfman Disease

Author: Jean-François Emile, Samia Boussouar, Q. Moyon, Fleur Cohen Aubart, Grégoire Prévot, Philippe Grenier, Nathalie Aladjidi, Philippe Maksud, Julien Haroche, Frédéric Charlotte, Zahir Amoura, and Jean Donadieu
Subjects: Pulmonary and Respiratory Medicine, Cobimetinib, Pathology, medicine.medical_specialty, business.industry, MEK inhibitor, Standardized uptake value, Disease, Critical Care and Intensive Care Medicine, medicine.disease, 3. Good health, 03 medical and health sciences, Histiocytosis, chemistry.chemical_compound, 0302 clinical medicine, 030228 respiratory system, chemistry, Pulmonary fibrosis, Medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business, Interstitial Disease, Rosai–Dorfman disease
Abstract: Poster: "ESTI 2019 / P-0109 / Lung involvement in Destombes-Rosai-Dorfman disease: clinical and radiological features, and response to the MEK inhibitor cobimetinib " by: "Q. moyon, S. Boussouar , F. cohen aubart, P. maksud, N. Aladjidi, G. Prevot, J. donadieu, Z. amoura, P. A. Grenier, J. haroche; Paris/FR"
Published: 2020

14. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial

Author: Makoto Miyara, Thi Huong Du Boutin, Patrick Cherin, Julien Haroche, Guy Gorochov, Hervé Devilliers, Micheline Pha, Marc Pineton de Chambrun, Fleur Cohen-Aubart, Miguel Hie, Zahir Amoura, Hans Yssel, and Alexis Mathian
Subjects: Adult, Male, medicine.medical_specialty, Immunology, Disease, General Biochemistry, Genetics and Molecular Biology, Maintenance Chemotherapy, law.invention, Rheumatology, Randomized controlled trial, Prednisone, law, Internal medicine, Secondary Prevention, medicine, Clinical endpoint, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Adverse effect, Glucocorticoids, Systemic lupus erythematosus, business.industry, Low dose, Middle Aged, Symptom Flare Up, medicine.disease, Clinical trial, Treatment Outcome, Withholding Treatment, Female, business, medicine.drug
Abstract: ObjectivesTo compare the efficacy to prevent flares of maintenance versus withdrawal of 5 mg/day prednisone in systemic lupus erythematosus (SLE) patients with clinically quiescent disease.MethodsA monocentric, 12-month, superiority, open-label, randomised (1:1) controlled trial was conducted with 61 patients continuing 5 mg/day prednisone and 63 stopping it. Eligibility criteria were SLE patients who, during the year preceding the inclusion, had a clinically inactive disease and a stable SLE treatment including 5 mg/day prednisone. The primary endpoint was the proportion of patient experiencing a flare defined with the SELENA-SLEDAI flare index (SFI) at 52 weeks. Secondary endpoints included time to flare, flare severity according to SFI and British Isles Lupus Assessment Group (BILAG) index and increase in the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI).ResultsProportion of patients experiencing a flare was significantly lower in the maintenance group as compared with the withdrawal group (4 patients vs 17; RR 0.2 (95% CI 0.1 to 0.7), p=0.003). Maintenance of 5 mg prednisone was superior with respect to time to first flare (HR 0.2; 95% CI 0.1 to 0.6, p=0.002), occurrence of mild/moderate flares using the SFI (3 patients vs 12; RR 0.2 (95% CI 0.1 to 0.8), p=0.012) and occurrence of moderate/severe flares using the BILAG index (1 patient vs 8; RR 0.1 (95% CI 0.1 to 0.9), p=0.013). SDI increase and adverse events were similar in the two treatment groups. Subgroup analyses of the primary endpoint by predefined baseline characteristics did not show evidence of a different clinical response.ConclusionMaintenance of long term 5 mg prednisone in SLE patients with inactive disease prevents relapse.Trial registration numberNCT02558517; Results
Published: 2019

15. Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study

Author: Johannes Visser, Anne Lutun, Elena Sieni, Fleur Cohen, Nabil Kabbara, Olga Slater, Jean-François Emile, Mathilde Jehanne, Alina Ferster, Michael Maschan, Houda Boudiaf, Pascale Schneider, Sarah Elitzur, Nathalie Aladjidi, Milen Minkov, Ahmed Idbaih, Matthew Collin, Michal Golan, Alexandra Kolenova, François Chalard, Karel Svojgr, Jean Donadieu, Anne Pagnier, Laurence Blanc, Nicolas Simon, Jean-Claude Alvarez, Islam Amine Larabi, Fanette Bernard, James Nicholson, Mohamed Barkaoui, Anne Sonntagbauer, Anne Lambilliote, Thomas Lehrnbecher, Dmitriy Evseev, Viktoria Efremova, Geneviève Plat, Martina Ahlmann, Jean Miron, Valérie Taly, Caroline Hutter, Julien Haroche, Zofia Hélias-Rodzewicz, Paul Milne, Sébastien Héritier, Andrej Lissat, Mathilde Tardieu, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Raymond Poincaré [AP-HP], Centre Hospitalier Universitaire [Grenoble] (CHU), Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Medizinische Universität Wien = Medical University of Vienna, Department Pediatric Hematology Oncology, Azienda Ospedaliero-Universitaria Meyer, Florence, Departments of Hematology, Université Paris Diderot - Paris 7 (UPD7), Groupe d'Etude des Histiocytoses (GEH), Groupe d'Etude des Histiocytoses, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Radiologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Newcastle University [Newcastle], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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 Pitié-Salpêtrière [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)-Institut E3M [CHU Pitié-Salpêtrière], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Centre Hospitalier Universitaire Félix-Guyon [Saint-Denis, La Réunion, France], Comenius University Children's Hospital Limbova 1 [Bratislava, Slovakia], Service Immuno Hémato-Onco Pédiatrique, CHU Grenoble, Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Toulouse [Toulouse], CHU Amiens-Picardie, Universitätsklinikum Frankfurt, Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), University Hospital [Minsk, Belarus], Universitätsklinikum Münster Klinik für Kinder [Münster, Germany], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Jeanne de Flandre [Lille], Hôpital Mustapha [Mustapha, Algeria], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University Hospital Motol [Prague, Czech Republic], Hôpitaux Universitaires de Genève (HUG), Schneider Children’s Medical Center of Israel [Petah Tikva], The Edmond and Lily Safra Children's Hospital [Tel-Hahsomer, Israel], Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology [Moscow, Russia], Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Great Ormond Street Hospital for Children [London] (GOSH), Sant'Anna Children's Hospital, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Cellular Medicine [Newcastle], Service de Pharmacologie Toxicologie [Garches], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [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)-Centre National de la Recherche Scientifique (CNRS), Comenius University in Bratislava, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'Onco-neurologie = Département de neurologie 2 [CHU Pitié Salpêtrière], TALY, Valerie, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Proto-Oncogene Proteins B-raf, Cancer Research, medicine.medical_specialty, Time Factors, Adolescent, Treatment outcome, Drug Resistance, [SDV.CAN]Life Sciences [q-bio]/Cancer, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Langerhans cell histiocytosis, Refractory, medicine, Humans, Child, Vemurafenib, Protein Kinase Inhibitors, 030304 developmental biology, 0303 health sciences, Childhood Langerhans Cell Histiocytosis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Age Factors, Infant, ORIGINAL REPORTS, medicine.disease, Dermatology, 3. Good health, Europe, Histiocytosis, Langerhans-Cell, Histiocytosis, Treatment Outcome, Oncology, Multicenter study, Pediatric Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Mutation, Female, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction, medicine.drug
Abstract: PURPOSE Off-label use of vemurafenib (VMF) to treat BRAFV600E mutation–positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated. PATIENTS AND METHODS Fifty-four patients from 12 countries took VMF 20 mg/kg/d. They were classified according to risk organ involvement: liver, spleen, and/or blood cytopenia. The main evaluation criteria were adverse events (Common Terminology Criteria for Adverse Events [version 4.3]) and therapeutic responses according to Disease Activity Score. RESULTS LCH extent was distributed as follows: 44 with positive and 10 with negative risk organ involvement. Median age at diagnosis was 0.9 years (range, 0.1 to 6.5 years). Median age at VMF initiation was 1.8 years (range, 0.18 to 14 years), with a median follow-up of 22 months (range, 4.3 to 57 months), whereas median treatment duration was 13.9 months (for 855 patient-months). At 8 weeks, 38 complete responses and 16 partial responses had been achieved, with the median Disease Activity Score decreasing from 7 at diagnosis to 0 ( P < .001). Skin rash, the most frequent adverse event, affected 74% of patients. No secondary skin cancer was observed. Therapeutic plasma VMF concentrations (range, 10 to 20 mg/L) seemed to be safe and effective. VMF discontinuation for 30 patients led to 24 LCH reactivations. The blood BRAFV600E allele load, assessed as circulating cell-free DNA, decreased after starting VMF but remained positive (median, 3.6% at diagnosis, and 1.6% during VMF treatment; P < .001) and was associated with a higher risk of reactivation at VMF discontinuation. None of the various empirical therapies (hematopoietic stem-cell transplantation, cladribine and cytarabine, anti-MEK agent, vinblastine, etc) used for maintenance could eradicate the BRAFV600E clone. CONCLUSION VMF seemed safe and effective in children with refractory BRAFV600E-positive LCH. Additional studies are needed to find effective maintenance therapy approaches.
Published: 2019

16. Case Report: Evolution of a Severe Vascular Refractory Form of ECD Requiring Liver Transplantation Correlated With the Change in the Monocyte Subset Analysis

Author: Francine Garnache-Ottou, Thibaud Soumagne, Bernard Bonnotte, Jerome Razanamahery, Anne Roggy, Julien Haroche, Jean-François Emile, Zaher Lakkis, Alexandre Malakhia, Fleur Cohen-Aubart, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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 Pitié-Salpêtrière [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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Pathology, medicine.medical_specialty, Myeloid, CD14, Immunology, Erdheim–Chester disease, Case Report, CD16, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, 030304 developmental biology, 0303 health sciences, business.industry, Monocyte, RC581-607, medicine.disease, 3. Good health, Transplantation, Histiocytosis, Vascular diagnosis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, monocyte, Erdheim-Chester disease, Immunologic diseases. Allergy, business, histiocytosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, transplantation
Abstract: Erdheim–Chester disease is a rare histiocytosis characterized by iconic features associated with compatible histology. Most patients have somatic mutations in the MAP-kinase pathway gene, and the mutations occur in CD14+ monocytes. Differentiation of the myeloid lineage plays a central role in the pathogenesis of histiocytosis. Monocytes are myeloid-derived white blood cells, divided into three subsets, but only the CD14++CD16− “classical monocyte” can differentiate into dendritic cells and tissue macrophages. Since most mutations occur in CD14+ cells and since ECD patients have a particular monocytic phenotype resembling CMML, we studied the correlation between disease activity and monocytic subset distribution during the course of a severe vascular form of ECD requiring liver transplantation. During early follow-up, increased CD14++CD16− “classical monocyte” associated with decreased CD14lowCD16++ “non-classical monocyte” correlated with disease activity. Further studies are needed to confirm the use of monocyte as a marker of disease activity in patients with ECD.
Published: 2021

17. Exposure to inorganic particles in paediatric sarcoidosis: the PEDIASARC study

Author: Véronique Houdouin, Catherine Cavalin, Antoine Deschildre, Jean-Marc Naccache, Catherine Chapelon-Abric, Céline Delestrain, Julien Haroche, Ralph Epaud, Ulrich Meinzer, Simon Chauveau, Fleur Cohen-Aubart, Mickaël Catinon, Florence Jeny, Odile Macchi, Sylvain Le Jeune, Hilario Nunes, Michel Vincent, Paul-André Rosental, Manon Brocvielle, Marie-Hélène Odièvre, Marie-Emeline Montagne, S. Mattioni, Dominique Valeyre, Karine Juvin, Annick Clement, Dominique Israël-Biet, A. Dossier, Nadia Nathan, Jacques Brouard, François Lionnet, Lucile Sesé, Rola Abou Taam, Christophe Delacourt, Marie Mittaine, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Pneumologie et allergologie pédiatriques [CHU Jeanne de Flandre, Lille], Hôpital Jeanne de Flandre [Lille], Université de Lille, Service de Pneumologie et d'Allergologie Pédiatriques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Service de Pneumologie, soins intensifs (Pneumo - HEGP), 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), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], CHU Tenon [AP-HP], Centre d'études européennes et de politique comparée (Sciences Po, CNRS) (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPC), Centre d'histoire de Sciences Po (Sciences Po) (CHSP), Sciences Po (Sciences Po), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Observatoire du Samu Social de Paris, CHU Necker - Enfants Malades [AP-HP], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre des maladies respiratoires rares Respirare [CHI Créteil], 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), AP-HP - Hôpital Bichat - Claude Bernard [Paris], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de médecine interne [Avicenne], Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [CHU Necker] (RAISE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Groupe Hospitalier Paris Saint-Joseph (hpsj), Laboratoire interdisciplinaire d'évaluation des politiques publiques (Sciences Po) (LIEPP), Centre d'études de l'emploi et du travail (CEET), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.)-Ministère du Travail, de l'Emploi et de la Santé, contract grant sponsor: European Research Council (ERC) / SILICOSISproject / Principal investigator: Paul-André Rosental, Contract grant number: ERC2011-ADG_20110406ˆProject ID: 295817. Statistical analysis: RespiFIL funds, European Project: 295449,EC:FP7:ERC,ERC-2011-ADG_20110406,DARTCH(2012), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université de Paris (UP), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Service de Médecine Interne [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 d'études européennes et de politique comparée (CEE), Centre d'histoire de Sciences Po (CHSP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], and Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po)
Subjects: Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, paediatric interstitial lung disease, [SDV]Life Sciences [q-bio], [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Occupational Exposure, medicine, Humans, sarcoidosis, Occupational lung disease, Occupations, Child, Inorganic particles, 030304 developmental biology, 0303 health sciences, Median score, rare lung diseases, business.industry, Dust, Environmental exposure, Environmental Exposure, medicine.disease, 3. Good health, 030228 respiratory system, Metal dust, Talc, Sarcoidosis, business, occupational lung disease
Abstract: International audience; Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.
Published: 2021

18. A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis

Author: Cécile Masson, Aurélien Corneau, Florence Moulin, Ghaith Abdessalem, Pedro Gonçalves, Marianne Leruez, James P. Di Santo, Mathie Lorrot, Julie Toubiana, Julien Haroche, Camille Bruneau, Isabelle Melki, Bruno Charbit, Zahra Belhadjer, Loïc de Pontual, Camille de Cevins, Brigitte Bader Meunier, Alain Fischer, Victor Garcia-Paredes, Brieuc P. Perot, Marine Luka, Damien Bonnet, Quentin Riller, Nikaïa Smith, Slimane Allali, Sonia Meynier, Aude Magérus, Christele Gras Leguen, Shen-Ying Zhang, Olivier Schwartz, Jean-Laurent Casanova, Frédéric Rieux-Laucat, Nicolas Cagnard, Francesco Carbone, Tinhinane Fali, Mélanie Parisot, Mickaël M. Ménager, Maxime Beretta, Mohammed Zarhrate, Christine Bole-Feysot, Vithura Pirabarakan, Ludivine Grzelak, Mehdi Oualha, Darragh Duffy, Laura Barnabei, Hugo Mouquet, Maxime Batignes, Alexandre Boullé, Boris Sorin, Marie-Claude Stolzenberg, Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Sanofi Aventis R&D [Chilly-Mazarin], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital universitaire Robert-Debré [Paris], Université Paris Cité (UPCité), CHU Trousseau [APHP], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Jean Verdier [AP-HP], Université Paris 13 (UP13), Collège de France (CdF (institution)), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and Université Paris Cité (UPC)
Subjects: Adult, Vascular Endothelial Growth Factor A, Chemokine, Myocarditis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MIS-C, Monocytes, chemistry.chemical_compound, Viewpoint, scRNA-seq, medicine, otorhinolaryngologic diseases, Humans, Kawasaki Disease, Child, Connective Tissue Diseases, biology, business.industry, SARS-CoV-2, Monocyte, NF-kappa B, COVID-19, General Medicine, Dendritic Cells, Gene signature, medicine.disease, Pathophysiology, Systemic Inflammatory Response Syndrome, Vascular endothelial growth factor, medicine.anatomical_structure, Cytokine, chemistry, TNF-α and NF-κB signaling, Immunology, biology.protein, Cytokines, Tumor necrosis factor alpha, lack of responses to type I and type II IFN secretion, Clinical and Translational Article, Chemokines, myocarditis, business, PIMS-TS
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. Methods To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. Findings The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. Conclusions These results provide potential for a better understanding of disease pathophysiology. Funding Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d’Excellence ‘‘Milieu Intérieur,” grant ANR-10-LABX-69-01; ANR-flash Covid19 “AIROCovid” and “CoVarImm”), Institut National de la Santé et de la Recherche Médicale (INSERM), and the “URGENCE COVID-19” fundraising campaign of Institut Pasteur., Graphical abstract, Context and significance Children with SARS-CoV-2 infection were initially thought to have only mild COVID-19 symptoms. However, several weeks into the first wave of SARS-CoV-2 infections, there was a surge of a postacute pathology called multisystem inflammatory syndrome in children (MIS-C). The authors recruited a cohort of children with suspicion of SARS-CoV-2 infection and uncovered hyperinflammation, hypoxic conditions, exacerbation of TNF-α signaling via NF-κB, and absence of responses to type I and type II IFN secretion in the most severe forms of MIS-C with severe myocarditis. This work led the authors to identify in monocytes and validate in peripheral blood mononuclear cells a molecular signature of 25 genes that allows discrimination of the most severe forms of MIS-C with myocarditis., Multiparametric analysis identifies, in monocytes and dendritic cells, a molecular signature of the most severe forms of multisystem inflammatory syndrome in children caused by SARS-CoV-2 infection. Severe myocarditis is characterized by an excess of TNF-α signaling via NF-κB, hypoxic conditions, and hyperinflammation in the absence of type I and type II interferon responses.
Published: 2021

19. Mineral exposures in pediatric sarcoidosis

Author: Jean-Marc Naccache, François Lionnet, Lucile Sesé, Ulrich Meinzer, Fleur Cohen Aubart, Karine Juvin, Marie-Hélène Odièvre, Véronique Houdouin, Catherine Cavalin, Antoine Deschildre, Dominique Valeyre, Dominique Israel-Biet, Paul-André Rosental, Florence Jeny, Michel Vincent, Sylvain Le Jeune, Annick Clement, Jacques Brouard, Nadia Nathan, Ralph Epaud, Odile Macchi, Simon Chauveau, S. Mattioni, Mickaël Catinon, Céline Delestrain, Marie-Emeline Montagne, Julien Haroche, Hilario Nunes, Rola Abou Taam, Catherine Chapelon-Abric, Christophe Delacourt, Marie Mittaine, and A. Dossier
Subjects: medicine.medical_specialty, Mineral, business.industry, medicine, Sarcoidosis, medicine.disease, business, Dermatology
Published: 2021

20. BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in Systemic Lupus Erythematosus

Author: Alexis Mathian, Micheline Pha, Q. Moyon, François Anna, Delphine Sterlin, Fleur Cohen-Aubart, Paul Breillat, Pierre Charneau, Hedi Chaieb, Guy Gorochov, Thi Huong Du Boutin, Pedro Macedo Flores, Sasi Mudumba, Makoto Miyara, Sophia de Alba, Pascale Ghillani-Dalbin, Julien Haroche, Raphael Lhote, Zahir Amoura, Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], 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 Pitié-Salpêtrière [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)-Institut E3M [CHU Pitié-Salpêtrière], Service d'Immunologie [CHU Pitié-Salpétrière], Laboratoire commun Pasteur-TheraVectys, Institut Pasteur [Paris] (IP)-TheraVectys-Université Paris Cité (UPCité), Virologie Moléculaire et Vaccinologie / Molecular Virology and Vaccinology, Institut Pasteur [Paris] (IP), Genalyte, The study was supported by the Agence Nationale de la Recherche (ANR Flash COVID19 program, MUCOVID, PI: DS) and by the SARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University ICOViD programs, PI: GG)., ANR-21-COVR-0037,MUCOVID,Evaluation de la capacité neutralisante des IgA contre les variants du SARS-CoV-2(2021), HAL-SU, Gestionnaire, Evaluation de la capacité neutralisante des IgA contre les variants du SARS-CoV-2 - - MUCOVID2021 - ANR-21-COVR-0037 - COVID-19 - VALID, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut Pasteur [Paris]-TheraVectys, Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière]
Subjects: Male, Antibodies, Viral, Severity of Illness Index, Immunogenicity, Vaccine, 0302 clinical medicine, Interferon, Lupus Erythematosus, Systemic, Immunology and Allergy, Prospective Studies, skin and connective tissue diseases, Prospective cohort study, 0303 health sciences, Systemic lupus erythematosus, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Middle Aged, 3. Good health, Vaccination, medicine.anatomical_structure, Antirheumatic Agents, Female, medicine.drug, Adult, T cell, Immunology, Naive B cell, Systemic Lupus Erythematosus, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Immune system, Rheumatology, Antigen, medicine, Humans, Adverse effect, BNT162 Vaccine, 030304 developmental biology, 030203 arthritis & rheumatology, Lupus erythematosus, SARS-CoV-2, business.industry, COVID-19, Mycophenolic Acid, systemic, medicine.disease, vaccination, Immunity, Humoral, Methotrexate, business, lupus erythematosus, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: ObjectivesOur aims were to evaluate Systemic Lupus Erythematosus (SLE) disease activity and SARS-CoV-2 specific immune responses after BNT162b2 vaccination.MethodsIn this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine, until day 15 after the second dose in 126 SLE patients. SARS-CoV-2 antibody responses were measured against wild-type spike antigen while serum-neutralizing activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T-cell responses were quantified by Interferon (IFN)-γ release assay after the second dose.ResultsBNT162b2 was well tolerated and no statistically significant variations of BILAG and SLEDAI scores were observed throughout the study in SLE patients with active and inactive disease at baseline. Mycophenolate Mofetil (MMF) and Methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody-response (β=-78; p=0.007, β=-122; pConclusionMMF, MTX and poor baseline humoral immune status, particularly: low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating SLE patients who might need adapted vaccine regimens and follow-up.KEY MESSAGESWhat is already known about this subject?BNT162b2 efficacy and safety has been described in studies mixing different RMDsWhat does this study add?No serious adverse effects, nor SLE flares have been documented after BNT162b2 in SLE patients.Not only MMF and MTX, but also a poor humoral immune status at baseline impair vaccine antibody responseAlbeit decreased, serum neutralizing activity against VOCs is conferred to vaccine-responders.How might this impact on clinical practice or future developments?These parameters could be helpful for physicians to delineate which patients should have antibody measurement after full BNT162b2 vaccination and should be proposed a third injection of BNT162b2 vaccine.
Published: 2021

21. Immune Thrombocytopenia Revealing Enriched IgG-4 Peri-Renal Rosai-Dorfman Disease Successfully Treated with Rituximab: A Case Report and Literature Review

Author: Sylvain Audia, Sébastien Humbert, Jean Fontan, Fleur Cohen-Aubart, Jean-François Emile, Philippe Maksud, Jerome Razanamahery, Julien Haroche, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de pathologie [CHU Ambroise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service de médecine nucléaire [CHU Pitié-Salpétrière], and Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière]
Subjects: Medicine (General), [SDV]Life Sciences [q-bio], Case Report, 03 medical and health sciences, 0302 clinical medicine, R5-920, rituximab, immune system diseases, hemic and lymphatic diseases, Biopsy, medicine, Platelet, Rosai–Dorfman disease, Histiocyte, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Pathophysiology, 3. Good health, Histiocytosis, Rosai Dorfman disease, immune thrombocytopenia, 030220 oncology & carcinogenesis, Erdheim Chester disease, Immunology, Erdheim–Chester disease, Medicine, Rituximab, business, histiocytosis, 030215 immunology, medicine.drug
Abstract: Immune thrombocytopenia (ITP) is a rare autoimmune-mediated condition characterized by isolated thrombocytopenia (MAP2K1mutation, although peri-renal infiltration is highly suggestive of Erdheim-Chester disease. This overlapping association was described in men with mutation inMAP2K1gene. Macrophages are implicated in the pathophysiology of ITP in multiple ways, notably by the phagocytosis of opsonized platelets and their function of antigen-presenting cells able to stimulate autoreactive T cells. Histiocytic cells derivate from monocyte-macrophage lineage. Activation of macrophages in active histiocytosis is responsible for consequential platelet destruction in ITP associated histiocytosis. Finally, this case highlights a rare presentation of ITP revealing histiocytosis, both being efficiently treated with rituximab.
Published: 2021

22. A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis

Author: Ludivine Grzelak, Maxime Beretta, Slimane Allali, Aude Magérus, Hugo Mouquet, Maxime Batignes, Isabelle Melki, Olivier Schwartz, Quentin Riller, Mehdi Oualha, Nicolas Cagnard, Christine Bole-Feysot, Camille de Cevins, James P. Di Santo, Christele Gras Leguen, Florence Moulin, Jean-Laurent Casanova, Cécile Masson, Aurélien Corneau, Damien Bonnet, Vithura Pirabarakan, Mickaël M. Ménager, Camille Bruneau, Brieuc P. Perot, Francesco Carbone, Darragh Duffy, Mohammed Zarhrate, Marie-Claude Stolzenberg, Alexandre Boullé, Mélanie Parisot, Boris Sorin, Ghaith Abdessalem, Alain Fischer, Marianne Leruez, Julie Toubiana, Victor Garcia-Paredes, Mathie Lorrot, Loïc de Pontual, Zahra Belhadjer, Bruno Charbit, Tinhinane Fali, Marine Luka, Nikaïa Smith, Brigitte Bader Meunier, Shen-Ying Zhang, Sonia Meynier, Fredéric Rieux Laucat, Julien Haroche, Pedro Gonçalves, Laura Barnabei, Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sanofi Aventis R&D [Chilly-Mazarin], Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Rockefeller University [New York], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [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), AP-HP Hôpital universitaire Robert-Debré [Paris], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département des urgences pédiatriques [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), Laboratoire de Virologie [CHU Necker], Département de Pédiatrie et maladies infectieuses [CHU Necker], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie [Jean Verdier], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Collège de France (CdF (institution)), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, The study was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), by the 'URGENCE COVID-19' fundraising campaign of Institut Pasteur, by the Atip-Avenir, Emergence ville de Paris program and fond de dotation Janssen Horizon and by government grants managed by the Agence National de la Recherche as part of the 'Investment for the Future' program (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01, Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010, Laboratoire d’Excellence ‘‘Milieu Intérieur', grant ANR-10-LABX-69-01), the Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to FRL and 'CoVarImm' to DD and JDS), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). The LabTech Single Cell@Imagine is supported by the Paris Region and the 'Investissements d’avenir' program through the 2019 ATF funding – Sésame Filières PIA (Grant N°3877871). CdC is the recipient of a CIFRE-PhD (Sanofi). L.B. was a recipient of an Imagine institute PhD international program supported by the Fondation Bettencourt Schueller. L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the Future' program. S.M. was a recipient of an INSERM and Institut Imagine post-doctorat program supported by the Fondation pour la Recherche Médicale (FRM N°SPF20170938825). NS was a recipient of the Pasteur-Roux-Cantarini Fellowship. VGP obtained an Imagine international PhD fellowship program supported by the Fondation Bettencourt Schueller. BPP is the recipient of an ANRS post-doctoral fellowship., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0303 health sciences, Chemokine, Myocarditis, biology, business.industry, Monocyte, Dendritic cell, Gene signature, medicine.disease_cause, medicine.disease, Pathophysiology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, biology.protein, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, business, Oxidative stress, 030304 developmental biology
Abstract: SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κB activity, TNF-α signaling, associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.
Published: 2021

23. Systemic erdheim-chester disease associated with braf-positive papillary thyroid carcinoma

Author: Gabrielle Deniziaut, Natalie Chereau, Andreea Banica, Iuliana Ilie, Bogdan Bercu, Luciana Oprea, Emile Jean Francois, Madalina Musat, Julien Haroche, Teodor Constantin, and Camille Buffet
Subjects: Thyroid carcinoma, Pathology, medicine.medical_specialty, business.industry, Erdheim–Chester disease, Medicine, business, medicine.disease
Published: 2021

24. Peritoneal or mesenteric tumours revealing histiocytosis

Author: Janick Selves, Sébastien Humbert, Peggy Dartigues, Manuela Delage-Corre, Chrystalla Prokopiou, Liana Veresezan, Jean Donadieu, Séverine Valmary-Degano, Patrick Tas, Olivier Lucidarme, Frédéric Charlotte, Andreas Seeber, Alexandre Malakhia, Julien Haroche, Zofia Hélias-Rodzewicz, Jerome Razanamahery, Fleur Cohen-Aubart, Merja Kunnamo, Abdellatif Tazi, Irena Ungureanu, Dominique Cazals-Hatem, Jean-François Emile, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Ambroise Paré [AP-HP], Emergency Hospital Floreasca Bucharest, Emergency Hospital Floreasca Bucharest, 8 Calea Floresca, Sector 1, 014461 Bucharest, Romania, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Gustave Roussy (IGR), Pathologie morphologique, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), CHU Limoges, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Limassol General Hospital, Innsbruck Medical University [Austria] (IMU), Hopital Saint-Louis [AP-HP] (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie [CHU Pitié-Salpétrière], Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Proto-Oncogene Proteins B-raf, Abdominal pain, Pathology, medicine.medical_specialty, Delayed Diagnosis, [SDV]Life Sciences [q-bio], RC799-869, Liposarcoma, Sclerosing mesenteritis, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Medicine, molecular biology, Humans, Mesentery, Histiocyte, Cancer, Retrospective Studies, business.industry, CD68, Gastroenterology, abdominal pain, Diseases of the digestive system. Gastroenterology, medicine.disease, 3. Good health, Histiocytosis, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Histiocytoses, 030211 gastroenterology & hepatology, medicine.symptom, business
Abstract: ObjectivePeritoneal or mesenteric tumours may correspond to several tumour types or tumour-like conditions, some of them being represented by histiocytosis. This rare condition often poses diagnostic difficulties that can lead to important time delay in targeted therapies. Our aim was to describe main features of histiocytoses with mesenteric localisation that can improve the diagnostic process.DesignWe performed a retrospective study on 22 patients, whose peritoneal/mesenteric biopsies were infiltrated by histiocytes.ResultsAbdominal pain was the revealing symptom in 10 cases, and 19 patients underwent surgical biopsies. The diagnosis of histiocytosis was proposed by initial pathologists in 41% of patients. The other initial diagnoses were inflammation (n=7), sclerosing mesenteritis (n=4) and liposarcoma (n=1). The CD163/CD68+CD1a- histiocytes infiltrated subserosa and/or deeper adipose tissues in 16 and 14 cases, respectively. A BRAFV600E mutation was detected within the biopsies in 11 cases, and two others were MAP2K1 mutated. The final diagnosis was histiocytosis in 18 patients, 15 of whom had Erdheim-Chester disease. The median diagnostic delay of histiocytosis was 9 months. Patients treated with BRAF or MEK inhibitors showed a partial response or a stable disease. One patient died soon after surgery, and five died by the progression of the disease.ConclusionDiagnosis of masses arising in the mesentery should be carefully explored as one of the possibilities in histiocytosis. This diagnosis is frequently missed on mesenteric biopsies. Molecular biology for detecting the mutations in BRAF or in genes of the MAP kinase pathway is a critical diagnostic tool.
Published: 2021

25. Profound systemic alteration of the immune phenotype and an immunoglobulin switch in Erdheim-Chester disease in 78 patients from a single center

Author: Lucie Poupel, Jean-François Emile, Fleur Cohen Aubart, Maryse Guerin, Julien Haroche, Frédéric Charlotte, Philippe Lesnik, Flora Saint-Charles, Eric Frisdal, Damien Roos-Weil, Wilfried Le Goff, Zahir Amoura, and Youssef Arsafi
Subjects: Proto-Oncogene Proteins B-raf, Erdheim-Chester Disease, Myeloid, genetic structures, medicine.medical_treatment, Immunoglobulin G, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Humans, Histiocyte, biology, business.industry, Hematology, medicine.disease, 3. Good health, Histiocytosis, Cytokine, medicine.anatomical_structure, Phenotype, Vemurafenib, 030220 oncology & carcinogenesis, Immunology, biology.protein, Cytokines, Antibody, business, 030215 immunology
Abstract: Erdheim-Chester disease (ECD) is a rare, systemic, non-Langerhans cell histiocytosis neoplasm, which is characterized by the infiltration of CD63+ CD1a- histiocytes in multiple tissues. The BRAFV600E mutation is frequently present in individuals with ECD and has been detected in hematopoietic stem cells and immune cells from the myeloid and systemic compartments. Immune cells and pro-inflammatory cytokines are present in lesions, suggesting that ECD involves immune cell recruitment. Although a systemic cytokine T-helper-1-oriented signature has been reported in ECD, the immune cell network orchestrating the immune response in ECD has yet to be described. To address this issue, the phenotypes of circulating leukocytes were investigated in a large, single-center cohort of 78 patients with ECD and compared with those of a group of 21 control individuals. Major perturbations in the abundance of systemic immune cells were detected in patients with ECD, with decreases in circulating plasmacytoid, myeloid 1, and myeloid 2 dendritic cells, mostly in BRAFV600E carriers, in comparison with individuals in the control group. Similarly, marked decreases in blood Thelper, cytotoxic, and B-lymphocyte numbers were observed in patients with ECD, relative to the control group. Measurement of circulating immunoglobulin concentrations revealed an immunoglobulin G switch, from IgG1 to IgG4 subclasses, which are more frequently associated with the BRAF mutation. First-line therapies, including pegylated interferon-a and vemurafenib, were able to correct most of these alterations. This study reveals a profound disturbance in the systemic immune phenotype in patients with ECD, providing important new information, helping to understand the physiopathological mechanisms involved in this rare disease and improving the therapeutic management of patients.
Published: 2021

26. Immune Reconstitution Syndrome After Nivolumab for Progressive Multifocal Leukoencephalopathy

Author: Fleur Cohen Aubart, Matthieu Peyre, Zahir Amoura, Neila Benameur, Karima Mokhtari, Julien Haroche, A. Idbaih, and Danielle Seilhean
Subjects: Pathology, medicine.medical_specialty, Immune system, business.industry, Progressive multifocal leukoencephalopathy, medicine, Case, Neurology (clinical), biochemical phenomena, metabolism, and nutrition, Nivolumab, medicine.disease, business
Abstract: Consider immune reconstitution syndrome in case of neurologic worsening during nivolumab treatment given for progressive multifocal leukoencephalopathy.
Published: 2020

27. The eclipse sign as a radiological presentation of neurosarcoidosis

Author: Marc Pineton de Chambrun, Fleur Cohen Aubart, Damien Galanaud, Julien Haroche, and Zahir Amoura
Subjects: 0301 basic medicine, medicine.medical_specialty, business.industry, General Neuroscience, Neurosarcoidosis, General Medicine, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Radiological weapon, Granuloma, Medicine, Radiology, Presentation (obstetrics), business, 030217 neurology & neurosurgery, Sign (mathematics), Eclipse
Abstract: Neurosarcoidosis is a rare inflammatory neurological condition. We describe a challenging radiological presentation of neurosarcoidosis. The eclipse sign refers to hypo T1-weighted parenchymal or leptomeningeal images surrounded by circular gadolinium enhancement. The eclipse sign was identified in 3 out of 46 patients with histologically-proven neurosarcoidosis. The eclipse sign may correspond to necrotizing parenchymal or leptomeningeal granuloma. This sign expands the spectrum of radiological presentations of neurosarcoidosis.
Published: 2019

28. Characterization of Interstitial Lung Disease Associated With Anti-Ribonucleoprotein Antibodies

Author: Alexis Mathian, Julien Haroche, Philippe Grenier, Micheline Pha, Makoto Miyara, Zahir Amoura, Raphael Lhote, Fleur Cohen Aubart, and Samia Boussouar
Subjects: Pathology, medicine.medical_specialty, Arthritis, 03 medical and health sciences, 0302 clinical medicine, Mixed connective tissue disease, Rheumatology, Fibrosis, Sicca syndrome, medicine, Humans, Lymphoid interstitial pneumonia, 030212 general & internal medicine, Myositis, Mixed Connective Tissue Disease, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, Interstitial lung disease, respiratory system, medicine.disease, respiratory tract diseases, Antibodies, Antinuclear, Crackles, medicine.symptom, Lung Diseases, Interstitial, Tomography, X-Ray Computed, business
Abstract: Objectives Interstitial lung disease (ILD) is a common feature of mixed connective tissue disease. However, many patients do not meet the criteria for mixed connective tissue disease and thus may be diagnosed as interstitial pneumonia with autoimmune features. The aim of this study was to characterize ILD associated with anti-ribonucleoprotein (RNP) antibodies. Methods Chest computed tomography scans of patients with anti-RNP antibody who were seen between January 2011 and October 2015 were reviewed. The underlying disease was classified with international criteria using clinical and serological features. Results Among 544 patients with anti-RNP antibodies, 188 had a chest computed tomography scan, and 48 (26%) of them had radiological features of ILD. The presence of ILD was significantly associated with dyspnea, crackles, arthritis, Raynaud phenomenon, myositis, and sicca syndrome. The most frequent pattern was nonspecific interstitial pneumonia in 39 patients (81%). Among patients with ILD, 17 (35%) had a radiological pattern consisting of cysts and ground-glass attenuation not fulfilling the lymphoid interstitial pneumonia criteria. In 3 patients, cysts were related to fibrosis; in 14 patients, cysts corresponded to an original ILD pattern. Conclusions Interstitial lung disease was found in 26% of patients with anti-RNP antibodies independently of the underlying disease. Anti-RNP-associated ILD mainly corresponds to nonspecific interstitial pneumonia or an original pattern consisting of cysts and ground-glass attenuation.
Published: 2019

29. Safety and effectiveness of transjugular renal biopsy for systemic lupus erythematosus and antiphospholipid antibody syndrome patients taking antithrombotics

Author: Micheline Pha, Zahir Amoura, Marc Pineton de Chambrun, Philippe Rouvier, Pierre Hausfater, Du Boutin-Le Thi Huong, Neila Benameur, Philippe Cluzel, Makoto Miyara, Maud Cazenave, Julien Haroche, Fleur Cohen-Aubart, Hubert Nielly, Isabelle Brocheriou, Alexis Mathian, Hassan Izzedine, and Miguel Hie
Subjects: Adult, Male, medicine.medical_specialty, Biopsy, medicine.medical_treatment, 030232 urology & nephrology, Lupus nephritis, Gastroenterology, Nephropathy, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Fibrinolytic Agents, Antiphospholipid syndrome, Internal medicine, medicine, Humans, Lupus Erythematosus, Systemic, Retrospective Studies, 030203 arthritis & rheumatology, Transplantation, medicine.diagnostic_test, business.industry, Antiphospholipid Syndrome, Prognosis, medicine.disease, Lupus Nephritis, Nephrectomy, Nephrology, Female, Renal biopsy, Jugular Veins, Complication, business, Fibrinolytic agent
Abstract: BackgroundRenal biopsy is the cornerstone of systemic lupus erythematosus (SLE) nephritis and antiphospholipid syndrome (APS) nephropathy management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed for those diseases. Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. The primary objective of the study was to describe the safety profile and diagnostic performance of TJRB in SLE and APS patients.MethodsAll SLE and/or APS patients who underwent a renal biopsy in our department (between January 2004 and October 2016) were retrospectively reviewed. Major complications were death, haemostasis nephrectomy, renal artery embolization, red blood cell transfusion, sepsis and vascular thrombosis; macroscopic haematuria, symptomatic perirenal/retroperitoneal bleeding and renal arteriovenous fistula without artery embolization were considered as minor complications.ResultsTwo hundred and fifty-six TJRBs—119 without antithrombotics (untreated), 69 under aspirin and 68 on anticoagulants and 54 TCRBs without antithrombotics—were analysed. Their major and minor complication rates, respectively, did not differ significantly for the four groups: 0 and 8% for untreated TJRBs, 1 and 6% for aspirin-treated, 6 and 10% for anticoagulant-treated and 2 and 2% for TCRBs. The number of glomeruli sampled and the biopsy contribution to establishing a histological diagnosis was similar for the four groups.ConclusionsTJRBs obtained from SLE and APS patients taking antithrombotics had diagnostic yields and safety profiles similar to those of untreated TCRBs. Thus, TJRB should be considered for SLE and APS patients at risk of bleeding.
Published: 2019

30. Erdheim-Chester disease with concomitant Rosai-Dorfman like lesions: a distinct entity mainly driven by MAP2K1

Author: Ronald S. Go, Neval Ozkaya, Ahmet Dogan, Fleur Cohen-Aubart, Omar Abdel-Wahab, Eli L. Diamond, Jean-François Emile, Giota Lourida, Jerome Razanamahery, Zahir Amoura, Gaurav Goyal, Julien Haroche, Zofia Hélias-Rodzewicz, Frédéric Charlotte, Benjamin H. Durham, and Karl-Heinz Plate
Subjects: Adult, Aged, 80 and over, Male, Erdheim-Chester Disease, medicine.medical_specialty, Extramural, business.industry, MAP Kinase Kinase 1, Hematology, Middle Aged, medicine.disease, Dermatology, Diagnosis, Differential, Concomitant, MAP2K1, Erdheim–Chester disease, medicine, Humans, Female, Online Only Articles, business, Aged
Published: 2019

31. Monitoring Disease Activity in Systemic Lupus Erythematosus With Single‐Molecule Array Digital Enzyme‐Linked Immunosorbent Assay Quantification of Serum Interferon‐α

Author: Alexis Mathian, Flore Rozenberg, Julien Haroche, Micheline Pha, Karim Dorgham, Laura Garrido Castillo, Fleur Cohen-Aubart, S. Mouries-Martin, Miguel Hie, Laura Barnabei, Delphine Sterlin, Frédéric Rieux-Laucat, Zahir Amoura, Guy Gorochov, Hervé Devilliers, Du Le Thi Huong, Makoto Miyara, Marc Pineton de Chambrun, and Elyes Ben Salah
Subjects: Adult, Male, 0301 basic medicine, Immunology, Alpha interferon, Enzyme-Linked Immunosorbent Assay, Severity of Illness Index, Disease activity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Interferon, Humans, Lupus Erythematosus, Systemic, Immunology and Allergy, Bioassay, Medicine, skin and connective tissue diseases, 030203 arthritis & rheumatology, chemistry.chemical_classification, Receiver operating characteristic, business.industry, Interferon-alpha, Biological activity, Middle Aged, Symptom Flare Up, Single Molecule Imaging, 3. Good health, Cross-Sectional Studies, 030104 developmental biology, Enzyme, chemistry, Biomarker (medicine), Female, business, medicine.drug
Abstract: No simple or standardized assay is available to quantify interferon-α (IFNα) in routine clinical practice. Single-molecule array (Simoa) digital enzyme-linked immunosorbent assay (ELISA) technology enables direct IFNα quantification at attomolar (femtogram per milliliter [fg/ml]) concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity.IFNα concentrations in serum samples from 150 consecutive SLE patients in a cross-sectional study were determined with digital ELISA and a functional biologic activity assay (bioassay). According to their Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) flare composite scores, patients were divided into groups with inactive SLE (SLEDAI score of4 or clinical SLEDAI score of 0) or active SLE (SLEDAI score of ≥4 or clinical SLEDAI score of0), and into groups with no flare or mild/moderate flare or severe flare.Based on serum samples from healthy blood donors, the abnormal serum IFNα level threshold value was 136 fg/ml. Next, using receiver operating characteristic curves for an SLE patient series that was widely heterogeneous in terms of disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/ml. The digital ELISA-assessed serum IFNα level was a better biomarker of disease activity than the Farr assay because its specificity, likelihood ratio for positive results, and positive predictive value better discerned active SLE or flare from inactive disease. The digital ELISA was more sensitive than the bioassay for detecting low-abnormal serum IFNα concentrations and identifying patients with low disease activity.Direct serum IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFNα treatment.
Published: 2019

32. Autoimmunity associated with Erdheim-Chester disease improves with BRAF/MEK inhibitors

Author: Makoto Miyara, Jean Donadieu, Fleur Cohen-Aubart, Paul Breillat, Jean-François Emile, Frédéric Charlotte, Zahir Amoura, Anaïs Roeser, and Julien Haroche
Subjects: Adult, Male, Proto-Oncogene Proteins B-raf, Oncology, Erdheim-Chester Disease, medicine.medical_specialty, MAP Kinase Signaling System, Treatment outcome, MEDLINE, Autoimmunity, medicine.disease_cause, Autoimmune Diseases, Internal medicine, Humans, Medicine, Online Only Articles, Protein Kinase Inhibitors, Aged, Autoantibodies, business.industry, Hematology, Middle Aged, medicine.disease, Treatment Outcome, Erdheim–Chester disease, Female, business
Published: 2019

33. Infliximab biosimilar for treating neurosarcoidosis: tolerance and efficacy in a retrospective study including switch from the originator and initiation of treatment

Author: Julien Haroche, Fleur Cohen Aubart, Patrick Tilleul, Neila Benameur, Makoto Miyara, Camille Cotteret, Miguel Hie, Quentin Riller, Helga Junot, Alexis Mathian, Zahir Amoura, Sorbonne Université (SU), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, musculoskeletal diseases, medicine.medical_specialty, Sarcoidosis, [SDV]Life Sciences [q-bio], Azathioprine, Neurosarcoidosis, Statistics, Nonparametric, 03 medical and health sciences, 0302 clinical medicine, Central Nervous System Diseases, Internal medicine, Humans, Medicine, 030212 general & internal medicine, skin and connective tissue diseases, Adverse effect, Biosimilar Pharmaceuticals, Retrospective Studies, Biosimilars, Drug Substitution, business.industry, Retrospective cohort study, Biosimilar, Middle Aged, medicine.disease, Infliximab, 3. Good health, Methotrexate, Treatment Outcome, Neurology, Antirheumatic Agents, Concomitant, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies, medicine.drug
Abstract: International audience; OBJECTIVES:Infliximab is increasingly used to treat neurosarcoidosis. We aimed to determine the efficacy and tolerance of an infliximab biosimilar for treating neurosarcoidosis.METHODS:We conducted a retrospective single-center study to describe the efficacy, safety and immunogenicity of an infliximab biosimilar in neurosarcoidosis patients. We compared the survival time without relapse while receiving the biosimilar or previous originator-infliximab treatment.RESULTS:Twenty patients with histologically documented neurosarcoidosis were treated with an infliximab biosimilar (initiation of treatment in 12 and switch from the originator drug in 8) between February 2016 and August 2018. All patients presenting with neurological involvement of one or more areas, including meningeal (n = 15), cerebral (n = 10), spinal cord (n = 9), and/or cranial nerves (n = 5); epilepsy (n = 3); and/or intracranial hypertension (n = 3) were enrolled. Eighteen patients received glucocorticoids during infliximab treatment, and 16 had methotrexate or azathioprine concomitant treatment. The median duration of follow-up was 25 months (19-28). Six patients relapsed during biosimilar treatment. Relapse rates and time-to-relapse did not differ between the infliximab originator previously received and biosimilar treatment groups (p = 0.40 and 0.51, respectively). Nine patients experienced 11 adverse events with the infliximab biosimilar, including infections (n = 5), urticaria (n = 4), headache (n = 1), and diarrhea (n = 1). All side effects were grade 2 or less using the WHO classification.CONCLUSIONS:In this retrospective study, the infliximab biosimilar was efficacious and safe for treating neurosarcoidosis.
Published: 2019

34. IgG4-related disease and Rosai-Dorfman-Destombes disease – Authors' reply

Author: Julien Haroche, Fleur Cohen-Aubart, Jean-François Emile, and Augusto Vaglio
Subjects: medicine.medical_specialty, business.industry, Immunoglobulin G, medicine, Humans, IgG4-related disease, Immunoglobulin G4-Related Disease, General Medicine, Disease, Histiocytosis, Sinus, business, medicine.disease, Dermatology
Published: 2021

35. A causality algorithm to guide diagnosis and treatment of catatonia due to autoimmune conditions in children and adolescents

Author: Elise Riquin, Federica Zibordi, Zahir Amoura, Priscille Gerardin, Bertrand Olliac, Marie Raffin, Nicolas Bodeau, Nardo Nardocci, Tiziana Granata, Xavier Benarous, Vladimir Ferrafiat, Elena Freri, Angèle Consoli, Julien Haroche, Sylvie Viaux, Jean Xavier, and David Cohen
Subjects: Male, medicine.medical_specialty, Adolescent, Catatonia, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Child and adolescent psychiatry, medicine, Humans, Prospective Studies, Child, Biological Psychiatry, Retrospective Studies, Immunosuppressive treatment, Receiver operating characteristic, business.industry, medicine.disease, Causality, 030227 psychiatry, Psychiatry and Mental health, Specific antibody, ROC Curve, Female, Autoimmune condition, business, Stepwise approach, Algorithm, Algorithms, 030217 neurology & neurosurgery
Abstract: Objectives Pediatric catatonia is a rare and life-threatening syndrome. Around 20% of juvenile catatonia is associated with organic condition (Consoli et al., 2012). Autoimmune conditions represent a diagnostic and therapeutic challenge since specific antibodies can be missed. To facilitate decision making, we recently formulated a causality assessment score (CAUS) using a stepwise approach and an immunosuppressive therapeutic challenge (Ferrafiat et al., 2016). Our objectives were to validate retrospectively CAUS and to define its threshold for an accurate distinction between organic catatonia and non-organic catatonia, and specifically between autoimmune catatonia and non-organic catatonia. Method To obtain a sufficient number of cases with organic catatonia, we pooled two samples ( N = 104) – one from a child psychiatry center, the other from neuro-pediatrics center – expert in catatonia and autoimmune conditions. Organic conditions were diagnosed using a multidisciplinary approach and numerous paraclinical investigations. Given the binary classification needs, we used receiver operating characteristic (ROC) analysis (Peacock and Peacock, 2010) to calculate the best classification threshold. Results The cohort included 67 cases of non-organic catatonia and 37 cases of organic catatonia. ROC analysis showed that the CAUS performance in discriminating both organic catatonia vs. non-organic catatonia, and autoimmune catatonia vs. non-organic catatonia was excellent (Area Under the Curve = 0.99). In both analyses, for a CAUS threshold ≥ 5, accuracy equaled to 0.96. Conclusion Regarding juvenile catatonia, the use of the CAUS score algorithm combining a therapeutic challenge and a threshold ≥ 5 may help to diagnose and treat autoimmune conditions even without formal identification of auto-antibodies.
Published: 2018

36. MRI features of intra-axial histiocytic brain mass lesions

Author: Jean Donadieu, Khê Hoang-Xuan, Damien Galanaud, Didier Dormont, Nafi Aygun, Aurélie Drier, Karima Mokhtari, Julien Haroche, Licia P. Luna, Nadine Martin-Duverneuil, Johns Hopkins University (JHU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [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)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Adolescent, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 030218 nuclear medicine & medical imaging, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Langerhans cell histiocytosis, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Effective diffusion coefficient, Radiology, Nuclear Medicine and imaging, Child, Histiocyte, Aged, Retrospective Studies, Brain Diseases, business.industry, Brain Mass, Brain, [INFO.INFO-CV]Computer Science [cs]/Computer Vision and Pattern Recognition [cs.CV], General Medicine, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Signal on, Histiocytosis, Homogeneous, Child, Preschool, 030220 oncology & carcinogenesis, [INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV], Brain lesions, Female, business, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing
Abstract: AIM To describe MRI features, including diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS), and perfusion-weighted imaging (PWI), of intra-axial tumour-like presentations of four different subtypes of histiocytosis. MATERIAL AND METHODS The brain MRI findings of 23 patients with histologically proven histiocytosis were reviewed retrospectively (11 Langerhans cell histiocytosis [LCH], eight Erdheim–Chester disease [ECD], one overlap form LCH/ECD, two Rosai–Dorfman disease [RDD], and one haemophagocytic lymphohistiocytosis [HLH]) with single or multiple enhancing intraparenchymal brain lesions. RESULTS Histiocytic brain mass lesions show some similar MRI features including Supra and/or infratentorial and/or paraventricular subcortical well-delineated masses, linear ependymal enhancement along the ventricles and brain stem lesions. Masses always present with mixed hyper- and hypointense signal on T2-weighted imaging (WI). Their enhancement is often homogeneous. Apparent diffusion coefficient (ADC) values are often normal or elevated. CONCLUSION The presence of multiple periventricular and subcortical enhancing lesions with mixed signal intensity on T2WI and normal or high ADC values should lead radiologists to consider the diagnosis of histiocytic lesions and search for associated systemic lesions.
Published: 2021

37. Psychiatric autoimmune conditions in children and adolescents: Is catatonia a severity marker?

Author: Tiziana Granata, Angèle Consoli, Elise Riquin, Nardo Nardocci, Renaud Jardri, Huges Pellerin, Xavier Benarous, David Cohen, Claire Corfiotti, Priscille Gerardin, Vladimir Ferrafiat, Zahir Amoura, Philippe Duverger, Elena Freri, François Medjkane, Julien Haroche, Marie Raffin, Alessandra Tozzo, Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Psychiatrie de l’Enfant et de l’Adolescent [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Université d'Angers (UA), Institut E3M [CHU Pitié-Salpêtrière], Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Abord dimensionnel des épisodes phychotiques de l'enfant et de l'adolescent : implications génétiques, métaboliques et auto-immunes (PSYDEV), Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Psychosis, medicine.medical_specialty, Adolescent, Catatonia, [SDV]Life Sciences [q-bio], Hashimoto Disease, Severity of Illness Index, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Acute onset, medicine, Humans, Child, Psychiatry, Biological Psychiatry, Retrospective Studies, Pharmacology, Immunosuppressive treatment, Autoimmune encephalitis, High prevalence, business.industry, Mental Disorders, medicine.disease, 3. Good health, 030227 psychiatry, Encephalitis, Female, Autoimmune condition, business
Abstract: Patients with autoimmune encephalitis (AE) are likely to exhibit an acute onset of severe psychiatric features, including psychosis and/or catatonia. Based on the high prevalence of catatonia in AE and our clinical experience, we hypothesized that catatonia might be a marker of severity requiring more aggressive treatment approaches.To reach a sufficient number of cases with brain-autoimmune conditions, we pooled two samples (N = 58): the first from the French National Network of Rare Psychiatric diseases and the second from the largest Italian neuro-pediatrics center for encephalopathies. Autoimmune conditions were diagnosed using a multidisciplinary approach and numerous paraclinical investigations. We retrospectively compared patients with and without catatonia for psychiatric and non-psychiatric clinical features, biological and imaging assessments, type of immunotherapy used and outcomes.The sample included 25 patients (43%) with catatonia and 33 (57%) without catatonia. Forty-two patients (72.4%) had a definite AE (including 27 anti-NMDA receptor encephalitis) and 16 (27.6%) suspected autoimmune encephalitis. Patients with catatonia showed significantly more psychotic features [18 (72%) vs 9 (27.3%), p 0.001)] and more movement disorders [25 (100%) vs 20 (60.6%), p 0.001] than patients without catatonia. First line (corticoids, immunoglobulin and plasma exchanges) and second line (e.g., rituximab) therapies were more effective in patients with catatonia, with 24 (96%) vs 22 (66.7%) (p = 0.006) and 17 (68%) vs 9 (27.3%) (p = 0.002), respectively. However, those with catatonia received more combinations of first and second line treatments and had more relapses during outcomes.Despite its exploratory design, the study supports the idea that autoimmune catatonia may be a marker of severity and morbidity in terms of initial presentation and relapses, requiring the need for early and aggressive treatment.
Published: 2021

38. A Monocyte/Dendritic Cell Molecular Signature of SARS-CoV-2 Related Multisystem Inflammatory Syndrome in Children (MIS-C) with Severe Myocarditis

Author: Camille de Cevins, Marine Luka, Nikaia Smith, Sonia Meynier, Aude Magérus, Francesco Carbone, Victor Garcia-Paredes, Laura Barnabei, Maxime Batignes, Alexandre Boullé, Marie-Claude Stolzenberg, Brieuc P. Pérot, Bruno Charbit, Tinhinane Fali, Vithura Pirabarakan, Boris Sorin, Quentin Riller, Ghaith Abdessalem, Maxime Beretta, Ludivine Grzelak, Pedro Goncalves, James Di Santo, Hugo Mouquet, Olivier Schwartz, Mohammed Zarhrate, Mélanie Parisot, Christine Bole-Feysot, Cécile Masson, Nicolas Cagnard, Aurelien Corneau, Camille Bruneau, Shen-Ying Zhang, Jean-Laurent Casanova, Brigitte Bader Meunier, Julien Haroche, Isabelle Melki, Mathie Lorrot, Mehdi Oualha, Florence Moulin, Damien Bonnet, Zahra Belhadjer, Mariane Leruez, Slimane Allali, Christele Gras Leguen, Loic de Pontual, Pediatric-Biocovid Study Group, Alain Fischer, Darragh Duffy, Frederic Rieux-Laucat, Julie Toubiana, and Mickaël Mathieu Ménager
Subjects: Gynecology, medicine.medical_specialty, Myocarditis, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Monocyte, education, Ethics committee, medicine.disease, medicine.anatomical_structure, Medicine, VEGF signaling, business
Abstract: SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κ B activity, TNF-α signaling, associated with decreased gene expression of NF-κ B inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology. Funding: The study was supported by the Institut National de la Sante et de la Recherche Medicale (INSERM), by the “URGENCE COVID-19” fundraising campaign of Institut Pasteur, by the Atip-Avenir, Emergence ville de Paris program and fond de dotation Janssen Horizon and by government grants managed by the Agence National de la Recherche as part of the “Investment for the Future” program (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01, Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010, Laboratoire d’Excellence ‘‘Milieu Interieur”, grant ANR-10-LABX-69-01), the Centre de Reference Deficits Immunitaires Hereditaires (CEREDIH), the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL and “CoVarImm” to DD and JDS), and by the FASTFoundation (French Friends of Sheba Tel Hashomer Hospital). The LabTech Single-Cell@Imagine is supported by the Paris Region and the “Investissements d’avenir” program through the 2019 ATF funding – Sesame Filieres PIA (Grant N°3877871).CdC is the recipient of a CIFRE-PhD (Sanofi). L.B. was a recipient of an Imagine institute PhD international program supported by the Fondation Bettencourt Schueller. L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Universite de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its“Investments for the Future” program. S.M. was a recipient of an INSERM and Institut Imagine post-doctorat program supported by the Fondation pour la Recherche Medicale (FRMN°SPF20170938825). NS was a recipient of the Pasteur-Roux-Cantarini Fellowship. VGP obtained an Imagine international PhD fellowship program supported by the Fondation Bettencourt Schueller. BPP is the recipient of an ANRS post-doctoral fellowship. Conflict of Interest: DD, FRL, JT and MMM are listed as inventors on a patent application related to this technology (European Patent Application no. EP21305197, entitled “Methods of predicting multisystem inflammatory syndrome (MIS-C) with severe myocarditis in subjects suffering from a SARS-CoV-2 infection”). Ethical Approval: The study was approved by the Ethics Committee (Comite de Protection des Personnes Ouest IV, n° DC-2017-2987).
Published: 2021

39. Oncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease

Author: Mihai G. Netea, Riccardo Biavasco, Lorenzo Dagna, Simone Cenci, Travis Nemkov, Giulio Cavalli, Philippe Maksud, Claudio Doglioni, Gianfranco Distefano, Daniela Cesana, Charles A. Dinarello, Eleonora Cantoni, Anna Kajaste-Rudnitski, Corrado Campochiaro, Simone Cardaci, Daniela Gnani, Isak W. Tengesdal, Julien Haroche, Samuel Zambrano, Alessandro Tomelleri, Giacomo De Luca, Davide Stefanoni, Francesco Piras, Ivan Merelli, Angelo D'Alessandro, Maddalena Panigada, Davide Mazza, Rob J.W. Arts, Jorge Domínguez-Andrés, Alessia Loffreda, Laura Cassina, Raffaella Molteni, Eugenio Montini, Alessandra Boletta, Leo A. B. Joosten, Elisabetta Ferrero, Marina Ferrarini, Biavasco, Riccardo, Molteni, Raffaella, Stefanoni, Davide, Nemkov, Travi, Netea, Mihai G., Domínguez-Andrés, Jorge, Arts, Rob JW, Merelli, Ivan, Mazza, Davide, Zambrano, S, Panigada, Maddalena, Cantoni, Eleonora, Tengesdal, Isak, Maksud, Philippe, Piras, Francesco, De Luca, Giacomo, Cassina, Laura, Distefano, Gianfranco, Loffreda, Alessia, Gnani, Daniela, Doglioni, Claudio, Tomelleri, Alessandro, Campochiaro, Corrado, Joosten, Leo, Dinarello, Charles A, Kajaste-Rudnitski, Anna, Haroche, Julien, Cardaci, Simone, Cenci, Simone, Dagna, Lorenzo, Ferrarini, Marina, Ferrero, Elisabetta, Boletta, Alessandra, D'Alessandro, Angelo, Montini, Eugenio, and Cavalli, Giulio
Subjects: Proto-Oncogene Proteins B-raf, Erdheim-Chester Disease, Myeloid, medicine.medical_treatment, Immunology, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Inflammation, Biochemistry, Myeloid Neoplasm, Proinflammatory cytokine, Epigenesis, Genetic, Pathogenesis, medicine, Humans, Point Mutation, Protein kinase B, Cells, Cultured, business.industry, Monocyte, Macrophages, Immunity, Cell Biology, Hematology, Oncogenes, Cytokine, medicine.anatomical_structure, Cancer research, medicine.symptom, business
Abstract: Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production. Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined. In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production. Mechanistically, myeloid cells expressing BRAFV600E exhibit all molecular features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacologic inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.
Published: 2021

40. Acute Pancreatitis From Treatment With BRAF Inhibitors in Erdheim-Chester Disease: A Report From 2 Tertiary Referral Centers

Author: Ronald S. Go, Gordon Ruan, Zahir Amoura, Nicole Straetmans, Mithun Vinod Shah, Julien Haroche, Neila Benameur, Fleur Cohen-Aubart, and Gaurav Goyal
Subjects: Adult, Male, Proto-Oncogene Proteins B-raf, Pediatrics, medicine.medical_specialty, Erdheim-Chester Disease, Paris, Referral, Endocrinology, Diabetes and Metabolism, Minnesota, MEDLINE, Tertiary Care Centers, Endocrinology, Oximes, Internal Medicine, Medicine, Humans, Protein Kinase Inhibitors, Aged, Retrospective Studies, Hepatology, business.industry, Imidazoles, Off-Label Use, Middle Aged, medicine.disease, Treatment Outcome, Pancreatitis, Vemurafenib, Erdheim–Chester disease, Mutation, Acute pancreatitis, Female, business
Published: 2020

41. Correspondence on 'Glucocorticoid-induced relapse of COVID-19 in a patient with sarcoidosis'

Author: Julien Haroche, Grégory Pugnet, Isabella Annesi-Maesano, Nathalie Freymond, Robin Dhote, Fleur Cohen-Aubart, Hilario Nunes, Nathalie Saindenberg, Aurélien Justet, Nicolas Belhomme, Yurdagul Uzunhan, Abdellatif Tazi, P. Gazengel, Alexis Mathian, Florence Jeny, Raphael Lhote, Stéphane Jouneau, Baptiste Hervier, Yacine Tandjaoui-Lambiotte, Emmanuel Bergot, Dominique Valeyre, Arsène Mekinian, Raphael Borie, Zahir Amoura, Gwenaël Lorillon, Jérôme Le Pavec, Miguel Hie, T. Chazal, and Dov Taieb
Subjects: medicine.medical_specialty, Sarcoidosis, medicine.medical_treatment, Immunology, General Biochemistry, Genetics and Molecular Biology, Pulmonary function testing, Rheumatology, Recurrence, Internal medicine, Diabetes mellitus, medicine, Immunology and Allergy, Humans, Respiratory system, Glucocorticoids, Lung, business.industry, Interstitial lung disease, COVID-19, Immunosuppression, medicine.disease, medicine.anatomical_structure, business, Glucocorticoid, medicine.drug
Abstract: Patients with interstitial lung disease have been considered at high risk of complications of COVID-19 because of their underlying lung disease and use of immunosuppressive agents.1 However, data on COVID-19 in patients with sarcoidosis are scarce.2–4 Several reasons for an increased risk of severe forms of COVID-19 among sarcoidosis patients have been hypothesised: the involvement of the lung in almost 90% of patients with COVID-19, some of whom have reduced pulmonary function and comorbidities such as diabetes or hypertension, which are largely associated with the use of glucocorticosteroids for treating sarcoidosis; and the use of immunosuppressive agents in a subset of these patients.5 Recently, Gyorfi et al 6 described the case of a patient with sarcoidosis who experienced a symptomatic SARS-CoV-2 infection with spontaneous clinical improvement, and a virological relapse after steroids treatment. This case illustrated the fact that immunosuppression with glucocorticoids may induce relapse of COVID-19 in patients with sarcoidosis. However, we lack data on the outcomes of patients with sarcoidosis affected by COVID-19. We retrospectively collected data for all patients with sarcoidosis and SARS-CoV-2 infection seen among 15 French centres between 1 March and 20 May 2020. The inclusion criteria were a sarcoidosis diagnosis based on the American Thoracic Society/European Respiratory Society/World Association for Sarcoidosis and other granulomatous diseases …
Published: 2020

42. Child–Adult Transition in Sarcoidosis: A Series of 52 Patients

Author: Simon Chauveau, Florence Jeny, Marie-Emeline Montagne, Rola Abou Taam, Véronique Houdouin, Ulrich Meinzer, Christophe Delacourt, Ralph Epaud, Fleur Cohen Aubart, Catherine Chapelon-Abric, Dominique Israël-Biet, Karine Juvin, Antoine Dossier, Bahram Bodaghi, Grégoire Prévot, Jean-Marc Naccache, Sarah Mattioni, Antoine Deschildre, Jacques Brouard, Abdellatif Tazi, Roderich Meckenstock, Morgane Didier, Julien Haroche, Annick Clement, Jean-François Bernaudin, Hilario Nunes, Dominique Valeyre, Nadia Nathan, and for the French Sarcoidosis Group (GSF)
Subjects: Pediatrics, medicine.medical_specialty, medicine.drug_class, Severe disease, lcsh:Medicine, Disease, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, children, transition of care, 0502 economics and business, medicine, sarcoidosis, Adverse effect, interstitial lung disease, Series (stratigraphy), Cumulative dose, business.industry, 05 social sciences, lcsh:R, Interstitial lung disease, General Medicine, medicine.disease, Corticosteroid, 050211 marketing, Sarcoidosis, business
Abstract: (1) Background: Pediatric sarcoidosis is a rare and mostly severe disease. Very few pediatric series with a prolonged follow-up are reported. We aimed to evaluate the evolution of pediatric sarcoidosis in adulthood. (2) Material and methods: Patients over 18-years-old with a pediatric-onset sarcoidosis (&le, 15-year-old) who completed at least a three-year follow-up in French expert centers were included. Clinical information at presentation and outcome in adulthood were studied. (3) Results: A total of 52 patients were included (34 prospectively in childhood and 18 retrospectively in adulthood), with a mean age of 12 (&plusmn, 2.7) at diagnosis. The median duration time of follow-up was 11.5 years (range 3&ndash, 44.5). Relapses mostly occurred during treatment decrease (84.5%), others within the three years after treatment interruption (9.1%), and rarely when the disease was stable for more than three years (6.4%). Sarcoidosis was severe in 11 (21.2%) in adulthood. Patients received a high corticosteroid cumulative dose (median 17,900 mg) for a median duration of five years (range 0&ndash, 32), resulting in mostly mild (18, 35.3%) and rarely severe (2, 3.8%) adverse events. (4) Conclusions: Pediatric-onset sarcoidosis needed a long-term treatment in almost half of the patients. Around one fifth of pediatric-onset sarcoidosis patients had severe sarcoidosis consequences in adulthood.
Published: 2020

43. Low rate of daily smokers in patients with symptomatic COVID-19

Author: Alain Combes, Said Lebbah, Capucine Morélot-Panzini, Valérie Martinez, Florence Tubach, Julie Pernet, Julien Haroche, Guy Gorochov, Thomas Similowski, Zahir Amoura, Eric Caumes, Pierre Hausfater, Elise Morawiec, and Makoto Miyara
Subjects: medicine.medical_specialty, education.field_of_study, Coronavirus disease 2019 (COVID-19), business.industry, Incidence (epidemiology), Population, Age and sex, University hospital, Internal medicine, medicine, In patient, Smoking status, Daily Smoker, education, business
Abstract: BackgroundIdentification of prognostic factors in COVID-19 remains a global challenge. The role of smoking is still controversial.ObjectiveTo evaluate the rate of daily smokers in patients with COVID-19.MethodsCOVID-19 in-and outpatients from a large French university hospital were systematically interviewed for their smoking status, use of e-cigarette and nicotinic substitutes. The rates of daily smokers in in-and outpatients were compared to those in the 2019 French general population, after standardization for sex and age.ResultsThe inpatient group was composed of 340 patients, median age 66 years: 203 men (59.7%) and 137 women (40.3%), median age for both 66 years, with a daily smokers rate of 4.1 % CI95% [2.3–6.9] (5.4% of men, 2.2% of women). The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6%, median age 43 years), and 77 women (55.4%, median age 44 years). The daily smoker rate was 6.1 % CI 95% [2.7 - 11.6] (5.1% of men, 6.8% of women). In the 2019 French population, the daily smoker rate was 24.0% (27.5% of men, 20.7% of women). Among inpatients, daily smokers represented 2.2% and 3.4% of the 45 dead patients and of the 29 patients transferred to ICU, respectively.The rate of daily smokers was significantly lower in COVID-19 patients, as compared to that in the French general population after standardization by age and sex, with Standardized Incidence Ratios of 0.24 [0.12-0.48] for outpatients and 0.24 [0.14-0.40] for inpatients.ConclusionDaily smokers rate in patients with symptomatic COVID-19 is lower as compared to the general population
Published: 2020
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44. Immune phenotyping of Erdheim-Chester disease through mass cytometry highlights decreased proportion of non-classical monocytes and increased proportion of Th17 cells

Author: Olivier Hermine, Aurélien Corneau, Jean-François Emile, Makoto Miyara, Fleur Cohen-Aubart, Thiago Trovati Maciel, Zahir Amoura, Brice Robin, Matthias Papo, Catherine Blanc, Julien Haroche, UPMC - Faculté de médecine Pitié Salpétrière, Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (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), 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 Pitié-Salpêtrière [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)-Institut E3M [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Erdheim-Chester Disease, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, genetic structures, medicine.medical_treatment, Immunology, Inflammation, medicine.disease_cause, Monocytes, General Biochemistry, Genetics and Molecular Biology, Immunophenotyping, Autoimmunity, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Immune system, Rheumatology, medicine, Humans, Immunology and Allergy, Histiocyte, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, Flow Cytometry, medicine.disease, 3. Good health, Histiocytosis, 030104 developmental biology, Cytokine, Erdheim–Chester disease, Th17 Cells, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Erdheim-Chester disease (ECD) is an histiocytosis of the L-group, characterised by multiorgan infiltration of histiocytes that often carry oncogenic mutations.1 In the past few years, several studies have progressively and carefully mapped ECD genome, and several mutations have been described, most of them activating the mitogen-activated protein kinases (MAPK) pathway.1 These discoveries led to new therapies targeting BRAF or MEK in patients with ECD.2 Despite these findings, ECD pathogenesis still remains undetermined. Patients with ECD present a systemic inflammatory disease, with not only macrophages but also several other immune cells infiltrating affected tissues. A few studies have tried to explore the immune phenotype of ECD, with cytokine dosage in plasma and/or immunohistochemistry analysis, suggesting a complex network of inflammatory cytokines and chemokines.3 In order to explore the inflammatory phenotype of ECD, we realised immune phenotyping of circulating immune cells of 13 patients with ECD (details on patients’ characteristics are available in online supplementary table 1) and …
Published: 2020

45. Low rate of daily active tobacco smoking in patients with symptomatic COVID-19

Author: Makoto Miyara, Elise Morawiec, Said Lebbah, Capucine Morélot-Panzini, Alain Combes, Pierre Hausfater, Valérie Pourcher, Julien Haroche, Guy Gorochov, Julie Pernet, Thomas Similowski, Zahir Amoura, Florence Tubach, and Eric Caumes
Subjects: medicine.medical_specialty, education.field_of_study, Coronavirus disease 2019 (COVID-19), business.industry, Cross-sectional study, Incidence (epidemiology), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, University hospital, Internal medicine, Epidemiology, medicine, In patient, business, education
Abstract: Importance: As the pandemic of COVID-19 is still under progression, identification of prognostic factors remains a global challenge. The role of smoking has been suggested among the disease risk factors, although it is highly controversial. Objective: To evaluate whether the rate of daily smokers in patients with COVID-19 was different to that in the French population. Participants: COVID-19-infected in- and outpatients in a large French university hospital between February 28, 2020 and March 30, 2020 for outpatients and from March 23, till April 9, 2020 for inpatients. Design: We systematically interviewed the patients on their smoking status, use of e-cigarette and nicotinic substitutes. The rate of daily smokers in inpatients and outpatients were compared to those in the 2018 French general population, after standardization for sex and age. Results: The inpatient group was composed of 340 patients, median age 66 years: 203 men (59.7%, median age 66 years) and 137 women (40.3%, median age 66 years),with a rate of daily smokers of 4.1% CI95% [2.3 – 6.9] (5.4% of men and 2.2% of women). The outpatient group was composed of 139 patients, median age 44 years: 62 men (44.6%, median age 43 years, and 77 women (55.4 %, median age 44 years). The daily smokers’ rate was 6.1 % CI95% [2.7 - 11.6] (5.1% of men and 6.8 % of women). In the French population, the daily smokers’ rate was 25.4% (28.2% of men and 22.9% of women). The rate of daily smokers was significantly lower in COVID-19 patients, as compared to that in the French general population after standardization by age and sex, with Standardized Incidence Ratios of 0.23 [0.11 - 0.45] for outpatients and 0.23 [0.14 - 0.39] for inpatients. These ratios did not significantly differ between the two groups (P=0.94). Conclusions and relevance: This cross sectional study in both COVID-19 out- and inpatients shows that daily smokers rate in patients with symptomatic COVID-19 is lower as compared to the general population.
Published: 2020

46. Clinical phenotypes of extrapulmonary sarcoidosis: an analysis of a French, multi-ethnic, multicentre cohort

Author: Fleur Cohen Aubart, Hilario Nunes, Nicolas Schleinitz, Matthieu Mahévas, Pierre Rufat, Dominique Valeyre, Karim Sacre, Isabella Annesi-Maesano, David Launay, Raphael Borie, François Lhote, Mohamed Hamidou, Julien Haroche, Philippe Bonniaud, Zahir Amoura, Raphael Lhote, Hervé Devilliers, Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital de la Timone [CHU - APHM] (TIMONE), Aix Marseille Université (AMU), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Sarcoidosis, Disease, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, White People, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Humans, Clinical significance, 030212 general & internal medicine, Lung, Retrospective Studies, Erythema nodosum, business.industry, Lupus pernio, medicine.disease, Phenotype, 030228 respiratory system, Cohort, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, business, Rare disease
Abstract: Sarcoidosis is a rare disease of unknown cause with wide heterogeneity in clinical features and outcomes. We aimed to explore sarcoidosis phenotypes and their clinical relevance with particular attention to extrapulmonary subgroups.The Epidemiology of Sarcoidosis (EpiSarc) study is a French retrospective multicentre study. Sarcoidosis patients were identified through national hospitalisation records using appropriate codes from 11 hospital centres between 2013 and 2016 according to a standardised protocol. Medical charts were reviewed. The phenotypes of sarcoidosis were defined using a hierarchical cluster analysis.A total of 1237 patients were included (562 men and 675 women). The mean age at sarcoidosis diagnosis was 43.5±13 years. Hierarchical cluster analysis identified five distinct phenotypes according to organ involvement and disease type and symptoms: 1) erythema nodosum, joint involvement and hilar lymph nodes (n=180); 2) eye, neurological, digestive and kidney involvement (n=137); 3) pulmonary involvement with fibrosis and heart involvement (n=630); 4) lupus pernio and a high percentage of severe involvement (n=41); and 5) hepatosplenic, peripheral lymph node and bone involvement (n=249). Phenotype 1 was associated with being European/Caucasian and female and with non-manual work, phenotype 2 with being European/Caucasian, and phenotypes 3 and 5 with being non-European/Caucasian. The labour worker proportion was significantly lower in phenotype 5 than in the other phenotypes.This multicentre study confirms the existence of distinct phenotypes of sarcoidosis, with a non-random distribution of organ involvement. These phenotypes differ according to sex, geographical origin and socioprofessional category.
Published: 2020

47. High frequency of clonal hematopoiesis in Erdheim-Chester disease

Author: Damien Roos-Weil, Alice Marceau-Renaut, Raphael Lhote, Véronique Della-Valle, Jean Donadieu, Jean-François Emile, Fleur Cohen Aubart, Florence Nguyen-Khac, Olivier A. Bernard, Julien Haroche, Zofia Hélias-Rodzewicz, Stéphanie Poulain, Nicolas Duployez, Zahir Amoura, Marine Armand, Karim Maloum, Omar Abdel-Wahab, and Frédéric Charlotte
Subjects: Adult, Male, Proto-Oncogene Proteins B-raf, Erdheim-Chester Disease, Myeloid, genetic structures, Immunology, CD34, Abnormal Karyotype, Biochemistry, Myeloid Neoplasm, Dioxygenases, Bone Marrow, Proto-Oncogene Proteins, Medicine, Neoplasm, Humans, Aged, business.industry, Age Factors, Cell Biology, Hematology, Exons, Middle Aged, medicine.disease, Neoplasm Proteins, DNA-Binding Proteins, Leukemia, Haematopoiesis, medicine.anatomical_structure, Cell Transformation, Neoplastic, Leukemia, Myeloid, Organ Specificity, Myelodysplastic Syndromes, Erdheim–Chester disease, Mutation, Cancer research, Disease Progression, Neoplastic Stem Cells, Female, Bone marrow, Clonal Hematopoiesis, business, Multiple Myeloma, Genes, Neoplasm
Abstract: Erdheim-Chester disease (ECD) is a clonal hematopoietic disorder characterized by the accumulation of foamy histiocytes within organs (in particular, frequent retroperitoneal involvement) and a high frequency of BRAFV600E mutations. Although ECD is not commonly recognized to have overt peripheral blood (PB) or bone marrow (BM) disease, we recently identified that ECD patients have a high frequency of a concomitant myeloid malignancy. We thus conducted a systematic clinical and molecular analysis of the BM from 120 ECD patients. Surprisingly, 42.5% of ECD patients (51 of 120) had clonal hematopoiesis whereas 15.8% of patients (19 of 120) developed an overt hematologic malignancy (nearly all of which were a myeloid neoplasm). The most frequently mutated genes in BM were TET2, ASXL1, DNMT3A, and NRAS. ECD patients with clonal hematopoiesis were more likely to be older (P < .0001), have retroperitoneal involvement (P = .02), and harbor a BRAFV600E mutation (P = .049) than those without clonal hematopoiesis. The presence of the TET2 mutation was associated with a BRAFV600E mutation in tissue ECD lesions (P = .0006) and TET2-mutant ECD patients were more likely to have vascular involvement than TET2 wild-type ECD patients. Clonal hematopoiesis mutations in ECD were detected in cells derived from CD34+CD38− BM progenitors and PB monocytes but less frequently present in PB B and T lymphocytes. These data identify a heretofore unrecognized high frequency of clonal hematopoiesis in ECD patients, reaffirm the development of additional high risk of myeloid neoplasms in ECD, and provide evidence of a BM-based precursor cell of origin for many patients with ECD.
Published: 2020

48. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): A multicentre cohort

Author: Marie Pouletty, Naim Ouldali, Fanny Bajolle, Guislaine Carcelain, Albert Faye, Isabelle Melki, Arielle Maroni, Constance Beyler, Zahir Amoura, Guillaume Morelle, Noémie Lachaume, Mehdi Oualha, Ulrich Meinzer, Juliette Chommeloux, Caroline Galeotti, Brigitte Bader-Meunier, Hanane Kouider, Samia Pichard, Corinne Pondarré, Philippe Bensaid, Julien Haroche, Irina Craiu, Isabelle Koné-Paut, Romain Basmaci, Marion Caseris, Anna Deho, Stéphane Bonacorsi, Charlotte Borocco, Hôpital Robert Debré Paris, Hôpital Robert Debré, Université Paris Cité (UPCité), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [Le Kremlin-Bicêtre] (CeRéMAIA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Service de Microbiologie [Hôpital Robert Debré - APHP], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de Référence associé Escherichia coli [Hôpital Robert Debré - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Louis Mourier - AP-HP [Colombes], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Victor Dupouy, Centre Hospitalier René Dubos [Pontoise], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Intercommunal de Créteil (CHIC), CHU Necker - Enfants Malades [AP-HP], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Faculté de Médecine [Université Paris Diderot - Paris 7], Université Paris Diderot - Paris 7 (UPD7), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre National de Référence associé Escherichia coli [Hôpital Robert Debré - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Service d'Immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Myocarditis, [SDV]Life Sciences [q-bio], Immunology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, 030225 pediatrics, Intensive care, Internal medicine, medicine, Immunology and Allergy, 030212 general & internal medicine, business.industry, medicine.disease, outcome and process assessment, health care, cytokines, 3. Good health, Systemic inflammatory response syndrome, inflammation, Cohort, Kawasaki disease, Differential diagnosis, business, Historical Cohort, Cohort study
Abstract: BackgroundCurrent data suggest that COVID-19 is less frequent in children, with a milder course. However, over the past weeks, an increase in the number of children presenting to hospitals in the greater Paris region with a phenotype resembling Kawasaki disease (KD) has led to an alert by the French national health authorities.MethodsMulticentre compilation of patients with KD in Paris region since April 2020, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (‘Kawa-COVID-19’). A historical cohort of ‘classical’ KD served as a comparator.ResultsSixteen patients were included (sex ratio=1, median age 10 years IQR (4·7 to 12.5)). SARS-CoV-2 was detected in 12 cases (69%), while a further three cases had documented recent contact with a quantitative PCR-positive individual (19%). Cardiac involvement included myocarditis in 44% (n=7). Factors prognostic for the development of severe disease (ie, requiring intensive care, n=7) were age over 5 years and ferritinaemia >1400 µg/L. Only five patients (31%) were successfully treated with a single intravenous immunoglobulin (IVIg) infusion, while 10 patients (62%) required a second line of treatment. The Kawa-COVID-19 cohort differed from a comparator group of ‘classical’ KD by older age at onset 10 vs 2 years (pConclusionKawa-COVID-19 likely represents a new systemic inflammatory syndrome temporally associated with SARS-CoV-2 infection in children. Further prospective international studies are necessary to confirm these findings and better understand the pathophysiology of Kawa-COVID-19.Trial registration numberNCT02377245
Published: 2020

49. The contribution of micrornas to the inflammatory and neoplastic characteristics of erdheim–chester disease

Author: Nir Pillar, Galia Stemer, Eli L. Diamond, Benjamin H. Durham, Ofer Shpilberg, Omar Abdel-Wahab, Zahir Amoura, Ran Weissman, Jean-François Emile, Julien Haroche, Fleur Cohen, Justin Buthorn, Michelle Ki, Gary A. Ulaner, Oshrat Hershkovitz-Rokah, Guy Shapira, Noam Shomron, Roei D Mazor, Ariel University, Memorial Sloane Kettering Cancer Center [New York], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hadassah Hebrew University Medical Center [Jerusalem], Tel Aviv University [Tel Aviv], Ha’Emek Medical Center [Afula, Israel], Pediatric Endocrine Institute [Afula, Israel], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Assuta Medical Centre-Rishon [Israel], P30 CA008748 Histiocytosis Association Novartis Janssen Biotech Sanofi National Heart and Lung Institute, NHLI National Cancer Institute, NCI Merck Genentech, Funding: This work was supported by the Histiocytosis Association of America research grant. This research was also funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748., and Conflicts of Interest: The authors declare no conflict of interest. O.A.-W. has received grants from the National Cancer Institute, National Heart Lung and Blood Institute, and H3B Biomedicine, as well as personal fees from H3B Biomedicine, Foundation Medicine, Merck, and Janssen. E.L.D. is supported by the Frame Fund, the Applebaum Foundation and by the Joy Family West Foundation. G.A.U. has consultant payments from Saonofi, and has received grant support from Sanofi, Novartis, Genentech, and Puma biotechnology.
Subjects: 0301 basic medicine, MAPK/ERK pathway, Cancer Research, Erdheim–Chester disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, Article, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Langerhans cell histiocytosis, Downregulation and upregulation, microRNA, Gene expression, Medicine, business.industry, MicroRNA, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, Histiocytosis, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, business
Abstract: The pathogenesis of histiocytic neoplasms is driven by mutations activating the MAPK/ERK pathway, but little is known about the transcriptional and post-transcriptional alterations involved in these neoplasms. We analyzed microRNA (miRNA) expression in plasma samples and tissue biopsies of Erdheim&ndash, Chester disease (ECD) and Langerhans cell histiocytosis (LCH) patients. In silico analysis revealed a potential role of miRNAs in regulating gene expression in these neoplasms as compared with healthy controls (HC). NanoString analysis revealed 101 differentially expressed plasma miRNAs in 16 ECD patients as compared with 11 HC, 95% of which were downregulated. MiRNAs-15a-5p, -15b-5p, -21-5p, -107, -221-3p, -320e, -630, and let-7 family miRNAs were further evaluated by qRT-PCR in an extended cohort of 32 ECD patients, seven LCH and 15 HC. Six miRNAs (let-7a, let-7c, miR-15a-5p, miR-15b-5p, miR-107 and miR-630) were highly expressed in LCH plasma and tissue samples as compared with ECD. Pathway enrichment analysis indicated the miRNA contribution to inflammatory and pro-survival signaling pathways. Moreover, the let-7 family members were downregulated in untreated ECD patients as compared with HC, while treatment with MAPK/ERK signaling inhibitors for 16 weeks resulted in their upregulation, which was in parallel with the radiologic response seen by PET-CT. The study highlights the potential contribution of miRNA to the inflammatory and neoplastic characteristics of ECD and LCH.
Published: 2020

50. Coronary artery disease in systemic lupus: A case-controlled angiographic study

Author: Julien Haroche, Mathieu Kerneis, Fleur Cohen Aubart, Pierre Rufat, T. Chazal, Paul Guedeney, Zahir Amoura, Alexis Mathian, Gilles Montalescot, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Service de Cardiologie [CHU Pitié-Salpêtrière], Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Département de Biostatistique, Santé Publique et Information Médicale [CHU Pitié-Salpêtrière] (BIOSPIM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Coronary Artery Disease, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Systemic lupus erythematosus, Internal medicine, medicine, Immunology and Allergy, Humans, Lupus Erythematosus, Systemic, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, 0303 health sciences, medicine.diagnostic_test, Systemic lupus, business.industry, Angiography, Heart, Middle Aged, medicine.disease, Atherosclerosis, Coronary heart disease, 3. Good health, Case-Control Studies, Cardiology, Female, business
Abstract: International audience
Published: 2020

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