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1. A software tool to support follow-up care in a French childhood cancer cohort: construction and feasibility

Author: Charlotte Demoor-Goldschmidt, Pascal Veillon, Maxime Esvan, Mathilde Leonard, Sophie Chauvet, Amandine Bertrand, Liana Carausu, Fanny Delehaye, Julien Lejeune, Jérémie Rouger, Pascale Schneider, Caroline Thomas, Frédéric Millot, Line Claude, Julie Leseur, Fernand Missohou, Stéphane Supiot, Nathalie Bihannic, Isabelle Debroise, Carole Jeanneaud, Esther Lebreton, Marianne Roumy, Les Aguerris, Jean-Marie Chrétien, Virginie Gandemer, and Isabelle Pellier
Subjects: Database, Medical tool, Personalized survivorship care plan, Childhood cancer, Adolescent cancer, Survivorship, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Background Treatment summaries and a personalized survivorship care plans based on internationally approved, organ-specific follow-up care recommendations are essential in preserving the health and quality of life for cancer survivors. Cohorts made up of survivors of childhood cancer have made significant contributions to the understanding of early mortality, somatic late complications, and psychosocial outcomes among former patients. New treatment protocols are needed to enhance survival and reduce the potential risk and severity of late effects, and working with treatment databases is crucial in doing so. Construction and content In the GOCE (Grand Ouest Cancer de l’Enfant [Western Region Childhood Cancer]) network, in a participative approach, we developed the LOG-after medical tool, on which health data are registered and can be extracted for analysis. Its name emphasizes the tool’s goal, referring to ‘logiciel’ (the French word for software) that focuses on the period “after” the acute phase. This tool is hosted on a certified health data server. Several interfaces have been developed that can be used depending on the user’s profile. Here we present this innovative co-constructed tool that takes national aspects into account, including the results of the feasibility/satisfaction study and its perspective. Utility and discussion The database contains data relating to 2558 patients, with samples from 1702 of these (66.54%) being held in a tumor bank. The average year in which treatment started was 2015 (ranging from December 1967 to November 2022: 118 patients were treated before 2012 and registered retrospectively when seen in long-term follow-up consultations or for another cancer since November 2021). A short questionnaire was distributed to healthcare professionals using the tool (physicians and research associates or technicians, n = 14), of whom 11 answered and were all satisfied. Access to the patient interface is currently open to 124 former patients. This was initially offered to 30 former patients who were over 15 years old, affected by the disease within the last 5 years, and had agreed to test it. Their opinions were collected by their doctor by e-mail, telephone, or during a consultation in an open-ended question and a non-directive interview. All patients were satisfied with the tool, with interest in testing it in the long term. Some former patients found that the tool provided them with some ease of mind; one, for instance, commented: "I feel lighter. I allow myself to forget. I know I will get a notification when the time comes." Conclusions Freely available to all users, LOG-after: (1) provides help with determining personalized survivorship care plans for follow-up; (2) builds links with general practitioners; (3) empowers the patient; and (4) enables health data to be exported for analysis. Database URL for presentation: https://youtu.be/2Ga64iausJE
Published: 2024
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2. Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer

Author: Jérémy Guillot, Chloé Dominici, Adrien Lucchesi, Huyen Thi Trang Nguyen, Angélique Puget, Mélanie Hocine, Martha M. Rangel-Sosa, Milesa Simic, Jérémy Nigri, Fabienne Guillaumond, Martin Bigonnet, Nelson Dusetti, Jimmy Perrot, Jonathan Lopez, Anders Etzerodt, Toby Lawrence, Pierre Pudlo, Florence Hubert, Jean-Yves Scoazec, Serge A. van de Pavert, Richard Tomasini, Sophie Chauvet, and Fanny Mann
Subjects: Science
Abstract: The autonomic nervous systems densely innervate the pancreas, but its contribution to pancreatic ductal adenocarcinoma (PDAC) progression is not fully understood. Here, the authors characterize the pattern of sympathetic innervation by 3D imaging in a murine model of PDAC and show that sympathectomy aggravates cancer progression.
Published: 2022
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3. Natural Killer Cell Large Granular Lymphocyte Leukemia-Induced Glomerulonephritis

Author: Pierre Isnard, Charel Linster, Julie Bruneau, Eric Thervet, Jean-Paul Duong Van Huyen, Julien Rossignol, Alexandre Karras, Sophie Chauvet, and Marion Rabant
Subjects: Diseases of the genitourinary system. Urology, RC870-923
Published: 2021
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4. Ex Vivo Test for Measuring Complement Attack on Endothelial Cells: From Research to Bedside

Author: Marie-Sophie Meuleman, Anna Duval, Véronique Fremeaux-Bacchi, Lubka T. Roumenina, and Sophie Chauvet
Subjects: complement, endothelial cells, diagnostics, prognostics, therapeutics, kidney injury, Immunologic diseases. Allergy, RC581-607
Abstract: As part of the innate immune system, the complement system plays a key role in defense against pathogens and in host cell homeostasis. This enzymatic cascade is rapidly triggered in the presence of activating surfaces. Physiologically, it is tightly regulated on host cells to avoid uncontrolled activation and self-damage. In cases of abnormal complement dysregulation/overactivation, the endothelium is one of the primary targets. Complement has gained momentum as a research interest in the last decade because its dysregulation has been implicated in the pathophysiology of many human diseases. Thus, it appears to be a promising candidate for therapeutic intervention. However, detecting abnormal complement activation is challenging. In many pathological conditions, complement activation occurs locally in tissues. Standard routine exploration of the plasma concentration of the complement components shows values in the normal range. The available tests to demonstrate such dysregulation with diagnostic, prognostic, and therapeutic implications are limited. There is a real need to develop tools to demonstrate the implications of complement in diseases and to explore the complex interplay between complement activation and regulation on human cells. The analysis of complement deposits on cultured endothelial cells incubated with pathologic human serum holds promise as a reference assay. This ex vivo assay most closely resembles the physiological context. It has been used to explore complement activation from sera of patients with atypical hemolytic uremic syndrome, malignant hypertension, elevated liver enzymes low platelet syndrome, sickle cell disease, pre-eclampsia, and others. In some cases, it is used to adjust the therapeutic regimen with a complement-blocking drug. Nevertheless, an international standard is lacking, and the mechanism by which complement is activated in this assay is not fully understood. Moreover, primary cell culture remains difficult to perform, which probably explains why no standardized or commercialized assay has been proposed. Here, we review the diseases for which endothelial assays have been applied. We also compare this test with others currently available to explore complement overactivation. Finally, we discuss the unanswered questions and challenges to overcome for validating the assays as a tool in routine clinical practice.
Published: 2022
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5. Circulating FH Protects Kidneys From Tubular Injury During Systemic Hemolysis

Author: Nicolas S. Merle, Juliette Leon, Victoria Poillerat, Anne Grunenwald, Idris Boudhabhay, Samantha Knockaert, Tania Robe-Rybkine, Carine Torset, Matthew C. Pickering, Sophie Chauvet, Veronique Fremeaux-Bacchi, and Lubka T. Roumenina
Subjects: complement – immunological term, complement factor H, hemolysis, kidney, acute tubular damage, Immunologic diseases. Allergy, RC581-607
Abstract: Intravascular hemolysis of any cause can induce acute kidney injury (AKI). Hemolysis-derived product heme activates the innate immune complement system and contributes to renal damage. Therefore, we explored the role of the master complement regulator Factor H (FH) in the kidney's resistance to hemolysis-mediated AKI. Acute systemic hemolysis was induced in mice lacking liver expression of FH (hepatoFH−/−, ~20% residual FH) and in WT controls, by phenylhydrazine injection. The impaired complement regulation in hepatoFH−/− mice resulted in a delayed but aggravated phenotype of hemolysis-related kidney injuries. Plasma urea as well as markers for tubular (NGAL, Kim-1) and vascular aggression peaked at day 1 in WT mice and normalized at day 2, while they increased more in hepatoFH−/− compared to the WT and still persisted at day 4. These were accompanied by exacerbated tubular dilatation and the appearance of tubular casts in the kidneys of hemolytic hepatoFH−/− mice. Complement activation in hemolytic mice occurred in the circulation and C3b/iC3b was deposited in glomeruli in both strains. Both genotypes presented with positive staining of FH in the glomeruli, but hepatoFH−/− mice had reduced staining in the tubular compartment. Despite the clear phenotype of tubular injury, no complement activation was detected in the tubulointerstitium of the phenylhydrazin-injected mice irrespective of the genotype. Nevertheless, phenylhydrazin triggered overexpression of C5aR1 in tubules, predominantly in hepatoFH−/− mice. Moreover, C5b-9 was deposited only in the glomeruli of the hemolytic hepatoFH−/− mice. Therefore, we hypothesize that C5a, generated in the glomeruli, could be filtered into the tubulointerstitium to activate C5aR1 expressed by tubular cells injured by hemolysis-derived products and will aggravate the tissue injury. Plasma-derived FH is critical for the tubular protection, since pre-treatment of the hemolytic hepatoFH−/− mice with purified FH attenuated the tubular injury. Worsening of acute tubular necrosis in the hepatoFH−/− mice was trigger-dependent, as it was also observed in LPS-induced septic AKI model but not in chemotherapy-induced AKI upon cisplatin injection. In conclusion, plasma FH plays a key role in protecting the kidneys, especially the tubules, against hemolysis-mediated injury. Thus, FH-based molecules might be explored as promising therapeutic agents in a context of AKI.
Published: 2020
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6. Post-endocytic sorting of Plexin-D1 controls signal transduction and development of axonal and vascular circuits

Author: Katja Burk, Erik Mire, Anaïs Bellon, Mélanie Hocine, Jeremy Guillot, Filipa Moraes, Yutaka Yoshida, Michael Simons, Sophie Chauvet, and Fanny Mann
Subjects: Science
Abstract: Molecular mechanisms controlling axonal growth cone behaviour are only partially understood. Here the authors reveal a role of an adaptor protein GIPC1 in Plexin-D1 receptor recycling, and show that this process is required for axon track formation and vascular patterning in mice.
Published: 2017
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7. Both Monoclonal and Polyclonal Immunoglobulin Contingents Mediate Complement Activation in Monoclonal Gammopathy Associated-C3 Glomerulopathy

Author: Sophie Chauvet, Lubka T. Roumenina, Pierre Aucouturier, Maria-Chiara Marinozzi, Marie-Agnès Dragon-Durey, Alexandre Karras, Yahsou Delmas, Moglie Le Quintrec, Dominique Guerrot, Noémie Jourde-Chiche, David Ribes, Pierre Ronco, Frank Bridoux, and Véronique Fremeaux-Bacchi
Subjects: complement, alternative pathway activation, C3 glomerulopathies, monoclonal gammopathy, autoantibodies, Immunologic diseases. Allergy, RC581-607
Abstract: C3 glomerulopathy (C3G) results from acquired or genetic abnormalities in the complement alternative pathway (AP). C3G with monoclonal immunoglobulin (MIg-C3G) was recently included in the spectrum of “monoclonal gammopathy of renal significance.” However, mechanisms of complement dysregulation in MIg-C3G are not described and the pathogenic effect of the monoclonal immunoglobulin is not understood. The purpose of this study was to investigate the mechanisms of complement dysregulation in a cohort of 41 patients with MIg-C3G. Low C3 level and elevated sC5b-9, both biomarkers of C3 and C5 convertase activation, were present in 44 and 78% of patients, respectively. Rare pathogenic variants were identified in 2/28 (7%) tested patients suggesting that the disease is acquired in a large majority of patients. Anti-complement auto-antibodies were found in 20/41 (49%) patients, including anti-FH (17%), anti-CR1 (27%), anti-FI (5%) auto-antibodies, and C3 Nephritic Factor (7%) and were polyclonal in 77% of patients. Using cofactor assay, the regulation of the AP was altered in presence of purified IgG from 3/9 and 4/7 patients with anti-FH or anti-CR1 antibodies respectively. By using fluid and solid phase AP activation, we showed that total purified IgG of 22/34 (65%) MIg-C3G patients were able to enhance C3 convertase activity. In five documented cases, we showed that the C3 convertase enhancement was mostly due to the monoclonal immunoglobulin, thus paving the way for a new mechanism of complement dysregulation in C3G. All together the results highlight the contribution of both polyclonal and monoclonal Ig in MIg-C3G. They provide direct insights to treatment approaches and opened up a potential way to a personalized therapeutic strategy based on chemotherapy adapted to the B cell clone or immunosuppressive therapy.
Published: 2018
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8. Characterization of Renal Injury and Inflammation in an Experimental Model of Intravascular Hemolysis

Author: Nicolas S. Merle, Anne Grunenwald, Marie-Lucile Figueres, Sophie Chauvet, Marie Daugan, Samantha Knockaert, Tania Robe-Rybkine, Remi Noe, Olivia May, Marie Frimat, Nathan Brinkman, Thomas Gentinetta, Sylvia Miescher, Pascal Houillier, Veronique Legros, Florence Gonnet, Olivier P. Blanc-Brude, Marion Rabant, Regis Daniel, Jordan D. Dimitrov, and Lubka T. Roumenina
Subjects: hemolysis, heme, kidney injury, endothelial activation, inflammation, hemopexin, Immunologic diseases. Allergy, RC581-607
Abstract: Intravascular erythrocyte destruction, accompanied by the release of pro-oxidative and pro-inflammatory components hemoglobin and heme, is a common event in the pathogenesis of numerous diseases with heterogeneous etiology and clinical features. A frequent adverse effect related to massive hemolysis is the renal injury and inflammation. Nevertheless, it is still unclear whether heme––a danger-associated molecular pattern––and ligand for TLR4 or upstream hemolysis-derived products are responsible for these effects. Well-characterized animal models of hemolysis with kidney impairment are needed to investigate how hemolysis drives kidney injury and to test novel therapeutic strategies. Here, we characterized the pathological processes leading to acute kidney injury and inflammation during massive intravascular hemolysis, using a mouse model of phenylhydrazine (PHZ)-triggered erythrocyte destruction. We observed profound changes in mRNA levels for markers of tubular damage (Kim-1, NGAL) and regeneration (indirect marker of tubular injury, Ki-67), and tissue and vascular inflammation (IL-6, E-selectin, P-selectin, ICAM-1) in kidneys of PHZ-treated mice, associated with ultrastructural signs of tubular injury. Moreover, mass spectrometry revealed presence of markers of tubular damage in urine, including meprin-α, cytoskeletal keratins, α-1-antitrypsin, and α-1-microglobulin. Signs of renal injury and inflammation rapidly resolved and the renal function was preserved, despite major changes in metabolic parameters of PHZ-injected animals. Mechanistically, renal alterations were largely heme-independent, since injection of free heme could not reproduce them, and scavenging heme with hemopexin in PHZ-administered mice could not prevent them. Reduced overall health status of the mice suggested multiorgan involvement. We detected amylasemia and amylasuria, two markers of acute pancreatitis. We also provide detailed characterization of renal manifestations associated with acute intravascular hemolysis, which may be mediated by hemolysis-derived products upstream of heme release. This analysis provides a platform for further investigations of hemolytic diseases and associated renal injury and the evaluation of novel therapeutic strategies that target intravascular hemolysis.
Published: 2018
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9. Urinary retinol binding protein is a marker of the extent of interstitial kidney fibrosis.

Author: Nicolas Pallet, Sophie Chauvet, Jean-François Chassé, Marc Vincent, Paul Avillach, Charlene Levi, Vannary Meas-Yedid, Jean-Christophe Olivo-Marin, Diane Nga-Matsogo, Philippe Beaune, Eric Thervet, and Alexandre Karras
Subjects: Medicine, Science
Abstract: Currently, a non-invasive method to estimate the degree of interstitial fibrosis (IF) in chronic kidney disease is not available in routine. The aim of our study was to evaluate the diagnostic performance of the measurement of urinary low molecular weight (LMW) protein concentrations as a method to determine the extent of IF. The urines specimen from 162 consecutive patients who underwent renal biopsy were used in the analysis. Numerical quantification software based on the colorimetric analysis of fibrous areas was used to assess the percentage IF. Total proteinuria, albuminuria, and the urinary levels of retinol binding protein (RBP), alpha1-microglobulin (α1MG), beta 2-microglobulin (β2MG), transferrin, and IgG immunoglobulins were measured. There was a significant correlation between the degree of IF and the RBP/creatinine (creat) ratio (R2: 0.11, p25% of the parenchyma was 95% when using a threshold of 20 mg/g creat. In conclusion, RBP appears to be a quantitative and non-invasive marker for the independent prediction of the extent of kidney IF. Because methods for the measurement of urinary RBP are available in most clinical chemistry departments, RBP measurement is appealing for implementation in the routine care of patients with chronic kidney disease.
Published: 2014
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10. Light Chain–Only Immunotactoid Glomerulopathy: A Case Report

Author: Lihong Bu, Vincent Javaugue, Sophie Chauvet, Jerold Napier, Surendra Dasari, Jason D. Theis, Julie A. Vrana, Ellen D. McPhail, and Samih H. Nasr
Subjects: Nephrology
Published: 2023
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11. Implication du complément dans les pathologies rénales

Author: Sophie Chauvet
Subjects: General Medicine
Published: 2022
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12. Rejet humoral et complément

Author: Noémie Simon and Sophie Chauvet
Subjects: General Medicine
Published: 2022
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13. Syndrome hémolytique et urémique atypique : aspects génétiques et physiopathologiques

Author: Marie Sophie Meuleman and Sophie Chauvet
Subjects: General Medicine
Published: 2022
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14. C3 Glomerulopathy With Concurrent Thrombotic Microangiopathy: Clinical and Immunological Features

Author: Melchior Chabannes, Marion Rabant, Carine El Sissy, Marie-Agnès Dragon-Durey, Paula Vieira Martins, Marie Sophie Meuleman, Alexandre Karras, David Buob, Frank Bridoux, Eric Daugas, Vincent Audard, Sophie Caillard, Jérôme Olagne, Christine Kandel, Sophie Ferlicot, Carole Philipponnet, Thomas Crepin, Eric Thervet, Didier Ducloux, Véronique Frémeaux-Bacchi, and Sophie Chauvet
Subjects: Nephrology
Published: 2023
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15. Stiripentol and Lumasiran as a Rescue Therapy for Oxalate Nephropathy Recurrence After Kidney Transplantation in an Adult Patient With Primary Hyperoxaluria Type 1

Author: Yannis Lombardi, Pierre Isnard, Nathalie Chavarot, Sophie Chauvet, Frank Martinez, Éric Thervet, Dany Anglicheau, and Alexandre Karras
Subjects: Nephrology
Published: 2023
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16. SARS Cov2 outbreak management on a landing helicopter dock: An observational retrospective study

Author: Philippe Aries, Pierre-Julien Cungi, Johan Schmitt, Sophie Vellieux, Marc Danguy des Déserts, Sophie Chauvet-Atin, Christophe Giacardi, and Emmanuel Genet
Subjects: Adult, Male, medicine.medical_specialty, Aircraft, Coronavirus disease 2019 (COVID-19), SARS Cov2, Crew, Disease, Asymptomatic, Disease Outbreaks, Young Adult, Military Facilities, medicine, Humans, Medical history, Austere environment, Retrospective Studies, business.industry, COVID-19, Outbreak, Retrospective cohort study, Landing helicopter dock, Infectious Diseases, Emergency medicine, Original Article, Female, Observational study, France, medicine.symptom, business
Abstract: Objectives Even though SARS Cov2 outbreak management has been well-described, scant information is available in military settings. We aimed to describe a SARS Cov2 outbreak and its management on the Dixmude, a French landing helicopter dock. Patients and methods We performed an observational retrospective and monocentric study in a ship. Role 1 was reinforced by additional roles 1 and 2. Our analysis included all infected crew personnel. We described demographic data, outbreak course, and biological samples including Covid-19 diagnosis. All infected patients were monitored for 10 days. Results Between February 16th 2021 and March 12th 2021, 54 patients (10% of the entire crew) were included. No patient had previously been vaccinated against SARS Cov2. The global mission was maintained. The crew members were healthy, male, and young (median age 28 years) with no medical history. Ranks of every status were concerned. Covid-19 disease was mainly diagnosed by real-time reverse-transcriptase polymerase chain reaction (rt-PCR). Thirty-two patients (59%) were symptomatic, four (8%) were presymptomatic and 18 (33%) remained asymptomatic. Conclusions The present work describes specific SARS Cov2 outbreak management in an austere military environment. Early individual and global measures were set and implemented on board.
Published: 2021
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17. B-cell treatment in ANCA-associated vasculitis

Author: Alexandre Karras, Sophie Chauvet, and Hélène Lazareth
Subjects: 0301 basic medicine, medicine.drug_class, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, ANCA-Associated Vasculitis, Monoclonal antibody, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Maintenance therapy, immune system diseases, Humans, Medicine, Pharmacology (medical), B cell, 030203 arthritis & rheumatology, B-Lymphocytes, business.industry, Anca vasculitis, Remission Induction, Pathogenicity, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Immunology, Rituximab, business, Vasculitis, medicine.drug
Abstract: The pivotal role of B-cells in ANCA-associated vasculitis has been suggested by experimental data that demonstrate the direct pathogenicity of ANCAs. Rituximab (RTX), an anti-CD20 monoclonal antibody that targets B-cells, has proven its efficacy for induction of remission in severe ANCA vasculitis. RTX is equivalent to CYC for induction of remission, and is probably superior in relapsing patients. Long-term B cell depletion by prolonged RTX treatment has been shown to significantly reduce the relapse rate, when compared with AZA maintenance therapy. Biomarkers, such as B-cell subpopulations or ANCA monitoring, may help the clinician to determine the optimal dose and duration of RTX therapy.
Published: 2020
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18. Light chain only variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits is associated with a high detection rate of the pathogenic plasma cell clone

Author: Lynn D. Cornell, Julie A. Vrana, Thomas Guincestre, Nelson Leung, Surendra Dasari, Christophe Sirac, Ziad A. Massy, Christopher P. Larsen, David Buob, Sophie Chauvet, Ellen D. McPhail, Vincent Javaugue, Samih H. Nasr, Eve Vilaine, Frank Bridoux, Vivette D. D'Agati, Guy Touchard, Samar M. Said, Jean Jacques Boffa, Jonathan J. Hogan, Stéphanie Toussaint, Camille Domenger, and Jason D. Theis
Subjects: Proteomics, 0301 basic medicine, Pathology, medicine.medical_specialty, Glomerulonephritis, Membranoproliferative, Plasma Cells, Paraproteinemias, 030232 urology & nephrology, Clone (cell biology), Plasma cell, Immunoglobulin light chain, 03 medical and health sciences, Glomerulonephritis, 0302 clinical medicine, Membranoproliferative glomerulonephritis, Humans, Medicine, Multiple myeloma, business.industry, Antibodies, Monoclonal, medicine.disease, Isotype, Clone Cells, 030104 developmental biology, medicine.anatomical_structure, Nephrology, Alternative complement pathway, business
Abstract: IgG (mainly IgG3) is the most commonly involved isotype in proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Here we describe the first series of PGNMID with deposition of monoclonal immunoglobulin light chain only (PGNMID-light chain). This multicenter cohort of 17 patients presented with nephritic or nephrotic syndrome with underlying hematologic conditions of monoclonal gammopathy of renal significance (71%) or multiple myeloma (29%). Monoclonal immunoglobulin was identified by serum and urine immunofixation in 65% and 73%, respectively, with abnormal serum free light chain in 83%, and a detectable bone marrow plasma cell clone in 88% of patients. Renal biopsy showed a membranoproliferative pattern in most patients. By immunofluorescence, deposits were restricted to glomeruli and composed of restricted light chain (kappa in 71%) and C3, with granular appearance and subendothelial, mesangial and subepithelial distribution by electron microscopy. Proteomic analysis in four cases of kappa PGNMID-light chain revealed spectra for kappa constant and variable domains, without evidence of Ig heavy chains; spectra for proteins of the alternative pathway of complement and terminal complex were detected in three. The classical pathway was not detected in three cases. After median follow up of 70 months, the renal response was dependent on a hematologic response and occurred in six of ten patients treated with plasma cell-directed chemotherapy but none of five patients receiving other therapies. Thus, PGNMID-light chain differs from PGNMID-IgG by higher frequency of a detectable pathogenic plasma cell clone. Hence, proper recognition is crucial as anti-myeloma agents may improve renal prognosis. Activation of an alternative pathway of complement by monoclonal immunoglobulin light chain likely plays a role in its pathogenesis.
Published: 2020
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19. VPS35 deficiency in the embryonic cortex leads to prenatal cell loss and abnormal development of axonal connectivity

Author: Micaela Roque, Diego Alves Rodrigues de Souza, Martha M. Rangel-Sosa, Mike Altounian, Mélanie Hocine, Jean-Christophe Deloulme, Emmanuel L. Barbier, Fanny Mann, Sophie Chauvet, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences, GIN, 38000, Grenoble, France, ANR-17-EURE-0029,nEURo*AMU,Marseille NeuroSchool, une formation d'excellence(2017), MANN, Fanny, and Marseille NeuroSchool, une formation d'excellence - - nEURo*AMU2017 - ANR-17-EURE-0029 - EURE - VALID
Subjects: Mammals, Neurons, Cell death, Axon guidance, Neurogenesis, [SDV]Life Sciences [q-bio], Vesicular Transport Proteins, Neurodegenerative Diseases, Cell Biology, Axons, [SDV] Life Sciences [q-bio], Cellular and Molecular Neuroscience, Mice, DTI, 3D imaging, Retromer, Animals, Molecular Biology, VPS35
Abstract: International audience; VPS35 is a core component of the retromer complex involved in familial forms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. In mice, VPS35 is expressed during early brain development. However, previous studies have reported that VPS35 activity is largely dispensable for normal neuronal development and initial elaboration of axonal projections. Here, we evaluated the role of VPS35 in the mouse embryonic brain using two Cre-driver lines that remove Vps35 from the cortex at different prenatal stages. We found that Vps35 mutant mice displayed microcephaly and decreased cortical thickness from the embryonic stages to adulthood. VPS35 also regulates cortical development by affecting a subpopulation of neural progenitor cells and the survival of postmitotic neurons. In addition, we showed that a lack of VPS35 leads to hypoplasia and misrouting of several axonal projections, including the anterior commissure and fornix. Furthermore, VPS35 deficiency impairs the non-autonomous development of thalamocortical axons (TCAs), which show severe disruption of innervation and terminal arborization in the cortex. Together, these data demonstrate that VPS35 plays a greater role in embryonic development of the mammalian brain than it was previously thought.
Published: 2022
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20. Les auteurs

Author: Alexandra Benachi, Dominique Luton, Laurent Mandelbrot, Olivier Picone, Hélène Affres, Nadine Ajzenberg, Laurence Amar, Pascale Amate, Djillali Annane, Rana Aoun, Elie Azria, Rakiba Belkhir, Ivan Berlin, Jacques Bernuau, Emmanuel Boleslawski, Claire Bonneau, Marie Bornes, Yoram Bouhnik, Corinne Bouteloup, Elisabeth Bouvet, Dominique Brémond-Gignac, Arnaud Bresset, Florence Bretelle, Léopoldine Bricaire, Marie Bruyère, Julie Carrara, Pierre-François Ceccaldi, Philippe Chanson, Sophie Chauvet, Bernard Clair, Élodie Clouqueur, Sarah Cohen, Chloé Comarmond-Ortoli, Jacqueline Conard, Sophie Conquy, Henri Copin, Anne-Gaël Cordier, Sophie Cordiez, Sarah Coscas, Nathalie Costedoat-Chalumeau, Emile Daraï, Amélie Delabaere, Philippe Deruelle, Marc Dommergues, Anne-Sophie Ducloy-Bouthors, Caroline Dubertret, Hubert Ducou Le Pointe, Bénédicte Dumont, Lise Duranteau, Elisabeth Elefant, Nejla Essafi, Hervé Fernandez, Julia Filippova, Renato Fior, Michael Frank, Jean-Baptiste de Fréminville, Diane Friedman, Frédéric Galacteros, Denis Gallot, Gilles Garcia, Jean-Yves Gauvrit, Anne Gervais, Robert Girot, Bertrand Godeau, Gilles Grangé, Dominique Grenet, Lionel Groussin-Rouiller, Gaëlle Guettrot-Imbert, Stéphanie Guillet, Anoosha Habibi, Smail Hadj-Rabia, Olivier Hermine, Véronique Houfflin-Debarge, Marie Houllier, Lucile Houyel, Marc Humbert, Laurence Iserin, Bernard Iung, Xavier Jaïs, Bérangère Joly, Guillaume Jondeau, Jean-Emmanuel Kahn, Gilles Kayem, Hawa Keita, Valentin Keller, Magalie Ladouceur, Cécile Lavenu-Bombled, Hélène Legardeur, Véronique Le Guern, Claude Lejeune, Claire Le Jeunne, null Lous, null Ray, Aurélien Lorthioir, Lynda Manamani-Bererhi, Isabelle Marie, Grégoire Martin de Frémont, Sophie Matheron, Amandine Maulard, Nadia Merbai, Emmanuel Messas, Sandra de Miranda, Anna Molto, Stéphanie Morgant, Simon Msika, Sophie Nebout, Jacky Nizard, Roseline d'Oiron, Violaine Ozenne, Gabriel Perlemuter, Sandrine Perol, Franck Perrotin, Brigitte Perrouin-Verbe, Edith Peynaud-Debayle, Violaine Peyronnet, Henri-Jean Philippe, Clément Picard, Geneviève Plu-Bureau, Laura Polivka, Brigitte Raccah-Tebeka, Emmanuelle de Raucourt, Jean-Antoine Ribeil, Thomas Ronzière, Valérie Roussel-Robert, Aude Rossi, Lucia Rugeri, David Saadoun, Lise Selleret, Pierre Sellier, Marie-Victoire Sénat, Raphaèle Seror, Damien Subtil, Camille Taillé, Sarah Tebeka, Denis Therby, Ngoc-Tram Tô, Bertrand de Toffol, Nathalie Trillot, Vassilis Tsatsaris, Géraud Tuyeras, Mathieu Uzzan, Morgane Valentin, David Vandendriessche, Roxane Vanspranghels-Gibert, Eric Verspyck, Aurélie Vincent-Rohfritsch, Sandra Vukusic, Bernard Wechsler, Norbert Winer, and Jacques-François Young
Published: 2022
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21. Anti-Factor B Antibodies and Acute Postinfectious GN in Children

Author: Ferielle Louillet, Guillaume Mestrallet, Aram G. Gyulkhandanyan, Amélie Ryckewaert, Bruno O. Villoutreix, Véronique Frémeaux-Bacchi, Magali Devriese, Paula Vieira Martins, Olivia Boyer, Caroline Rousset-Rouvière, Elodie Merieau, Morgane Mignotet, Lubka T. Roumenina, Tania Robe-Rybkine, Eric Thervet, Maria A. Miteva, Sophie Chauvet, J. Hogan, Tim Ulinski, and Romain Berthaud
Subjects: Male, Complement factor B, Nephritic syndrome, Glomerulonephritis, Glomerulopathy, medicine, Humans, Child, Complement Activation, Autoantibodies, Retrospective Studies, Complement C3 Nephritic Factor, business.industry, Editorials, Autoantibody, Complement C3, General Medicine, medicine.disease, C3-convertase, Complement system, Nephrology, Child, Preschool, Immunology, Alternative complement pathway, Female, France, business, Complement Factor B
Abstract: Background The pathophysiology of the leading cause of pediatric acute nephritis, acute postinfectious GN, including mechanisms of the pathognomonic transient complement activation, remains uncertain. It shares clinicopathologic features with C3 glomerulopathy, a complement-mediated glomerulopathy that, unlike acute postinfectious GN, has a poor prognosis. Methods This retrospective study investigated mechanisms of complement activation in 34 children with acute postinfectious GN and low C3 level at onset. We screened a panel of anticomplement protein autoantibodies, carried out related functional characterization, and compared results with those of 60 children from the National French Registry who had C3 glomerulopathy and persistent hypocomplementemia. Results All children with acute postinfectious GN had activation of the alternative pathway of the complement system. At onset, autoantibodies targeting factor B (a component of the alternative pathway C3 convertase) were found in a significantly higher proportion of children with the disorder versus children with hypocomplementemic C3 glomerulopathy (31 of 34 [91%] versus 4 of 28 [14%], respectively). In acute postinfectious GN, anti-factor B autoantibodies were transient and correlated with plasma C3 and soluble C5b-9 levels. We demonstrated that anti-factor B antibodies enhance alternative pathway convertase activity in vitro, confirming their pathogenic effect. We also identified crucial antibody binding sites on factor B, including one correlated to disease severity. Conclusions These findings elucidate the pathophysiologic mechanisms underlying acute postinfectious GN by identifying anti-factor B autoantibodies as contributing factors in alternative complement pathway activation. At onset of a nephritic syndrome with low C3 level, screening for anti-factor B antibodies might help guide indications for kidney biopsy to avoid misdiagnosed chronic glomerulopathy, such as C3 glomerulopathy, and to help determine therapy.
Published: 2020
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22. Ifosfamide nephrotoxicity in adult patients

Author: Dominique Nochy, Jean-François Augusto, Rémi Boudet, Gaël Ensergueix, Alexandre Karras, Sophie Chauvet, Eric Thervet, Claire Trivin, Hélène Lazareth, Marie Essig, Charlène Levi, Nicolas Pallet, Dominique Joly, Guy Touchard, and Hail Aboudagga
Subjects: Nephrology, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Gastroenterology, Nephrotoxicity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, mitochondrial toxicity, AcademicSubjects/MED00340, Acute tubular necrosis, chronic kidney injury, Transplantation, Kidney, Chemotherapy, Ifosfamide, ifosfamide, business.industry, nephrotoxicity, Acute kidney injury, Original Articles, medicine.disease, medicine.anatomical_structure, acute kidney injury, 030220 oncology & carcinogenesis, business, proximal tubular dysfunction, medicine.drug, Kidney disease
Abstract: BackgroundIfosfamide, a widely prescribed antineoplasic agent, is frequently associated with kidney dysfunction. Its nephrotoxicity is well documented in children, but data are lacking in adult patients.MethodsThe aim of this retrospective study was to describe the clinical, biological and histological characteristics of ifosfamide nephrotoxicity.ResultsWe report 34 patients (median age: 41 years) admitted in six French nephrology departments for kidney failure and/or tubular dysfunction. Fifteen patients (44.1%) received cisplatin as part of their chemotherapy. In 6 patients (17.7%), ifosfamide nephrotoxicity was revealed by a proximal tubular dysfunction (PTD), in 5 patients (14.4%) by an acute kidney injury (AKI), in 6 patients (17.7%) by a chronic kidney disease (CKD) and in 17 patients (49.7%) by an association of PTD and AKI. Fourteen renal biopsies (41.2%) were performed and revealed acute tubular necrosis (85.7%), vacuolation (78.6%) and nuclear atypias (71.4%) of renal epithelial cells, interstitial inflammation (71.4%) and fibrosis (57.1%). Electron microscopy showed mitochondrial enlargement and dysmorphic changes suggestive of mitochondrial toxicity. Ten patients (29.4%) progressed to Stage 5 CKD, six (17.6%) required haemodialysis and six patients died during a median follow-up period of 31 months. Risk factors for Stage 5 CKD were age and cisplatin co-administration.
Published: 2019
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23. Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome

Author: David Navarro, Sophie Caillard, Leila Tricot, Marie Frimat, Rebecca Sberro Soussan, Jamal Bamoulid, Antoine Thierry, Christophe Legendre, Nassim Kamar, Pierre-François Westeel, Laetitia Albano, Magali Louis, Christophe Charasse, Chantal Loirat, Emilie Cornec-Le Gall, Dominique Bertrand, Jean-Philippe Rerolle, Lionel Couzi, Philippe Gatault, Cyril Garrouste, Aude Servais, Marie-Noëlle Peraldi, Sophie Chauvet, Joseph Rivalan, Yahsou Delmas, Guillaume Claisse, Jean-Philippe Coindre, Ziad A. Massy, Maryvonne Hourmant, Claire Pouteil-Noble, Michelle Elias, Johnny Sayegh, Charlotte Colosio, Luc Frimat, Nadia Arzouk, Noemie Jourde-Chiche, Eric Rondeau, Moglie Le Quintrec, Florent Petitprez, Raphaël Gaisne, Khalil El Karoui, Fadi Fakhouri, Véronique Frémeaux-Bacchi, Julien Zuber, Valérie Chatelet, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), and Emmanuel Boussard Foundation Fukuda Foundation for Medical TechnologyKayamori FoundationKayamori Foundation of Informational Science AdvancementSENSHIN Medical Research FoundationSasagawa Scientific Research GrantMukai Science and Technology Foundation
Subjects: Male, [SDV]Life Sciences [q-bio], Mutant Chimeric Proteins, 030232 urology & nephrology, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Epidemiology, Secondary Prevention, Medicine, complement, Registries, Kidney transplantation, Atypical Hemolytic Uremic Syndrome, education.field_of_study, Graft Survival, General Medicine, Middle Aged, Eculizumab, 3. Good health, Nephrology, Female, France, Cohort study, medicine.drug, Adult, medicine.medical_specialty, Population, kidney transplantation, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Clinical Research, Internal medicine, Preoperative Care, Atypical hemolytic uremic syndrome, Complement C3b Inactivator Proteins, Humans, INHIBITOR ECULIZUMAB, RECURRENCE, education, Proportional Hazards Models, Retrospective Studies, MUTATIONS, business.industry, Complement System Proteins, medicine.disease, Complement Inactivating Agents, hemolytic uremic syndrome, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.Methods To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.Results The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.Conclusions Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.
Published: 2019
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24. Results from a nationwide retrospective cohort measure the impact of C3 and soluble C5b-9 levels on kidney outcomes in C3 glomerulopathy

Author: Sophie Chauvet, Jill J. Hauer, Florent Petitprez, Marion Rabant, Paula Vieira Martins, Véronique Baudouin, Yahsou Delmas, Noémie Jourde-Chiche, Alexandre Cez, David Ribes, Sylvie Cloarec, Aude Servais, Mohamad Zaidan, Eric Daugas, Michel Delahousse, Alain Wynckel, Amélie Ryckewaert, Anne Laure Sellier-Leclerc, Olivia Boyer, Eric Thervet, Alexandre Karras, Richard J.H. Smith, and Véronique Frémeaux-Bacchi
Subjects: Adult, Complement C3 Nephritic Factor, Rare Diseases, Nephrology, Glomerulonephritis, Membranoproliferative, Kidney Glomerulus, Humans, Kidney Diseases, Complement C3, Complement Membrane Attack Complex, Child, Biomarkers, Retrospective Studies
Abstract: C3 glomerulopathy (C3G) is a rare complement-mediated disease. Specific treatments are not yet available and factors predictive of kidney survival such as age, kidney function and proteinuria are not specific to C3G. The prognostic value of biomarkers of complement activation, which are pathognomonic of the diseases, remains unknown. In a large cohort of 165 patients from the French National registry, we retrospectively assess the prognostic value of C3, soluble C5b-9 (sC5b-9), C3 nephritic factor, and rare disease-predicting variants in complement genes in predicting clinical outcome of patients. By multivariate analysis age (adult onset), reduced kidney function (defined by estimated glomerular filtration rate under 60ml/min) and presence of rare disease-predicting variants in complement genes predicted risk of progression to kidney failure. Moreover, by multivariate analysis, normal C3/high sC5b-9 levels or low C3/normal sC5b-9 levels remained independently associated with a worse kidney prognosis, with the relative risk 3.7- and 8-times higher, respectively. Subgroup analysis indicated that the complement biomarker profiles independently correlated to kidney prognosis in patients with adult but not pediatric onset. In this subgroup, we showed that profiles of biomarkers C3 and/or sC5b-9 correlated with intra glomerular inflammation and may explain kidney outcomes. In children, only the presence of rare disease-predicting variants correlated with kidney survival. Thus, in an adult population, we propose a three-point C3G prognostic score based on biomarker profiles at risk, estimated glomerular filtration rate at presentation and genetic findings, which may help stratify adult patients into subgroups that require close monitoring and more aggressive therapy.
Published: 2021

25. Complement Activation and Thrombotic Microangiopathy Associated With Monoclonal Gammopathy: A National French Case Series

Author: Manon Martins, Frank Bridoux, Jean Michel Goujon, Marie Sophie Meuleman, David Ribes, Eric Rondeau, Mary-Jane Guerry, Yahsou Delmas, Bénédicte Levy, Didier Ducloux, Christine Kandel-Aznar, Awena Le Fur, Cyril Garrouste, François Provot, Jean-Baptiste Gibier, Eric Thervet, Patrick Bruneval, Marion Rabant, Alexandre Karras, Marie Agnès Dragon Durey, Veronique Fremeaux-Bacchi, and Sophie Chauvet
Subjects: Adult, Nephrology, Thrombotic Microangiopathies, Paraproteinemias, Humans, Complement System Proteins, Antibodies, Monoclonal, Humanized, Complement Activation, Atypical Hemolytic Uremic Syndrome, Retrospective Studies
Abstract: Hemolytic uremic syndrome (HUS), a thrombotic microangiopathy (TMA) with kidney involvement, is a rare condition in patients with monoclonal gammopathy. In the absence of known causes of TMA, the role of complement activation in endothelial injury in patients with monoclonal gammopathy remains unknown and was the focus of this investigation.Case series.We studied the 24 patients in the French national registry of HUS between 2000 and 2020 who had monoclonal gammopathy without other causes of secondary TMA. We provide the clinical histories and complement studies of these patients.Monoclonal gammopathy-associated TMA with kidney involvement is estimated to be 10 times less frequent than adult atypical HUS (aHUS) in the French national registry. It is characterized by severe clinical features, with 17 of 24 patients requiring dialysis at disease onset, and with median renal survival of only 20 months. TMA-mediated extrarenal manifestations, particularly cutaneous and neurological involvement, were common and associated with poor overall prognosis. Complement studies identified low C3, normal C4, and high soluble C5b-9 levels in 33%, 100%, and 77% of tested patients, respectively, indicating a contribution of the alternative and terminal complement pathways in the pathophysiology of the disease. Genetic abnormalities in complement genes known to be associated with aHUS were found in only 3 of 17 (17%) who were tested.Retrospective study without comparison group; limited number of patients, limited available blood samples.Within the spectrum of TMA, TMA associated with monoclonal gammopathy represents a distinct subset. Our findings suggest that HUS associated with monoclonal immunoglobulin is a complement-mediated disease akin to aHUS.
Published: 2021

26. Detection of C3 Nephritic Factor by Hemolytic Assay

Author: Melchior, Chabannes, Véronique, Frémeaux-Bacchi, and Sophie, Chauvet
Subjects: Complement C3 Nephritic Factor, Erythrocytes, Glomerulonephritis, Sheep, Complement Pathway, Alternative, Animals, Humans, Complement Activation, Complement Hemolytic Activity Assay, Hemolysis, Rats
Abstract: C3 nephritic Factor (C3NeF) is autoantibody that binds neoepitopes of the C3 convertase C3bBb, resulting in a stabilization of the enzyme. First functional characterizations of C3NeF were performed by hemolytic assays using preactivated sheep erythrocytes (bearing C3b). Sheep erythrocytes are beforehand sensitized with an anti-sheep red blood cell stroma antibody produced in rabbit (hemolysin). Sensitized sheep erythrocytes will initiate cascade complement activation via the classic pathway, followed by alternative pathway amplification loop, resulting in C3b covalent binding to cell surface. Sheep erythrocytes bearing C3b permit the alternative pathway exploration, in particular decay of alternative pathway C3 convertase.
Published: 2021

27. Facteurs pronostiques de survie rénale dans la glomérulopathie à dépôts de C3 : impact des biomarqueurs du complément, C3 et sC5b-9

Author: Marion Rabant, A. Ryckewaert, Véronique Frémeaux-Bacchi, Aude Servais, David Ribes, Noémie Jourde-Chiche, Yahsou Delmas, Anne-Laure Sellier-Leclerc, Olivia Boyer, and Sophie Chauvet
Subjects: Nephrology
Published: 2021
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28. Proteinuria and Clinical Outcomes in Hospitalized COVID-19 Patients: A Retrospective Single-Center Study

Author: Alexandre Karras, Eric Thervet, Nicolas Pallet, Jean Luc Diehl, Hélène Lazareth, Sophie Chauvet, Antoine Fayol, Marie Aude Penet, Tristan Mirault, Anne Godier, Jean-Sébastien Hulot, Marine Livrozet, Anne-Sophie Jannot, Nicolas Benichou, Olivier Sanchez, HULOT, Jean-Sébastien, 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), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE)
Subjects: medicine.medical_specialty, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Renal function, Critical Care and Intensive Care Medicine, law.invention, Acute renal failure, Interquartile range, law, Internal medicine, medicine, Proximal tubule, education, Tubular epithelium, Dialysis, Transplantation, education.field_of_study, Proteinuria, business.industry, COVID-19, Retrospective cohort study, Original Articles, Prognosis, Intensive care unit, [SDV] Life Sciences [q-bio], Nephrology, Albuminuria, medicine.symptom, business
Abstract: International audience; Background and objectives Kidney involvement is frequent among patients with coronavirus disease 2019 (COVID-19), and occurrence of AKI is associated with higher mortality in this population. The objective of this study was to describe occurrence and significance of proteinuria in this setting. Design , setting, participants & measurements We conducted a single-center retrospective study to describe the characteristic features of proteinuria measured within 48 hours following admission among patients with COVID-19 admitted in a tertiary care hospital in France, and to evaluate its association with initiation of dialysis, intensive care unit admission, and death. Results Among 200 patients with available data, urine protein-creatinine ratio at admission was ≥1 g/g for 84 (42%), although kidney function was normal in most patients, with a median serum creatinine of 0.94 mg/dl (interquartile range, 0.75–1.21). Median urine albumin-creatinine ratio was 110 mg/g (interquartile range, 50–410), with a urine albumin-protein ratio
Published: 2021
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29. Ex Vivo Complement Activation on Endothelial Cells: Research and Translational Value

Author: Véronique Frémeaux-Bacchi, Lubka T. Roumenina, Marie-Sophie Meuleman, Sophie Chauvet, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Roumenina, Lubka, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: 0301 basic medicine, Complement, Biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 03 medical and health sciences, 0302 clinical medicine, Kidney injury, Humans, Molecular Biology, Complement Activation, Diagnostics, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Complement Inhibitors, Endothelial Cells, Complement System Proteins, Immunity, Innate, 3. Good health, Cell biology, Complement (complexity), Complement system, Clinical Practice, 030104 developmental biology, Complement Inactivating Agents, Molecular Medicine, 030217 neurology & neurosurgery, Ex vivo
Abstract: International audience; The spectrum of human diseases with complement contribution is ever increasing. Tools to study the complement contribution and the potential interest of novel complement inhibitors in clinical practice are lacking. Here we discuss a functional ex-vivo assay to monitor complement activation on endothelial cells, which can answer to this need.
Published: 2021
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30. Detection of C3 Nephritic Factor by Hemolytic Assay

Author: Sophie Chauvet, Véronique Frémeaux-Bacchi, and Melchior Chabannes
Subjects: 0301 basic medicine, chemistry.chemical_classification, biology, Chemistry, Cell, 030232 urology & nephrology, Autoantibody, Hemolysin, Molecular biology, C3-convertase, Complement system, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Enzyme, biology.protein, medicine, Alternative complement pathway, Antibody
Abstract: C3 nephritic Factor (C3NeF) is autoantibody that binds neoepitopes of the C3 convertase C3bBb, resulting in a stabilization of the enzyme. First functional characterizations of C3NeF were performed by hemolytic assays using preactivated sheep erythrocytes (bearing C3b). Sheep erythrocytes are beforehand sensitized with an anti-sheep red blood cell stroma antibody produced in rabbit (hemolysin). Sensitized sheep erythrocytes will initiate cascade complement activation via the classic pathway, followed by alternative pathway amplification loop, resulting in C3b covalent binding to cell surface. Sheep erythrocytes bearing C3b permit the alternative pathway exploration, in particular decay of alternative pathway C3 convertase.
Published: 2021
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31. Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

Author: Cécile Couchoud, Florian Bayer, Carole Ayav, Clémence Béchade, Philippe Brunet, François Chantrel, Luc Frimat, Roula Galland, Maryvonne Hourmant, Emmanuelle Laurain, Thierry Lobbedez, Lucile Mercadal, Olivier Moranne, Abdelhamid Abbassi, Alain Debure, Abdallah Guerraoui, Abdelatif Benmoussa, Abdelaziz Hamani, Abdelaziz Ziane, Abdelhamid Nefti, Abdelkader Hadj, Abderrahim El Amari, Abderrahmane Ghazali, Abo Bakr Abd El Fatah Mohamed, Achour Laradi, Adel Ben Ahmed, Adel Sahar, Adele Pillet, Adeline Lacraz, Adnan Moinat, Afshin Massoumi, Agathe Pardon, Agnes Caillette Beaudoin, Agnes Chapelet Debout, Agnes Mariot, Ahmed Rachi, Aida Afiani, Aime Remy Boula, Al Jalaby, Alain Cremault, Alain Fournier, Alain Jeanson, Alain Lyon, Alain Nony, Alain Robert, Alain Slingeneyer, Alanor Agnes Labatide, Albane Brodin Sartorius, Albert Bensman, Albert Fournier, Alex Ranlin, Alex Vido Sandor, Alexandra Colombo, Alexandra Duhem, Alexandra Stancu, Alexandre Dufay, Alexandre Dumoulin, Alexandre Ebel, Alexandre Klein, Alexandre Martin, Alexandre Mouneimne, Alexandre Seidowsky, Alfio De Martin, Alfredo Zannier, Ali Aizel, Ali Hafi, Ali Zineddine Diddaoui, Alim Heyani, Alina Mocanu, Alina Preda, Aline Hafi, Aline Talaszka, Alyette Duquesne, Amar Amaouche, Amel Ghemmour, Amelie Simon, Amina Skalli, Amine Boukadida, Amr Ekhlas Ragab Eid, Ana Fedorca, Anabelle Baillet, Anais Poyet, Ancuta Bouffandeau Giorgita, Anderson Ratsimbazafy, Andre Pruna, Angel Argiles, Angelo Testa, Ann Karolien Vandooren, Anne Jolivot, Anne Kolko Labadens, Anne Lataste, Anne Maisin, Anne Paris, Anne Sechet, Anne Wuillai, Anne Elisabeth Heng, Anne Gaelle Josse, Anne Helene Querard, Anne Helene Reboux, Anne Laure Adra, Anne Laure Faller, Anne Laure Leclerc, Anne Laure Poitou, Annie Lahoche Manucci, Antoine Jacquet, Antoine Pommereau, Antoine Thierry, Arezki Adem, Arielle Chapelet, Arnaud Del Bello, Arnaud Delezire, Arnaud Garnier, Arnaud Guerard, Arnaud Klisnick, Arnaud Lionet, Arnaud Roccabianca, Arnaud Stolz, Arthur Capdeville, Asma Allal, Assem Alrifai, Assetou Diarrassouba, Assia Djema, Assia Ferhat Carre, Astrid Godron Dubrasquet, Atman Haddj Elmrabet, Audrey Jegado, Aurelia Bertholet Thomas, Aurelie Davourie Salandre, Aurelie Pajot, Aurelien Lorthioir, Aurelien Tiple, Aurore Sury, Ayman Abokasem, Ayman Sarraj, Bachir Henaoui, Baher Chaghouri, Bassem Wehbe, Beatrice Ball, Beatrice Viron, Belkassem Issad, Benedicte Hodemon Corne, Benedicte Janbon, Benjamin Deroure, Benjamin Savenkoff, Benoit Jonon, Benoit Vendrely, Benyakoub Djelaleddine, Bernard Ohry, Bernard Painchart, Bernard Strullu, Bernard Temperville, Bertin Ebikili, Bertrand Hacq, Bertrand Morel, Bilal Aoun, Blanca Muniz, Bouchra Chlih, Brahim Amara, Brice Mayor, Brigitte Gilson, Brigitte Llanas, Brigitte Zins, Bruno Bourgeon, Bruno Coevoet, Bruno Guery, Bruno Legallicier, Bruno Paris, Bruno Ranchin, Bruno Seigneuric, Camelia Ghiciuc Dita, Camelia Prelipcean, Carine Achard Hottelart, Carine Diet, Carlos Frangie, Carlos Vela, Carmina Muresan, Carole Deprele, Caroline Araujo, Caroline Bidault, Caroline Creput, Caroline Delclaux, Caroline Du Halgouet, Caroline Favennec, Caroline Freguin, Caroline Gourraud Vercel, Caroline Mesguen, Caroline Ndomo Obama, Caroline Poitou, Caroline Preissig Dirhold, Caroline Roubiou, Catherine Albert, Catherine Bessin, Catherine De Marion Gaja, Catherine Godart, Catherine Lasseur, Catherine Leocardi, Catherine Lumbroso, Catherine Melander, Catherine Michel, Catherine Quere Maurouard, Catherine Rouannet, Catherine Taddei, Cathy Verove, Cecile Guiraud, Cecile Tafelin, Cecile Turc Baron, Cedric Formet, Cedric Pinier, Celia Lessore De Ste Foy, Celine Granolleras, Chaouki Bennini, Charles Cartou, Charles Chazot, Charlotte Jouzel, Cherif Badid, Christa Roubicek, Christel Viaud, Christelle Verrier, Christian Chuet, Christian Combe, Christian Dabot, Christian Duvic, Christian Emond, Christian Lagarde, Christian Lamotte, Christian Pain, Christiane Mousson, Christie Lorriaux, Christine Beauchamp, Christine Fumeron, Christine Le Gurun, Christine Leroy, Christine Pietrement, Christine Richer, Christophe Bouaka, Christophe Charasse, Christophe Goupy, Christophe Ridel, Cindy Castrale, Cindy Detourne, Clair Francois, Claire Presne, Claire Trivin, Clarissa Von Kotze, Claude Bernard, Claude Bonniol, Claude Desvergnes, Claude Raharivelina, Claudia Nistor, Claudine Gueret, Claudine Lloret, Claudine Saltiel, Clelia Rosati, Clementine Rabate, Corina Stanescu, Corinne Ferrandini, Corinne Guibergia, Corinne Lemoine, Corinne Passeron, Cynthia Kahil, Cyril Garrouste, Cyril Vo Van, Cyrille Jolimoy, Dalila Kesraoui, Damien Jolly, Damien Thibaudin, Dan Teboulle, Daniel Daubresse, Daniel Louvet, Daniel Rasamimanantsoa, Daniel Toledano, Daniela Babici, Daniela David, Daniela Dincu, Danielle Bruno, Delia May, Delphine Haussaire, Delphine Henriet Viprey, Denis Bugnon, Denis Fouque, Denis Morin, Derradji Nour, Diab Mohamed Mahmoud, Diana Istrati Cristescu, Didier Aguilera, Didier Coste, Didier Hamel, Didier Le Chapois, Didier Testou, Dilaver Erbilgin, Djamal Dahmane, Doan Bui Quang, Dominique Bertrand, Dominique Besnier, Dominique Blanchier, Dominique Briffa, Dominique Caux, Dominique Durand, Dominique Fleury, Dominique Guerrot, Dominique Hestin, Dominique Jaubert, Dominique Joly, Dominique Lombart, Dominique Pagniez, Dominique Pierre, Dominique Schohn, Donatien Ikonga, Dorina Visanica, Dorothee Bazin, Edouard Boury, Edouard Maksour, Ekoue Agbonon, Elarbi Harrami, Elena Marcu, Elena Tudorache, Elisabeth Caniot, Elisabeth Semjen, Elisabeth Tomkiewicz, Elise Scheidt, Elke Gaboriau, Elodie Lamouroux, Elsa Guiard, Elsa Martin Passos, Emerson Nsembani, Emilie Fache, Emilie Kalbacher, Emilie Pambrun, Emilie Pincon, Emma Allain Launay, Emmanuel Baron, Emmanuel Dupuis, Emmanuel Villar, Emmanuelle Charlin, Emmanuelle Hecquet, Emmanuelle Kohler, Emmanuelle Rosier, Enrique Figueroa, Eric Azoulay, Eric Canivet, Eric Daugas, Eric Gauthier, Eric Laruelle, Eric Le Guen, Eric Legrand, Eric Moumas, Eric Postec, Eric Prinz, Eric Renaudineau, Estelle Desport, Estelle Ricard Sutra, Etienne Berard, Etienne Ged, Etienne Robin, Eve Vilaine, Evelyne Bargas, Evelyne Mac Namara, François Combarnous, Fatima Yazbeck, Fabien Gerard, Fabien Metivier, Fabien Parazols, Fabien Soulis, Fabrice Garnier, Fadhila Pech Messaoudene, Fadi Haidar, Fanny Boullenger, Fanny Lepeytre, Fanny Leroy, Fares Frejate, Farid Bellahsene, Farid Bellhasene, Farid Saidani, Fatouma Toure, Faycal Kriaa, Fazia Nemmar, Fernando Vetromile, Florence Chalmin, Florence Lucats, Florence Sens, Florence Villemain, Florent Plasse, Fouad Lebhour, Francis Schillinger, Franck Berge, Franck Bourdon, Franck Bridoux, Franck Reynaud, Francois Babinet, Francois Basse, Francois Chantrel, Francois Clair, Francois Coulomb, Francois De Cornelissen, Francois Glowacki, Francois Marchal, Francois Maurice, Francois Nobili, Francois Pourreau, Francois Provot, Francois Roux Amani, Francoise Broux, Francoise Bulte, Francoise Heibel, Francoise Leonetti, Francoise Moussion Schott, Frank Le Roy, Frederic Besson, Frederic Lavainne, Frederic Tollis, Frederique Bocquentin, Frederique Meeus, Frederique Vecina, Friederike Von Ey, Gabriel Balit, Gabriel Choukroun, Gabriel Gruget, Gabriel Huchard, Gabriella Golea, Gabrielle Duneau, Gaelle Lefrancois, Gaelle Pelle, Gaetan Lebrun, Genevieve Dumont, Georges Brillet, Georges Deschenes, Georges Mourad, Georges Stamatakis, Geraldine Cazajous, Geraldine D'ythurbide, Geraldine Robitaille Wiart, Gerard Cardon, Gerard Champion, Gerard Deschodt, Gerard Mangenot, Gerard Motte, Gerard Schortgen, Ghada Boulahia, Ghassan Maakaroun, Ghylene Bourdat Michel, Gilbert Zanetta, Gilles Hufnagel, Gilles Messier, Giorgina Piccoli, Gregoire Couvrat Desvergnes, Guillaume Bobrie, Guillaume Bonnard, Guillaume Clement, Guillaume Jean, Guillaume Queffeulou, Guillaume Seret, Guillaume Vernin, Guy Delavaud, Guy Lambrey, Guy Rostoker, Gwenaelle Poussard, Gwenaelle Roussey Kesler, H. Leon, Habib Aboubekr, Hacene Boulechfar, Hacene Sekhri, Hadia Hebibi, Hadjira Benalia, Hafed Fessi, Hafsabhai Atchia, Haiat Bittar, Hakim Maiza, Hakim Mazouz, Hamid El Ali, Hammouche Bougrida, Hans Van Der Pijl, Hassan Lokmane, Hassane Izzedine, Hassen Adda, Helene De Preneuf, Helene Leray, Helene Philippot, Henri Boulanger, Henri Merault, Henri Renaud, Herve Bonarek, Herve Maheut, Hilaire Nzeyimana, Hocine Mehama, Hocine Zaidi, Hugo Weclawiak, Hugues Flodrops, Huseyin Karaaslan, Ibrahim Haskour, Ihssen Belhadj, Imad Almoubarak, Imad Haddad, Ines Castellano, Ines Ferrandiz, Ioana Daniliuc, Ioana Darie, Ioana Enache, Ionut Prunescu, Irenee Djiconkpode, Irina Shahapuni, Isabelle Bouchoule, Isabelle Devriendt, Isabelle Kazes, Isabelle Kolb, Isabelle Landru, Isabelle Poli, Isabelle Rey, Isabelle Segalen, Isabelle Selcer, Isabelle Vernier, Isabelle Vrillon, Ismahane Guenifi, J. Dominique Gheerbrandt, Jacky Potier, Jacques Becart, Jacques Cledes, Jacques Ducros, Jacques Duvic, Jacques Fourcade, Jacques Gaultier, Jacques Jurine, Jacques Lebleu, Jacques Ollier, Jacques Ibsen Charles, Jamal Yazji, Janette Mansour, Jean Arnautou, Jean Brocard, Jean Carolfi, Jean Montoriol, Jean Baptiste Gouin, Jean Bernard Palcoux, Jean Christophe Bendini, Jean Claude Aldigier, Jean Claude Alphonse, Jean Daniel Delbet, Jean Francois Bonne, Jean Francois Cantin, Jean Francois De Fremont, Jean Francois Dessassis, Jean Francois Subra, Jean Francois Valentin, Jean Francois Verdier, Jean Jacques Dion, Jean Jacques Haultier, Jean Jacques Montseny, Jean Louis Bacri, Jean Louis Bouchet, Jean Luc Mahe, Jean Marc Chalopin, Jean Marc Gabriel, Jean Marc Hurot, Jean Marc Lanau, Jean Marie Batho, Jean Marie Coulibaly, Jean Michel Hardin, Jean Michel Marc, Jean Michel Poux, Jean Michel Rebibou, Jean Michel Tivollier, Jean Noel Ottavioli, Jean Paul Faucon, Jean Paul Imiela, Jean Paul Jaulin, Jean Paul Masselot, Jean Paul Ortiz, Jean Philippe Bourdenx, Jean Philippe Devaux, Jean Philippe Hammelin, Jean Pierre Rivory, Jean Pierre Wauquier, Jean Rene Larue, Jean Rene Mondain, Jean Sebastien Borde, Jean Simon Virot, Jean Yves Bosc, Jedjiga Achiche, Jennifer Parasote, Jeremie Diolez, Jerome Harambat, Jerome Potier, Jerome Sampol, Jihad Mustel, Jean Jacques Lefevre, Jocelyne Maurizi, Joel Gamberoni, Joelle Claudeon, Joelle Terzic, Joffrey Rogol, Johnny Sayegh, Jorge Cardozo, Jose Brasseur, Jose Guiserix, Joseph Barsumau, Julie Albaret, Julie Beaume, Julie Sohier Attias, Julien Dehay, Julien Hogan, Julien Journet, Julien Ott, Juliette Baleynaud, Justine Bacchetta, Justine Faucher, Kamel Yousfi, Karim Dardim, Karine Clabault, Karine Moreau, Kedna Thomas, Khaled Sirajedine, Khalil Chedid, Khalil El Kaeoui, Khalil El Karoui, Khedidja Bouachi, Kheira Hue, Khuzama El Nasser, Kodso Akposso, Kristian Kunz, Krzysztof Bijak, Lilia Kihal, L. Rasoloarijaona, Laid Harbouche, Larbi Bencheikh, Larbie Lamriben, Latifa Hanafi, Laura Braun Parvez, Laure Champion, Laure Croze, Laure Eprinchard, Laure Patrier, Laurence Nicolet, Laurence Vrigneaud, Laurent Duflot, Leandre Mackaya, Leila Chenine, Leon Odry, Lili Taghipour Tamiji, Lilia Antri Bouzar, Liliane Ngango Nga Messi, Lionel Le Mouellic, Lise Mandart, Lise Weis, Lise Marie Pouteau, Lora Georgieva, Lorita Vitanova, Lotfi Chalabi, Luc Delvallez, Luc Fromentin, Luc Marty, Luc Monjot, Luciana Spataru, Lucie Bessenay, Lucie Boissinot, Lucie Wajsbrot, Lucien Rakoff, Ludivine Lebourg, Lydie Perez, Lyliane Lafage, Lynda Azzouz, Madeleine Dumoulin, Messaoud Ouziala, Maan Joseph, Mabrouk Brahimi, Maeva Wong Fat, Magalie Fort, Magued Nakhla, Mahdi Abtahi, Mahen Albadawy, Mahmoud Alouach, Mahmoud Mezghani, Maite Daroux, Maklouf Boukelmoune, Malek Dhib, Malik Touam, Malina Dubau, Mamadou Balde, Man Nguyen Khoa, Manfred Ismer, Manolie Mehdi, Manon Laforet, Marc Bouiller, Marc Eugene, Marc Fila, Marc Hazzan, Marc Kribs, Marc Ladriere, Marc Lebot, Marc Padilla, Marc Souid, Marcel Marraoui, Maren Burbach, Maria Manescu, Maria Eugenia Noguera Gonzalez, Mariana Revenco, Marianne Terrasse, Marie Essi, Marie Alice Macher, Marie Beatrice Nogier, Marie Cecile Cazin, Marie Christine Schweitzer Camoin, Marie Christine Thouret, Marie Claude Hannaert, Marie France Servel, Marie Helene Chabannier, Marie Jeanne Coudert Krier, Marie Noelle Catoliquot, Marie Paule Guillodo, Marie Sophie Gavard, Marie Xaviere Vairon Codaccioni, Marina Rabec, Marine Freist, Marion Gauthier, Marion Lemaire, Marion Mehrenberger, Marion Venot, Marios Pongas, Marlene Beaubrun Diant, Martial Levannier, Martine Bertaux, Mathieu Jablonski, Mathieu Sacquepee, Mathilde Dargelos, Mathilde Lemoine, Mathilde Tamain, Matthieu Monge, Matthieu Reberolle, Maud Cousin, Maud Francois, Maurice Baron, Maxime Hoffmann, Maxime Ingwiller, Maxime Touzot, Mederick Mohajer, Mehadji Maaz, Melanie Hanoy, Melanie Marroc, Melodie Cuny, Menno Van Der Straaten, Mf. Serveaux, Michel Basteri, Michel Fen Chong, Michel Hecht, Michel Massad, Michel Normand, Michel Olmer, Michel Tolani, Michel Tsimaratos, Michele Hemery, Michele Kessler, Miguel Esposito, Milad Shenouda, Mimi Kareche, Mina Khalili, Mirella Diaconita, Mohamad Khair Rifard, Mohamed Aladib, Mohamed Belmouaz, Mohamed Brahim, Mohamed Diouani, Mohamed Fodil Cherif, Mohamed Jamali, Mohamed Maghlaoua, Mohamed Meddeb, Mohamed Ramdane, Mohamed Rifaat, Mohamed Sharifull Islam, Mohamed Adnan Abbade, Mokhtar Amrandi, Mokhtar Chawki, Monica Ciobotaru, Monica Indrieis, Monique Chanas, Monique Hoarau, Monzer Tomeh, Moufida Bellou, Mouloud Bouzernidj, Mounia Ammor, Mounir Guergour, Mountassir Benzakour, Mourad Hachicha, Moussa Coulibaly, Mustafa Smati, Mustapha Al Morabiti, Mustapha Amirou, Myriam Isnard, Myriam Pastural, Myriam Pujo, Nourredine Boumendjel, Nabil Majbri, Nabila Goumri, Nadege Mingat, Nader Bassilios, Nadia Kerkeni, Nadia Sedrati, Nadia Soltani, Nadine Maroun, Nadine Neyrat, Nahn Luang, Najeh El Esper, Naji Ammar, Nasredine Ghali, Nasser Hamdini, Natacha Noel, Natacha Potelune, Nathalie Maisonneuve, Nathalie Pertuiset, Nathalie Raynal, Nathalie Vittoz, Nazim Terki, Nelly Castin, Nestor Nankeu, Nicolas Bouvier, Nicolas Keller, Nicolas Legros, Nicolas Peters, Nicolas Quirin, Nicole Lefrancois, Nicole Monnier, Nicole Rance, Niels Bruckmann, Noel Mertens, Nolwenn Lorcy, Olivia Gilbert, Olivier Coldefy, Olivier Drouineau, Olivier Dunand, Olivier Fritz, Olivier Imhoff, Olivier Kourilsky, Olivier Lavelle, Olivier Papin, Olivier Roques, Ophelie Le Maner, Oussamah Fikri Benbrahim, Pablo Antonio Erina Torres, Pablo Antonio Urena Torres, Paolo Malvezzi, Pascal Bindi, Pascal Cluzel, Pascal Fontanier, Pascal Wheatley, Pascale Depraetre, Pascale Dubosq, Pascale Halin, Pascale Sebahoun, Pascale Siohan, Pascale Testevuide, Patrice Deteix, Patrice Nolen, Patricia Hue, Patricia Lemarchand, Patrick Donnadieu, Patrick Fievet, Patrick Fohrer, Patrick Francais, Patrick Giraud, Patrick Hallonet, Patrick Henri, Patrick Michaut, Patrick Niaudet, Patrick Pauly, Patrick Thomas, Patrik Deleaval, Paul Finielz, Paul Stroumza, Paule Hardy Yverneau, Pauline Caillard, Pedro Palacin, Perrine Aubertin, Philippe Attias, Philippe Chauveau, Philippe Coindre, Philippe Coste, Philippe Dubot, Philippe Fournier, Philippe Hiernaux, Philippe Jousset, Philippe Lan Yue Wah, Philippe Lang, Philippe Le Cacheux, Philippe Martin Dupont, Philippe Michel, Philippe Mirgaine, Philippe Moriniere, Philippe Nicoud, Philippe Rieu, Philippe Rousseau, Philippe Sporer, Philippe Thorel, Philippe Vanhille, Philippe Vigeral, Philippe Zaoui, Pierre Bataille, Pierre Brignon, Pierre Filipozzi, Pierre Housset, Pierre Peyronnet, Pierre Ramperez, Pierre Vautrin, Pierre Alexandre Michel, Pierre Francois Westeel, Pierre Louis Carron, Pierre Yves Durand, Pierrot Parent, Piotr Seniuta, François Kuentz, Rabah Fraoui, Rachel Tetaz, Rachid Amaria, Rachid Bourouma, Rachid Djeffal, Rachida Nebbad, Radia Allal, Radu Dimulescu, Rafaat Boustani, Rafik Mesbah, Raifat Makdassi, Raji Diab, Raluca Puslenghea, Raoul Roura, Rateb Khayat, Raymond Azar, Raymond Frayssinet, Regine Monkam, Rehouni Boulahrouz, Remi Boudet, Renato Demontis, Renaud Gansey, Rene Cuvelier, Renee Schmitt, Reschad Noordally, Reynald Binaut, Rezkallah Latif, Richard Dufresne, Richard Montagnac, Richard Reade, Robert Genin, Robert Novo, Rocsana Fickl, Roger Dufresne, Roger Magnol, Roland Issautier, Romain Mortelette, Ronan Delaval, Ronan Lohro, Roseline M'barga, S. Beau, Clémentine Dupuis, Marie Jacques Vidil, Sabria Hacini, Said Dahmoune, Saliha Lekhal, Salima Ahriz Sakso, Salima Saksi, Salvatore Citarda, Samir Boubenider, Samuel Kassis, Sandra Verhille, Sandrine Genestier, Sandrine Muller, Saoussen Krid, Sarah Richter, Sebastien Delbes, Sebastien Mailliez, Sebastien Veillon, Sébastien Nony, Seddick Benarbia, Severine Beaudreuil, Sidi Ali Benyaghla, Simon Duquennoy, Simona Baluta, Simona Boncila, Sonia Mzoughi, Sonia Ribal, Sophie Acamer, Sophie Chauvet, Sophie Girerd, Sophie Ozenne, Sophie Parahy, Sophie Rubens Duval, Sophie Taque, Soraya Menouer, Soumaya Chargui, Stanislas Bataille, Stephane Barbier, Stephane Billion, Stephane Roueff, Stephane Torner, Stephane Jean Martin, Stephanie Coupel, Sylvie Cloarec, Sylvie Lavaud, Sylvie Leou, T. Chatelet, Tania Onesta, Tassadit Benhabib, Tayeb Bensalem, Theodora Dimulescu, Theophile Sawadogo, Thibault Dolley Hitze, Thierry Baranger, Thierry Boudemaghe, Thierry Hannedouche, Thierry Krummel, Thierry Milcent, Thomas Dervaux, Thomas Guincestre, Thomas Kofman, Thomas Raphael, Thomas Sadreux, Tim Ulinski, Tiphaine Guyon Roger, Tomas Serrato, Tomek Kofman, Tony Wong, Toufik Boubia, Ubald Assogba Gbindoun, Usama Khuzaie, Valerie Caudwell, Valerie Chatelet, Valerie Crougneau, Valerie De Precigout, Valerie Drouillat, Valerie Galantine, Valerie Granveau Hugot, Valerie Leroy, Veronique Boubia, Veronique Falque, Veronique Fournier, Veronique Queron, Veronique Viviani, Victor Gueuttin, Victor Panescu, Victorio Menoyo Calonge, Viet Nguyen, Vincent Allot, Vincent Delattre, Vincent Leduc, Vincent Pradier, Violaine Emal Aglae, Viorica Badulescu, Virginia Molina, Virginie Besson, Virginie Chaigne, Waddah Jaber, Wael Boudi, Wael El Haggan, Wen Qin Guillon, Wided Tabbi Aneni, William Hanf, Wladimir Kohn, Xavier Bellenfant, Xavier Moreau Gaudry, Yahsou Delmas, Yannick Knefati, Yannick Saingra, Yannick Tirolien, Youssef Mann, Yvan Brunak, Yves Dimitrov, Yves Doussy, Yves Tanter, Zaid Benabid, Zaara Soltani, Zacharia Boukerroucha, Zafer Takla, Zana Ramanantsialonina, Zara Dickson, Zead Tubail, Zoe Koochaki Pour, Zohra Boukhalfa, Zohra Jacquot, Agence de la biomédecine [Saint-Denis la Plaine], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université de Caen Normandie (UNICAEN), Normandie Université (NU), CALYDIAL Vienne, Partenaires INRAE, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Armand Trousseau [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] (Pôle S2R), Centre Universitaire des Maladies Rénales [CHU Caen] (CUMR Caen), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Assistance Publique - Hôpitaux de Marseille (APHM), Service de diabétologie [CHU Pitié-Salpétrière], 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 Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Service de Diabétologie [CHU Pitié-Salpétrière], 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: 0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Hemodialysis, Home, Disease, MESH: COVID-19 / therapy, registry, Ambulatory Care Facilities, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Aged, 80 and over, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, 80 and over, Prevalence, covid, dialysis, epidemiology, mortality, Aged, Aged, 80 and over, COVID-19, Case-Control Studies, Critical Care, Female, France, Humans, Incidence, Middle Aged, Patient Acuity, Protective Factors, Registries, Renal Dialysis, SARS-CoV-2, Sex Factors, Hypoalbuminemia, MESH: France / epidemiology, education.field_of_study, Incidence (epidemiology), 3. Good health, MESH: COVID-19 / epidemiology, Nephrology, Hemodialysis, medicine.medical_specialty, Population, Lower risk, Article, 03 medical and health sciences, MESH: Sex Factors, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Renal Dialysis / statistics & numerical data, education, Dialysis, Vascular disease, business.industry, medicine.disease, Former Smoker, MESH: Critical Care / statistics & numerical data, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Home, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Hemodialysis, Home / statistics & numerical data
Abstract: The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract
Published: 2020
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32. Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer

Author: Adrien Lucchesi, Fabienne Guillaumond, Pierre Pudlo, Florence Hubert, Chloé Dominici, Jean-Yves Scoazec, Fanny Mann, Sophie Chauvet, Jérémy Nigri, Thi Trang Huyen Nguyen, Jeremy Guillot, Nelson Dusetti, Martin Bigonnet, Anders Etzerodt, Richard Tomasini, Serge A. van de Pavert, and Toby Lawrence
Subjects: 0303 health sciences, Pathology, medicine.medical_specialty, Tumor microenvironment, Sympathetic nervous system, business.industry, medicine.medical_treatment, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Sympathectomy, Immunity, Pancreatic cancer, medicine, Macrophage, business, CD163, 030217 neurology & neurosurgery, 030304 developmental biology, Sprouting
Abstract: Recent evidence has highlighted the presence of neuronal nerve processes in the tumor microenvironment. However, the origin of intra-tumoral nerves remains poorly known, in part because of technical difficulties in tracing nerve fibers via regular histological preparations. Here, we employed three-dimensional (3D) imaging of cleared tissues for a comprehensive analysis of sympathetic innervation in pancreatic ductal adenocarcinoma (PDAC). The results support two independent, but coexisting, mechanisms: passive engulfment of pre-existing nerves within tumors and active, localized sprouting of nerve terminals into non-neoplastic lesions and tumor periphery. Nerve ablation revealed an inverse correlation between sympathetic innervation and tumor growth and spread. Furthermore, sympathectomy increased CD163+macrophage levels, which contributed to worse outcomes. Altogether, our findings revealed protective properties of the sympathetic nervous system in PDAC immunity and progression that could pave the way for new treatments.
Published: 2020
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33. Coping Strategies and Factors Related to Problematic Substance Use and Behavioral Addictions Among Adolescents and Young Adults with Cancer

Author: E. Seigneur, Tanguy Leprince, Kristopher Lamore, Nadège Corradini, Perrine Marec-Berard, Daniela Silva Moura, Valérie Laurence, Cécile Flahault, Nicolas Blin, Solène Grégoire, and Sophie Chauvet
Subjects: Adult, Male, Behavioral addiction, Coping (psychology), Adolescent, Substance-Related Disorders, media_common.quotation_subject, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Adaptation, Psychological, medicine, Humans, 030212 general & internal medicine, Cannabis Dependence, media_common, Alcohol Use Disorders Identification Test, biology, business.industry, Addiction, biology.organism_classification, medicine.disease, humanities, Behavior, Addictive, Eating disorders, Oncology, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Anxiety, Female, Cannabis, medicine.symptom, business, Clinical psychology
Abstract: Purpose: This study aimed to explore and identify the factors associated with problematic substance use (alcohol, tobacco, and cannabis) and behavioral addictions (internet and eating disorders) over time in adolescents and young adults (AYAs) treated for cancer. Methods: AYAs newly diagnosed with cancer, 15-25 years of age, completed a questionnaire during their hospitalization (T1), assessing their consumption of alcohol, tobacco, and cannabis (The Alcohol Use Disorders Identification Test; The Smoking Behavior Questionnaire; and The Cannabis Abuse Screening Test), their internet use (The Internet Addiction Test), their body preoccupations (The Eating Attitudes Test), as well as their coping strategies (Brief COPE) and emotional adjustment (The Hospital Anxiety and Depression Scale). Questionnaires were completed again 6 months later (T2). Results: Seventy-three AYAs were included at T1 and 21 AYAs at T2. Nearly one out of two (46.58%) AYAs had a problematic substance use or behavioral addiction after cancer diagnosis (T1). Problematic use of internet was frequently reported (23.29%), as well as harmful alcohol consumption or addiction (16.44%) and cannabis dependence (12.33%). The main factor related to problematic substance use was being older, while the main factor related to behavioral addiction was having a higher anxiety score. Substance use as a coping strategy was used more frequently by AYAs with problematic substance use and emotional support as a coping strategy was used more frequently by AYAs with a behavioral addiction. Conclusions: High rates of problematic substance use and behavioral addiction were reported in our sample. AYAs surveyed had high problematic use of cannabis and high internet use. Attention to substance use and addictive behaviors is recommended to ensure optimal care.
Published: 2020

34. Complement C3-targeted therapy in C3 glomerulopathy, a prototype of complement-mediated kidney diseases

Author: Marie-Sophie, Meuleman, Anne, Grunenwald, and Sophie, Chauvet
Subjects: Immunology, Immunology and Allergy
Abstract: C3 glomerulopathy (C3G) is a rare and complex kidney disease that primarily affects young adults. Renal outcomes remain poor in the absence of specific treatment. C3G is driven by uncontrolled overactivation of the alternative complement pathway, which is mainly of acquired origin. Functional characterization of complement abnormalities (i.e., autoantibodies targeting complement components and variants in complement genes) identified in patients and experimental models of the disease improved the understanding of the disease, making C3G a prototype of complement-mediated diseases. The contribution of C3 convertase, as well as C5 convertase, in disease occurrence, phenotype, and severity is now well established, offering various potential therapeutic interventions. However, the lack of sufficient efficiency in anti-C5 therapy highlights the extreme complexity of the disease and the need for new therapeutic approaches based on C3 and C3 convertase axis inhibition. Here, we provide an overview of the complement activation mechanism involved in C3G and discuss therapeutic options based on complement inhibitors, with a specific focus on C3 inhibition.
Published: 2022
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35. Complement activation is a crucial driver of acute kidney injury in rhabdomyolysis

Author: Francesca Lucibello, Véronique Frémeaux-Bacchi, Conrad A. Farrar, Juliette Leon, Marie V. Daugan, Patrick Girardie, Pascale de Lonlay, Amandine Ydee, Lubka T. Roumenina, Caroline Rambaud, Romain Berthaud, Moglie Le Quintrec, Victoria Poillerat, Sophie Chauvet, Idris Boudhabhay, Peter Garred, Khalil El Karoui, Marion Rabant, Carine Torset, Anne Grunenwald, Marie Frimat, Viviane Gnemmi, Steven H. Sacks, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), King‘s College London, University of Copenhagen = Københavns Universitet (UCPH), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte [CHU Necker] (MaMEA Necker), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Raymond Poincaré [AP-HP], Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Roumenina, Lubka, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie [Paris], Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), University of Copenhagen = Københavns Universitet (KU), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: 0301 basic medicine, hemopexin, 030232 urology & nephrology, lectin pathway, Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Rhabdomyolysis, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, C3 deposition, Animals, Humans, complement, heme, Complement Activation, biology, rhabdomyolysis-induced acute kidney injury, Myoglobin, business.industry, Acute kidney injury, Hemopexin, Acute Kidney Injury, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Complement system, 030104 developmental biology, medicine.anatomical_structure, Integrin alpha M, Nephrology, Lectin pathway, Alternative complement pathway, Cancer research, biology.protein, business
Abstract: International audience; Rhabdomyolysis is a life-threatening condition caused by skeletal muscle damage with acute kidney injury being the main complication dramatically worsening the prognosis. Specific treatment for rhabdomyolysis-induced acute kidney injury is lacking and the mechanisms of the injury are unclear. To clarify this, we studied intra-kidney complement activation (C3d and C5b-9 deposits) in tubules and vessels of patients and mice with rhabdomyolysis-induced acute kidney injury. The lectin complement pathway was found to be activated in the kidney; likely via an abnormal pattern of Fut2-dependent cell fucosylation, recognized by the pattern recognition molecule collectin-11 and this proceeded in a C4-independent, bypass manner. Concomitantly, myoglobin-derived heme activated the alternative pathway. Complement deposition and acute kidney injury were attenuated by pre-treatment with the heme scavenger hemopexin. This indicates that complement was activated in a unique double-trigger mechanism, via the alternative and lectin pathways. The direct pathological role of complement was demonstrated by the preservation of kidney function in C3 knockout mice after the induction of rhabdomyolysis. The transcriptomic signature for rhabdomyolysis-induced acute kidney injury included a strong inflammatory and apoptotic component, which were C3/complement-dependent, as they were normalized in C3 knockout mice. The intra-kidney macrophage population expressed a complement-sensitive phenotype, overexpressing CD11b and C5aR1. Thus, our results demonstrate a direct pathological role of heme and complement in rhabdomyolysis-induced acute kidney injury. Hence, heme scavenging and complement inhibition represent promising therapeutic strategies.
Published: 2020
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36. Développement d’une nouvelle technique de détection du C3 Nephritic Factor : impact sur la prise en charge de la glomérulonéphrite à dépôts de C3

Author: E. Devêvre, Maria-Chiara Marinozzi, Véronique Frémeaux-Bacchi, Sophie Chauvet, N. Simon-Tillaux, H. Fohrer-Ting, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: 03 medical and health sciences, 0302 clinical medicine, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Nephrology, 030232 urology & nephrology, [SDV.CAN]Life Sciences [q-bio]/Cancer, 030204 cardiovascular system & hematology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Introduction La glomerulonephrite a depots de C3 (GC3) est associee a la presence d’un auto-anticorps stabilisant la C3 convertase alterne (C3bBb), le C3 Nephritic Factor (C3NeF), conduisant a une activation incontrolee du complement. Cependant, sa technique de detection, le test hemolytique (TH), n’est pas standardisee et reservee aux laboratoires specialises. Nous avons donc developpe la recherche de C3NeF par Luminex®. Methodes La capacite de fixation et de stabilisation d’une C3 convertase alterne, formee sur bille, par des immunoglobulines G (IgG) de patients atteints de GC3 a ete etudiee. Ces resultats ont ete confrontes a ceux du TH. Les anticorps anti-C3b ont ete egalement recherches. La C3Bb est formee avec du facteur B et D sur des billes recouvertes de C3b. Les IgG purifiees de patients sont ensuite ajoutees, puis la fixation des IgG anti-C3bBb (ou anti-C3b sur billes seules) est quantifiee par un anticorps anti-IgG couple a la phycoerythrine (PE). La stabilisation de la C3 convertase alterne est revelee par un anticorps anti-Bb biotinyle, melange a la streptavidine-PE. Le seuil de positivite des tests (moyenne + 2 ecarts-types) est determine a partir des IgG de 30 donneurs sains et exprime en intensite de fluorescence moyenne (MFI). Resultats obtenus ou attendus Trente deux patients positifs en TH ont ete testes. 21/24 etaient positifs en stabilisation (p = 0,62 versus TH, kappa = 0,82) et 24/29 en fixation de la C3bBb (p = 1 versus TH, kappa = 0,72). 15/31 patients presentaient des anticorps anti-C3b. Trois patients negatifs en TH presentant une GC3 etaient positifs en IgG anti-C3bBb, suggerant une meilleure sensibilite du Luminex®. La MFI de l’IgG anti-C3bBb etait inversement correlee au dosage plasmatique de C3 (p = 0,0001). Conclusion Cette technique, simple de mise en œuvre, presente une bonne correlation avec le TH, et permettrait une meilleure detection des C3NeF et des anticorps anti-C3b. Ce test pourrait devenir l’outil de reference pour le diagnostic et le suivi des GC3.
Published: 2019
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37. Clinicopathological spectrum of renal parenchymal involvement in B-cell lymphoproliferative disorders

Author: Laure Ecotiere, Jean-Michel Goujon, Sophie Chauvet, Vincent Delwail, Cécile Vigneau, Nathalie Rioux-Leclerc, Arnaud Jaccard, Elise Gand, Antoine Thierry, Cécile Tomowiak, Vincent Javaugue, Xavier Leleu, Céline Debiais-Delpech, Frank Bridoux, Jean-Paul Fermand, Estelle Desport, Stéphanie Guidez, Mathilde Nouvier, Guy Touchard, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hopital Saint-Louis, Assistance Publique – Hôpitaux de Paris (AP-HP), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Kidney Cortex, Adolescent, Biopsy, [SDV]Life Sciences [q-bio], kidney biopsy, 030232 urology & nephrology, Lymphoproliferative disorders, Gastroenterology, Nephropathy, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, Multiple myeloma, Aged, Retrospective Studies, Aged, 80 and over, Kidney, business.industry, urogenital system, B-cell lymphoma, Incidence, monoclonal gammopathy, Acute kidney injury, Macroglobulinemia, Middle Aged, medicine.disease, Lymphoproliferative Disorders, 3. Good health, Proteinuria, 030104 developmental biology, medicine.anatomical_structure, acute kidney injury, Nephrology, Female, business, Enlarged kidney, Kidney disease
Abstract: International audience; The clinicopathological characteristics of kidney infiltration in B-cell lymphoproliferative disorders remain poorly described. We retrospectively studied 52 adults with biopsy-proven malignant B-cell kidney infiltration, including Waldenström's macroglobulinemia (n=21), chronic lymphocytic leukemia (n=11), diffuse large B-cell lymphoma (DLBCL) (n=8), other lymphoma (n=11), and multiple myeloma (n=1). Kidney disease varied according to the underlying lymphoproliferative disorder. In DLBCL, malignant kidney infiltration was prominent, resulting in acute kidney injury (AKI, 75%) and kidney enlargement (88%). In the other types, associated immunoglobulin-related nephropathy (most commonly AL amyloidosis) was more common (45%), and chronic kidney disease with proteinuria was the primary presentation. All patients received chemotherapy. Over a median follow-up of 31 months, 20 patients died and 21 reached end-stage kidney disease. Renal response, achieved in 25 patients (48%), was associated with higher overall survival (97 vs. 37 months in non-renal responders). In univariate analysis, percentage of sclerotic glomeruli, kidney enlargement, and complete hematological response at 6 months were predictive of renal response. In multivariate analysis, concomitant immunoglobulin-related nephropathy was the sole independent predictor of poor renal outcome. In conclusion, clinical presentation of renal lymphomatous infiltration depends on the nature of the underlying lymphoproliferative disorder. In DLBCL, massive renal infiltration manifests with enlarged kidneys and AKI, and the diagnosis primarily relies on lymph node biopsy. In other B-cell lymphoproliferative disorders, the clinicopathological spectrum is more heterogeneous, with a high frequency of immunoglobulin-related nephropathy that may affect renal outcome; thus kidney biopsy is required for early diagnosis and prognostic assessment. © 2019 International Society of Nephrology
Published: 2019
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38. Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

Author: Marie Frimat, Georges Deschênes, Christophe Legendre, Alexandre Hertig, Dominique Bertrand, Jérôme Olagne, Bruno Moulin, Tim Ulinski, Véronique Frémeaux-Bacchi, Stéphane Burtey, Lubka T. Roumenina, Michel Delahousse, Sophie Chauvet, Moglie Le Quintrec, Maria Chiara Marinozzi, Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Etudes sur les Réformes, l'Humanisme et l'Age Classique (CERHAC), Institut d'Histoire de la Pensée Classique (IHPC), Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP, Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, Vascular research center of Marseille (VRCM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de transplantation rénale, Hôpital Foch [Suresnes], Service de Néphrologie et Transplantation, CHU Strasbourg, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [APHP], Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie Pédiatrique [Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)
Subjects: Adult, Male, 0301 basic medicine, Adolescent, Glomerulonephritis, Membranoproliferative, [SDV]Life Sciences [q-bio], Complement receptor 1, Complement factor B, Young Adult, 03 medical and health sciences, Clinical Research, Glomerulopathy, Humans, Medicine, complement, Child, ComputingMilieux_MISCELLANEOUS, Autoantibodies, Retrospective Studies, biology, business.industry, Autoantibody, General Medicine, Middle Aged, medicine.disease, C3-convertase, In vitro, 3. Good health, chronic glomerulonephritis, 030104 developmental biology, Nephrology, Immunoglobulin G, Complement C3b, Immunology, Alternative complement pathway, Female, biology.gene, business, Nephrotic syndrome, Complement Factor B, clinical immunology
Abstract: International audience; In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9. In vitro, IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment.
Published: 2017
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39. Caractérisation clinique et immunologique des formes mixtes associant glomérulonéphrite à C3 et SHU atypique : résultats d’une étude rétrospective multicentrique

Author: Sophie Caillard, Sophie Chauvet, Marion Rabant, V. Fremeaux Bacchi, A. Karras, M. Chabannes, Karine Dahan, Thomas Crepin, and Didier Ducloux
Subjects: Nephrology
Abstract: Introduction La glomerulopathie a C3 (GC3) et le syndrome hemolytique et uremique atypique sont deux pathologies renales differentes, resultant d’une deregulation de la voie alterne (VA) du complement. De rares observations de formes mixtes GC3/microangiopathie thrombotique (MAT) ont ete rapportees. L’objectif de cette etude a ete de mieux caracteriser ces atteintes. Methodes Ont ete inclus les patients de la cohorte francaise de GC3 presentant en plus des lesions histologiques de MAT apres relecture centralisee par un anatomopathologiste. Les donnees cliniques et immunologiques au diagnostic, les traitements recus et le suivi renal ont ete analyses. Resultats Entre 2009 et 2019, 19 patients, soit 6 % de la cohorte GC3 repondent aux criteres d’inclusion. Au diagnostic, 37 % sont des hommes avec un âge median de 45,6 ans. L’atteinte renale est severe : tous ont une insuffisance renale (> stade 3 CKD) et 4 (21 %) requierent la dialyse. Quatre-vingt-deux pour cent des patients ont des stigmates de MAT biologiques, et 32 % des criteres d’HTA maligne. Sur le plan immunologique, 47 % des patients ont un C3 bas. Aucun patient n’a de C3nef, 21 % ont un anti-FH de faible titre, et 63 % un variant rare/pathogene des proteines de la VA. Six sur 19 (32 %) ont une gammapathie monoclonale. Sur le plan therapeutique, 66 % ont recu de l’eculizumab, 63 % un traitement immunosuppresseur (IS) et 32 % un traitement hematologique. Apres un recul median de 57,9 mois, 63 % des patients sont en IRCT. Conclusion Nous rapportons la 1re serie de patients atteints de GC3/MAT. L’association est rare, touchant preferentiellement la femme adulte et est de pronostic particulierement severe. La GC3/MAT est associee a des anomalies de la VA differentes de la GC3 seule, et doit faire rechercher un variant des proteines du complement mais aussi une gammapathie monoclonale. La question d’un continuum physiopathologique et donc d’un traitement sequentiel par eculizumab + IS ou traitement hematologique est soulevee.
Published: 2020
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40. Detection of Autoantibodies to Complement Components by Surface Plasmon Resonance-Based Technology

Author: Remi, Noe, Sophie, Chauvet, Shambhuprasad K, Togarsimalemath, Maria Chiara, Marinozzi, Maria, Radanova, Vasil V, Vasilev, Veronique, Fremeaux-Bacchi, Marie-Agnes, Dragon-Durey, and Lubka T, Roumenina
Subjects: Immunoglobulin G, Humans, Complement System Proteins, Antigens, Surface Plasmon Resonance, Dialysis, Autoantibodies
Abstract: The innate immune complement system is a powerful defense cascade against pathogens, but can induce host tissue damage when overactivated. In pathological conditions, mainly but not restricted to renal diseases, such as lupus nephritis, atypical hemolytic uremic syndrome, and C3 glomerulopathies, complement is overactivated or dysregulated by autoantibodies directed against its components and regulators. Among the key autoantibody targets are the initiator of the classical complement pathway C1q, the alternative pathway regulator Factor H, the components of the alternative pathway C3 convertase complex C3 and Factor B and the convertase complex itself. This methodological article describes our experience with a method for detection of anti-complement autoantibodies in real time using surface plasmon resonance-based technology. It allows label-free evaluation of the binding efficacy and stability of the formed antigen-antibody complexes.
Published: 2018

41. Developmental Upregulation of Ephrin-B1 Silences Sema3C/Neuropilin-1 Signaling during Post-crossing Navigation of Corpus Callosum Axons

Author: Sophie Chauvet, Fanny Mann, Mélanie Hocine, Elsa Bazellières, Thomas Jungas, Erik Mire, Alice Davy, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Centre de biologie du développement (CBD), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille-Luminy (IBDML), and Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, semaphorins, Neuropilins, neuropilins, ephrins, [SDV]Life Sciences [q-bio], Ephrin-B1, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Corpus callosum, General Biochemistry, Genetics and Molecular Biology, corpus callosum, 03 medical and health sciences, Mice, Semaphorin, medicine, Ephrin, Animals, Gene Silencing, ComputingMilieux_MISCELLANEOUS, axon guidance, Erythropoietin-producing hepatocellular (Eph) receptor, Gene Expression Regulation, Developmental, Commissure, Axons, Neuropilin-1, 030104 developmental biology, medicine.anatomical_structure, cortex, nervous system, Cerebral cortex, Axon guidance, General Agricultural and Biological Sciences, Neuroscience
Abstract: International audience; The corpus callosum is the largest commissure in the brain, whose main function is to ensure communication between homotopic regions of the cerebral cortex. During fetal development, corpus callosum axons (CCAs) grow toward and across the brain midline and then away on the contralateral hemisphere to their targets. A particular feature of this circuit, which raises a key developmental question, is that the outgoing trajectory of post-crossing CCAs is mirror-symmetric with the incoming trajectory of pre-crossing axons. Here, we show that post-crossing CCAs switch off their response to axon guidance cues, among which the secreted Semaphorin-3C (Sema3C), that act as attractants for pre-crossing axons on their way to the midline. This change is concomitant with an upregulation of the surface protein Ephrin-B1, which acts in CCAs to inhibit Sema3C signaling via interaction with the Neuropilin-1 (Nrp1) receptor. This silencing activity is independent of Eph receptors and involves a N-glycosylation site (N-139) in the extracellular domain of Ephrin-B1. Together, our results reveal a molecular mechanism, involving interaction between the two unrelated guidance receptors Ephrin-B1 and Nrp1, that is used to control the navigation of post-crossing axons in the corpus callosum.
Published: 2018
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42. Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis

Author: Remi Noe, Lubka T. Roumenina, Véronique Frémeaux-Bacchi, Boriana Deliyska, Vasil Vasilev, Sophie Chauvet, Jordan D. Dimitrov, Marie-Agnès Dragon-Durey, and Valentin J. Lazarov
Subjects: Adult, Male, Complement receptor 1, education, Lupus nephritis, Biochemistry, Complement factor B, Cohort Studies, Young Adult, immune system diseases, medicine, Humans, skin and connective tissue diseases, Molecular Biology, Aged, Autoantibodies, biology, Autoantibody, Molecular Bases of Disease, Complement C3, Cell Biology, Middle Aged, medicine.disease, Lupus Nephritis, humanities, Anti-thyroid autoantibodies, C3-convertase, Complement system, Immunology, Female, biology.gene, Anti-SSA/Ro autoantibodies
Abstract: Lupus nephritis (LN) is a complication of the autoimmune disease systemic lupus erythematosus. Because the complement system plays a critical role in orchestrating inflammatory and immune responses as well as in the clearance of immune complexes, autoreactivity to complement components may have considerable pathological consequences. Autoantibodies against the central complement component C3 have been reported in systemic lupus erythematosus, but their molecular mechanism and functional relevance are not well understood. The objective of this study was to evaluate the frequency and the functional properties of the anti-C3 autoantibodies. Anti-C3 autoantibodies were measured in plasma of 39 LN patients, and identification of their epitopes on the C3 molecule was performed. By using surface plasmon resonance, we analyzed the influence of patient-derived IgG antibodies on the interaction of C3b with Factor B, Factor H, and complement receptor 1. The capacity of these antibodies to dysregulate the C3 convertase on the surface of endothelial cell was measured by flow cytometry. Here we report that the frequency of anti-C3 autoantibodies in LN is ∼30%. They inhibited interactions of the negative complement regulators Factor H and complement receptor 1 with C3b. An enhanced C3 deposition was also observed on human endothelial cells in the presence of C3 autoantibodies. In addition, anti-C3 autoantibody levels correlated with disease activity. In conclusion, the anti-C3 autoantibodies in LN may contribute to the autoimmune pathology by their capacity to overactivate the complement system.
Published: 2015
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43. Mapping interactions between complement C3 and regulators using mutations in atypical hemolytic uremic syndrome

Author: T. Sakari Jokiranta, Valerie Wilson, Véronique Frémeaux-Bacchi, Paula Vieira-Martins, Tania Rybkine, Richard J.H. Smith, John P. Atkinson, Sophie Chauvet, Christophe Hue, Elisabetta Valoti, Tara Maga, Timothy H.J. Goodship, Marina Noris, Elizabeth C. Schramm, and Lubka T. Roumenina
Subjects: Male, Models, Molecular, Complement receptor 1, Immunology, medicine.disease_cause, Biochemistry, Complement factor B, Cohort Studies, Atypical hemolytic uremic syndrome, medicine, Humans, Protein Interaction Maps, Binding site, Atypical Hemolytic Uremic Syndrome, Genetics, Mutation, Binding Sites, biology, CD46, Complement C3, Cell Biology, Hematology, medicine.disease, Molecular biology, 3. Good health, Complement system, Alternative complement pathway, Female, biology.gene
Abstract: The pathogenesis of atypical hemolytic uremic syndrome (aHUS) is strongly linked to dysregulation of the alternative pathway of the complement system. Mutations in complement genes have been identified in about two-thirds of cases, with 5% to 15% being in C3. In this study, 23 aHUS-associated genetic changes in C3 were characterized relative to their interaction with the control proteins factor H (FH), membrane cofactor protein (MCP; CD46), and complement receptor 1 (CR1; CD35). In surface plasmon resonance experiments, 17 mutant recombinant proteins demonstrated a defect in binding to FH and/or MCP, whereas 2 demonstrated reduced binding to CR1. In the majority of cases, decreased binding affinity translated to a decrease in proteolytic inactivation (known as cofactor activity) of C3b via FH and MCP. These results were used to map the putative binding regions of C3b involved in the interaction with MCP and CR1 and interrogated relative to known FH binding sites. Seventy-six percent of patients with C3 mutations had low C3 levels that correlated with disease severity. This study expands our knowledge of the functional consequences of aHUS-associated C3 mutations relative to the interaction of C3 with complement regulatory proteins mediating cofactor activity.
Published: 2015
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44. Intravascular hemolysis activates complement via cell-free heme and heme-loaded microvesicles

Author: Anne Grunenwald, Viviane Gnemmi, Sara Petrillo, Samantha Knockaert, Dominique Charue, Olivier Blanc-Brude, Marion Rabant, Sylvain Le Jeune, Helena Rajaratnam, Lubka T. Roumenina, Tania Robe-Rybkine, Sylvia Miescher, Jordan D. Dimitrov, Pascal Houillier, Emanuela Tolosano, Marie-Lucile Figueres, Sanah Bouzekri, Nicolas S. Merle, Véronique Frémeaux-Bacchi, Marie Frimat, Marie Le-Hoang, Nathan Brinkman, Monika Edler, Remi Noe, Sophie Chauvet, and Thomas Gentinetta
Subjects: 0301 basic medicine, Erythrocytes, Inflammation, Anemia, Sickle Cell, Complement Membrane Attack Complex, Heme, Kidney, Hemolysis, Receptors, G-Protein-Coupled, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Hemopexin, medicine, Animals, Hepatitis A Virus Cellular Receptor 1, Receptor, Anaphylatoxin C5a, Cell-Free System, CD46, Chemistry, Endothelial Cells, General Medicine, Complement C3, Acute Kidney Injury, medicine.disease, Molecular biology, Microvesicles, Complement system, Mice, Inbred C57BL, Red blood cell, Disease Models, Animal, P-Selectin, 030104 developmental biology, medicine.anatomical_structure, Female, medicine.symptom, 030215 immunology, Research Article
Abstract: In hemolytic diseases, such as sickle cell disease (SCD), intravascular hemolysis results in the release of hemoglobin, heme, and heme-loaded membrane microvesicles in the bloodstream. Intravascular hemolysis is thus associated with inflammation and organ injury. Complement system can be activated by heme in vitro. We investigated the mechanisms by which hemolysis and red blood cell (RBC) degradation products trigger complement activation in vivo. In kidney biopsies of SCD nephropathy patients and a mouse model with SCD, we detected tissue deposits of complement C3 and C5b-9. Moreover, drug-induced intravascular hemolysis or injection of heme or hemoglobin in mice triggered C3 deposition, primarily in kidneys. Renal injury markers (Kim-1, NGAL) were attenuated in C3-/- hemolytic mice. RBC degradation products, such as heme-loaded microvesicles and heme, induced alternative and terminal complement pathway activation in sera and on endothelial surfaces, in contrast to hemoglobin. Heme triggered rapid P selectin, C3aR, and C5aR expression and downregulated CD46 on endothelial cells. Importantly, complement deposition was attenuated in vivo and in vitro by heme scavenger hemopexin. In conclusion, we demonstrate that intravascular hemolysis triggers complement activation in vivo, encouraging further studies on its role in SCD nephropathy. Conversely, heme inhibition using hemopexin may provide a novel therapeutic opportunity to limit complement activation in hemolytic diseases.
Published: 2017

45. Pemetrexed-induced acute kidney injury leading to chronic kidney disease

Author: Sophie Chauvet, Marie Courbebaisse, Emmanuelle Plaisier, and Pierre Ronco
Subjects: medicine.medical_specialty, Lung Neoplasms, Side effect, Antineoplastic Agents, Pemetrexed, Adenocarcinoma, urologic and male genital diseases, Gastroenterology, Nephrotoxicity, chemistry.chemical_compound, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Edema, Humans, Renal Insufficiency, Chronic, Acute tubular necrosis, business.industry, Acute kidney injury, General Medicine, Acute Kidney Injury, Kidney Tubular Necrosis, Acute, Middle Aged, Prognosis, medicine.disease, Discontinuation, chemistry, Nephrology, Antifolate, Eyelid Diseases, Carcinoma, Large Cell, Female, Cisplatin, Neoplasm Recurrence, Local, business, medicine.drug, Kidney disease
Abstract: There is little data availableon the nephrotoxicity of pemetrexed, a new generation antifolate agent that is increasingly used in the treatment of numerous malignant tumors. We report the observation of two patients suffering from non-small cell lung cancer who developed acute kidney injury (AKI) after administration of pemetrexed. In one case, pemetrexed was used as a single agent treatment. In the other, pemetrexed was first co-administered with cisplatin, then alone, with AKI worsening 2 months after the discontinuation of cisplatin. The two patients concomitantly developed edema of the face, which is a rare adverse side effect of pemetrexed. Renal biopsies showed acute tubular necrosis and interstitial fibrosis. In both cases, chronic kidney disease (CKD) persisted despite drug discontinuation. Herein, we discuss renal presentation, risk factors, and prognosis of pemetrexed-induced nephrotoxicity.
Published: 2014
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46. Glomérulopathies à C3

Author: Sophie Chauvet, Véronique Frémeaux-Bacchi, and Aude Servais
Subjects: Nephrology
Abstract: Resume Les glomerulopathies a depots de C3 regroupent un ensemble de glomerulopathies chroniques rares, histologiquement caracterisees par la presence de depots exclusifs de C3 en immunofluorescence. Elles se manifestent par une proteinurie glomerulaire, de degre variable, parfois de rang nephrotique, une hematurie microscopique, parfois macroscopique, une hypertension arterielle et une insuffisance renale. Leur pronostic est pejoratif, avec une evolution vers l’insuffisance renale chronique terminale dans 35 a 50 % des cas apres 10 ans de suivi. De plus, les depots reapparaissent constamment apres transplantation renale et sont responsables d’une perte du greffon renal dans 40 a 60 % des cas. Biologiquement, une hypocomplementemie en rapport avec une activation systemique de la voie alterne du complement est souvent observee. L’apport des modeles animaux et la mise en evidence chez l’homme d’anomalies acquises ou constitutionnelles des proteines de la voie alterne du complement ont recemment confirme le role de cette voie d’activation dans la survenue des lesions renales. En l’absence de traitement specifique, leur prise en charge est essentiellement basee sur un traitement nephroprotecteur associe a un traitement immunosuppresseur dont les modalites restent a definir. L’anticorps monoclonal anti-C5 a recemment ete teste dans cette maladie renale et pourrait etre benefique dans certaines formes de la maladie.
Published: 2014
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47. Spatial gene's (Tbata) implication in neurite outgrowth and dendrite patterning in hippocampal neurons

Author: Miriam Yammine, Catherine Nguyen, Murielle Saade, Sophie Chauvet, Conseil Régional Provence-Alpes-Côte d'Azur, and Association Française contre les Myopathies
Subjects: Neurite, Neurogenesis, Kinesins, Neuronal polarization, Biology, Hippocampal formation, Hippocampus, Mice, Cellular and Molecular Neuroscience, Neurotrophic factors, Cell Line, Tumor, Nerve Growth Factor, Neurites, medicine, Animals, Humans, Axon, Molecular Biology, Cells, Cultured, KIF17, Neurite outgrowth, Nuclear Proteins, Cell Biology, Cell biology, Protein Transport, medicine.anatomical_structure, Nerve growth factor, nervous system, Kinesin Kif17, Kinesin, Neuron, Spatial gene, Neuroscience
Abstract: The unique architecture of neurons requires the establishment and maintenance of polarity, which relies in part on microtubule-based kinesin motor transport to deliver essential cargo into axons and dendrites. In developing neurons, kinesin trafficking is essential for delivering organelles and molecules that are crucial for elongation and guidance of the growing axonal and dendritic termini. In mature neurons, kinesin cargo delivery is essential for neuron dynamic physiological functions which are critical in brain development. In this work, we followed Spatial (Tbata) gene expression during primary hippocampal neuron development and showed that it is highly expressed during dendrite formation. Spatial protein exhibits a somatodendritic distribution and we show that the kinesin motor Kif17, among other dendrite specific kinesins, is crucial for Spatial localization to dendrites of hippocampal neurons. Furthermore, Spatial down regulation in primary hippocampal cells revealed a role for Spatial in maintaining neurons' polarity by ensuring proper neurite outgrowth. This polarity is specified by intrinsic and extracellular signals that allow neurons to determine axon and dendrite fate during development. Neurotrophic factors, such as the Nerve Growth Factor (NGF), are candidate extracellular polarity-regulating cues which are proposed to accelerate neuronal polarization by enhancing dendrite growth. Here, we show that NGF treatment increases Spatial expression in hippocampal neurons. Altogether, these data suggest that Spatial, in response to NGF and through its transport by Kif17, is crucial for neuronal polarization and can be a key regulator of neurite outgrowth. © 2013., This work was supported by the Inserm, the Provence-Alpes-Côte d'Azur region and the “Association Francaise contre les Myopathies” (AFM)
Published: 2014
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48. Navigation rules for vessels and neurons: cooperative signaling between VEGF and neural guidance cues

Author: Sophie Chauvet, Katja Burk, Fanny Mann, Institut de Biologie du Développement de Marseille (IBDM), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Vascular Endothelial Growth Factor A, MESH: Signal Transduction, MESH: Axons, MESH: Lymphatic Vessels, Angiogenesis, MESH: Receptors, Eph Family, VEGF receptors, Cellular differentiation, MESH: Neurons, Receptors, Cell Surface, MESH: Semaphorins, Semaphorins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Animals, Humans, MESH: Animals, Neuropilins, Growth cone, Molecular Biology, Neural cell, Lymphatic Vessels, Receptors, Eph Family, MESH: Receptors, Cell Surface, 030304 developmental biology, Neurons, Pharmacology, 0303 health sciences, MESH: Humans, MESH: Vascular Endothelial Growth Factor Receptor-2, MESH: Vascular Endothelial Growth Factor A, MESH: Blood Vessels, Cell Biology, Anatomy, Vascular Endothelial Growth Factor Receptor-2, Axons, Lymphatic system, biology.protein, Blood Vessels, Molecular Medicine, Axon guidance, MESH: Neuropilins, Signal transduction, Neuroscience, 030217 neurology & neurosurgery, Signal Transduction
Abstract: International audience; Many organs, such as lungs, nerves, blood and lymphatic vessels, consist of complex networks that carry flows of information, gases, and nutrients within the body. The morphogenetic patterning that generates these organs involves the coordinated action of developmental signaling cues that guide migration of specialized cells. Precision guidance of endothelial tip cells by vascular endothelial growth factors (VEGFs) is well established, and several families of neural guidance molecules have been identified to exert guidance function in both the nervous and the vascular systems. This review discusses recent advances in VEGF research, focusing on the emerging role of neural guidance molecules as key regulators of VEGF function during vascular development and on the novel role of VEGFs in neural cell migration and nerve wiring.
Published: 2013
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49. Neuropilin-Dependent Signaling and Neuropilin-Independent Signaling of the Guidance Molecule Sema3E

Author: Sophie Chauvet and Fanny Mann
Subjects: animal structures, Neuropilins, Chemistry, Papez circuit, Cell, Gating, Cell biology, medicine.anatomical_structure, Semaphorin, Hes3 signaling axis, embryonic structures, Neuropilin, medicine, sense organs, Receptor
Abstract: Neuropilins are receptors for all but one secreted (class 3) Semaphorins. The exception is Sema3E that directly binds and activates the Plexin-D1 receptor to induce cell repulsion. In this chapter, we review works that identified an unexpected role of Neuropilin-1 as a gating switch in Sema3E/Plexin-D1 signaling, that converts repulsion into attraction, and discuss the implications of this finding for brain wiring.
Published: 2017
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50. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Author: Stéphane Burtey, Laurence Vrigneaud, Moglie Le Quintrec, Véronique Frémeaux-Bacchi, Arnaud François, Vincent Javaugue, Laurent Daniel, Guy Touchard, Alexandre Karras, Frank Bridoux, Gabriel Choukroun, Yahsou Delmas, Pierre Ronco, Florent Petitprez, Bertrand Arnulf, David Ribes, Jean Michel Goujon, Sophie Chauvet, Dominique Guerrot, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Unité de Soins Intensifs Médicaux, CHU Amiens-Picardie-Département de Néphrologie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre National de Référence Maladies Rares: Amylose al et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Université de Poitiers, Service de Néphrologie [Valenciennes], Centre Hospitalier de Valenciennes, Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et de Cytologie Pathologiques [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Project: 305608,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EURENOMICS(2012), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), DIGNAT-GEORGE, Françoise, European Consortium for High-Throughput Research in Rare Kidney Diseases - EURENOMICS - - EC:FP7:HEALTH2012-10-01 - 2017-09-30 - 305608 - VALID, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service d'Anatomie et Cytologie Pathologique [Rouen], Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: Adult, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Databases, Factual, medicine.medical_treatment, Immunology, Kidney Glomerulus, 030232 urology & nephrology, Paraproteinemias, 030204 cardiovascular system & hematology, Biochemistry, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Drug Therapy, Glomerulopathy, Internal medicine, medicine, Humans, Molecular Targeted Therapy, Multiple myeloma, Aged, Retrospective Studies, Aged, 80 and over, Chemotherapy, Kidney, B-Lymphocytes, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Cell Biology, Hematology, Complement C3, Middle Aged, medicine.disease, Chemotherapy regimen, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, medicine.anatomical_structure, Treatment Outcome, Kidney Diseases, France, business, Nephrotic syndrome, Monoclonal gammopathy of undetermined significance, Kidney disease
Abstract: International audience; The high frequency of monoclonal gammopathy in adult patients with C3 glomerulopathy (C3G) emphasizes the role of monoclonal immunoglobulin (MIg) in the occurrence of renal disease and raises the issue of the therapeutic management. The aim of the study was to evaluate the effect of chemotherapy in a large cohort of patients with MIg-associated C3G. Fifty adult patients with MIg and biopsy-proven C3G were extracted from the French national database of C3G. We retrospectively compared renal outcomes in patients who either received or did not receive chemotherapy targeting the underlying B-cell clone. At diagnosis, renal disease was severe, with nephrotic-range proteinuria in 20/46 (43%) patients and chronic kidney disease stage 3 or above in 42/49 (86%) patients. Monoclonal gammopathy was of IgG type in 47 (94%) patients. Hematological diagnosis was monoclonal gammopathy of renal significance in 30 (60%), multiple myeloma in 17 (34%), and chronic lymphocytic leukemia in 3 (6%) patients. Complement studies showed low C3 level in 22/50 (43%) and elevated soluble C5b-9 level in 27/34 (79%) patients. Twenty-nine patients received chemotherapy (including bortezomib in 22), whereas 8 and 13 patients received various immunosuppressive drugs or symptomatic measures alone, respectively. Patients who achieved hematological response after chemotherapy had higher renal response rates (P = .0001) and median renal survival (hazard ratio, 0.22; 95% confidence interval, 0.05-0.92; P = .009) than those receiving conservative/immunosuppressive therapy. In conclusion, our results suggest that chemotherapy adapted to the B-cell clone may constitute an efficient strategy for C3G in the setting of MIg, as rapid achievement of hematological response appears to result in improved renal survival.
Published: 2017
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