1. IgG N-glycosylation from Patients with Pemphigus Treated with Rituximab
- Author
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Guillaume Font, Marie-Laure Walet-Balieu, Marie Petit, Carole Burel, Maud Maho-Vaillant, Vivien Hébert, Philippe Chan, Manuel Fréret, Olivier Boyer, Pascal Joly, Sébastien Calbo, Muriel Bardor, Marie-Laure Golinski, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale (Glyco-MEV), Normandie Université (NU)-Normandie Université (NU), Plate-forme de Protéomique PISSARO, Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-High-tech Research Infrastructures for Life Sciences (HeRacLeS), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), High-tech Research Infrastructures for Life Sciences (HeRacLeS), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Biochemistry & Molecular Biology ,[SDV.BIO]Life Sciences [q-bio]/Biotechnology ,glycosylation ,IgG ,Medicine (miscellaneous) ,N-glycans ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Research & Experimental Medicine ,FC-GAMMA-RIII ,General Biochemistry, Genetics and Molecular Biology ,DISEASE ,rituximab ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,SIALYLATION LEVELS ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,[SDV.BV]Life Sciences [q-bio]/Vegetal Biology ,pemphigus ,N-glycome ,sialic acid ,Pharmacology & Pharmacy ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,SIALIC-ACID ,Science & Technology ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy ,RHEUMATOID-ARTHRITIS ,GALACTOSYLATION ,OLIGOSACCHARIDES ,[SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding ,Medicine, Research & Experimental ,B-CELLS ,ANTIBODIES ,AUTOANTIBODIES ,Life Sciences & Biomedicine - Abstract
Pemphigus is a life-threatening auto-immune blistering disease of the skin and mucous membrane that is caused by the production of auto-antibodies (auto-Abs) directed against adhesion proteins: desmoglein 1 and 3. We demonstrated in the "Ritux3" trial, the high efficacy of rituximab, an anti-CD20 recombinant monoclonal antibody, as the first-line treatment for pemphigus. However, 25% of patients relapsed during the six-month period after rituximab treatment. These early relapses were associated with a lower decrease in anti-desmoglein auto-Abs after the initial cycle of rituximab. The N-glycosylation of immunoglobulin-G (IgG) can affect their affinity for Fc receptors and their serum half-life. We hypothesized that the extended half-life of Abs could be related to modifications of IgG N-glycans. The IgG N-glycome from pemphigus patients and its evolution under rituximab treatment were analyzed. Pemphigus patients presented a different IgG N-glycome than healthy donors, with less galactosylated, sialylated N-glycans, as well as a lower level of N-glycans bearing an additional N-acetylglucosamine. IgG N-glycome from patients who achieved clinical remission was not different to the one observed at baseline. Moreover, our study did not identify the N-glycans profile as discriminating between relapsing and non-relapsing patients. We report that pemphigus patients present a specific IgG N-glycome. The changes observed in these patients could be a biomarker of autoimmunity susceptibility rather than a sign of inflammation. ispartof: BIOMEDICINES vol:10 issue:8 ispartof: location:Switzerland status: published
- Published
- 2022