Modifications of the Transcriptomic Profile of Autoreactive BCells From Pemphigus Patients After Treatment With Rituximab or a StandardCorticosteroid Regimen
| العنوان: | Modifications of the Transcriptomic Profile of Autoreactive BCells From Pemphigus Patients After Treatment With Rituximab or a StandardCorticosteroid Regimen |
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| المؤلفون: | Vivien, Hébert, Marie, Petit, Maho-Vaillant, Maud, Marie-Laure, Golinski, Derambure, Céline, Boyer, Olivier, Joly, Pascal, Calbo, Sébastien, Riou, Gaetan |
| المساهمون: | Derambure, Céline, 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), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND) |
| المصدر: | Frontiers in Immunology Frontiers in Immunology, Frontiers, 2019 |
| بيانات النشر: | HAL CCSD, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | rituximab, autoreactive B cell, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: autoreactive B cell, corticosteriods, pemphigus, transcriptomic analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] |
| الوصف: | International audience; Pemphigus Vulgaris is an autoimmune disease of the skin and mucous membranes, which is due to the production of pathogenic autoantibodies targeting desmoglein (DSG) 1 and 3, which are adhesion proteins of the keratinocytes. Rituximab is an anti-CD20 mAb which induces a prolonged depletion of blood B cells. We recently showed that rituximab was more effective than a standard oral corticosteroid (CS) treatment, allowing 90% of patients to achieve complete remission (CR). Additionally, we showed that DSG-specific-B (DSG positive) cells were still detectable during the B cell recovery which follows the initial rituximab-induced B cell depletion, even in patients in CR. In order to characterize DSG positive B cells in patients in CR after rituximab or CS treatment relative to those detectable at baseline in patients with an active pemphigus, we studied the expression profile of 31 genes of interest related to inflammatory cytokines, TNF receptors and activation markers. Using quantitative Polymerase Chain Reaction performed on one cell with a microfluidic technique, we found that patients' autoreactive B cells collected at baseline had a significantly higher expression of genes encoding for IL-1β, IL-23p19, and IL-12p35 pro-inflammatory cytokines and the IRF5 transcription factor, than non-autoreactive B cells. Surprisingly, the gene expression profile of DSG positive B cells collected after rituximab treatment in patients in CR was close to that of DSG positive B cells at baseline in patients with active pemphigus, except for the IL-1β and the CD27 memory marker genes, which were under-expressed after rituximab compared to baseline. Conversely, we observed a decreased expression of genes encoding for IL-1β and IL-23p19 in patients treated with CS relative to baseline. This study showed that: (i) DSG positive autoreactive B cells have a different gene expression profile than non-autoreactive B cells; (ii) rituximab and CS have different effects on the genes' expression in autoreactive DSG positive B cells from pemphigus patients. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::b3cc0a048566b7bcaa548f2185595ea5Test https://hal.archives-ouvertes.fr/hal-02329471Test |
| رقم الانضمام: | edsair.dedup.wf.001..b3cc0a048566b7bcaa548f2185595ea5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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