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Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen

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...

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Autores principales: Hébert, Vivien, Petit, Marie, Maho-Vaillant, Maud, Golinski, Marie-Laure, Riou, Gaëtan, Derambure, Céline, Boyer, Olivier, Joly, Pascal, Calbo, Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693356/
https://www.ncbi.nlm.nih.gov/pubmed/31440235
http://dx.doi.org/10.3389/fimmu.2019.01794
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author Hébert, Vivien
Petit, Marie
Maho-Vaillant, Maud
Golinski, Marie-Laure
Riou, Gaëtan
Derambure, Céline
Boyer, Olivier
Joly, Pascal
Calbo, Sébastien
author_facet Hébert, Vivien
Petit, Marie
Maho-Vaillant, Maud
Golinski, Marie-Laure
Riou, Gaëtan
Derambure, Céline
Boyer, Olivier
Joly, Pascal
Calbo, Sébastien
author_sort Hébert, Vivien
collection PubMed
description 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.
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spelling pubmed-66933562019-08-22 Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen Hébert, Vivien Petit, Marie Maho-Vaillant, Maud Golinski, Marie-Laure Riou, Gaëtan Derambure, Céline Boyer, Olivier Joly, Pascal Calbo, Sébastien Front Immunol Immunology 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. Frontiers Media S.A. 2019-08-07 /pmc/articles/PMC6693356/ /pubmed/31440235 http://dx.doi.org/10.3389/fimmu.2019.01794 Text en Copyright © 2019 Hébert, Petit, Maho-Vaillant, Golinski, Riou, Derambure, Boyer, Joly and Calbo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Hébert, Vivien
Petit, Marie
Maho-Vaillant, Maud
Golinski, Marie-Laure
Riou, Gaëtan
Derambure, Céline
Boyer, Olivier
Joly, Pascal
Calbo, Sébastien
Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen
title Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen
title_full Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen
title_fullStr Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen
title_full_unstemmed Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen
title_short Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen
title_sort modifications of the transcriptomic profile of autoreactive b cells from pemphigus patients after treatment with rituximab or a standard corticosteroid regimen
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693356/
https://www.ncbi.nlm.nih.gov/pubmed/31440235
http://dx.doi.org/10.3389/fimmu.2019.01794
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