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2. The emergence of circulating activated autoreactive desmoglein 3-specific follicular regulatory T cells is associated with long-term efficacy of rituximab in patients with pemphigus vulgaris.

Author

Hébert, Vivien, Novarino, Julien, Maho-Vaillant, Maud, Perals, Corine, Calbo, Sébastien, Golinski, Marie-Laure, Martinez, Fanny, Joly, Pascal, and Fazilleau, Nicolas

Subjects
REGULATORY T cells, HLA histocompatibility antigens, PEMPHIGUS vulgaris, T cells, PEPTIDES
Abstract

Background Pemphigus vulgaris (PV) is characterized by autoantibodies targeting keratinocyte adhesion proteins desmoglein (Dsg) 1 and 3, and by the human leukocyte antigen (HLA) predisposition allele HLA-DRB1*0402. Treatment using rituximab (RTX) combined with short-term corticosteroids (CS) allows disease control and long-lasting remission. Objectives The principal aim of this study was to evaluate the impact of RTX on the circulating subpopulations of Dsg3-specific T lymphocytes that specifically regulate B-cell responses: follicular helper T (Tfh) and follicular regulatory T (Tfr) lymphocytes. Methods Using the HLA-DRB1*0402 tetramer loaded with the Dsg3 immunodominant peptide, we used flow cytometry to analyse the frequency, polarization and activation status of blood Dsg3-specific follicular T-cell populations at baseline, month (M) 6 and long-term follow-up (M60–90) from patients with PV. Results At baseline, we observed a predominance of Tfh1* and Tfh17 subsets and an underrepresentation of the Tfh2 subset among autoreactive Dsg3-specific Tfh cells compared with nonautoreactive Tfh cells. RTX treatment induced a decrease of autoreactive Tfh cells with no effect on their polarization during follow-up. In parallel, we observed the emergence of a Dsg3-specific Tfr subpopulation with a significant overexpression of the surface activation markers PD1, ICOS and CD25 that was not observed at the surface of autoreactive Tfh and nonautoreactive Tfr cells of the same patients with PV. In contrast, very few Dsg3-specific Tfr cells were observed in patients with PV who were treated with CS alone. Conclusions Here we show that the emergence of circulating autoreactive Dsg3-specific Tfr cells is associated with the long-term efficacy of RTX in patients with PV. Graphical Abstract Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Published
2024
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5. Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial.

Author

Tedbirt, Billal, Maho-Vaillant, Maud, Houivet, Estelle, Mignard, Claire, Golinski, Marie-Laure, Calbo, Sébastien, Prost-Squarcioni, Catherine, Labeille, Bruno, Picard-Dahan, Catherine, Chaby, Guillaume, Richard, Marie-Aleth, Tancrede-Bohin, Emmanuelle, Duvert-Lehembre, Sophie, Delaporte, Emmanuel, Bernard, Philippe, Caux, Frédéric, Alexandre, Marina, Musette, Philippe, Ingen-Housz-Oro, Saskia, and Vabres, Pierre

Published
2024
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6. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial

Author

Joly, Pascal, Maho-Vaillant, Maud, Prost-Squarcioni, Catherine, Hebert, Vivien, Houivet, Estelle, Calbo, Sébastien, Caillot, Frédérique, Golinski, Marie Laure, Labeille, Bruno, Picard-Dahan, Catherine, Paul, Carle, Richard, Marie-Aleth, Bouaziz, Jean David, Duvert-Lehembre, Sophie, Bernard, Philippe, Caux, Frederic, Alexandre, Marina, Ingen-Housz-Oro, Saskia, Vabres, Pierre, Delaporte, Emmanuel, Quereux, Gaelle, Dupuy, Alain, Debarbieux, Sebastien, Avenel-Audran, Martine, D'Incan, Michel, Bedane, Christophe, Bénéton, Nathalie, Jullien, Denis, Dupin, Nicolas, Misery, Laurent, Machet, Laurent, Beylot-Barry, Marie, Dereure, Olivier, Sassolas, Bruno, Vermeulin, Thomas, Benichou, Jacques, and Musette, Philippe

Published
2017
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9. IgG N-glycosylation from Patients with Pemphigus Treated with Rituximab

Author

Font, Guillaume, primary, Walet-Balieu, Marie-Laure, additional, Petit, Marie, additional, Burel, Carole, additional, Maho-Vaillant, Maud, additional, Hébert, Vivien, additional, Chan, Philippe, additional, Fréret, Manuel, additional, Boyer, Olivier, additional, Joly, Pascal, additional, Calbo, Sébastien, additional, Bardor, Muriel, additional, and Golinski, Marie-Laure, additional

Published
2022
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10. FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells

Author

Maho-Vaillant, Maud, Sips, Magdalena, Golinski, Marie-Laure, Vidarsson, Gestur, Goebeler, Matthias, Stoevesandt, Johanna, Bata-Csörgő, Zsuzsanna, Balbino, Bianca, Verheesen, Peter, Joly, Pascal, Hertl, Michael, Calbo, Sébastien, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, AII - Inflammatory diseases, and Landsteiner Laboratory

Subjects
B cells, Immunology, Infant, Newborn, Infant, pemphigus foliaceus (PF), Newborn, Autoimmune Diseases, FcRn, immunoglobulin G, Immunoglobulin G, Immunology and Allergy, Humans, efgartigimod, Desmogleins, Pemphigus, Autoantibodies, pemphigus vulgaris (PV)
Abstract

BackgroundImmunoglobulin G (IgG) levels are maintained by the IgG-recycling neonatal Fc-receptor (FcRn). Pemphigus vulgaris and pemphigus foliaceus are debilitating autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. Recently, a phase 2 clinical trial (NCT03334058; https://clinicaltrials.gov/NCT03334058) was completed in participants with pemphigus using efgartigimod, an FcRn inhibitor, in combination with prednisone. Efgartigimod demonstrated an early effect on diease activity and was well tolerated. In addition to the safety and efficacy assessment, clinical trials present an opportunity to gain more insights into the mechanism of disease, the mode of action of treatment, and potential for corticosteroid-sparing activity.ObjectiveThe aim of our study was to assess the impact of FcRn antagonism by efgartigimod on immunological parameters known to be directly involved in pemphigus pathology, such as cellular and serological responses.MethodsWe investigated total and antigen-specific IgG subclass level kinetics during and after treatment, assessed antigen-specific B-cell responses, followed T- and B-cell immunophenotypes, and analyzed how different immunophenotypes link to clinical response.ResultsTreatment resulted in reduction of total IgG as well as autoreactive IgG antibody levels. Surprisingly, unlike total IgG and vaccine- or natural-infection-elicited IgG, which returned to baseline levels after stopping efgartigimod treatment, autoreactive antibody levels remained low in several study participants. Efgartigimod showed no effect on total leukocytes, neutrophils, monocytes, or lymphocytes in patients treated with extended efgartigimod therapy. Intriguingly, antigen-specific analyses revealed a loss of desmoglein-specific B cells in several participants responding to efgartigimod, in line with prolonged reduction of pathogenic IgG levels.ConclusionsEfgartigimod treatment of participants with pemphigus improved their conditions and exerted an immunomodulatory effect beyond the blockade of IgG recycling. Further studies in larger populations with an appropriate placebo control are needed to confirm these potentially important observations to establish long-term clinical responses in autoimmune diseases.

Published
2022

11. FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus

Author

Maho-Vaillant, Maud, Sips, Magdalena, Golinski, Marie-Laure, Vidarsson, Gestur, Goebeler, Matthias, Stoevesandt, Johanna, Bata-Csörgő, Zsuzsanna, Balbino, Bianca, Verheesen, Peter, Joly, Pascal, Hertl, Michael, Calbo, Sébastien, Maho-Vaillant, Maud, Sips, Magdalena, Golinski, Marie-Laure, Vidarsson, Gestur, Goebeler, Matthias, Stoevesandt, Johanna, Bata-Csörgő, Zsuzsanna, Balbino, Bianca, Verheesen, Peter, Joly, Pascal, Hertl, Michael, and Calbo, Sébastien

Abstract

BACKGROUND: Immunoglobulin G (IgG) levels are maintained by the IgG-recycling neonatal Fc-receptor (FcRn). Pemphigus vulgaris and pemphigus foliaceus are debilitating autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. Recently, a phase 2 clinical trial (NCT03334058; https://clinicaltrials.gov/NCT03334058) was completed in participants with pemphigus using efgartigimod, an FcRn inhibitor, in combination with prednisone. Efgartigimod demonstrated an early effect on diease activity and was well tolerated. In addition to the safety and efficacy assessment, clinical trials present an opportunity to gain more insights into the mechanism of disease, the mode of action of treatment, and potential for corticosteroid-sparing activity.OBJECTIVE: The aim of our study was to assess the impact of FcRn antagonism by efgartigimod on immunological parameters known to be directly involved in pemphigus pathology, such as cellular and serological responses.METHODS: We investigated total and antigen-specific IgG subclass level kinetics during and after treatment, assessed antigen-specific B-cell responses, followed T- and B-cell immunophenotypes, and analyzed how different immunophenotypes link to clinical response.RESULTS: Treatment resulted in reduction of total IgG as well as autoreactive IgG antibody levels. Surprisingly, unlike total IgG and vaccine- or natural-infection-elicited IgG, which returned to baseline levels after stopping efgartigimod treatment, autoreactive antibody levels remained low in several study participants. Efgartigimod showed no effect on total leukocytes, neutrophils, monocytes, or lymphocytes in patients treated with extended efgartigimod therapy. Intriguingly, antigen-specific analyses revealed a loss of desmoglein-specific B cells in several participants responding to efgartigimod, in line with prolonged reduction of pathogenic IgG levels.CONCLUSIONS: Efgartigimod treatment of part

Published
2022

12. FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus

Author

Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Maho-Vaillant, Maud, Sips, Magdalena, Golinski, Marie-Laure, Vidarsson, Gestur, Goebeler, Matthias, Stoevesandt, Johanna, Bata-Csörgő, Zsuzsanna, Balbino, Bianca, Verheesen, Peter, Joly, Pascal, Hertl, Michael, Calbo, Sébastien, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Maho-Vaillant, Maud, Sips, Magdalena, Golinski, Marie-Laure, Vidarsson, Gestur, Goebeler, Matthias, Stoevesandt, Johanna, Bata-Csörgő, Zsuzsanna, Balbino, Bianca, Verheesen, Peter, Joly, Pascal, Hertl, Michael, and Calbo, Sébastien

Published
2022

13. The Diversity of Serum Anti-DSG3 IgG Subclasses Has a Major Impact on Pemphigus Activity and Is Predictive of Relapses After Treatment With Rituximab

Author

Golinski, Marie-Laure, primary, Lemieux, Alexandre, additional, Maho-Vaillant, Maud, additional, Barray, Marion, additional, Drouot, Laurent, additional, Schapman, Damien, additional, Petit, Marie, additional, Hertl, Michael, additional, Boyer, Olivier, additional, Calbo, Sébastien, additional, Joly, Pascal, additional, and Hébert, Vivien, additional

Published
2022
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17. Longitudinal Pathogenic Properties and N-Glycosylation Profile of Antibodies from Patients with Pemphigus after Corticosteroid Treatment

Author

Petit, Marie, primary, Walet-Balieu, Marie-Laure, additional, Schapman, Damien, additional, Golinski, Marie-Laure, additional, Burel, Carole, additional, Barray, Marion, additional, Drouot, Laurent, additional, Maho-Vaillant, Maud, additional, Hébert, Vivien, additional, Boyer, Olivier, additional, Bardor, Muriel, additional, Joly, Pascal, additional, and Calbo, Sébastien, additional

Published
2021
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19. Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy

Author

Mignard, Claire, Maho-Vaillant, Maud, Golinski, Marie-Laure, Balayé, Pierre, Prost-Squarcioni, Catherine, Houivet, Estelle, Calbo, Sé Bastien, Labeille, Bruno, Picard-Dahan, Catherine, Konstantinou, Maria Polina, Chaby, Guillaume, Richard, Marie-Aleth, Bouaziz, Jean-David, Duvert-Lehembre, Sophie, Delaporte, Emmanuel, Bernard, Philippe, Caux, Frédéric, Alexandre, Marina, Ingen-Housz-Oro, Saskia, Vabres, Pierre, Quéreux, Gaelle, Dupuy, Alain, Debarbieux, Sebastien, Avenel-Audran, Martine, d'Incan, Michel, Bedane, Christophe, Beneton, Nathalie, Jullien, Denis, Dupin, Nicolas, Misery, Laurent, Machet, Laurent, Beylot-Barry, Marie, Dereure, Olivier, Sassolas, Bruno, Bénichou, Jacques, Joly, Pascal, Hebert, Vivien, Calbo, Sébastien, Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de biostatistiques [CHU Rouen], University Hospital of St-Etienne, Department of Dermatology, Service de Dermatologie, Hôpital Bichat, AP-HP, Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Département de dermatologie, CHU Marseille, CHU Marseille, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, Immunodermatologie, Cytokines, Cancer - EA 7319 (ICA), Université de Reims Champagne-Ardenne (URCA), Service de dermatologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Dermatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Dermatologie [CHU Limoges], CHU Limoges, Centre Hospitalier Le Mans (CH Le Mans), Club Rhumatismes et Inflammation, EA1833, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Bordeaux [Bordeaux], Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Charles Nicolle [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de Dermatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), CHU Henri Mondor [Créteil], Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

Subjects
integumentary system, immune system diseases, [SDV]Life Sciences [q-bio], education, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances
Abstract

International audience; Importance: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus.Objective: To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab.Design, setting, and participants: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019.Exposure: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen.Main outcomes and measures: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated.Results: Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab.Conclusions and relevance: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy.Trial registration: NCT00784589.

Published
2020

21. Modifications of the Transcriptomic Profile of Autoreactive BCells From Pemphigus Patients After Treatment With Rituximab or a StandardCorticosteroid Regimen

Author

Vivien, Hébert, Marie, Petit, Maho-Vaillant, Maud, Marie-Laure, Golinski, Derambure, Céline, Boyer, Olivier, Joly, Pascal, Calbo, Sébastien, Riou, Gaetan, 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), and Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND)

Subjects
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]
Abstract

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.

Published
2019

23. Longitudinal study of anti-DSG3 IgG repertoire by proteomics in Pemphigus following Rituximab treatment

Author

Petit, Marie, Walet-Balieu, Marie-Laure, Song, Philippe Chan Tchi, Drouot, Laurent, Burel, Carole, Maho-Vaillant, Maud, Lecrocq, Thierry, Cosette, Pascal, Vaudry, David, Boyer, Olivier, Bardor, Muriel, Joly, Pascal, Calbo, Sébastien, 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), 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)-Université de Rouen Normandie (UNIROUEN), Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale (Glyco-MEV), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Lehner, Arnaud, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BDD] Life Sciences [q-bio]/Development Biology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

27. Human Regulatory B Cells Combine Phenotypic and Genetic Hallmarks with a Distinct Differentiation Fate

Author

Lin, Wenyu, primary, Cerny, Daniela, additional, Chua, Edmond, additional, Duan, Kaibo, additional, Yi, June Tai Jing, additional, Shadan, Nurhidaya Binte, additional, Lum, Josephine, additional, Maho-Vaillant, Maud, additional, Zolezzi, Francesca, additional, Wong, Siew Cheng, additional, Larbi, Anis, additional, Fink, Katja, additional, Musette, Philippe, additional, Poidinger, Michael, additional, and Calbo, Sébastien, additional

Published
2014
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29. Long-Term Remissions of Severe Pemphigus After Rituximab Therapy Are Associated with Prolonged Failure of Desmoglein B Cell Response

Author

Colliou, Natacha, primary, Picard, Damien, additional, Caillot, Frédérique, additional, Calbo, Sébastien, additional, Le Corre, Stéphanie, additional, Lim, Annick, additional, Lemercier, Brigitte, additional, Le Mauff, Brigitte, additional, Maho-Vaillant, Maud, additional, Jacquot, Serge, additional, Bedane, Christophe, additional, Bernard, Philippe, additional, Caux, Frédéric, additional, Prost, Catherine, additional, Delaporte, Emmanuel, additional, Doutre, Marie-Sylvie, additional, Dreno, Brigitte, additional, Franck, Nathalie, additional, Ingen-Housz-Oro, Saskia, additional, Chosidow, Olivier, additional, Pauwels, Christine, additional, Picard, Catherine, additional, Roujeau, Jean-Claude, additional, Sigal, Michèle, additional, Tancrede-Bohin, Emmanuelle, additional, Templier, Isabelle, additional, Eming, Rüdiger, additional, Hertl, Michael, additional, D’Incan, Michel, additional, Joly, Pascal, additional, and Musette, Philippe, additional

Published
2013
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31. Human Regulatory B Cells Combine Phenotypic and Genetic Hallmarks with a Distinct Differentiation Fate.

Author

Wenyu Lin, Cerny, Daniela, Chua, Edmond, Duan, Kaibo, June Tai Jing Yi, Shadan, Nurhidaya Binte, Lum, Josephine, Maho-Vaillant, Maud, Zolezzi, Francesca, Siew Cheng Wong, Larbi, Anis, Fink, Katja, Musette, Philippe, Poidinger, Michael, and Calbo, Sébastien

Subjects
*B cells, *INTERLEUKIN-10, *CD11 antigen, *ANTIGEN presenting cells, *IMMUNOLOGY of inflammation
Abstract

The article offers information on a research conducted by the authors on phenotype of human regulatory B-cells (B-regs) and production of interleukin-10 (IL-10) from CD27 memory cells and naive B-cells. Topics discussed include ability of B-cells lacking CD11c to produce IL-10 after stimulation with IL-21, derivation of B-regs from antigen (Ag) experienced B-cells, upregulation of TLR9 by B cells to mediate efficient activation, and production of IL-10 to suppress inflammation.

Published
2014
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32. Methods to Study the Transcriptome of Regulatory B Cells.

Author

Maho-Vaillant M and Calbo S

Subjects
Animals, B-Lymphocyte Subsets cytology, B-Lymphocyte Subsets metabolism, B-Lymphocytes cytology, B-Lymphocytes metabolism, B-Lymphocytes, Regulatory cytology, Cell Lineage genetics, Humans, Mice, Oligonucleotide Array Sequence Analysis methods, Real-Time Polymerase Chain Reaction methods, B-Lymphocytes, Regulatory metabolism, Gene Expression Profiling methods, Transcriptome genetics
Abstract

Regulatory B cells do not constitute a distinct cell lineage because no unique marker or set of markers can exclusively identify neither murine nor human regulatory B cells, and efficient IL-10 production is their only known distinguishing feature. After purification of IL-10-secreting B cells, one may want to characterize them by analyzing their gene expression profile. This goal can be achieved by using different technologies: RT-qPCR, microarrays, Nanostring's nCounter technology, Biomark HD are techniques that will allow you to analyze their gene expression, whether in a targeted (RT-qPCR), extended but targeted (Nanostring's nCounter technology, Biomark HD) or exhaustive (Microarray) way. Aim of this chapter is the description of these techniques in the view of their application to the study and characterization of regulatory B cells.

Published
2021
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33. Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy: A Post Hoc Analysis of a Randomized Clinical Trial.

Author

Mignard C, Maho-Vaillant M, Golinski ML, Balayé P, Prost-Squarcioni C, Houivet E, Calbo SB, Labeille B, Picard-Dahan C, Konstantinou MP, Chaby G, Richard MA, Bouaziz JD, Duvert-Lehembre S, Delaporte E, Bernard P, Caux F, Alexandre M, Ingen-Housz-Oro S, Vabres P, Quereux G, Dupuy A, Debarbieux S, Avenel-Audran M, D'Incan M, Bédane C, Bénéton N, Jullien D, Dupin N, Misery L, Machet L, Beylot-Barry M, Dereure O, Sassolas B, Benichou J, Joly P, and Hébert V

Subjects
Adult, Aged, Autoantibodies immunology, Desmoglein 3 immunology, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Pemphigus physiopathology, Predictive Value of Tests, Recurrence, Severity of Illness Index, Time Factors, Immunologic Factors administration & dosage, Pemphigus drug therapy, Prednisone administration & dosage, Rituximab administration & dosage
Abstract

Importance: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus., Objective: To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab., Design, Setting, and Participants: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019., Exposure: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen., Main Outcomes and Measures: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated., Results: Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab., Conclusions and Relevance: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy., Trial Registration: NCT00784589.

Published
2020
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34. CD11c + B Cells Are Mainly Memory Cells, Precursors of Antibody Secreting Cells in Healthy Donors.

Author

Golinski ML, Demeules M, Derambure C, Riou G, Maho-Vaillant M, Boyer O, Joly P, and Calbo S

Subjects
Adult, Aged, Antigen Presentation, Cells, Cultured, Female, Healthy Volunteers, Humans, Lymphocyte Activation immunology, Male, Middle Aged, Pemphigus immunology, Phenotype, Young Adult, CD11c Antigen metabolism, Cell Differentiation immunology, Immunologic Memory, Plasma Cells immunology, Receptors, Antigen, B-Cell metabolism
Abstract

CD11c + B cells have been reported to be increased in autoimmune diseases, but they are detected in the blood of healthy individuals as well. We aimed to characterize CD11c + B cells from healthy donors by flow cytometry, microarray analysis, and in vitro functional assays. Here, we report that CD11c + B cells are a distinct subpopulation of B cells, enriched in the memory subpopulation even if their phenotype is heterogeneous, with overexpression of genes involved in B-cell activation and differentiation as well as in antigen presentation. Upon activation, CD11c + B cells can differentiate into antibody-secreting cells, and CD11c could be upregulated in CD11c - B cells by B-cell receptor activation. Finally, we show that patients with pemphigus, an autoimmune disease mediated by B cells, have a decreased frequency of CD11c + B cell after treatment, relative to baseline. Our findings show that CD11c + B cells are mainly memory B cells prone to differentiate into antibody secreting cells that accumulate with age, independently of gender., (Copyright © 2020 Golinski, Demeules, Derambure, Riou, Maho-Vaillant, Boyer, Joly and Calbo.)

Published
2020
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