title: Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response.
abstract: Pemphigus is a severe blistering condition of the skin and mucosa caused by autoantibodies directed against desmogleins, which are a type of keratinocyte adhesion protein. B cell depletion by rituximab has short-term efficacy against pemphigus. We aimed to assess the long-term course of pemphigus patients after B cell depletion and to understand the immunological mechanisms that mediate long-lasting remissions. We evaluated the clinical course of 22 pemphigus patients treated with rituximab after a 79-month median follow-up and compared the anti-desmoglein B cell response and B and T lymphocyte subpopulations and repertoire between patients who achieved complete remission (CR) and those who had incomplete remission (IR). Thirteen patients (59%) experienced CR during the study, including 10 patients off treatment and 3 patients with prednisone doses <10 mg/day; 9 patients had IR. A marked increase was observed in the ratio of CD19(+)CD27(-) naïve B cells to CD19(+)CD27(+) memory B cells. Indeed, patients in CR had a fourfold higher number of transitional B cells and interleukin-10-secreting regulatory B cells than those in IR. Furthermore, CR was associated with modification of the initial B cell repertoire and the disappearance of desmoglein-specific circulating immunoglobulin G-positive (IgG(+)) B lymphocytes, whereas a skewed B cell repertoire was observed in patients in IR. Thus, a blockage of B cell maturation, a prolonged repopulation with naïve B cells, and a delayed reappearance of memory B cells, which resulted in the disappearance of circulating desmoglein-specific IgG(+) B lymphocytes, contribute to the long-lasting effectiveness of rituximab for treating pemphigus.
authors: Department of Dermatology, Inserm U905, Institute for Research and Innovation in Biomedicine, Rouen University Hospital, University of Normandy, Rouen 76031, France.
authors: Natacha
authors: N
authors: Colliou
authors: Damien
authors: D
authors: Picard
authors: Frédérique
authors: F
authors: Caillot
authors: Sébastien
authors: S
authors: Calbo
authors: Stéphanie
authors: S
authors: Le Corre
authors: Annick
authors: A
authors: Lim
authors: Brigitte
authors: B
authors: Lemercier
authors: Brigitte
authors: B
authors: Le Mauff
authors: Maud
authors: M
authors: Maho-Vaillant
authors: Serge
authors: S
authors: Jacquot
authors: Christophe
authors: C
authors: Bedane
authors: Philippe
authors: P
authors: Bernard
authors: Frédéric
authors: F
authors: Caux
authors: Catherine
authors: C
authors: Prost
authors: Emmanuel
authors: E
authors: Delaporte
authors: Marie-Sylvie
authors: MS
authors: Doutre
authors: Brigitte
authors: B
authors: Dreno
authors: Nathalie
authors: N
authors: Franck
authors: Saskia
authors: S
authors: Ingen-Housz-Oro
authors: Olivier
authors: O
authors: Chosidow
authors: Christine
authors: C
authors: Pauwels
authors: Catherine
authors: C
authors: Picard
authors: Jean-Claude
authors: JC
authors: Roujeau
authors: Michèle
authors: M
authors: Sigal
authors: Emmanuelle
authors: E
authors: Tancrede-Bohin
authors: Isabelle
authors: I
authors: Templier
authors: Rüdiger
authors: R
authors: Eming
authors: Michael
authors: M
authors: Hertl
authors: Michel
authors: M
authors: D'Incan
authors: Pascal
authors: P
authors: Joly
authors: Philippe
authors: P
authors: Musette
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology*; D051182:Desmogleins / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D010392:Pemphigus / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D051182:Desmogleins; D000069283:Rituximab