Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response

N Colliou, D Picard, F Caillot, S Calbo… - Science translational …, 2013 - science.org
N Colliou, D Picard, F Caillot, S Calbo, S Le Corre, A Lim, B Lemercier, B Le Mauff…
Science translational medicine, 2013science.org
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 …
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 naļve 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 naļve 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.
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