Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response.
Sci Transl Med
; 5(175): 175ra30, 2013 Mar 06.
Article
en En
| MEDLINE
| ID: mdl-23467561
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Pénfigo
/
Desmogleínas
/
Anticuerpos Monoclonales de Origen Murino
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Sci Transl Med
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Francia