Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity.
J Clin Invest
; 122(4): 1393-402, 2012 Apr.
Article
en En
| MEDLINE
| ID: mdl-22426210
ABSTRACT
The B cell-depleting IgG1 monoclonal antibody rituximab can persistently suppress disease progression in some patients with autoimmune diseases. However, the mechanism underlying these long-term beneficial effects has remained unclear. Here, we evaluated Ig gene usage in patients with anti-myelin-associated glycoprotein (anti-MAG) neuropathy, an autoimmune disease of the peripheral nervous system that is mediated by IgM autoantibodies binding to MAG antigen. Patients with anti-MAG neuropathy showed substantial clonal expansions of blood IgM memory B cells that recognized MAG antigen. The group of patients showing no clinical improvement after rituximab therapy were distinguished from clinical responders by a higher load of clonal IgM memory B cell expansions before and after therapy, by persistence of clonal expansions despite efficient peripheral B cell depletion, and by a lack of substantial changes in somatic hypermutation frequencies of IgM memory B cells. We infer from these data that the effectiveness of rituximab therapy depends on efficient depletion of noncirculating B cells and is associated with qualitative immunological changes that indicate reconfiguration of B cell memory through sustained reduction of autoreactive clonal expansions. These findings support the continued development of B cell-depleting therapies for autoimmune diseases.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos B
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Depleción Linfocítica
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Enfermedades Autoinmunes del Sistema Nervioso
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Anticuerpos Monoclonales de Origen Murino
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Memoria Inmunológica
Tipo de estudio:
Clinical_trials
/
Qualitative_research
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Invest
Año:
2012
Tipo del documento:
Article
País de afiliación:
Suiza