Effect of rituximab on B cell phenotype and serum B cell-activating factor levels in patients with thrombotic thrombocytopenic purpura.
Clin Exp Immunol
; 179(3): 414-25, 2015 Mar.
Article
em En
| MEDLINE
| ID: mdl-25339550
ABSTRACT
Autoantibodies inhibiting the activity of the metalloproteinase, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), underlie the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Rituximab (RTX) combined with plasma-exchange (PEX) is an effective treatment in TTP. Patients can remain in remission for extended periods following PEX/RTX, and this is associated with continuing reduction in antibodies to ADAMTS13. Factors controlling B cell differentiation to autoantibody production, including stimulation through the B cell receptor and interactions with the B cell-activating factor (BAFF), may thus impact length of remission. In this cross-sectional study, we measured naive and memory B cell phenotypes [using CD19/immunoglobulin (Ig)D/CD27] following PEX/RTX treatment in TTP patients at B cell return (n=6) and in 12 patients in remission 10-68 months post-RTX. We also investigated relationships among serum BAFF, soluble CD23 (sCD23(-) a surrogate measure of acquiring B memory (CD27(+) ) phenotype) and BAFF receptor (BAFF-R) expression. At B cell return after PEX/RTX, naive B cells predominated and BAFF-R expression was reduced compared to healthy controls (P<0.001). In the remission group, despite numbers of CD19(+) B cells within normal limits in most patients, the percentage and absolute numbers of pre-switch and memory B cells remained low, with sCD23 levels at the lower end of the normal range. BAFF levels were correlated inversely with BAFF-R expression and time after therapy. In conclusion, the long-term effects of RTX therapy in patients with TTP included slow regeneration of memory B cell subsets and persistently reduced BAFF-R expression across all B cell subpopulations. This may reflect the delay in selection and differentiation of potentially autoreactive (ADAMTS13-specific) B cells, resulting in relatively long periods of low disease activity after therapy.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Púrpura Trombocitopênica Trombótica
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Linfócitos B
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Subpopulações de Linfócitos B
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Anticorpos Monoclonais Murinos
Tipo de estudo:
Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged80
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article