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Publication Detail
Effect of rituximab on B cell phenotype and serum B cell-activating factor levels in patients with thrombotic thrombocytopenic purpura.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Becerra E, Scully MA, Leandro MJ, Heelas EO, Westwood J-P, De La Torre I, Cambridge G
  • Publication date:
    03/2015
  • Pagination:
    414, 425
  • Journal:
    Clin Exp Immunol
  • Volume:
    179
  • Issue:
    3
  • Status:
    Published
  • Country:
    England
  • Language:
    eng
  • Keywords:
    B cells, BAFF, BAFF-R, TTP, rituximab, ADAM Proteins, ADAMTS13 Protein, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived, Antigens, CD, Autoantibodies, B-Cell Activating Factor, B-Cell Activation Factor Receptor, B-Lymphocyte Subsets, B-Lymphocytes, Biomarkers, Cell Differentiation, Cells, Cultured, Cross-Sectional Studies, Disease Progression, Female, Follow-Up Studies, Gene Expression Regulation, Humans, Immunologic Memory, Immunophenotyping, Lymphocyte Activation, Male, Middle Aged, Plasma Exchange, Purpura, Thrombotic Thrombocytopenic, Rituximab, Treatment Outcome, Young Adult
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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