NDLI: Effect of rituximab on B cell phenotype and serum B cell-activating factor levels in patients with thrombotic thrombocytopenic purpura.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Becerra, E. Scully, M. A. Leandro, M. J. Heelas, E. O. Westwood, J-P De La Torre, I. Cambridge, G.
Description	Country affiliation: United kingdom Author Affiliation: Becerra E ( Department of Rheumatology, University College London, London, UK.)
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.
File Format	HTM / HTML
ISSN	00099104
e-ISSN	13652249
DOI	10.1111/cei.12472
Journal	Clinical & Experimental Immunology
Issue Number	3
Volume Number	179
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2015-03-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Immunology Antibodies, Monoclonal, Murine-derived Therapeutic Use B-lymphocyte Subsets Drug Effects B-lymphocytes Purpura, Thrombotic Thrombocytopenic Therapy Adam Proteins Immunology Adolescent Antigens, Cd Metabolism Autoantibodies B-cell Activating Factor Blood B-cell Activation Factor Receptor Genetics Biological Markers Cell Differentiation Cells, Cultured Cross-sectional Studies Disease Progression Gene Expression Regulation Immunologic Memory Immunophenotyping Lymphocyte Activation Plasma Exchange Rituximab Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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