Effect of rituximab on B cell phenotype and serum B cell‐activating factor levels in patients with thrombotic thrombocytopenic purpura

Summary Autoantibodies inhibiting the activity of the metalloproteinase, ADAMTS 13 (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 ADAMTS 13. 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 CD 19/immunoglobulin ( Ig)D / CD 27] 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 CD 23 (s CD 23 – a surrogate measure of acquiring B memory ( CD 27 + ) 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 CD 19 + B cells within normal limits in most patients, the percentage and absolute numbers of pre‐switch and memory B cells remained low, with s CD 23 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 ( ADAMTS 13‐specific) B cells, resulting in relatively long periods of low disease activity after therapy.