Literatür Detay Bilgisi
Effect of rituximab on B-cell phenotype and serum B-cell activating factor levels in patients with Thrombotic Thrombocytopenic Purpura.

Yazarlar : Becerra E, Scully MA, Leandro MJ et al

Yayın : Clin Exp Immunol.

Yayın Yılı : 2014

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/25339550

Konu : Diğer

Literatür İçeriği :  

Abstract

Autoantibodies inhibiting the activity of the metalloproteinase, ADAMTS13, underlay 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 B-cell activating factor (BAFF) may thus impact length of remission. In this cross-sectional study, we measured naïve and memory B-cell phenotypes (using CD19/IgD/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 amongst 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, naïve 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, % 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 inversely correlated 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 sub-populations. 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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