A distinct plasmablast and naive B-cell phenotype in primary immune thrombocytopenia

作者：Flint Shaun M; Gibson Adele; Lucas Geoff; Nandigam Raghava; Taylor Louise; Provan Drew; Newland Adrian C; Savage Caroline O; Henderson Robert B

来源：Haematologica-The Hematology Journal, 2016, 101(6): 698-706.

DOI：10.3324/haematol.2015.137273

Primary immune thrombocytopenia is an autoimmune disorder in which platelet destruction is a consequence of both B-and T-cell dysregulation. Flow cytometry was used to further characterize the B-and T-cell compartments in a cross-sectional cohort of 26 immune thrombocytopenia patients including antiplatelet antibody positive (n=14) and negative (n=12) patients exposed to a range of therapies, and a cohort of matched healthy volunteers. Markers for B-cell activating factor and its receptors, relevant B-cell activation markers (CD95 and CD21) and markers for CD4(+) T-cell subsets, including circulating T-follicular helper-like cells, were included. Our results indicate that an expanded population of CD95(+) naive B cells correlated with disease activity in immune thrombocytopenia patients regardless of treatment status. A population of CD21-naive B cells was specifically expanded in autoantibody-positive immune thrombocytopenia patients. Furthermore, the B-cell maturation antigen, a receptor for B-cell activating factor, was consistently and strongly up-regulated on plasmablasts from immune thrombocytopenia patients. These observations have parallels in other autoantibody-mediated diseases and suggest that loss of peripheral tolerance in naive B cells may be an important component of immune thrombocytopenia pathogenesis. Moreover, the B-cell maturation antigen represents a potential target for plasma cell directed therapies in immune thrombocytopenia.

• 出版日期2016-6