T cell receptor VB repertoire diversity in patients with immune thrombocytopenia following splenectomy


Dr Cynthia E. Dunbar, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10, Room 7C103, 10 Center Drive, MSC 1652, Bethesda, MD 20892–1652 USA.
E-mail: dunbarc@nhlbi.nih.gov


In recent years, a pathophysiological role for T cells in immune thrombocytopenia (ITP) has been established. We applied cDNA size distribution analysis of the T cell receptor (TCR) β-variable (VB) complementarity-determining region 3 (CDR3) in order to investigate T cell repertoire diversity among immune thrombocytopenia patients who had either responded or not responded to splenectomy, and compared them to normal controls. ITP patients who had had a durable platelet response to splenectomy showed a mean 2·8 ± 2·1 abnormal CDR3 size patterns per patient, similar to healthy volunteers (2·9 ± 2·0 abnormal CDR3 size patterns). In contrast, patients unresponsive to splenectomy demonstrated evidence of significantly more clonal T cell expansions than patients who had responded to splenectomy or controls (11·3 ± 3·3 abnormal CDR3 size patterns per patient; P < 0·001). Of the VB subfamilies analysed, VB3 and VB15 correlated with response or non-response to splenectomy, each demonstrating oligoclonality in non-responding patients (P < 0·05). These findings suggest that removal of the spleen may lead directly or indirectly to reductions in T cell clonal expansions in responders, or that the extent of T cell clonality impacts responsiveness to splenectomy in patients with ITP.