PLATELETS AND THROMBOPOIESIS Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents

Immune thrombocytopenia (ITP) is an autoantibody-mediated bleeding disorder with both accelerated platelet destruction and impaired platelet production. We and others have described impaired regulatory CD4 CD25hi T cells (Treg) numbers and/or suppressive function in ITP patients. Clinical trials using thrombopoietic agents to stimulate platelet production have shown favorable outcomes in ITP patients, but information on the immunologic responses of treated patients are lacking. We studied the immunologic profile of chronic ITP patients before (n 10) and during treatment with thrombopoietin receptor (TPO-R) agonists (n 9). Treg activity, as measured by suppression of proliferation of autologous CD4 CD25 cells, was improved in patients on treatment (P < .05), and the improvement correlated with reduction in interleukin-2– producing CD4 cells, consistent with dampening of immune responses. There was a concomitant increase in total circulating transforming growth factor1 (TGF1) levels (P .002) in patients on treatment, and the levels of TGF1 correlated with the degree of improvement in platelet counts (r .8, P .0002). This suggests that platelets in patients on TPO-R treatment may play a role in improving Treg function, either directly or indirectly by enhanced release of TGF1 as a result of greater platelet turnover. In conclusion, our findings suggest that thrombopoietic agents in patients with ITP have profound effects to restore immune tolerance. (Blood. 2010;116(22): 4639-4645)