Improved Regulatory T Cell Activity in Patients with Chronic Immune Thrombocytopenia Purpura Treated with Thrombopoietic Agents.

Immune thrombocytopenic purpura (ITP) is an autoimmune, autoantibody-mediated disease with accelerated platelet destruction and impaired platelet production resulting in. thrombocytopenia and bleeding due to breakdown of immune tolerance. We and others have reported impaired regulatory CD4⁺CD25^hi T cells (Treg) suppressive function in ITP patients. Clinical trials using thrombopoietic agents to stimulate platelet production have shown favorable outcomes in ITP patients with increased platelet counts and reduced bleeding. Two such agents, romiplostim (Nplate) and eltrombopag (Promacta), were recently licensed in the USA and elsewhere. Information on the immune responses of patients treated with these drugs pertaining to prognosis and response to treatment are lacking. We therefore studied the immunological profile of ITP patients with an average platelet counts of 21×10⁹/L before treatment (n=6) and those who had been more than 3 months on treatment (total n=12, average platelet count 133 ×10⁹/L) with either Nplate (n=5), eltrombopag (n=2) or an investigational thrombopoietic agent AKR-501 (n=5). We found no statistically significant differences in the Treg frequencies (Foxp3⁺CD25^hi in the CD4+ population) of patients pre- and on-treatment (2.4± 0.6% versus 2.9± 0.5, p=0.5). However, the Treg activity as measured by suppression of proliferation of autologous CD4⁺CD25 cells at 1:1 and 1:4 ratios of Tregs : CD4⁺CD25 cells was significantly improved in patients on treatment compared to the pre-treatment group (at 1:1 ratio, 60% on-treatment versus 41% pre-treatment, p=0.001 and at 1:4 ratio, 44% versus 24%, p=0.04) and comparable to the overall Treg activity of controls (p=0.9).