Anti-C-Mpl Antibodies in Immune Thrombocytopenia Suppress Thrombopoiesis and Decrease Response to Rhtpo

INTRODUCTION: Anti-TPO receptor (anti-c-Mpl) antibodies exist and could affect rhTPO treatment in ITP. MATERIALS AND METHODS: Anti-c-Mpl autoantibodies and TPO levels were measured in serum from 187 ITP patients and 59 healthy controls. The anti-c-Mpl-antibody-positive (anti-c-Mpl+) and anti-c-Mpl-antibody-negative (anti-c-Mpl-) IgG from ITP patients were assessed on megakaryocyte proliferation, polyploidy, apoptosis, and platelet release with rhTPO treatment. RESULTS: Anti-c-Mpl antibodies were detected in 54/187 ITP patients but in none of the controls. ITP patients with anti-c-Mpl antibodies had higher serum TPO levels, but lower megakaryocyte and platelet counts compared with anti-c-Mpl- patients. Antibodies targeting platelet glycoprotein (GP) were also more frequently identified in anti-c-Mpl+ ITP patients. Moreover, patients with anti-c-Mpl antibodies were less responsive to rhTPO treatment than patients without anti-c-Mpl antibodies. Additionally, the anti-c-Mpl antibody titer decreased in ITP patients following treatment. In vitro study, lower megakaryopoiesis, platelet generation and percent of polyploidy were observed in anti-c-Mpl+ group compared with the anti-c-Mpl- group in the presence of rhTPO. CONCLUSIONS: Our findings demonstrated that the anti-c-Mpl antibody represents a novel indicator of poor prognosis and may be a potential therapeutic target in ITP.