Anti-c-Mpl antibodies in immune thrombocytopenia suppress thrombopoiesis and decrease response to rhTPO.

Abstract

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.

• Authors: Fang-Miao Jing, Xiao-Lin Zhang, Fan-Li Meng, Xiao-Ming Liu, Yan Shi, Ping Qin, Lin Wang, Hai Zhou, Yu Hou, Qiang Song, Jun Peng, Ming Hou
• Journal: Thrombosis research (Thromb Res) Vol. 170 Pg. 200-206 (10 2018) ISSN: 1879-2472 [Electronic] United States
• PMID: 30199786 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Topics

• Adult
• Female
• Humans
• Male
• Middle Aged
• Thrombocytopenia (drug therapy)
• Thrombopoiesis (physiology)