Fang-Miao Jing1, Xiao-Lin Zhang2, Fan-Li Meng1, Xiao-Ming Liu3, Yan Shi1, Ping Qin1, Lin Wang1, Hai Zhou1, Yu Hou1, Qiang Song1, Jun Peng4, Ming Hou5. 1. Department of Hematology, Qilu Hospital, Shandong University, Jinan, China. 2. Department of Hematology, Qilu Hospital, Shandong University, Jinan, China. Electronic address: sunnyzxl@126.com. 3. Department of Health Care, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China. 4. Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China. 5. Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China; Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Qilu Hospital, Shandong University, Jinan, China. Electronic address: qlhouming@sina.com.cn.
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.
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.