Ren He, Zhao Hui, Wang Tingting, Yang Yanhui, Han Zhibo, Liu Bin, Wu Zida, Tao Jie, Zhou Bin, Zhang Lei, Yang Renchi, Han Zhong Chao
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, PR China.
Clin Immunol. 2006 Aug;120(2):205-11. doi: 10.1016/j.clim.2006.04.573. Epub 2006 Jun 13.
Chronic idiopathic thrombocytopenic purpura (ITP) is an organ-specific autoimmune disease characterized by the production of antibodies against antigens on the membranes of platelets, resulting in enhanced destruction of the platelets by macrophages. Leptin, a cytokine-like hormone, plays a role in the pathogenesis of several autoimmune diseases. In this study, we observed significantly increased plasma leptin levels combined with decreased soluble leptin receptor (sOB-R) levels in 18 chronic ITP patients compared with 14 controls. We also demonstrated significantly elevated mRNA expression of long form leptin receptor (Ob-Rb) on peripheral blood mononuclear cells (PBMCs) from chronic ITP patients. Treatment with recombinant leptin or serum with high leptin levels enhanced in vitro secretion of IgG antiplatelet antibodies by splenocytes and PBMCs from patients with chronic ITP. After depletion of CD4(+) T cells from splenocytes, leptin lost this function. Further studies showed that leptin could increase platelet reactive T cells. These findings suggest that leptin may be involved in the pathogenesis of chronic ITP and might offer a potential target for the treatment of this disease.
慢性特发性血小板减少性紫癜(ITP)是一种器官特异性自身免疫性疾病,其特征是产生针对血小板膜上抗原的抗体,导致巨噬细胞对血小板的破坏增强。瘦素是一种细胞因子样激素,在几种自身免疫性疾病的发病机制中起作用。在本研究中,我们观察到与14名对照相比,18名慢性ITP患者的血浆瘦素水平显著升高,同时可溶性瘦素受体(sOB-R)水平降低。我们还证明慢性ITP患者外周血单个核细胞(PBMC)上长型瘦素受体(Ob-Rb)的mRNA表达显著升高。用重组瘦素或高瘦素水平的血清处理可增强慢性ITP患者脾细胞和PBMC体外分泌抗血小板IgG抗体。从脾细胞中去除CD4(+) T细胞后,瘦素失去了这种功能。进一步研究表明,瘦素可增加血小板反应性T细胞。这些发现提示瘦素可能参与慢性ITP的发病机制,并可能为该病的治疗提供潜在靶点。