Liu Yuan, Liao Xining, Wang Ying, Chen Shiju, Sun Yuechi, Lin Qingyan, Shi Guixiu
Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
Medical College, Xiamen University, Xiamen, Fujian, China.
Oncotarget. 2017 Feb 28;8(9):14306-14313. doi: 10.18632/oncotarget.14882.
Primary Sjogren's Syndrome (pSS) is one of the autoimmune diseases characterized by polyclonal autoantibody production. The human homologue of the mouse double minute 2 (MDM2) is an important negative regulator of p53. Our previous study indicated that autoantibody to MDM2 can be detected in systemic lupus erythematosus patients. The purpose of this study is to study anti-MDM2 autoantibody in pSS patients.
Anti-MDM2 autoantibody in sera from 100 pSS patients and 74 normal controls was investigated by ELISA. Positive samples were further confirmed by western blotting. Expression of MDM2 in labial gland tissue from pSS patients and normal controls was checked by immunohistochemistry. The difference in clinical characteristics and laboratory findings between anti-MDM2 positive and anti-MDM2 negative pSS patients was analyzed.
The presence of anti-MDM2 autoantibody in pSS patients was 21.0%, significantly higher than normal controls (5.40%). MDM2 was overexpressed in labial gland from pSS patients. pSS patients with positive anti-MDM2 were characterized by longer disease duration and more lymphocytes focal gathering in labial gland. Prevalence of anemia, thrombocytopenia and anti-SSB was significantly higher in pSS patients with anti-MDM2 autoantibody. Titer of anit-MDM2 was negatively associated with hemoglobin level, platelet count, complement 3 level and complement 4 level, positively associated with European Sjogren's syndrome disease activity index (ESSDAI) and level of IgG.
Anti-MDM2 autoantibody may be used as a potential serological biomarker in pSS disease activity evaluation. Study on the role of anti-MDM2 or MDM2 in pSS may help us know the pathogenesis mechanism of pSS better.
原发性干燥综合征(pSS)是一种以多克隆自身抗体产生为特征的自身免疫性疾病。小鼠双微体2(MDM2)的人类同源物是p53的重要负调节因子。我们之前的研究表明,系统性红斑狼疮患者可检测到抗MDM2自身抗体。本研究旨在探讨pSS患者中的抗MDM2自身抗体。
采用酶联免疫吸附测定(ELISA)检测100例pSS患者和74例正常对照血清中的抗MDM2自身抗体。阳性样本通过蛋白质印迹法进一步确认。采用免疫组织化学法检测pSS患者和正常对照唇腺组织中MDM2的表达。分析抗MDM2阳性和抗MDM2阴性pSS患者临床特征和实验室检查结果的差异。
pSS患者中抗MDM2自身抗体的阳性率为21.0%,显著高于正常对照(5.40%)。pSS患者唇腺中MDM2表达上调。抗MDM2阳性的pSS患者病程较长,唇腺淋巴细胞灶性聚集较多。抗MDM2自身抗体阳性的pSS患者贫血、血小板减少和抗SSB的患病率显著更高。抗MDM2滴度与血红蛋白水平、血小板计数、补体3水平和补体4水平呈负相关,与欧洲干燥综合征疾病活动指数(ESSDAI)和IgG水平呈正相关。
抗MDM2自身抗体可能作为pSS疾病活动评估的潜在血清学生物标志物。研究抗MDM2或MDM2在pSS中的作用可能有助于我们更好地了解pSS的发病机制。