CD154在活动期系统性红斑狼疮B淋巴细胞中的表达

Abnormal expression of CD154 in the peripheral blood B lymphocytes from lupus patients and its implication in the pathogenesis

目的探讨CD154在系统性红斑狼疮(SLE)中的异常表达及其在狼疮发病中的作用机制。方法16例活动期SLE及14名正常健康人,分离外周血CD19阳性B细胞,以流式细胞仪荧光抗体标记检测其CD154的表达,并体外观察抗CD154抗体对外周血B细胞的增生及IgG分泌的影响。结果①活动期SLE外周血B淋巴细胞中CD154阳性率(36±17)%及表达强度(364±238)均显著高于正常健康人,后者分别为(10±8)%,124±97%(P均<0.001);②体外单独培养,活动期SLE外周血B淋巴细胞自身即可异常增生并分泌IgG,[3H]-TdR掺入及体外培养上清液IgG浓度与正常人相比,差异有显著性(P值分别<0.0001和0.001)。抗CD154抗体可显著抑制活动期SLE外周血B淋巴细胞的异常增生及IgG的异常分泌,[3H]TdR掺入及体外培养上清液IgG浓度与对照抗体组相比,差异有显著性(P值分别为0.027和0.034)。结论CD154在活动期SLE的B淋巴细胞中有异常表达,其异常调控可能是导致分泌自身抗体B细胞克隆增生的主要原因。

Objective To determine the expression level of CD154 in systemic lupus erythematosus(SLE) and its role in the pathogenesis. Methods CD154 were detected by flow cytometry in CD19+ peripheral blood lymphocytes from 16 active lupus patients and 14 healthy controls. Effects of anti-CD154, on the proliferation and IgG secretion by peripheral B lymphocytes were also observed. Results ① The positive rates and mean fluroscence intensity of CD154 in peripheral blood B lymphocytes from active lupus [(36±17)%,364±238] were significantly higher than from normal controls[(10±8)%, 124±97], (P<0.001 res-pectively); ② Peripheral B cells from lupus patients cultured in vitro spontaneously proliferated and secreted IgG, -TdR incorporation (cpm) and IgG concentration in their supernatants were significantly higher than in healthy control, P<0.0001 and 0.001 respectively; Compared to control antibody, anti-CD154 antibody could significantly inhibit in vitro B cell proliferation and IgG secretion in these active lupus patients. P=0.027 and 0.034 respectively. Conclusions CD154 is abnormally expressed in B lymphocytes from active lupus, indicating abberant regulation of germinal center immune response, suggesting abnormal CD154 regulation leads to the proliferation of abnormal B cell clones that secrete pathogenic autoantibodies.