CD154在活动期SLE的改变

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31例活动期SLE及20例正常健康人,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(35±14)%及表达强度(312±108)均显著高于正常健康人,后者分别为(9±7)%、(98±41)(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0.01和0.05)。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 rule in the pathogenesis. Methods CD154 were detected by flow cytometry in CD19 ^＋ peripheral blood lymphocytes from 31 active lupus patienhs and 20 healthy controls. Effects of anti-CD154, on the proliferation and IgG secretion by peripheral B lymphocytes were also observed. Results （ 1 ） The positive sates and mean fluroscence intensity of CD154 in peripheral blood B lymphocytes from active lupus [ （35 ± 14）% ,312 ± 108] were significantly higher than that from normal controls [ （9 ± 7） % ,98 ± 41 ], （ P 〈 0. 001 respectively） ; （2） Peripheral B cells from lupus patients cultured in vitro can spontaneously proliferate and secrete IgG. [^3H]-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. 01 and P 〈 0.05 respectively. Conclusions CD154 was 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.