Liphaus Bernadete L, Kiss Maria H B, Carrasco Solange, Goldenstein-Schainberg Claudia
Rheumatology Unit, Department of Pediatrics, School of Medicine, Children's Institute, University of São Paulo, Brazil.
Clin Dev Immunol. 2006 Jun-Dec;13(2-4):283-7. doi: 10.1080/17402520600877786.
Defective regulation of apoptosis may play a role in the development of autoimmune diseases. Fas and Bcl-2 proteins are involved in the control of apoptosis. The aims of this study were to determine the expression of Fas antigen and Bcl-2 protein on peripheral blood T and B lymphocytes from patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDM). Thirty-eight patients with JSLE, 19 patients with JRA, 10 patients with JDM and 25 healthy controls entered the study. Freshly isolated peripheral blood mononuclear cells (PBMC) were stained for lymphocyte markers CD3, CD4, CD8, CD19 and for Fas and Bcl-2 molecules. Expressions were measured by three-color flow cytometry. Statistical analysis was performed using Kruskal-Wallis test. Percentages of freshly isolated T lymphocytes positively stained for Fas protein from JSLE patients were significantly increased compared to healthy controls, patients with JRA and patients with JDM. Percentages of B lymphocytes positive for Fas from JSLE patients were higher than healthy controls and JRA patients. In addition, Fas expression on T cells from patients with JRA was increased compared to JDM patients. Otherwise, Fas expression on T and B cells from JRA and JDM patients were similar to healthy controls. MFI of Bcl-2 positive T lymphocytes from JSLE patients were significantly increased compared to healthy controls and JRA patients. MFI of Bcl-2 protein on B lymphocytes from JSLE patients was similar to healthy controls and patients with JRA and JDM. Bcl-2 expression did not differ between JRA and JDM patients and healthy controls. In conclusion, increased expression of Fas and Bcl-2 proteins observed in circulating T and B lymphocytes from patients with JSLE, but not from patients with JRA and JDM, suggests that abnormalities of apoptosis may be related to the pathogenesis of JSLE and probably are not a result of chronic inflammation.
细胞凋亡调节缺陷可能在自身免疫性疾病的发展中起作用。Fas和Bcl-2蛋白参与细胞凋亡的调控。本研究的目的是确定青少年型系统性红斑狼疮(JSLE)、青少年类风湿性关节炎(JRA)和青少年皮肌炎(JDM)患者外周血T和B淋巴细胞上Fas抗原和Bcl-2蛋白的表达。38例JSLE患者、19例JRA患者、10例JDM患者和25名健康对照者进入本研究。新鲜分离的外周血单个核细胞(PBMC)用淋巴细胞标志物CD3、CD4、CD8、CD19以及Fas和Bcl-2分子进行染色。通过三色流式细胞术测量表达情况。使用Kruskal-Wallis检验进行统计分析。与健康对照者、JRA患者和JDM患者相比,JSLE患者中Fas蛋白阳性染色的新鲜分离T淋巴细胞百分比显著增加。JSLE患者中Fas阳性的B淋巴细胞百分比高于健康对照者和JRA患者。此外,与JDM患者相比,JRA患者T细胞上的Fas表达增加。否则,JRA和JDM患者T和B细胞上的Fas表达与健康对照者相似。与健康对照者和JRA患者相比,JSLE患者Bcl-2阳性T淋巴细胞的平均荧光强度(MFI)显著增加。JSLE患者B淋巴细胞上Bcl-2蛋白的MFI与健康对照者、JRA患者和JDM患者相似。JRA和JDM患者与健康对照者之间Bcl-2表达无差异。总之,在JSLE患者而非JRA和JDM患者的循环T和B淋巴细胞中观察到Fas和Bcl-2蛋白表达增加,这表明细胞凋亡异常可能与JSLE的发病机制有关,且可能不是慢性炎症的结果。