目的 检测SLE患者外周血淋巴细胞表面诱导共刺激分子(ICOS)和诱导共刺激分子配体(ICOSL)的表达,以及血浆中可溶性ICOSL的表达,探讨其临床意义.方法 流式细胞术检测45例SLE患者和39名健康志愿者外周血CD4+、CD8+T细胞表面ICOS及CD14+单核细胞、CD19+B细胞表面ICOSL的表达;ELISA检测血浆可溶性ICOSL的表达,分析临床意义.采用Levene方差齐性检验,组间比较采用t检验,两变量间相关性采用Pearson相关分析.结果 与健康志愿者相比,SLE患者外周血CD4+、CD8+T细胞表面ICOS的表达均显著升高[(19.1±1.7)%与(14.0±1.5)%,t=2.156,P=0.035]、[(10.0±1.0)%与(6.4±1.0)%,t=2.587,P=0.012].CD14+单核细胞上ICOSL的表达高于健康志愿者个体[(2.94±0.88)%与(0.89±0.21)%,t=2.152,P=0.04],且与患者血浆C3、C4水平呈正相关(r=0.401,P=0.031;r=0.44,P=0.017).活动期组SLE患者血浆sICOSL的浓度显著高于非活动期组[(362±25) ng/ml与(278±15) ng/ml,t=2.356,P=0.025],且与CD14+单核细胞和CD19+B细胞表面ICOSL的表达均呈负相关(r=-0.4243,P=0.022;r=-0.4099,P=0.025).MMPI可显著抑制sICOSL产生.结论 SLE患者外周血淋巴细胞表面ICOS和ICOSL,以及血浆sICOSL异常表达,且与疾病活动度密切相关.提示ICOS/ICOSL信号通路可能参与SLE免疫病理进程.
Objective To investigate the expression of inducible co-stimulator (ICOS) and inducible co-stimulator ligand (ICOSL) on PBMCs,and the plasma concentrations of soluble forms of ICOSL and their clinical relationship with systemic lupus erythematosus (SLE) patients.Methods Peripheral blood samples were collected from 45 SLE patients and 39 healthy subjects (HC).The expressions of ICOS and ICOSL on peripheral blood mononuclear cells (PBMCs) were detected by flow cytometry.The concentrations of soluble ICOSL were assessed by measured by enzyme linked immunosorbent assay (ELISA).And the relationship between their expression levels and patients' clinical manifestations were analyzed.Levene F test was used for statistical analysis,the comparison between groups was conducted using t test,and the correlation between two variables were tested by Pearson correlation analysis.Results The expression of ICOS on CD4+ and CD8+ T cells were significantly higher than that of the HC [(19.1±1.7)% vs (14.0±1.5)%,t=2.156,P=0.035],[(10.0± 1.0)% vs (6.4±1.0)%,t=2.587,P=0.012].The expression of ICOSL on CD14+ mononuclear cells in SLE patients was significantly higher than that in the HC group [(2.94±0.88)% vs (0.89 ±0.21)%,t=2.152,P=0.04].Plasma ICOSL concentrations in patients with active SLE were significantly higher than those of patients with inactive SLE [(362±25) ng/ml vs (278±15) ng/ml,t=2.356,P=0.025].We also found a significant negative correlation between the soluble ICOSL expression and the surface ICOSL expression on both mononuclear cells and B cells (r=-0.4243,P=0.022;r=-0.4099,P=0.025).MMPI induced an evident reduction in sICOSL levels released from the cells,which was statistically significant in comparison with untreated cells (P〈0.05).Conclusion The up-regulated expressions of ICOS and ICOSL on peripheral lymphocytes and the high levels of plasma concentration of soluble ICOSL are closely correlated with the severity of the disease,sugg