CD4^+/CD8^+比值异常系统性红斑狼疮患者PD-L1和IFN-α血清水平检测及其临床意义

Detection of serum PD-L1 and IFN-α levels and its clinical significance in patients with systemic lupus erythematosus with abnormal CD4^+/CD8^+ ratio

目的:通过检测CD4^+/CD8^+比值异常的系统性红斑狼疮(systemic lupus erythematosus,SLE)患者血清程序性凋亡受体配体1(programmed cell death ligand 1,PD-L1)和α-干扰素(interferon-α,IFN-α)水平,探讨PD-L1和IFN-α与SLE患者CD4^+/CD8^+比值异常的关系。方法:73例SLE患者以CD4^+/CD8^+参考范围(1.5~2.5)为标准,分为CD4^+/CD8^+倒置组(29例),CD4^+/CD8^+升高组(17)例,CD4^+/CD8^+正常组(27例),另选取20位健康体检者为健康对照组;采用流式细胞术检测SLE患者CD3^+C D 4^+和CD3^+CD8^+T细胞,ELISA法检测血清PD-L1,IFN-α和抗dsDNA抗体水平,分析PD-L1,IFN-α与抗dsDNA抗体的相关性。结果:CD4^+/CD8^+倒置和升高组补体C3和C4水平显著低于其余二组(均P<0.01)。CD4^+/CD8^+倒置和升高组C-反应蛋白(C-reactive protein,CRP)水平显著高于正常组和健康组(均P<0.01),而升高组CRP水平显著高于倒置组(P<0.01)。CD4^+/CD8^+倒置及升高组SLE患者抗dsDNA抗体滴度、SLE疾病活动度评分(SLE disease activity index,SLEDAI)明显高于正常和健康组(均P<0.01)。CD4^+/CD8^+倒置和升高组PD-L1,IFN-α水平均显著高于健康组(均P<0.05);倒置组PD-L1,IFN-α水平均显著高于正常组,而升高组IFN-α与正常组差异无统计学意义(P>0.05)。CD4^+/CD8^+倒置和升高组SLE患者血清PD-L1和IFN-α均与抗dsDNA抗体滴度成正相关(均P<0.01)。CD4^+/CD 8^+异常组SLE患者病原体感染率显著高于其余二组(均P<0.01)。结论:病原体感染是SLE患者CD4^+/CD8^+比值异常的直接原因,CD4^+/CD8^+异常SLE患者血清PD-L1和IFN-α水平均升高且与抗dsDNA抗体呈正相关,提示PD-L1和IFN-α调节T细胞活化共同参与免疫过程。

Objective： To discuss the relationship between serum level of programmed cell death 1 ligand 1（PD-L1）, interferon-α（IFN-α） and abnormal ratio of CD4~＋/CD8~＋ ratio in patients with systemic lupus erythematosus（SLE）. Methods： A total of 73 cases of SLE patients were divided into CD4~＋/CD8~＋ inversion, CD4~＋/CD8~＋elevated, CD4~＋/CD8~＋ normal group, and the cases were 29, 17, 27 respectively; moreover, 20 healthy persons were collected as the control group. CD3~＋CD4~＋and CD3~＋CD8~＋T cells in SLE patients were detected by flow cytometry. The serum levels of PD-L1, IFN-α and anti-dsDNA antibodies were detected by ELISA, and the correlation between PD-L1, IFN-α and anti dsDNA antibody was analyzed. Results： The serum levels of complement C3 and C4 in CD4~＋/CD8~＋ inversion and elevated group were significantly lower than the other two groups（all P〈0.01）. The serum levels of C-reactive protein（CRP） in the inversion and uprising groups were significantly higher than healthy and normal group（P〈0.05）, and the inversion group was significantly lower than the uprising group（P〈0.05）. The titers of anti-dsDNA antibody and SLE disease activity index（SLEDAI） in CD4~＋/CD8~＋inversion and elevation SLE patients were significantly higher than the healthy and normal groups（all P〈0.05）. The serum levels of PD-L1 and INF-α in CD4~＋/CD8~＋ inversion and the uprising group were significantly higher than the healthy control group（P〈0.05）. PD-L1 and INF-α serum levels in the CD4~＋/CD8~＋ inversion group were significantly higher than the normal group（P〈0.01）, but INF-α serum level in the uprising group had no statistical significance compared with the normal group（P〈0.05）. PD-L1 and IFN-α serum levels were positively correlated with anti dsDNA antibody titers in CD4~＋/CD8~＋ inversion and elevated SLE patients（all P〈0.01）. The infection rates of SLE in CD4~＋/CD8~＋ abnormal group were significantly higher than other two groups（all P〈0.01）. Conclusion： The pathogen infection is the direct cause of the abnormal CD4~＋/CD8~＋ ratio in SLE patients. PD-L1 and IFN-α serum levels in CD4~＋/CD8~＋ abnormal group were elevated and positively correlated with anti dsDNA antibody, suggesting that PD-L1 and IFN-α could regulate the activation of T cells and participate in the immune process together.