系统性红斑狼疮患者外周血中性粒细胞PD-L1表达和临床意义

摘要

目的 探讨程序性死亡配体1(PD-L1)在系统性红斑狼疮(SLE)患者外周血中性粒细胞上的表达及临床意义.方法 应用流式细胞仪检测77例SLE患者和43例健康对照者外周血中性粒细胞表面PD-L1表达百分率,比较SLE组和对照组之间以及SLE活动组和稳定组中性粒细胞表面PD-L1表达百分率,分析其与SLE临床表现及实验室检查指标的相关性,并检测10例SLE患者治疗前后中性粒细胞PD-L1的表达.结果 ① SLE组外周血PD-L1+中性粒细胞百分率高于对照组,差异有统计学意义(P<0.000 1);活动组PD-L1+中性粒细胞百分率高于稳定组,差异有统计学意义(P=0.002 7).② SLE患者PD-L1+中性粒细胞百分率与SLE疾病活动性评分(SLEDAI)、抗核抗体(ANA)、免疫球蛋白G(IgG)、红细胞沉降率(ESR)呈正相关性,与红细胞计数(RBC)、血红蛋白(HGB)浓度、红细胞压积(HCT)呈负相关性,对这些呈线性相关的变量进行线性回归分析显示SLE患者PD-L1+中性粒细胞百分率与ANA和ESR的线性回归差异有统计学意义(P=0.020、0.005).以外,在低补体3(C3)组和低白细胞计数(WBC)组中,SLE患者PD-L1+中性粒细胞百分率与C3、WBC呈负相关性.SLE患者中低WBC、低血小板计数(PLT)、高中性粒细胞数、高中性粒细胞百分比阳性组PD-L1+中性粒细胞百分率均高于对应的阴性组,差异均有统计学意义(P<0.05).③ SLE患者发热、皮肤表现、低白细胞血症、低红细胞血症、低血小板血症、贫血和血尿阳性组PD-L1+中性粒细胞百分率均高于对应的阴性组,且差异均有统计学意义(P<0.05).④ SLE患者有效治疗后PD-L1+中性粒细胞百分率降低(P<0.01).结论 SLE患者外周血中性粒细胞表面PD-L1表达异常,与疾病的活动性和严重程度以及抗体产生有关.%Objective To investigate the expression of PD-L1 on neutrophils from the patients with systemic lupus erythematosus(SLE) and analyze the clinical relevance to disease severity.Methods The expression of PD-L1 on neutrophils was examined from 77 SLE patients and 27 healthy controls (HC) by the technique of flow cytometry.The percentage of PD-L1+ neutrophils was compared between SLE patients and HC, and also between inactive and active SLE patients.Moreover, its correlation was analyzed with clinical manifestation and laboratory inspection.We also analyzed regular treatment influence on frequency of PD-L1-expressing neutrophils.Results ① The percentage of PD-L1+ neutrophils from SLE patients significantly elevated compared with HC (P<0.000 1), and the percentage of PD-L1+ neutrophils from active SLE patients significantly elevated compared with inactive (P<0.002 7).② The percentages of PD-L1+ neutrophils in SLE patients were positively associated with SLEDAI, ANA, IgG and ESR, while they were inversely associated with RBC count, HGB, HCT, decresaed WBC count and decreased C3.After performing multiple linear regression analyses, we only found the percentages of PD-L1+ neutrophils in SLE patients significantly correlated with ANA and ESR(P=0.02,P=0.005).And, the percentages of PD-L1+ neutrophils were signifiantly increased in SLE patients with decreased WBC count, decreased PLT count, increased neutrophils count and increased neutrophils percentage (P<0.05).③ The percentages of PD-L1+ neutrophils were signifiantly increased in SLE patients with fever, cutaneous manifestations, leucopenia, erythrocytopenia, thrombocytopenia, anemia andhematuria compared with patients without the clinical features (P<0.05).④ The percentages of PD-L1+ neutrophils are significantly decreased after effective treameat (P=0.007 5).Conclusion The aberrations percentages of PD-L1+ neutrophil are observed in patients with SLE.Increased percentages of PD-L1+neutrophil are correlated with disease activity and severity, and also the production of antibody.