淋巴细胞亚群与系统性红斑狼疮继发严重感染的关系探究

Exploration of the relationship between lymphocyte subsets and severe infection in systemic lupus erythematosus

目的通过系统性红斑狼疮(systemic lupus erythematosus,SLE)患者的临床数据和外周血淋巴细胞亚群水平,分析SLE患者继发感染和继发严重感染的危险因素,进一步探究淋巴细胞亚群与SLE继发严重感染的关系。方法收集SLE患者的临床数据,使用流式细胞术检测外周血淋巴细胞亚群水平;比较SLE患者感染组和非感染组临床数据的差异;比较SLE患者感染组、非感染组和健康对照组淋巴细胞亚群的差异;使用多因素二元逻辑回归分析SLE患者发生感染的危险因素;进一步比较SLE患者严重感染组、非严重感染组和健康对照组淋巴细胞亚群的差异,再采用多因素二元逻辑回归分析淋巴细胞亚群对SLE患者继发严重感染的危险因素,绘制出受试者工作特征曲线(即ROC曲线),分析其对SLE患者继发严重感染的临界值。结果研究共纳入382名SLE患者,发生感染的患者有94名,感染发生率为24.6%。其中,严重感染为4.5%。最常见的感染部位是肺,占43.7%;其次是上呼吸道,占13.6%。最常见的病原体是细菌,占64.9%;其次是病毒,占12.8%。与非感染组相比,SLE患者感染组外周血中的CD4+T细胞、CD8+T细胞水平显著下降(P均<0.05),B细胞和NK细胞差异无统计学意义(P>0.05)。多因素二元逻辑回归分析SLE患者继发感染的危险因素为C反应蛋白(P=0.012)、白蛋白(P=0.005)以及激素用量(P=0.026)。与SLE患者非严重感染组和健康对照组相比,严重感染组的CD4+T细胞、CD8+T细胞、B细胞和NK细胞均减少,差异均有统计学意义(P均<0.05)。NK细胞(P=0.039,P<0.05)和红细胞沉降率(P=0.037,P<0.05)是SLE患者继发严重感染的危险因素,其中NK细胞诊断SLE继发严重感染临界值为18个/μL,诊断的敏感性和特异性分别为93.2%和77.8%。结论从SLE病例数据分析,SLE患者发生感染的危险因素为:白蛋白的减少、激素用量增加和C反应蛋白水平增加。外周血NK细胞减少是SLE患者继发严重感染的危险因素,可能对SLE患者继发严重感染具有很好的预测价值。

Objective To analyze the risk factors for infections and severe infections in SLE patients,and further explore the relationship between lymphocyte subsets and severe infections in SLE.Methods The clinical data of SLE patients were collected,and the levels of peripheral blood lymphocyte subsets were detected by flow cytometry.The clinical data of SLE patients with infection group and non-infection group were compared.The differences of lymphocyte subsets among the infected group,non-infected group and healthy control group were compared.Multivariate binary logistic regression was used to analyze the risk factors of infection in SLE patients.We further compare the differences of lymphocyte subsets in SLE patients with severe infections,non-severe infections and those in the healthy control group,and then use multivariate binary logistic regression to analyze the risk factors of lymphocyte subsets for severe infection in SLE patients,draw the receiver operating characteristic curve(ROC curve)to analyze its critical value for severe infection diagnosis in SLE patients.Results A total of 382 SLE patients were included in the study,94 patients had infection,and the incidence of infection was 24.6%.Among them,4.5%were severely infected.The most common site of infection was the lung,accounting for 43.7%,followed by the upper respiratory tract,accounting for 13.6%.The most common pathogen was bacteria,accounting for 64.9%,followed by viruses,accounting for 12.8%.Compared with the non-infected group,the levels of CD4~+T cells and CD8~+T cells in the peripheral blood of the infected group of SLE patients were significantly decreased(all P<0.05),and there was no significant difference in B cells and NK cells.Among the risk factors of secondary infection in SLE patients analyzed by multivariate binary logistic regression,the differences of C-reactive protein(P=0.012),albumin(P=0.005)and hormone dosage(P=0.026)were statistically significant(all P<0.05).Compared with non-severe infection group and healthy control group,CD4~+T cells,CD8~+T cells,B cells and NK cells in severe infection group were significantly decreased(P<0.05).NK cells(P=0.039,P<0.05)and erythrocyte sedimentation rate(P=0.037,P<0.05)were the risk factors of severe infection in SLE patients,and the critical value of NK cells for the diagnosis of severe infection in SLE was 18/μL.The sensitivity and specificity of diagnosis were 93.2%and 77.8%.Conclusion According to the analysis of SLE cohort data,the risk factors of infection in SLE patients are the decrease of albumin,the increase of hormone dosage and the increase of C-reactive protein level.The decrease of NK cells in peripheral blood is a risk factor for severe infection in SLE patients,which might have a promising predictive value for severe infection in SLE patients.