系统性红斑狼疮外周血固有淋巴细胞变化与其临床相关性  

Correlation between the changes of innate lymphoid cells in peripheral blood of systemic lupus erythematosus and its clinical significance

作　　者：储荟 方璇 谭震 郑旭 吴若兰 李向培 汪国生 王怡平[2] 厉小梅 Chu Hui;Fang Xuan;Tan Zhen;Zhen Xu;Wu Ruolan;Li Xiangpei;Wang Guosheng;Wang Yiping;Li Xiaomei(Department of Rheumatology and Immunology,Anhui Provincial Hospital affiliated with Anhui Medical University,Hefei 230001,China;Centre for Transplantation and Renal Research,Westmead Insitute for Medical Research,the University of Sydney,Westmead 2145 NSW,Australia)

机构地区：[1]安徽医科大学附属省立医院风湿免疫科,合肥230001 [2]悉尼大学医学院Westmead研究所移植和肾脏病研究中心,Westmead 2145 NSW

出　　处：《中华医学杂志》2019年第3期169-173,共5页National Medical Journal of China

基　　金：国家自然科学基金面上项目(81871271);安徽省重点研究与开发计划(1804b06020354).

摘　　要：目的探究固有淋巴细胞(ILC)在系统性红斑狼疮(SLE)患者外周血中的水平及其临床相关性。方法选取2017年11月至2018年5月就诊于安徽医科大学附属省立医院风湿免疫科患者和同期年龄匹配并排除免疫相关疾病及家族遗传史的健康人群,流式细胞术检测外周血中ILC、B细胞、CD4+T和CD8+T细胞百分比例,分析ILC各亚组间变化差异,分别与B细胞、T细胞亚群之间的相关性。酶联免疫吸附实验(ELISA)检测血浆中白细胞介素(IL)-4、-33和干扰素-γ等细胞因子水平,同时分析ILC亚群与各因子的相关性。结果SLE活动组(P=0.0037)和SLE稳定组(P=0.0462)分别与健康对照组相比,外周血中ILC百分比均增高,随ILC2百分比的增加,SLE疾病活动度(SLEDAI)评分随之降低,二者呈负相关(r=0.1272,P=0.0239);ILC1百分比SLE活动组与健康对照组相比显著增加[(22.33±2.52)%比(14.56±1.28)%,P=0.0181];ILC2百分比SLE稳定组[(19.67±1.83)%比(42.48±3.46)%,P<0.0001]和活动组[(8.67±0.83)%比(19.67±1.83)%,P<0.0001]中均显著降低;SLE活动组[(5.72±1.08)%比(14.35±2.40)%,P=0.0013]中ILC3明显降低;活动组中ILC2百分比与CD4+T百分比呈负相关(r=0.2339,P=0.0308),且SLE患者ILC2百分比与血清IgG含量呈负相关(r=0.1492,P=0.0138)。SLE患者血浆中干扰素-γ(F=10.91,P=0.0001)和IL-4(F=6.046,P=0.0047)水平均较健康对照组升高明显升高,IL-33在SLE活动组中显著减低(F=6.645,P=0.0027)。SLE患者中ILC2(r=0.1543,P=0.0288)和ILC3百分比(r=0.3136,P=0.0011)均与IL-4水平呈正相关。结论SLE患者ILC细胞百分比失调且与疾病活动有关,细胞因子异常表达也参与其中,其功能与作用有待进一步探究。Objective To explore the function and role of innate lymphoid cells in the pathogenesis of systemic lupus erythematosus (SLE) at different disease activity levels. Methods From Nov 2017 to May 2018, 40 patients with SLE and 15 age-matched healthy non-immune-related diseases controls were enrolled from Anhui provincial hospital. According to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K, the patients were divided into active group (n=20) and remission group (n=20). The frequency of ILCs, B cells, CD4+T and CD8+T cells from peripheral blood mononuclear cells (PBMCs) was detected by flow cytometry. The subsets of ILCs in each group were compared with the subsets of B cells and T cell respectively. The levels of IL-4, IL-33 and IFN-γ in each group were tested by ELISA. Result Compared with the control group, ILC1 percentage was significantly increased in SLE active group [(22.33%±2.52%) vs (14.56%±1.28%), P=0.018 1];ILC2 percentage was decreased significantly in both remission group [(19.67%±1.83%) vs (42.48%±3.46%), P<0.000 1] and active group [(8.67%±0.83%) vs (19.67%±1.83%), P<0.000 1];ILC3 percentage was decreased significantly in active group [(5.72%±1.08%) vs (14.35%±2.40%), P=0.001 3]. SLEDAI score was negatively correlated with the percentage of ILC2 (P=0.023 9) in all patients. The percentage of ILCs in the remission group (P=0.046 2) and activity group (P=0.003 7) were both increased significantly. Moreover, the percentage of ILC2 in active group was negatively correlated with CD4+T cells (P=0.030 8), and the serum IgG was negatively correlated with ILC2% in all patients (P=0.013 8). Compared with control group or remission group, the levels of IFN-γ (F=10.91, P=0.000 1) and IL-4 (F=6.046, P=0.004 7) in active group were remarkable higher. However, IL-33 was significantly reduced in active group (F=6.645, P=0.002 7). The percentage of ILC2 (r=0.154 3, P=0.028 8) and ILC3 (r=0.313 6, P=0.001 1) in all patients with SLE were positively correlated with the level of IL-4. Conclus

关 键 词：固有淋巴细胞 系统性红斑狼疮 B细胞 T细胞 

分 类 号：R593.241[医药卫生—内科学]