贝利尤单抗联合常规治疗对系统性红斑狼疮患者外周血自然杀伤细胞影响初步探讨  

Preliminary study on the effects of belimumab combined with classic therapy on peripheral blood NK cells in patients with systemic lupus erythematosus

作　　者：张晓英[1] 程浩[1] 于震 杨惠丹 温鸿雁[1] Zhang Xiaoying;Cheng Hao;Yu Zhen;Yang Huidan;Wen Hongyan(Department of Rheumatology,the Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第二医院风湿免疫科,太原030001

出　　处：《中华风湿病学杂志》2023年第6期378-384,共7页Chinese Journal of Rheumatology

基　　金：山西省自然科学基金面上项目(20210302123268);山西省重大科技攻关专项(2021XM08);山西省基础研究计划青年科学研究项目(202103021223442)。

摘　　要：目的探讨贝利尤单抗联合常规治疗对SLE患者外周血NK细胞的影响。方法回顾性分析2020年1月至2022年3月山西医科大学第二医院风湿免疫科完成贝利尤单抗联合常规治疗24周及外周血淋巴细胞亚群检测的40例SLE患者的临床资料。同时收集性别及年龄匹配的78名健康成年人外周血淋巴细胞亚群检测作为对照。采用配对样本t检验、秩和检验、Spearman相关、广义线性混合模型方法进行统计学分析。结果贝利尤单抗联合常规治疗前SLE患者NK细胞计数显著低于健康对照组[276.0(179.8,384.0)个/μl与61.4(43.0,105.1)个/μl;Z=-7.32,P<0.001],治疗后较治疗前显著升高[61.4(43.0,105.1)个/μl与107.7(72.5,186.5)个/μl;Z=-3.22,P<0.001]。广义线性混合模型结果显示补体C3(t=-2.94,P=0.006)和NK细胞计数(t=-2.25,P=0.031)的增加与抗dsDNA抗体值减少相关。治疗后NK细胞升高38.5个/μl时,预测疗效的灵敏度为61.9%,特异度为81.2%,受试者工作特征曲线(ROC)曲线下面积为0.714。与治疗后NK细胞升高≤38.5个/μl者相比,NK细胞升高>38.5个/μl者治疗后抗dsDNA抗体下降值更大[49.2(0.2,207.2)与156.2(19.8,260.7);Z=-1.55,P=0.120],治疗后SLEDAI-2000下降值更大[4.5(0.0,10.0)与13.0(4.5,18.0);Z=-2.52,P=0.012]。结论NK细胞数量的变化可能成为评估SLE治疗反应的生物标志物,贝利尤单抗联合常规治疗可能通过提高NK细胞计数控制SLE病情。Objective To assess the changes of peripheral blood NK cells in patients with systemic lupus erythematosus(SLE)following belimumab and classic therapy.Methods From January 2020 to March 2022,peripheral lymphocyte subsets were detected by flow cytometry in SLE patients treated with Belimumab and classic therapy.The duration of treatment was 24 weeks.A total of 40 treated SLE patients were enrolled.The lymphocyte subsets in healthy donors were used as normal control group.Paired sample t-test,rank-sum test,Spearman correlation and generalized linear mixed model were used for statistical analysis.Results In contrast to healthy subjects,the numbers of NK cells in SLE patients before treatment were significantly decreased[276.0(179.8,384.0)cells/μl vs.61.4(43.0,105.1)cells/μl;Z=-7.32,P<0.001],although that after treatment was higher than that before treatment[61.4(43.0,105.1)cells/μl vs.107.7(72.5,186.5)cells/μl;Z=-3.22,P<0.001].Generalized linear mixed model results showed that the increase in serum levels of C3(t=-2.94,P=0.006)and NK cells(t=-2.25,P=0.031)were associated with a decrease of anti-dsDNA antibody titers.The cutoff value of elevated counts of NK cells after treatment was equal or more than 38.5 cells/μl with a sensitivity of 61.9% and a specificity of 81.2%.Compared with those with elevated counts of NK cells≤38.5 cells/μl,patients with elevated counts of NK cells>38.5 cells/μl had a bigger difference anti-dsDNA antibody[49.2(0.2,207.2)vs.156.2(19.8,260.7);Z=-1.55,P=0.120]and a bigger difference of SLEDAI-2000[4.5(0.0,10.0)vs.13.0(4.5,18.0);Z=-2.52,P=0.012].Conclusion The change in the numbers of NK cells may serve as biomarkers for evaluating the therapeutic responses of SLE.Combinatory approaches employing belimumab and classic therapy may control SLE disease by increasing the number of NK cells.

关 键 词：红斑狼疮 系统性 淋巴细胞亚群 自然杀伤细胞 贝利尤单抗 

分 类 号：R593.241[医药卫生—内科学]