白细胞介素17在特发性炎症性肌病中的表达及临床意义

Expression and clinical significance of IL-17 in idiopathic inflammatory myositis

目的本文通过检测IL-17在特发性炎症性肌病(IIM)患者和正常对照组肌肉组织的表达,初步探讨IL-17在IIM发病机制中的作用。方法纳入2019年10月至2021年8月首次就诊于我院经肌活检和自身抗体检测后明确诊断为IIM的患者28例[(皮肌炎DM组)20例,抗合成酶综合征(ASS组)8例]。纳入同期年龄和性别相匹配的健康人12名的正常肌肉组织作为对照组。采用蛋白免疫印迹法和免疫组织化学技术检测肌肉组织中IL-17的表达水平,采用ELISA法检测血清IL-6水平。采用Mann-Whitney U秩和检验比较2组肌肉组织中IL-17的表达差异,多组间比较采用非参数检验;采用χ^(2)检验和Spearman秩相关分析;P<0.05为差异有统计学意义。结果①IIM肌肉组织中IL-17表达水平升高[1.63(1.30,2.05)pg/ml],与对照组[1.00(0.96,1.00)pg/ml]相比,差异有统计学意义(Z=-3.52,P<0.001);DM[1.94(1.58,2.14)pg/ml]与抗合成酶抗体综合征(ASS)[1.22(1.04,1.55)pg/ml]组间比较差异有统计学意义(Z=-3.20,P=0.001);②与健康对照组[4.08(3.01,5.67)pg/ml]相比,IIM[8.88(4.93,13.64)pg/ml]血清中IL-6高表达(Z=-3.01,P=0.003),与IL-17表达呈正相关(r=0.42,P=0.027);③肌肉组织中IL-17在伴有肌无力[1.91(1.56,2.14)pg/ml与1.50(1.04,2.00)pg/ml](Z=-1.38,P=0.020)、吞咽困难[2.06(1.99,2.14)pg/ml与1.62(1.52,2.04)pg/ml](Z=-2.74,P=0.01)和皮肤受累[1.98(1.57,2.14)pg/ml与1.04(0.86,1.61)pg/ml](Z=-3.20,P<0.01)的IIM中表达更高,差异均有统计学意义(P<0.05)。④IL-17与MYOACT_(总活动度)(r=0.51,P=0.006)、MYOACT_(肌肉症状)(r=0.45,P=0.016)、ESR(r=0.48,P=0.020)、肌酶升高(r=0.56,P=0.002)呈正相关。结论IL-17与IL-6协同参与IIM的发病,提示IL-17是IIM治疗靶点。

Objective In this study,the role of IL-17 in the pathogenesis of idiopathic myositis(IIM)was preliminarily investigated by detecting the expression of IL-17 in the muscle tissues of patients with idiopathic inflammatory myositis(IIM)and normal controls.Methods Twenty-eight patients(20 in DM group with dermatomyositis and 8 in ASS group with anti-synthase syndrome)who were diagnosed with IIM after muscle biopsy and autoantibody detection in our hospital for the first time from October 2019 to August 2021 were included.Twelve cases with normal muscle tissue matched for age and sex were included as the control group.Western blot and immunohistochemical techniques were used to detect the expression level of IL-17 in muscle tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect serum IL-6.Mann-Whitney U rank sum test was used to compare the difference of IL-17 expression in muscle tissue between the two groups,and non-parametric test was used for comparison between multiple groups.Chi-square test and Spearman rank correlation analysis were used,and P<0.05 was considered statistically significant.Results①The expression level of IL-17 in IIM muscle tissue[1.63(1.30,2.05)pg/ml] was higher than that in control group[1.00(0.96,1.00)pg/ml],and the difference was statistically significant(Z=-3.52,P<0.001).The difference be-tween DM[1.94(1.58,2.14)pg/ml]and ASS[1.22(1.04,1.55)pg/ml was statistically significant(Z=-3.20,P=0.001)].②Compared with healthy control group[4.08(3.01,5.67)pg/ml],the expression of IL-6 inⅡM serum[8.88(4.93,13.64)was high(Z=-3.01,P=0.003)],which was positively correlated with the expression of IL-17(r=0.42,P=0.027).③The ex-pression of IL-17 in muscle tissue was higher in IIM associated with muscle weakness[1.91(1.56,2.14)pg/ml vs 1.50(1.04,2.00)pg/ml](Z=-1.38,P=0.020),dysphagia[2.06(1.99,2.14)pg/ml vs 1.62(1.52,2.04)pg/ml](Z=-2.74,P=0.010)and skin involvement[1.98(1.57,2.14)pg/ml vs 1.04(0.86,1.61)pg/ml](Z=-3.20,P<0.010),and the differences were statistically significant(P<0.05).④IL-17 was positively correlated with Myoact-total activity(r=0.51,P=0.006),Myoact-muscle symptom(r=0.45,P=0.016),erythrocyte sedimen tation(r=0.48,P=0.020),and myoenzyme increase(r=0.56,P=0.002).Conclusion IL-17 and IL-6 are synergistically involved in the pathogenesis of IIM,suggesting that IL-17 is the therapeutic target of IIM.