白细胞介素18在抗黑色素瘤分化相关基因5抗体阳性皮肌炎患者血清中表达水平的研究  

Study on IL-18 level in patients with anti-melanoma differentiation-associated gene 5 antibodies positive dermatomyositis

作　　者：毛桐俊 何倩 贾兰兰 赵心悦 忻钰棋 谈文峰[3] Mao Tongjun;He Qian;Jia Lanlan;Zhao Xinyue;Xin Yuqi;Tan Wenfeng(Department of Rheumatology and Immunology,The First Affiliated Hospital of Wannan Medical College,Anhui Province Clinical Research Center for Critical Respiratory Medicine,Anhui 241001,China;School of Anes-thesiology,Wannan Medical College,Wuhu 241002,China;Department of Rheumatology and Immunology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]皖南医学院第一附属医院风湿免疫科、安徽省危重症呼吸疾病临床医学研究中心,芜湖241001 [2]皖南医学院麻醉学院,芜湖241002 [3]南京医科大学第一附属医院风湿免疫科,南京210029

出　　处：《中华风湿病学杂志》2024年第6期367-373,共7页Chinese Journal of Rheumatology

基　　金：教育部国家级大学生创新创业训练计划项目(202210368053);安徽省危重呼吸疾病临床医学研究中心校级开放课题(LC202207)。

摘　　要：目的探讨IL-18在抗黑色素瘤分化相关基因5(MDA5)抗体阳性皮肌炎(MDA5-DM)发病过程中的作用。方法本研究中纳入2018年8月至2020年12月南京医科大学第一附属医院与皖南医院第一附属医院风湿免疫科收治MDA5-DM患者28例, 其中合并快速进展型间质性肺炎(RPILD)15例、非RPILD 13例, 同时纳入抗合成酶综合征(ASS)28例, 健康志愿者(HC)组28名, 分别收集MDA5-DM组、ASS组患者临床资料和实验室、影像学资料;应用ELISA法检测各组血清IL-18水平。采用独立t检验、Mann-WhitneyU检验、χ^(2)检验和Fisher确切概率法进行分析。结果 MDA5-DM组、ASS组及HC组在LDH、羟丁酸脱氢酶(HBDH)、ESR、CRP、血清铁蛋白(SFE)及IL-18等指标上差异有统计学意义(F=46.65, P<0.001;F=43.19, P<0.001;F=31.28, P<0.001;F=23.94, P<0.001;F=30.94, P<0.001;F=49.44, P<0.001)。3组间淋巴细胞计数、血红蛋白水平差异有统计学意义(F=35.26, P<0.001;F=18.59, P<0.001)。MDA5-DM患者Gottron征、向阳疹、甲周红斑、皮肤溃疡、RPILD发生率均高于ASS组患者(χ^(2)=20.96, P<0.001;χ^(2)=5.85, P=0.016;χ^(2)=13.69, P<0.001;χ^(2)=9.16, P=0.002;χ^(2)=4.79, P=0.029), 而技工手发生率低于ASS组患者(χ^(2)=3.90, P=0.048)。MDA5-DM治疗前IL-18水平为104.28(71.96, 151.10)pg/ml, 治疗后IL-18明显下降78.30(56.20, 94.80)pg/ml(Z=2.27, P=0.023);ASS组患者治疗前IL-18水平为72.30(61.39, 95.94)pg/ml, 治疗后IL-18明显下降45.30(29.00, 84.10)pg/ml(Z=2.69, P=0.007);而MDA5-DM合并RPILD组患者治疗前后IL-18水平变化差异无统计学意义[99.49(77.65, 130.87)pg/ml与89.40(54.80, 120.20)pg/ml, Z=0.65, P=0.515]。MDA5-DM存活组患者治疗后IL-18水平[59.45(53.58, 81.63)pg/ml]明显较治疗前[106.37(83.62, 152.07)pg/ml]下降(Z=2.80, P=0.005);而MDA5-DM死亡组患者治疗前后IL-18水平变化差异无统计学意义[99.49(56.70, 140.15)pg/ml与94.80(71.40, 155.45)pg/ml, Z=1.75, P=0.080]。结论 MDA5-DM组患者在临床表现及实验室检查方面Objective To explore the role of interleukin-18(IL-18)in the pathogenesis of dermatomyositis(DM)associated with positive anti-melanoma differentiation-associated gene 5 antibodies(MDA5-DM).Methods Twenty-eight cases of MDA5-DM in the department of rheumatology and immunology,the first hospital of Nanjing medical university and the first affiliated hospital od Wannan medical colledge from August 2018 to December 2011 were included in this study,comprising 15 cases with combined rapidly progressive interstitial pneumonia(RPILD)and 13 cases without RPILD(nonRPILD).Additionally,28 cases of antisynthetase syndrome(ASS)and 28 healthy volunteers(HC)were included for comparison.Clinical,laboratory,and imaging data were collected for both the DM and ASS groups.Serum IL-18 levels were measured using ELISA.Independent t test,Mann-whitney U test,χ^(2) test and Fisher′s exact probability method were used for analysis.Results Significant differences were observed in LDH,hydroxybutyrate dehydrogenase(HBDH),ESR,CRP,serum ferritin(SFE),and IL-18 levels between the MDA5-DM group,the ASS group and the HC group(F=46.65,43.19,31.28,23.94,30.94,49.44,all P<0.001).Additionally,lymphocyte counts and hemoglobin levels differed significantly among the three groups(F=35.26,P<0.001;F=18.59,P<0.001).MDA5-DM patients exhibited higher incidences of Gottron′s sign,helitrope rash,periungual erythema,skin ulcers,and RPILD compared to ASS patients(χ^(2)=20.96,P<0.001;χ^(2)=5.85,P=0.016;χ^(2)=13.69,P<0.001;χ^(2)=9.16,P=0.002;χ^(2)=4.79,P=0.029).However,the incidence of mechanic′s hand was lower in MDA5-DM patients(χ^(2)=3.90,P=0.048).The level of IL-18 significantly decreased in MDA5-DM after treatment[(104.28(71.96,151.10)pg/ml vs.78.30(56.20,94.80)pg/ml,=2.27,P=0.023)].Similar reductions were observed in the ASS group[(72.30(61.39,95.94)pg/ml vs.45.30(29.00,84.10)pg/ml,Z=2.691,P=0.007].The IL-18 level changes in the MDA5-DM combined with RPILD group were not statistically significant[99.49(77.65,130.87)pg/ml vs.89.40(54.80,120.20)pg/

关 键 词：白细胞介素18 皮肌炎 抗黑色素瘤分化相关基因5抗体 间质性肺病 快速进展型 

分 类 号：R593.26[医药卫生—内科学]