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-Whitney U检验、x2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(x2=20.96,P＜0.001;x2=5.85,P=0.016;x2=13.69,P＜0.001;x2=9.16,P=0.002;x2=4.79,P=0.029),而 技工手发生率低于 ASS 组患者(x2=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有别于ASS患者;IL-18在MDA5-DM及ASS活动期表达水平升高,并随着病情缓解而下降;可能与DM并发ILD中具有重要的作用.持续高水平IL-18与MDA5-DM发生RPILD及死亡相关,可以作为预测MDA5-DM发生RPILD潜在性的生物标志物.
Abstract
Objective To explore the role of interleukin-18(IL-18)in the pathogenesis of dermatomyositis(DM)associated with positiv e 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,x2 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(x2=20.96,P＜0.00 1;x2=5.85,P=0.016;x2=13.69,P＜0.001;x2=9.16,P=0.002;x2=4.79,P=0.029).However,the incidence of mechanic's hand was lower in MDA5-DM patients(x2=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/ml,Z=0.65,P=0.515].In the MDA5-DM survival group,IL-18 levels decreased significantly after treatment[59.45(53.58,81.63)pg/ml vs.106.37(83.62,152.07)pg/ml,Z=2.80,P=0.005],while the changes in the IL-18 levels of patients in the MDA5-DM death group were not statistically significant[99.49(56.70,140.15)pg/ml vs.94.80(71.40,155.45)pg/ml,Z=1.75,P=0.080].Conclusion MDA5-DM patients are different from the ASS patients in clinical manifestations and indicators involved in laboratory tests.The expression level of IL-18 tends to increase during the active phase of MDA5-DM and ASS,and decrease with remission of the disease.MDA5-DM may play an important role in the pathogenesis,and persistent high level of IL-18 is responsible for RPILD and death of MDA5-DM.Sustained high level of IL-18 can be used as a potential biomarker for the estimating development of MDA5-DM into RPILD.
基金项目
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)
NETL
NSTL
万方数据