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.
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