Objective:To explore the independent risk factors and early diagnosis of dermatomyositis (DM) with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody.Methods:A total of 223 DM patients admitted to the Department of Rheumatology and Immunology, Affiliated Hospital of Xuzhou Medical University from January 2012 to June 2021 were retrospectively analyzed, according to whether the anti-MDA5 antibody was positive or not, the patients were divided into anti-MDA5 antibody positive group ( n= 34) and anti-MDA5 antibody negative group ( n=189). The demographic data, clinical manifestations and laboratory test results of the two groups were compared. The risk factors of DM patients with positive anti-MDA5 antibody were analyzed by binary Logistic regression, and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of various risk factors for anti-MDA5 antibody positive DM patients. Results:The incidence of skin ulcer [20.6%(7/34) vs 9.0%(17/189), χ2=4.03, P=0.045], the positive rate of anti-Ro52 antibody [61.8%(21/34) vs 21.2%(40/189), χ2=23.90, P<0.001], the incidence of interstitial lung disease (ILD) [91.2% (31/34) vs 38.6%(73/189), χ2=31.98, P<0.001] and rapidly progressive interstitial lung disease (RP-ILD) [67.6%(23/34) vs 5.3%(10/189), χ2=88.87, P<0.001], the levels of D-dimer [1.87(1.23, 2.56) μg/ml vs 1.15(0.59, 1.29) μg/ml, χ2=4.68, P<0.001] and serum ferritin (SF) [931.65(579.12, 1 160.43) ng/ml vs 507.40(200.40, 588.55) ng/ml, χ2=5.60, P<0.001] in the anti-MDA5 antibody positive group were higher than those in the anti-MDA5 antibody negative group, wherease the creatine kinase (CK) level in the anti-MDA5 anti-body positive group was significantly lower than that in the anti-MDA5 antibody negative group [85.50(61.25, 1 55.00) U/L vs 263.00(66.50, 1 111.14) U/L, χ2=3.08, P=0.002]. Multivariate Logistic regression analysis showed that positive anti-Ro52 antibody [ OR(95% CI)=5.027(1.632, 15.483), P=0.005], increased D-dimer level [ OR(95% CI)=1.665(1.124, 2.466), P=0.011], occurrence of ILD [ OR(95% CI)=10.071(2.061, 49.207), P=0.004] and RP-ILD[ OR(95% CI)=10.91(3.294, 36.134), P<0.001] were independent risk factors for anti-MDA5 antibody positive DM patients. The ROC curve showed that the areas under the curve (95% CI) of anti-Ro52 antibody, D-dimer, ILD and RP-ILD were 0.703(0.615, 0.791), 0.752(0.661, 0.843)], 0.763(0.703, 0.822), 0.812(0.730, 0.893) respectively. The P value of all these parameters were <0.001 and their value in predicting anti-MDA5 antibody positive DM was high. Conclusion:Positive anti-Ro52-Ab, increased D-dimer level, presence of ILD and RP-ILD are independent risk factors for anti-MDA5 antibody positive DM patients, and they have certain early diagnostic value for DM patients with positive anti-MDA5 antibody.