Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is an autoimmune disease frequently complicated by rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This study aims to systematically elucidate the differences in clinical characteristics, complication risks, and long-term survival outcomes among patients with different serum anti-MDA5 antibody concentrations using a large retrospective cohort, and to establish a prognostic prediction model.

A total of 455 patients with MDA5-DM treated between January 2019 and June 2024 were included. Based on the multiples of the upper limit of normal (ULN), patients were stratified into Low (1-5×ULN, n=158), Medium (5-7×ULN, n=257), and High (>7×ULN, n=40) concentration groups using optimal cut-off values determined by X-tile software. Clinical and laboratory data were collected. Kaplan-Meier survival analysis, Cox proportional hazards regression models, and a Nomogram model were employed to analyze prognostic factors and perform risk stratification.

Baseline characteristics showed that higher antibody concentrations were significantly associated with older age and increased incidence of RP-ILD, dyspnea, skin ulcers, and Gottron’s sign (P<0.05). Laboratory findings indicated that the high-concentration group had higher levels of serum ferritin, AST, and anti-Ro52 antibody positivity, along with significantly lower lymphocyte counts and serum albumin. Survival analysis revealed that the 3-year mortality rates for Low, Medium, and High groups were 18.99%, 31.91%, and 37.50% respectively (P=0.006). A significant "plateau effect" was observed, with no statistical difference in survival between the Medium and High groups. Multivariate Cox regression confirmed that anti-MDA5 antibody level is an independent risk factor for mortality; compared to the Low group, the Medium (HR=2.43) and High (HR=2.72) groups had significantly increased risks. Other independent risk factors included RP-ILD, pulmonary infection, and anti-Ro52 antibody positivity. The developed Nomogram model demonstrated good discrimination (C-index = 0.896) and calibration.

Serum anti-MDA5 antibody level is an independent risk factor for poor prognosis in MDA5-DM patients. There is a non-linear "threshold effect" between antibody concentration and mortality risk; 5 times the upper limit of normal (5×ULN) serves as a critical cut-off, beyond which mortality risk significantly increases and plateaus. The prediction model incorporating antibody stratification facilitates early identification of high-risk patients and guides stratified clinical management.