Dual anti-MDA5/anti-Ro52 positivity defines a high-risk subgroup for GAP stages II-III interstitial lung disease in idiopathic inflammatory myopathies

Abstract Background Interstitial lung disease (ILD) is a major cause of morbidity and mortality in idiopathic inflammatory myopathies (IIMs). Although Gender-Age-Physiology (GAP) staging is widely used for prognostic stratification, it relies on pulmonary function testing, underscoring the need for practical markers to facilitate timely risk stratification. Methods We conducted a retrospective cohort study of 47 IIM patients with ILD at Tongji Hospital. ILD was confirmed by baseline high-resolution CT and severity was staged using the GAP index. Patients were categorized as GAP stage I (0–3 points, n = 25) or GAP stages II-III (4–8 points, n = 22). Routine laboratory parameters and anti-MDA5/anti-Ro52 profiles were compared between groups. Multivariable logistic regression was performed with GAP stages II-III (vs GAP stage I) as the outcome to evaluate the association between antibody-defined subgroups and ILD severity. Results Patients with GAP stages II-III were older than those with GAP stage I (median 58.0 vs 52.0 years, p = 0.030) and had a higher 28-day mortality (27.27% vs 0%). Anti-MDA5 positivity was more frequent in GAP stages II-III ILD than in GAP stage I (72.7% vs 40.0%, p = 0.024). Compared with GAP stage I, GAP stages II-III were characterized by reduced absolute lymphocyte counts and lymphocyte proportions, increased neutrophil proportions, elevated fibrinogen levels, and lower uric acid, while most liver and muscle injury markers were comparable. Fungal infections were more common in GAP stages II-III than in stage I (45.5% vs 16.0%, p = 0.028). In multivariable logistic regression (reference: double-negative), concurrent anti-MDA5/anti-Ro52 positivity independently associated with GAP stages II-III ILD (adjusted OR 12.03, 95% CI 1.53–94.73, p = 0.018). Conclusions Routinely available laboratory indices combined with anti-MDA5/anti-Ro52 profiling may aid rapid identification of IIM patients at high risk for GAP stages II-III ILD.