Candidate molecular endotypes and dynamic risk prediction in anti-MDA5-positive dermatomyositis-associated interstitial lung disease: a systematic scoping review

Abstract

Background Anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5+ DM) spans pulmonary states from no detectable interstitial lung disease (ILD) to rapidly progressive ILD (RP-ILD). We mapped molecular programs and prediction evidence to determine how recurrent biological states may support dynamic stratification. Methods PubMed, Web of Science, Ovid and Embase were searched from inception to 22 August 2026. Two reviewers independently screened records and extracted data. Reporting followed PRISMA-ScR; evidence was synthesized across molecular and prediction domains. Results Of 4, 166 records, 2, 317 remained after deduplication, 349 underwent full-text assessment, and 95 sources (80 primary studies and 15 syntheses) were included. Type I/III interferon signaling was the most reproducible program. Myeloid inflammatory-remodeling, adaptive activation with lymphocyte or natural-killer-cell loss, vascular-coagulation injury, and immunometabolic disturbance formed additional overlapping axes aligned with pulmonary-state transitions. Clinical and radiomic models showed strong short-term discrimination; harmonized landmarks, calibration, geographic validation, and decision-timed molecular sampling would strengthen clinical use. Conclusion The evidence supports an integrated map linking recurrent molecular programs to dynamic pulmonary risk. A calibrated clinical–imaging backbone, augmented by parsimonious molecular modules with incremental value and updated at prespecified landmarks, offers a practical framework for prospective endotype validation and treatment-aware prediction in anti-MDA5+ DM-ILD. Systematic review registration https://doi.org/10.37766/inplasy2026.10.0018 , identifier INPLASY2026100018.