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Clinical Characteristics and Concordance of Anti‐ MDA5 Antibodies: A Multicenter Australian Study

Year: 2026

Type: article

Abstract: OBJECTIVE: In Australia, anti-MDA5 antibodies are exclusively tested by a line immunoblot assay (LIA). The clinical concordance of an LIA-positive anti-MDA5 result is unclear. We aimed to describe the clinical features and determine the clinical concordance of patients with anti-MDA5 antibodies. METHODS: Electronic records of a multisite cohort (patients with positive anti-MDA5 on LIA from three states in Australia from January 2017 to September 2024) were reviewed for clinical features of dermatomyositis (cutaneous manifestations, proximal weakness, interstitial lung disease [ILD]), laboratory investigations and other myositis autoantibodies, and imaging pertaining to the muscles and lungs. RESULTS: Complete clinical data were available for 108 of 118 patients with anti-MDA5 antibodies. A positive test was determined to be clinically concordant in 21 of 108 (19.4%) patients; these patients had higher signal intensity than those with clinical discordance (52 vs 19.5; P < 0.0001). The median age was 65 years (interquartile range 48-74), and 67% were female. The cohort was predominantly White (n = 14), followed by Southeast Asian (n = 3), African (n = 3), and Middle Eastern (n = 1). All 21 patients with anti-MDA5 dermatomyositis had ILD; 7 of 9 with rapidly progressive ILD (RP-ILD) were deceased at time of review. Patients with RP-ILD had higher ferritin levels (1,226 vs 262 μg/L; P < 0.05) and a higher neutrophil to lymphocyte ratio (4.1 vs 2.6; P < 0.05) than patients without RP-ILD. Pneumomediastinum developed in 7 of 21 (33%); of these, 6 had RP-ILD, and 4 subsequently died. Other manifestations included myositis (n = 8), cutaneous features (n = 14), polyarthritis (n = 6), and myocarditis (n = 1). CONCLUSION: Higher anti-MDA5 signal intensity on LIA was associated with greater clinical concordance. Pneumomediastinum is common and associated with high mortality.

Source: Arthritis Care & Research

DOI: 10.1002/acr.80144