Clinical characteristics and concordance of anti-MDA5 autoantibodies: A multicentre Australian study.

Abstract

In Australia, anti-MDA5 antibodies are exclusively tested by line immunoblot assay (LIA). The clinical concordance of a 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. Electronic records of a multisite cohort (patients with positive anti-MDA5 on LIA from three states in Australia from 01/2017-09/2024) 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. Complete clinical data were available for 108/118 patients with positive anti-MDA5 antibodies. A positive test was determined to be clinically concordant in 21/108 (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 (IQR 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; 7/9 with rapidly progressive ILD (RP-ILD) were deceased at time of review. Patients with RP-ILD had higher ferritin levels (1226 vs 262 μg/L, p<0.05) and neutrophil-to-lymphocyte ratio (4.1 vs 2.6, p<0.05) than patients without RP-ILD. Pneumomediastinum developed in 7/21 (33%); of these, six had RP-ILD, and four subsequently died. Other manifestations included myositis (n=8), cutaneous features (n=14), polyarthritis (n=6) and myocarditis (n=1). Higher anti-MDA5 signal intensity on LIA was associated with greater clinical concordance. Pneumomediastinum is common and associated with high mortality.