Background/Purpose:

Autoantibodies to MDA5 have been previously reported in Japanese patients with dermatomyositis (DM) and are associated with clinically-amyopathic DM and rapidly progressing interstitial lung disease (ILD). These autoantibodies also occur in juvenile Japanese DM patients in association with ILD. Anti-MDA5 has also been reported in a cohort of mixed ethnicity, where it was found to be associated with ILD and severe vasculopathy. Here we report on the frequency and clinical manifestations of anti-MDA5 autoantibodies in a large international multicenter cohort of Caucasian adult and juvenile myositis patients.

Methods:

Serum was available from 1331 adult myositis patients (480 DM) recruited to the EuMyoNet repository and 172 JDM patients recruited to the UK JDRG. Sera were screened for autoantibodies by immunoprecipitation (IPP) using radio-labelled K562 cell extract. Sera with immunoprecipitates at approximately 140 kDa were tested for anti-MDA5 autoantibodies by ELISA using recombinant MDA5 (Cambridge BioSciences). Clinical data were collected on standardised proformas. Sera from 169 systemic sclerosis, 40 SLE and 50 healthy controls were also analyzed by IPP. Statistical analysis was performed using SPSS and Fishers Exact Test.

Results:

Anti-MDA5 autoantibodies were found in the sera of 12 JDM patients and 25 adults. The frequency in the JDM cohort was 7.0%, in comparison to 1.9% in the overall adult myositis population and 3.8% in the adult DM group. Anti-MDA5 autoantibodies were not found in any patients with PM or any control sera. As with previous reports, there was an association between ILD and anti-MDA5 (p=0.044) in the adult DM patients. However, contrary to previous reports, this was not seen to be rapidly progressing, with no known ILD related fatalities in the anti-MDA5 positive group. In comparison, ILD was not found to be a significant association in the JDM anti-MDA5 positive group, with no patients having ILD reported as a clinical manifestation. Similarly to previous report, anti-MDA5 positive patients had significantly more ulceration (skin: p=0.047 and mouth: p=0.039), in the JDM cohort, compared with the anti-MDA5 negative group. Whilst ulceration data was unavailable in the adult population, the presence of anti-MDA5 was significantly associated with Gottron’s papules (p<0.001).

Conclusion:

We report the presence of anti-MDA5 autoantibodies in a large cohort of Caucasian JDM and adult myositis patients. The frequency of anti-MDA5 autoantibodies varies between adults and children, along with differences in the clinical profile. As with previous reports, the presence of anti-MDA5 is associated with the presence of severe cutaneous features in both JDM and adults. However, in this study ILD was only an association in the adult population, suggesting differences in pathogenesis or aetiology. This study also highlights differences in clinical manifestations between different ethnic groups, with the ILD in our adult patients being much less severe in comparison to previous reports on Japanese patients.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-phenotypes-of-caucasian-adult-and-juvenile-dermatomyositis-patients-with-anti-mda5-autoantibodies/