Background/Purpose: Dermatomyositis (DM) is a heterogeneous systemic disease with specific autoantibodies (Abs) which correlate with unique clinical phenotypes.  Melanoma differentiation-associated gene 5 (MDA5) Abs have been described (in several Japanese DM patient cohorts and one US DM cohort) in conjunction with amyopathic DM and rapidly progressive interstitial lung disease (ILD).    Given the widening spectrum of associated clinical findings, we sought to determine prevalence of Abs to MDA5, associated clinical findings and whether Ab titers correlated with clinical course in a longitudinal cohort of myositis patients. 

Methods: This is a retrospective case series review of clinical and serologic features of eleven DM patients with MDA5 Abs who were evaluated at the JHU Myositis Center. In addition, six MDA5 + patients with longitudinal data and banked serologic samples were evaluated for clinical correlations (MRC scale strength, cutaneous features, arthritis, ILD) with Ab titers.

All patients were evaluated as part of routine clinical care between 2006 and 2012. Informed consent was obtained, and 165 consecutive DM patients (for whom banked serum samples were available) were tested for the presence of MDA5 Abs.  Patient sera were screened for autoantibodies by immunoprecipitation (IP) of in vitro transcribed/translated (IVTT), radiolabeled MDA5. When multiple serum samples were available from the same patient, IPs were performed simultaneously and run on the same gel for comparison.  Patient sera were further screened for antibodies against Jo-1 and Ro52 by ELISA, and Mi-2 and NXP2 by IP of IVTT generated protein. 

Results: MDA5 was targeted in 11/165 (6.7%) patients with DM.  In our cohort of 11 MDA5+ patients, 82% (9/11) presented with a symmetric polyarthropathy;  5% (5/11) demonstrated overt clinical myopathy; and only 64% (7/11) had ILD.  The majority of ILD stabilized with immunosuppression. Only two patients had progressive ILD, and both were anti-Ro 52 positive. All MDA5+ positive patients remained Ab positive over the entire course of follow-up. Longitudinal MDA5 antibody titers were assessed in 6 patients; with the exception of one patient, titers did not vary significantly over time, nor did they track with clinical course. Jo-1 was negative in all MDA5+ patients, while anti-Ro52, frequently found in Jo-1 positive patients, was seen in 3 of 11 patients. 

Conclusion: This report adds to our growing understanding of the expanding phenotype of MDA5+ DM. The MDA 5 phenotype can overlap with the antisynthetase syndrome (e.g. mechanics hands, arthritis, myositis, fever and ILD),; however autoantibodies to Jo-1 were not found concomitantly. Many patients presented initially with an inflammatory arthritis that looked clinically similar to RA, and many patients had an overt myopathy. While MDA5 autoantibodies remained positive throughout disease course and relative titer did not correlated with clinical course, even patients with a relatively fulminant clinical course of disease with regard to ILD, myositis, cutaneous disease, and arthritis were often able to attain sustained clinical remission, in some cases even after discontinuation of immunosuppression.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expanding-the-clinical-and-serological-spectrum-of-mda5-associated-dermatomyositis/