Background/Purpose: Anti-MDA5 autoantibodies (Abs) have been associated with clinically amyopathic and classic dermatomyositis (DM), with rapidly progressive interstitial lung disease (ILD) and poor prognosis in Japanese patients (pts). The aim of this study was to examine the frequency and characteristics of anti-MDA5 Abs associated with juvenile DM (JDM) in North America.        

Methods: Demographic, clinical, laboratory and outcome features of 34 pts with anti-MDA5 Abs were compared to those of 60 Ab (MSA/MAA) negative, 164 anti-p155/140 Ab+ and 116 MJ Ab+ JDM and JCTM/DM pts meeting probable or definite Bohan and Peter criteria. Differences were evaluated by Fisher’s exact and Mann-Whitney tests. Kaplan-Meier and Log-rank tests were used for time-to-event treatment analysis. Myositis Abs were tested by standard immunoprecipitation (IP) and MDA-5, p155/140 and MJ Abs tested by reverse IP-immunoblot. Significant univariable results were examined in multivariable logistic regression.  

Results:   Anti-MDA5 Abs were identified in 34 (7.5%) pts from a cohort of 453 JDM and JCTM/DM pts. Characteristics of MDA5 Ab+ compared to MSA/MAA-, anti-p155/140 Ab+ and anti-MJ Ab+ pts are shown in the Table. MDA5+ were older at diagnosis and had a slower disease onset compared to p155/140 + and MJ Ab+. Anti-MDA5 Ab+ had lower serum CK levels and more frequent fever, weight loss, adenopathy, arthralgia, arthritis, abnormal PFTs, dyspnea, ILD compared to MSA/MAA-, p155/140+ and MJ Ab+. The median skeletal, pulmonary, constitutional and overall total clinical system scores at diagnosis were higher in MDA5 Ab+ (p<0.0001).  There were no differences in gender distribution, delay to diagnosis, and onset severity among the four groups. Total number of medications received was fewer (4.0 [IQR 3- 6] vs.5.0 [IQR 4- 8], p=0.04), treatment duration was shorter (23.2 mths [IQR 13- 54] vs. 38.2 [IQR 22- 66], p=0.04) in MDA5 Ab+ vs. p155/140 Ab+. MDA5 Ab+ had fewer flares (48% vs. 71%, p=0.035) and shorter time to discontinue steroid therapy (24.7 mths [IRQ 16-37] vs. 33.0 [IRQ 18-61], p=0.046) vs. p155/140 Ab+. Multivariable analysis revealed weight loss, arthritis and lower serum CK level as significantly associated with anti-MDA5 Ab+ vs Ab-, whereas weight loss, arthritis, arthralgia, ILD were significantly associated with anti-MDA5 Ab+ vs. p155/140 Ab+, and weight loss, arthritis, ILD, lower serum aldolase level, older age at diagnosis were significantly associated with anti-MDA5 Ab+ vs. MJ Ab+. There were no differences in disease course, status at most recent evaluation, and mortality of MDA5 Ab+ vs. other Ab groups.  

Conclusion:  Anti-MDA5 Abs are seen in a distinct subset of JDM with frequent arthritis, arthralgia, weight loss, adenopathy, and ILD, but lower serum CK and aldolase. MDA5+ have comparable outcomes, but with the ability to discontinue steroids more rapidly and less frequent flares compared to p155/140 Ab+ pts.  

Table.