Background/Purpose: JDM is a complex autoimmune disease with an interferon (IFN) signature, with a reported correlation with disease activity.  Clinical features vary among myositis-specific autoantibody (MSA) groups, but partially overlap with 2 genetically defined autoinflammatory syndromes, Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) caused by mutations in proteasome genes and Sting-Associated Vasculopathy with onset during Infancy (SAVI) caused by mutations in TMEM173/ STING.  The comparison of an IFN score in JDM versus CANDLE and SAVI may help elucidate the role of IFN in JDM.  Evaluation of IFN scores by MSA group and disease activity in JDM may pilot their potential as biomarkers.

Methods: A standardized 25 gene IFN score (IFN_s) previously developed in CANDLE patients (H. Kim, A&R 2014) was assessed in JDM patient RNA extracted from whole blood using the Nanostring nCounter gene expression system (Seattle, WA). JDM sera were characterized for MSAs by validated immunoprecipitation and immunoblotting methods; physician global disease activity (PGA) was clinically assessed on a visual analog scale. CANDLE and SAVI samples were positive IFN-mediated disease controls.  Non-IFN controls were NOMID (IL-1 mediated autoinflammatory monogenic disease) and healthy controls (HCs).  Nonparametric tests were used for non-normally distributed data; MSA group analysis was done if n>5. IFN score comparisons among disease groups and MSAs were performed by Mann-Whitney test. Spearman correlation was performed between PGA versus IFN_s for JDM, and by MSA group.

Results:

JDM IFN_s was significantly lower than CANDLE and SAVI and significantly higher than HCs and NOMID (Table 1, Figure 1A). IFN_s was higher in MDA5 and MSA-neg groups (compared to anti-TIF1, MJ), but was not statistically significant. The 4 MSA groups remained significantly higher than HC and NOMID and significantly lower than CANDLE and SAVI.  PGA (median 2.3, IQR 1.5-3.7) correlated significantly with IFN_s in JDM overall (Figure 1B), though correlation of IFN_s with PGA was not significant within the MSA groups analyzed.

Conclusion: Though JDM IFN_s is significantly higher than HCs and NOMID, it is significantly lower than CANDLE and SAVI, indicating IFN may not be the sole driver of pathogenesis in JDM.  PGA does correlate with IFN score as a potential biomarker.  No significant differences were found among MSA groups but further study is needed to identify what factors affect the IFN_s in JDM. This research was supported by the Intramural Research Program of the NIH, NIEHS, NIAID, NIAMS and the CC.