Single nucleotide polymorphisms associated with myositis-specific antibodies in juvenile dermatomyositis 9267

Abstract Description Juvenile dermatomyositis (JDM) is an autoimmune disease of the muscle and skin with significant morbidity. Autoreactive antibodies often target ubiquitous intracellular antigens yet also correlate with distinct clinical profiles. We likely have not identified all myositis specific antibodies (MSA). One MSA, anti-MDA5, correlates with pronounced rashes and lung disease but often milder myositis. It is unclear how or if MSA contribute directly to disease pathology. Methods We performed whole exome sequencing on 51 patients with JDM and collected clinical information. Correlations between continuous/ordinal variables were analyzed via the Mann Whitney U test, and between categorical variables by Fisher’s exact test. Results All patients with anti-MDA5 were found to harbor the same mutation in tyrosinase, Ser192Tyr. The most enriched mutation identified by WES (rs979369776) was in RPL10, which encodes for a ribosomal protein important in several ribosomal and extra-ribosomal functions. DISCUSSION: The association between single nucleotide variants and autoantibodies bears more investigation. Such correlations suggest possible pathways involved in JDM pathogenesis, especially the relationship between anti-MDA5 and TYR(Ser192Tyr). Our data also raise the question of whether anti-RPL10 antibodies play a role in JDM or other autoimmune diseases. MSAs are frequently used to guide treatment decisions; surrogate genetic testing would be less laborious, time consuming, and expensive. Funding Sources Supported by a Cure JM foundation grant Topic Categories Basic Autoimmunity (BA)