B41-13 Association of a Common Human Sting Genotype in Patients With Myositis-Related Interstitial Lung Disease: A Pilot Study

Abstract Introduction STING (stimulator of type I Interferon genes) is a key player in cytosolic DNA-induced immune responses, including anti-viral, anti-tumor immunity, and tissue inflammation. Rare human STING mutations cause STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant autoinflammatory disease. WT/SAVI patients present with neonatal or infantile onset systemic inflammation, small vessel vasculopathy, and progressive interstitial lung disease (ILD). Notably, there are over 10 different common STING genotypes (population frequency 1%) in the U.S population. The WT/WT STING genotype accounts for only ∼50% of non-Hispanic Whites, Hispanics, ∼36% of African Americans, and ∼22% of East Asians. A recent case-control study with 15,000 individuals revealed that two common STING genotypes are associated with increased or reduced risk of Alzheimer’s Disease, respectively. Myositis is a highly inflammatory disease, and it is unknown why some patients develop ILD and others do not. Here, we hypothesize that common human STING genotypes confer different risks to ILD in Myositis patients. Methods A total of 21 myositis patients were recruited for this pilot study: 11 with ILD and 10 without ILD. Cheek swabs were obtained for DNA collection. These samples were then processed for STING gene sequencing to determine genotype. Physiologic, radiographic, and laboratory data to describe the patient’s disease severity were obtained through chart review. Data was analyzed using simple descriptive statistics. Results Phenotypically, most patients with ILD were positive for anti-synthetase antibodies, with Jo-1 the most common antibody. Most patients without ILD were ANA positive with different myositis-specific antibodies. Genetically, a common STING genotype (WT/Q293) was found exclusively in Myositis patients with ILD (4 out of 11), but not in those without ILD (0 out of 10). Conclusions The WT/Q293 STING genotype may be associated with an increased risk of ILD in patients with myositis. Notably, ∼3.4% of African Americans are WT/Q293. The 293 residue is identical in mouse and human STING. Future research will focus on i) using ILD animal models to establish that the WT/Q293 STING promotes ILD; ii) understanding the mechanism by which the WT/Q293 STING genotype promotes ILD; iii) evaluating STING-targeting therapy in improving ILD healthcare. This abstract is funded by: None