Anti-Xist RNP antibodies (AXA) in autoimmune disease diagnosis and prognosis

Project Summary Substantial heterogeneity within autoimmune diseases and overlapping traits across diseases have limited our ability to tailor effective therapies and sensitive diagnostics specific to each autoimmune disease. Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) are three autoimmune diseases with a long history of challenges in disease classification, prognostication, and therapeutic intervention. All three diseases are more prevalent in females than males. This project leverages the recent discovery that patients with several autoimmune diseases have elevated levels of circulating autoantibodies against the female specific XIST ribonucleoprotein (RNP) complex, collectively termed anti-Xist RNP antibodies (AXA). We will employ a newly developed protein array to comprehensively characterize AXA and discover their diagnostic and translational potential. We will evaluate how patterns of AXA can distinguish patients with SLE, SSc, vs DM, disease subtypes, and severity. We will further evaluate the prognostic value of AXA in longitudinal progression of scleroderma, using carefully chosen longitudinal samples of patients with early SSc. Finally, we will evaluate the predictive value of AXA in the response of SSc to therapy. These studies will illuminate the diagnostic and prognostic potential of novel autoantibodies against a female-specific RNP complex.