CEC Pilot Project – Somatic Genetic Variation as a Driver of Anti-XIST Autoimmunity
Siva Kasinathan, MD, PhD

Immune cells acquire somatic mutations throughout life, yet their contribution to sex-biased autoimmunity is unknown. This pilot project will determine if somatic genetic variants in leukocytes shape anti-XIST autoantibody (AXA) responses in lupus and systemic sclerosis. Cell type-specific deep sequencing of peripheral immune cells from patients and controls will be used to catalog protein-altering variants in XIST-associated proteins and quantify mosaic loss of the X and Y chromosomes. In partnership with SCORE-X investigators, we will profile AXA reactivity by bead array in paired plasma and link somatic variants to autoantibody breadth and clinical severity, nominating candidate neoantigens and biomarkers of sex-biased autoimmunity.

CEC Pilot Project – Human Cell-based GPCR Autoantibody Array for Profiling Sex-biased Autoimmunity

Tyler Prestwood, MD, PhD

Tyler Prestwood, MD, PhD, is a Clinical Assistant Professor in the Department of Psychiatry and Behavioral Sciences at Stanford University. His research focuses on the role of autoantibodies in immune-mediated disease and the development of technologies to identify and functionally characterize disease-relevant antibody responses. As part of Stanford SCORE-X, he is applying a novel multiplexed, cell-based GPCR antigen array to investigate sex differences in autoimmunity across systemic sclerosis, systemic lupus erythematosus, and myositis. By integrating GPCR autoantibody profiles with anti-XIST ribonucleoprotein autoreactivity and clinical phenotypes, his work aims to identify receptor-directed antibody responses that may contribute to vascular, fibrotic, and inflammatory disease mechanisms.