Identification of varying human ICAM-1-targeting autoantibodies across populations and disease 3201

Abstract Description Autoantibodies are host-targeting antibodies typically removed through immune tolerance mechanisms. The presence of autoantibodies is commonly associated with autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis, however recent large cohort studies have identified healthy individuals possess autoantibodies with ability to regulate immune response. The origin and functions of autoantibodies in individuals without autoimmune disease is not well characterized. Here, we identified autoantibodies directed against intracellular adhesion molecule 1 (ICAM-1), a cell surface glycoprotein important for inflammation and immune cell adhesion that is widely exploited by pathogens for cell entry. Serum from healthy individuals maintained heterogenous levels of anti-ICAM-1 antibodies and ICAM-1 autoantibody levels were associated with age. Individuals with inflammatory conditions, such as severe COVID-19 or autoimmune disease, had significantly less anti-ICAM-1 antibodies compared to healthy controls. Using peptide microarrays, we determined immunodominant epitopes targeted across individuals by ICAM-1 autoantibodies. Finally, we identified that anti-ICAM-1 antibodies could inhibit cellular adhesion of immune cells, disrupting immune system function. The findings of this study elucidate autoantibodies against ICAM-1 could play a role in immunoregulation during inflammation and may provide a future target for managing immune response. Funding Sources Supported by Children’s Mercy Research Partners, Children’s Mercy Research Institute, and Paul Henson Endowment Clinical Scholar Award Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)