TY - JOUR TI - Identification of novel, clinically correlated autoantigens in the monogenic autoimmune syndrome APS1 by proteome-wide PhIP-Seq AU - Vazquez, Sara E AU - Ferré, Elise MN AU - Scheel, David W AU - Sunshine, Sara AU - Miao, Brenda AU - Mandel-Brehm, Caleigh AU - Quandt, Zoe AU - Chan, Alice Y AU - Cheng, Mickie AU - German, Michael AU - Lionakis, Michail AU - DeRisi, Joseph L AU - Anderson, Mark S A2 - Rosen, Antony A2 - Rath, Satyajit A2 - Craft, Joe VL - 9 PY - 2020 DA - 2020/05/15 SP - e55053 C1 - eLife 2020;9:e55053 DO - 10.7554/eLife.55053 UR - https://doi.org/10.7554/eLife.55053 AB - The identification of autoantigens remains a critical challenge for understanding and treating autoimmune diseases. Autoimmune polyendocrine syndrome type 1 (APS1), a rare monogenic form of autoimmunity, presents as widespread autoimmunity with T and B cell responses to multiple organs. Importantly, autoantibody discovery in APS1 can illuminate fundamental disease pathogenesis, and many of the antigens found in APS1 extend to more common autoimmune diseases. Here, we performed proteome-wide programmable phage-display (PhIP-Seq) on sera from a cohort of people with APS1 and discovered multiple common antibody targets. These novel APS1 autoantigens exhibit tissue-restricted expression, including expression in enteroendocrine cells, pineal gland, and dental enamel. Using detailed clinical phenotyping, we find novel associations between autoantibodies and organ-restricted autoimmunity, including a link between anti-KHDC3L autoantibodies and premature ovarian insufficiency, and between anti-RFX6 autoantibodies and diarrheal-type intestinal dysfunction. Our study highlights the utility of PhIP-Seq for extensively interrogating antigenic repertoires in human autoimmunity and the importance of antigen discovery for improved understanding of disease mechanisms. KW - APECED KW - autoantigens KW - PhIP-Seq KW - autoimmunity KW - enteroendocrine cells KW - ovarian insufficiency JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -