REAP: A platform to identify autoantibodies that target the human exoproteome
REAP: A platform to identify autoantibodies that target the human exoproteome
Abstract Autoantibodies that recognize extracellular proteins (the “exoproteome”) exert potent biological effects but have proven challenging to detect with existing screening technologies. Here, we developed Rapid Extracellular Antigen Profiling (REAP) as a technique for comprehensive, high-throughput discovery of exoproteome-targeting autoantibodies. With REAP, patient samples are applied to a genetically-barcoded library containing 2,688 human extracellular proteins displayed on the surface of yeast. Antibody-coated cells are isolated by magnetic selection and deep sequencing of their barcodes is used to identify the displayed antigens. To benchmark the performance of REAP, we screened 77 patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). REAP sensitively and specifically detected known autoantibody reactivities in APECED in addition to numerous previously unidentified reactivities. We further screened 106 patients with systemic lupus erythematosus (SLE) and identified novel autoantibody reactivities against a diverse set of antigens including growth factors, extracellular matrix components, cytokines, and immunomodulatory proteins. Several of these responses were associated with disease severity and specific clinical manifestations of SLE and exerted potent functional effects on cell signaling ex vivo. These findings demonstrate the utility of REAP to atlas the expansive landscape of exoproteome-targeting autoantibodies and their impacts on patient health outcomes.
Wang Eric Y.、Dai Yile、Schmitt Monica M.、Liu Feimei、Hinchcliffe Monique、Koumpouras Fotios、Lionakis Michail S.、Ring Aaron M.、Ferr¨| Elise M. N.、Dong Mei X.、Rosen Connor E.、Gonzalez-Hernandez Jaime A.、Yang Yi、Meffre Eric
Department of Immunobiology, Yale School of MedicineDepartment of Immunobiology, Yale School of MedicineFungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of HealthDepartment of Immunobiology, Yale School of MedicineDepartment of Internal Medicine, Yale School of MedicineDepartment of Internal Medicine, Yale School of MedicineFungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of HealthDepartment of Immunobiology, Yale School of Medicine||Department of Pharmacology, Yale School of MedicineFungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy & Infectious Diseases, National Institutes of HealthDepartment of Internal Medicine, Yale School of MedicineDepartment of Immunobiology, Yale School of MedicineDepartment of Immunobiology, Yale School of MedicineDepartment of Immunobiology, Yale School of MedicineDepartment of Immunobiology, Yale School of Medicine
医学研究方法基础医学生物科学研究方法、生物科学研究技术
Wang Eric Y.,Dai Yile,Schmitt Monica M.,Liu Feimei,Hinchcliffe Monique,Koumpouras Fotios,Lionakis Michail S.,Ring Aaron M.,Ferr¨| Elise M. N.,Dong Mei X.,Rosen Connor E.,Gonzalez-Hernandez Jaime A.,Yang Yi,Meffre Eric.REAP: A platform to identify autoantibodies that target the human exoproteome[EB/OL].(2025-03-28)[2025-05-02].https://www.biorxiv.org/content/10.1101/2021.02.11.430703.点此复制
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