biostudies-literatureWang EYNCI NIH HHSNIH HHS100172https://www.ebi.ac.uk/biostudies/studies/S-EPMC8967185biostudies-literatureUnknown2(2)Autoantibodies that recognize extracellular proteins (the exoproteome) exert potent biological effects but are challenging to detect. Here, we developed rapid extracellular antigen profiling (REAP), a high-throughput technique for the comprehensive discovery of exoproteome-targeting autoantibodies. Patient samples are applied to a genetically barcoded yeast surface display library containing 2,688 human extracellular proteins. Antibody-coated yeast are isolated, and sequencing of barcodes is used to identify displayed antigens. To benchmark REAP's performance, we screened 77 patients with autoimmune polyglandular syndrome type 1 (APS-1). REAP sensitively and specifically detected both known and previously unidentified autoantibodies in APS-1. We further screened 106 patients with systemic Cell reports methodsHigh-throughput identification of autoantibodies that target the human exoproteome.PMC8967185DP5 OD023088P30 CA016359Schmitt MMMeffre EGonzalez-Hernandez JADong MXKoumpouras FDai YWang EYRosen CEYang YHinchcliff MRing AMFerre EMNLionakis MSLiu FfalseHigh-throughput identification of autoantibodies that target the human exoproteome.Autoantibodies that recognize extracellular proteins (the exoproteome) exert potent biological effects but are challenging to detect. Here, we developed rapid extracellular antigen profiling (REAP), a high-throughput technique for the comprehensive discovery of exoproteome-targeting autoantibodies. Patient samples are applied to a genetically barcoded yeast surface display library containing 2,688 human extracellular proteins. Antibody-coated yeast are isolated, and sequencing of barcodes is used to identify displayed antigens. To benchmark REAP's performance, we screened 77 patients with autoimmune polyglandular syndrome type 1 (APS-1). REAP sensitively and specifically detected both known and previously unidentified autoantibodies in APS-1. We further screened 106 patients with systemic 2022-01-01T00:00:00Z2022 Feb2026-05-31T11:12:46.535Z2024-11-20T15:47:12.315ZS-EPMC89671853536070610.1016/j.crmeth.2022.100172