{"doi":"10.1101/2023.04.07.535899","title":"Validation of a murine proteome-wide phage display library for the identification of autoantibody specificities","abstract":"ABSTRACT Autoimmunity is characterized by loss of tolerance to tissue-specific as well as systemic antigens, resulting in complex autoantibody landscapes. Here, we introduce and extensively validate the performance characteristics of a murine proteome-wide library for phage display immunoprecipitation and sequencing (PhIP-seq), to profile mouse autoantibodies. This system and library were validated using seven genetic mouse models across a spectrum of autoreactivity. Mice deficient in antibody production ( Rag2 -/- and μMT) were used to model non-specific peptide enrichments, while cross-reactivity was evaluated using anti-ovalbumin B cell receptor (BCR)-restricted OB1 mice as a proof of principle. The PhIP-seq approach was then utilized to interrogate three distinct autoimmune disease models. First, serum from Lyn -/- IgD +/- mice with lupus-like disease was used to identify nuclear and apoptotic bleb reactivities, lending support to the hypothesis that apoptosis is a shared origin of these antigens. Second, serum from non-obese diabetic (NOD) mice, a polygenic model of pancreas-specific autoimmunity, enriched peptides derived from both insulin and predicted pancreatic proteins. Lastly, Aire -/- mouse sera were used to identify numerous auto-antigens, many of which were also observed in previous studies of humans with autoimmune polyendocrinopathy syndrome type 1 (APS1) carrying recessive mutations in AIRE. Among these were peptides derived from Perilipin-1, a validated autoimmune biomarker of generalized acquired lipodystrophy in humans. Autoreactivity to Perilipin-1 correlated with lymphocyte infiltration in adipose tissue and underscores the approach in revealing previously unknown specificities. These experiments support the use of murine proteome-wide PhIP-seq for antigenic profiling and autoantibody discovery, which may be employed to study a range of immune perturbations in mouse models of autoimmunity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393132,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9223,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1054813,"name":"Irina Proekt","orcid":"0000-0003-3818-1102","position":1,"is_corresponding":false},{"id":1094286,"name":"Haleigh S. Miller","orcid":"0000-0002-0920-7169","position":2,"is_corresponding":false},{"id":246842,"name":"Akshaya Ramesh","orcid":"0000-0003-0205-0688","position":3,"is_corresponding":false},{"id":1026640,"name":"Jeremy F. Brooks","orcid":"0000-0002-0710-0544","position":4,"is_corresponding":false},{"id":818669,"name":"Andrew F. Kung","orcid":null,"position":5,"is_corresponding":false},{"id":308641,"name":"Caleigh Mandel‐Brehm","orcid":"0000-0001-7764-6529","position":6,"is_corresponding":false},{"id":721285,"name":"David Yu","orcid":null,"position":7,"is_corresponding":false},{"id":284366,"name":"Colin R. Zamecnik","orcid":"0000-0002-9477-1388","position":8,"is_corresponding":false},{"id":854460,"name":"Rebecca Bair","orcid":"0000-0002-2056-735X","position":9,"is_corresponding":false},{"id":308639,"name":"Sara E. Vazquez","orcid":"0000-0002-0601-7001","position":10,"is_corresponding":false},{"id":239644,"name":"Sara Sunshine","orcid":"0000-0002-1897-5063","position":11,"is_corresponding":false},{"id":333839,"name":"Clare L. Abram","orcid":"0000-0002-9204-2640","position":12,"is_corresponding":false},{"id":322389,"name":"Clifford A. Lowell","orcid":"0000-0002-0467-7073","position":13,"is_corresponding":false},{"id":685261,"name":"Gabrielle Rizzuto","orcid":"0000-0003-3052-0253","position":14,"is_corresponding":false},{"id":109296,"name":"Michael R. Wilson","orcid":"0000-0002-8705-5084","position":15,"is_corresponding":false},{"id":672165,"name":"Julie Zikherman","orcid":"0000-0002-0873-192X","position":16,"is_corresponding":false},{"id":235418,"name":"Mark S. Anderson","orcid":"0000-0002-3093-4758","position":17,"is_corresponding":false},{"id":107235,"name":"Joseph L. DeRisi","orcid":"0000-0002-4611-9205","position":18,"is_corresponding":false},{"id":233431,"name":"Elze Rackaityte","orcid":"0000-0003-3889-8082","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:01.355412Z","pmid":"37066405","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}