{"doi":"10.1002/art.41276","title":"Citrulline Not a Major Determinant in the Recognition of Peptidylarginine Deiminase 2 and 4 by Autoantibodies in Rheumatoid Arthritis","abstract":"OBJECTIVE: Citrullinated proteins are hallmark targets of autoantibodies in rheumatoid arthritis (RA). Our study was undertaken to determine the effect of autocitrullination on the recognition of peptidylarginine deiminases (PADs) 2 and 4 by autoantibodies in RA. METHODS: Autocitrullination sites in PAD2 and PAD4 were determined by mass spectrometry and literature review. Antibodies against native and autocitrullinated PADs in 184 patients with RA were detected by enzyme-linked immunosorbent assay. Linear regression analysis, outlier calculations, and competition assays were performed to evaluate antibody reactivity to native and citrullinated PADs. RESULTS: Autocitrullination of PAD2 and PAD4 was detected in 16 (48%) of 33 arginine residues and 7 (26%) of 27 arginine residues, respectively. Despite robust autocitrullination, autoantibodies bound similarly to native and citrullinated PAD2 or PAD4 (ρ = 0.927 and ρ = 0.903, respectively; each P < 0.0001). Although subsets of anti-PAD-positive sera were identified as exhibiting preferential recognition of native or citrullinated PAD2 (40.5% or 4.8%, respectively) or PAD4 (11.7% or 10.4%, respectively), competition assays confirmed that the majority of anti-PAD reactivity was attributed to a pool of autoantibodies that bound irrespective of citrullination status. CONCLUSION: Autocitrullination does not affect autoantibody reactivity to PADs in the majority of patients with RA, demonstrating that anti-PAD antibodies are distinct from anti-citrullinated protein antibodies in their dependence on citrullination for binding.","journal":"Arthritis & Rheumatology","year":2020,"id":81028,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9701,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":419696,"name":"Ryan L. Davis","orcid":"0000-0003-0512-8989","position":1,"is_corresponding":false},{"id":419697,"name":"Ashley M. Curran","orcid":"0000-0001-7735-0437","position":2,"is_corresponding":false},{"id":419698,"name":"Pooja Naik","orcid":"0000-0002-9767-3193","position":3,"is_corresponding":false},{"id":419699,"name":"Ruiqiang Chen","orcid":"0000-0001-7390-8800","position":4,"is_corresponding":false},{"id":305261,"name":"Chan Hyun Na","orcid":"0000-0002-3622-2938","position":5,"is_corresponding":false},{"id":343707,"name":"Jon T. Giles","orcid":"0000-0002-8792-0402","position":6,"is_corresponding":false},{"id":343705,"name":"Felipe Andrade","orcid":"0000-0003-3415-0704","position":7,"is_corresponding":false},{"id":419695,"name":"Erika Darrah","orcid":"0000-0003-1119-0279","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-18T21:52:34.401799Z","pmid":"32255561","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":[]}