{"doi":"10.1002/acr2.11740","title":"<scp>SOX</scp>‐5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women","abstract":"OBJECTIVE: Adaptive immunity mediates psoriatic disease pathogenesis. We aimed to identify novel psoriatic autoantigens and their phenotypic associations in deeply characterized patient cohorts. METHODS: Sera from psoriatic arthritis (PsA) patients were used for autoantibody discovery. Immunoprecipitations performed with cell lysates were on-bead digested, and autoantigens were identified by mass spectrometry. Prevalence and clinical features associated with anti-SRY-Box transcription factor-D (SOX-D) antibodies were determined by screening discovery cohorts of patients with PsA (n = 135), patients with psoriasis without PsA (n = 24), and healthy controls (n = 41). A PsA validation cohort (n = 325) and disease control samples of individuals with rheumatoid arthritis (RA; n = 66) and systemic lupus erythematosus (SLE, n = 66) were assayed for anti-SOX5 antibodies. Disease characteristics were compared by antibody status. Longitudinal data were analyzed using linear mixed-effects models with patient-specific intercept to ascertain associations. We also tested PsA sera for the recently described anti-ADAMTS-L5 autoantibody in PsA. RESULTS: The novel autoantigens identified were SOX-D transcription factors, with SOX-5 being the focus of this analysis. Anti-SOX5 antibodies were present in 8.9% (12 of 135) and 4.3% (14 of 323) of patients in the PsA discovery and validation cohorts, respectively, 12.5% of patients (3 of 24) in the psoriasis group, 2.4% (1 of 41) of healthy controls, and 7.6% (5 of 66) each of patients in the RA and SLE groups. Anti-SOX5 were associated with female sex in both PsA cohorts (discovery: 15.7% women, 2.6% men, P = 0.006; validation: 6.3% women, 1.4% men, P = 0.049). In a longitudinal analysis adjusted for sex, anti-SOX5 associated with biologic disease-modifying antirheumatic drug treatment (95% vs 61%; P = 0.001; n = 96) and with differences in estimated treatment effects by mechanism of action. Anti-ADAMTS-L5 autoantibodies were identified in 8 of 124 patients (6.5%) in the PsA group. CONCLUSION: SOX-D transcription factors are novel psoriatic autoantigens. Anti-SOX5 antibodies were preferentially found in women with PsA and associated with specific clinical and treatment characteristics, suggesting that anti-SOX5 antibodies may identify mechanistic subgroups. We independently validated anti-ADAMTS-L5 autoantibodies in PsA.","journal":"ACR Open Rheumatology","year":2024,"id":469027,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":738770,"name":"David Fiorentino","orcid":"0000-0001-7951-3674","position":1,"is_corresponding":false},{"id":257456,"name":"Jamie Perin","orcid":"0000-0002-5482-6620","position":2,"is_corresponding":false},{"id":419695,"name":"Erika Darrah","orcid":"0000-0003-1119-0279","position":3,"is_corresponding":false},{"id":1030979,"name":"Qingyuan Yang","orcid":"0000-0001-8808-1113","position":4,"is_corresponding":false},{"id":260832,"name":"Laura Gutierrez‐Alamillo","orcid":null,"position":5,"is_corresponding":false},{"id":55628,"name":"Clifton O. Bingham","orcid":"0000-0002-4752-5029","position":6,"is_corresponding":false},{"id":278767,"name":"Michelle Petri","orcid":"0000-0003-1441-5373","position":7,"is_corresponding":false},{"id":343704,"name":"Antony Rosen","orcid":"0000-0002-8374-4763","position":8,"is_corresponding":false},{"id":257451,"name":"Livia Casciola‐Rosen","orcid":"0000-0002-4172-1539","position":9,"is_corresponding":false},{"id":376863,"name":"Ana‐Maria Orbai","orcid":"0000-0001-8644-8567","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:05:28.027781Z","pmid":"39218617","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":[]}