{"doi":"10.1186/s13075-023-03044-4","title":"Quantitative proteomic screening uncovers candidate diagnostic and monitoring serum biomarkers of ankylosing spondylitis","abstract":"BACKGROUND: We sought to discover serum biomarkers of ankylosing spondylitis (AS) for diagnosis and monitoring disease activity. METHODS: We studied biologic-treatment-naïve AS and healthy control (HC) patients' sera. Eighty samples matched by age, gender, and race (1:1:1 ratio) for AS patients with active disease, inactive disease, and HC were analyzed with SOMAscan™, an aptamer-based discovery platform. T-tests tests were performed for high/low-disease activity AS patients versus HCs (diagnosis) and high versus low disease activity (Monitoring) in a 2:1 and 1:1 ratio, respectively, to identify differentially expressed proteins (DEPs). We used the Cytoscape Molecular Complex Detection (MCODE) plugin to find clusters in protein-protein interaction networks and Ingenuity Pathway Analysis (IPA) for upstream regulators. Lasso regression analysis was performed for diagnosis. RESULTS: Of the 1317 proteins detected in our diagnosis and monitoring analyses, 367 and 167 (317 and 59, FDR-corrected q < .05) DEPs, respectively, were detected. MCODE identified complement, IL-10 signaling, and immune/interleukin signaling as the top 3 diagnosis PPI clusters. Complement, extracellular matrix organization/proteoglycans, and MAPK/RAS signaling were the top 3 monitoring PPI clusters. IPA showed interleukin 23/17 (interleukin 22, interleukin 23A), TNF (TNF receptor-associated factor 3), cGAS-STING (cyclic GMP-AMP synthase, Stimulator of Interferon Gene 1), and Jak/Stat (Signal transducer and activator of transcription 1), signaling in predicted upstream regulators. Lasso regression identified a Diagnostic 13-protein model predictive of AS. This model had a sensitivity of 0.75, specificity of 0.90, a kappa of 0.59, and overall accuracy of 0.80 (95% CI: 0.61-0.92). The AS vs HC ROC curve was 0.79 (95% CI: 0.61-0.96). CONCLUSION: We identified multiple candidate AS diagnostic and disease activity monitoring serum biomarkers using a comprehensive proteomic screen. Enrichment analysis identified key pathways in AS diagnosis and monitoring. Lasso regression identified a multi-protein panel with modest predictive ability.","journal":"Arthritis Research & Therapy","year":2023,"id":333786,"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":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9601,"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":417983,"name":"Shervin Assassi","orcid":"0000-0002-8059-9978","position":1,"is_corresponding":false},{"id":1062184,"name":"Jim Zheng","orcid":null,"position":2,"is_corresponding":false},{"id":918037,"name":"Jessica Castillo","orcid":null,"position":3,"is_corresponding":false},{"id":1061570,"name":"Reyna Fabiola Osuna-Chávez","orcid":"0000-0001-6539-7828","position":4,"is_corresponding":false},{"id":278760,"name":"Kamala Vanarsa","orcid":"0000-0002-7602-4709","position":5,"is_corresponding":false},{"id":278769,"name":"Chandra Mohan","orcid":"0000-0001-7896-5740","position":6,"is_corresponding":false},{"id":31725,"name":"John D. Reveille","orcid":"0000-0001-5950-0913","position":7,"is_corresponding":false},{"id":788635,"name":"Mark C. Hwang","orcid":"0000-0003-2160-1481","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-19T01:09:44.297718Z","pmid":"37041650","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":[]}