{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:26:43Z","timestamp":1789576003973,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ankylosing spondylitis (AS) frequently coexists with other autoimmune diseases, leading to increased clinical heterogeneity and diagnostic complexity. Early identification of autoimmune comorbidity in AS remains challenging in routine practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A multicenter, retrospective, cross-sectional study was conducted, where clinical and laboratory data were collected from three independent tertiary centers between 2012 and 2025. Patients were classified into three groups: AS alone, autoimmune diseases alone, and AS with autoimmune comorbidities. Routinely available variables, including demographic characteristics, systemic inflammatory indices, hematological parameters, and liver and renal function markers, were analyzed. Multiple machine learning algorithms were developed for two clinically relevant classification tasks: AS alone vs. AS with autoimmune comorbidities, and autoimmune diseases alone vs. AS with autoimmune comorbidities. Model performance was evaluated using AUC, calibration, decision curve analysis, and clinical impact curves. SHapley Additive exPlanations (SHAP) were applied to enhance interpretability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among all models, LightGBM consistently demonstrated superior and stable performance across discrimination, calibration, and clinical utility metrics. In distinguishing AS alone from AS with autoimmune comorbidities, key contributors included age, gender, renal function\u2013related markers (eGFR, CysC, BUN, UA), and protein and hepatobiliary indices (ALB, DBIL). In comparisons between autoimmune diseases alone and AS with autoimmune comorbidities, SHAP highlighted metabolic- and synthesis-related features (GLOB, PREALB, CHE, ALP), acid\u2013base balance (HCO\n                      <jats:sub>3<\/jats:sub>\n                      ), and inflammatory activity (ESR). These patterns suggest that AS-associated autoimmune comorbidity represents a distinct systemic inflammatory\u2013metabolic phenotype rather than a simple amplification of inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Using routinely available clinical data, an explainable machine learning framework enables accurate identification and characterization of autoimmune comorbidity in AS. This approach has practical potential for early risk stratification and clinical decision support in real-world settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1775877","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T06:53:10Z","timestamp":1772088790000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A multicenter explainable machine learning analysis of autoimmune disease comorbidity in ankylosing spondylitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jichong","family":"Zhu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengqian","family":"Huang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Youjiang Medical University for Nationalities, Spinal Orthopedic Surgery","place":["Baise, China"]},{"name":"Key Laboratory of Molecular Pathology in Tumors of GuangxiHigher Education Institutions","place":["Baise, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lin","sequence":"additional","affiliation":[{"name":"Guilin People\u2019s Hospital","place":["Guilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyou","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ren","sequence":"additional","affiliation":[{"name":"Guilin People\u2019s Hospital","place":["Guilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Xue","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Cheng","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]},{"name":"Nanxishan Hospital of Guangxi Zhuang Autonomous Region (The Second People\u2019s Hospital of Guangxi Zhuang Autonomous Region), Department of Trauma Orthopaedics and Hand Surgery","place":["Guilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinli","family":"Zhan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41413-019-0057-8","article-title":"Ankylosing spondylitis: etiology, pathogenesis, and treatments","volume":"7","author":"Zhu","year":"2019","journal-title":"Bone Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2011.06.006","article-title":"Extra-articular manifestations of ankylosing spondylitis: prevalence, characteristics and therapeutic implications","volume":"22","author":"El Maghraoui","year":"2011","journal-title":"Eur J Internal Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X12458372","article-title":"Management and evaluation of extra-articular manifestations in spondyloarthritis","volume":"4","author":"van der Horst-Bruinsma","year":"2012","journal-title":"Ther Adv musculoskeletal Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)02263-3","article-title":"Axial spondyloarthritis","volume":"405","author":"Navarro-Comp\u00e1n","year":"2025","journal-title":"Lancet (London England)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1670965","article-title":"The association between ankylosing spondylitis and the risk of venous thromboembolism: a meta-analysis","volume":"16","author":"Hu","year":"2025","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41392-024-01952-8","article-title":"Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders","volume":"9","author":"Song","year":"2024","journal-title":"Signal transduction targeted Ther"},{"key":"B7","doi-asserted-by":"publisher","first-page":"101857","DOI":"10.1016\/j.berh.2023.101857","article-title":"The association between comorbidities and disease activity in spondyloarthritis - A narrative review","volume":"37","author":"Bosch","year":"2023","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41591-018-0300-7","article-title":"High-performance medicine: the convergence of human and artificial intelligence","volume":"25","author":"Topol","year":"2019","journal-title":"Nat Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4274\/dir.2024.242631","article-title":"The future of multimodal artificial intelligence models for integrating imaging and clinical metadata: a narrative review","volume":"31","author":"Simon","year":"2025","journal-title":"Diagn Interv Radiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7326\/M18-1990","article-title":"Ensuring fairness in machine learning to advance health equity","volume":"169","author":"Rajkomar","year":"2018","journal-title":"Ann Internal Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1136\/ard-2022-223296","article-title":"ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update","volume":"82","author":"Ramiro","year":"2023","journal-title":"Ann rheumatic Dis"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-078378","article-title":"TRIPOD+AI statement: updated guidance for reporting clinical prediction models that use regression or machine learning methods","volume":"385","author":"Collins","year":"2024","journal-title":"BMJ (Clinical Res ed)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.7150\/jca.94360","article-title":"Decoding gastric cancer: machine learning insights into the significance of COMMDs family in immunotherapy and diagnosis","volume":"15","author":"Wan","year":"2024","journal-title":"J Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s41512-019-0064-7","article-title":"A simple, step-by-step guide to interpreting decision curve analysis","volume":"3","author":"Vickers","year":"2019","journal-title":"Diagn prognostic Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1188725","article-title":"Integrated machine learning and bioinformatic analyses used to construct a copper-induced cell death-related classifier for prognosis and immunotherapeutic response of hepatocellular carcinoma patients","volume":"14","author":"Zhao","year":"2023","journal-title":"Front Pharmacol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s42256-019-0138-9","article-title":"From local explanations to global understanding with explainable AI for trees","volume":"2","author":"Lundberg","year":"2020","journal-title":"Nat Mach Intell"},{"key":"B17","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13075-018-1705-x","article-title":"Are gender-specific approaches needed in diagnosing early axial spondyloarthritis? Data from the SPondyloArthritis Caught Early cohort","volume":"20","author":"Ortolan","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"B18","doi-asserted-by":"publisher","first-page":"55","DOI":"10.4103\/jrms.jrms_623_25","article-title":"Polyautoimmunity and multiple autoimmune syndromes: A neglected clinical challenge","volume":"30","author":"Mottaghi","year":"2025","journal-title":"J Res Med sciences: Off J Isfahan Univ Med Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14145143","article-title":"Clinical predictors of polyautoimmunity in autoimmune liver diseases: insights into disease complexity","volume":"14","author":"G\u00fc\u00e7bey T\u00fcrker","year":"2025","journal-title":"J Clin Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"15755","DOI":"10.1038\/s41598-025-99274-4","article-title":"The association and clinical significance of hematological biomarkers in ankylosing spondylitis","volume":"15","author":"Rapapa","year":"2025","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","first-page":"300060519893167","DOI":"10.1177\/0300060519893167","article-title":"Clinical significance of the monocyte:lymphocyte ratio for ankylosing spondylitis patients with thoracolumbar kyphotic deformities","volume":"48","author":"Zhuang","year":"2020","journal-title":"J Int Med Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2018.407","article-title":"Liver enzyme elevation in patients with ankylosing spondylitis treated with tumor necrosis factor inhibitors: a single-center historical cohort study","volume":"35","author":"Choi","year":"2020","journal-title":"Korean J Internal Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1097\/BSD.0000000000001306","article-title":"Spine surgery and ankylosing spondylitis: optimizing perioperative management","volume":"36","author":"Joaquim","year":"2023","journal-title":"Clin Spine Surg"},{"key":"B24","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.csbj.2023.11.045","article-title":"A holistic approach to understanding immune-mediated inflammatory diseases: bioinformatic tools to integrate omics data","volume":"23","author":"Borrego-Yaniz","year":"2024","journal-title":"Comput Struct Biotechnol J"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2014.04.004","article-title":"Gender differences in autoimmune disease","volume":"35","author":"Ngo","year":"2014","journal-title":"Front Neuroendocrinol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI180076","article-title":"Mechanisms underlying sex differences in autoimmunity","volume":"134","author":"Fairweather","year":"2024","journal-title":"J Clin Invest"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-012-2624-9","article-title":"Renal involvement in ankylosing spondylitis: prevalence, pathology, response to TNF-a blocker","volume":"33","author":"Lee","year":"2013","journal-title":"Rheumatol Int"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.1129021","article-title":"Editorial: The kidney in auto-immune and auto-inflammatory processes: Definitions, mechanisms, and biomarkers","volume":"9","author":"Vaglio","year":"2022","journal-title":"Front Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2020.03.012","article-title":"Spondyloarthritis-associated igA nephropathy","volume":"5","author":"Champtiaux","year":"2020","journal-title":"Kidney Int Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S102819","article-title":"Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements","volume":"9","author":"Levitt","year":"2016","journal-title":"Int J Gen Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2024.00156","article-title":"The multifaceted role of bilirubin in liver disease: A literature review","volume":"12","author":"Ram\u00edrez-Mej\u00eda","year":"2024","journal-title":"J Clin Trans Hepatol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"103738","DOI":"10.1016\/j.autrev.2024.103738","article-title":"Immunometabolic shifts in autoimmune disease: Mechanisms and pathophysiological implications","volume":"24","author":"Chen","year":"2025","journal-title":"Autoimmun Rev"},{"key":"B33","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s13098-025-01720-w","article-title":"Prevalence of metabolic syndrome in ankylosing spondylitis: a multi national meta-analysis study","volume":"17","author":"Nayak","year":"2025","journal-title":"Diabetol Metab syndrome"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.809449","article-title":"Reduced serum cholinesterase is an independent risk factor for all-cause mortality in the pediatric intensive care unit","volume":"9","author":"Yue","year":"2022","journal-title":"Front Nutr"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2206346","article-title":"Humoral innate immunity and acute-phase proteins","volume":"388","author":"Mantovani","year":"2023","journal-title":"New Engl J Med"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnac031","article-title":"Bone turnover markers: basic biology to clinical applications","volume":"44","author":"Schini","year":"2023","journal-title":"Endocrine Rev"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1599995","article-title":"Beyond inflammation: the molecular basis of bone remodeling in axial spondyloarthritis and psoriatic arthritis","volume":"16","author":"Lopalco","year":"2025","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.090329","article-title":"Serum anion gap, bicarbonate and biomarkers of inflammation in healthy individuals in a national survey","volume":"182","author":"Farwell","year":"2010","journal-title":"CMAJ: Can Med Assoc J = J l'Association medicale Can"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1775877\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T06:53:11Z","timestamp":1772088791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1775877\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2026.1775877"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1775877","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]},"article-number":"1775877"}}