{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:01:46Z","timestamp":1792706506060,"version":"4.5.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"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><jats:title>Background<\/jats:title><jats:p>Ankylosing spondylitis (AS) is an immune-mediated chronic inflammatory disease. When AS is complicated by intervertebral disc degeneration (IVDD), disease complexity increases substantially, often resulting in poor long-term outcomes. Although previous studies have explored the mechanisms linking AS and IVDD, reliable tools for precise risk prediction and early intervention remain scarce.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this retrospective study, we enrolled 144 patients with AS (60 with and 84 without IVDD). Their clinical features, immune status, and inflammatory cytokine levels were analyzed. A nomogram prediction model was constructed using multivariable logistic regression. Model performance was evaluated via receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multivariable analysis identified body mass index (BMI), peripheral blood Th2 cell percentage (Th2%), and serum IL-4 levels as independent risk factors for IVDD in patients with AS. All associations remained statistically significant after Benjamini\u2013Hochberg correction (BMI: BH-adjusted P = 0.001; Th2%: BH-adjusted P = 0.019; IL-4: BH-adjusted P = 0.019). Incorporation of these factors into a nomogram yielded excellent discriminative performance (area under the curve, AUC = 0.83) and calibration, outperforming a simplified model based solely on BMI (AUC = 0.74). This improvement in predictive accuracy was statistically significant, as determined by DeLong\u2019s test (P = 0.018). DCA revealed that at a threshold probability of 60.8%, the nomogram effectively distinguished high-risk patients, underscoring its strong clinical applicability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study is the first to highlight the critical roles of Th2 cells and IL-4 in AS complicated by IVDD, and establishes a nomogram that accurately predicts the risk of IVDD in AS. Beyond offering a tool for early detection and personalized management, these findings open avenues for investigating overlapping pathogenic mechanisms and potential immunotherapeutic targets in AS-IVDD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1556738","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T05:40:15Z","timestamp":1747028415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Precision prediction of intervertebral disc degeneration in ankylosing spondylitis using a nomogram model reveals the pivotal role of Th2-type immune dysregulation"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiao-nan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-tian","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run-tian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-zhang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-feng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dou-dou","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"131814","DOI":"10.1016\/j.ijbiomac.2024.131814","article-title":"miRNAs dysregulation in ankylosing spondylitis: A review of implications for disease mechanisms, and diagnostic markers","volume":"268","author":"Mohammed","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2014.01.015","article-title":"The classification and diagnostic criteria of ankylosing spondylitis","author":"Raychaudhuri","year":"2014","journal-title":"J Autoimmun"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01038-9","article-title":"Predominant ligament-centric soft-tissue involvement differentiates axial psoriatic arthritis from ankylosing spondylitis","volume":"19","author":"McGonagle","year":"2023","journal-title":"Nat Rev Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e2406876","DOI":"10.1002\/advs.202406876","article-title":"Extracellular vesicles derived from ligament tissue transport interleukin-17A to mediate ligament-to-bone crosstalk in ankylosing spondylitis","volume":"11","author":"Wang","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-022-06321-w","article-title":"Degenerative changes of lumbar spine and their clinical implications in patients with axial spondyloarthritis","volume":"42","author":"Kilic","year":"2023","journal-title":"Clin Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-024-01207-4","article-title":"Insights into IVDD pathogenesis in 2024","volume":"21","author":"Sakai","year":"2024","journal-title":"Nat Rev Rheumatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01034-z","article-title":"Pan American League of Associations for Rheumatology recommendations for the management of axial spondyloarthritis","volume":"19","author":"Bautista-Molano","year":"2023","journal-title":"Nat Rev Rheumatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2023.11.006","article-title":"Unlocking the secrets of aging: Epigenetic reader BRD4 as the target to combatting aging-related diseases","volume":"63","author":"Sun","year":"2024","journal-title":"J Adv Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1177\/2192568220980702","article-title":"Factors associated with major complications and mortality during hospitalization in patients with ankylosing spondylitis undergoing surgical management for a spine fracture","volume":"12","author":"Ull","year":"2022","journal-title":"Global Spine J"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(22)00334-4","article-title":"Role of neutrophil interleukin-23 in spondyloarthropathy spectrum disorders","volume":"5","author":"Macleod","year":"2023","journal-title":"Lancet Rheumatol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"103638","DOI":"10.1016\/j.autrev.2024.103638","article-title":"Treatment strategies for Spondyloarthritis: Implementation of precision medicine - 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