{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T06:12:34Z","timestamp":1776147154611,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"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:p>Psoriasis vulgaris (PV), a chronic immune-mediated inflammatory dermatosis, is associated with a significant burden of systemic comorbidities. Traditional comorbidity research methods struggle to reveal its complex interconnectedness. Based on large-scale retrospective cohort data, we constructed a PV comorbidity network using the Ising model from statistical physics. Weighted network centrality analysis was used to identify core and hub nodes and elucidate shared molecular mechanisms at the multiomics level (nontargeted proteomics and lipid peroxidation metabolomics). Finally, the impact of IL-17A inhibition (IL-17Ai) on PV and atherosclerosis (assessed by carotid Doppler color ultrasound) was evaluated using a prospective intervention study. The Ising model identified atherosclerosis- coronary heart disease (CHD) as the core comorbidity (degree centrality &amp;gt;10), with pulmonary nodules, hypertension, and fatty liver serving as key hub nodes (betweenness centrality &amp;gt;60). Multiomics analysis revealed a core molecular mechanism in PV, involving immune inflammation, oxidative stress, lipid metabolism disorder, and coagulation abnormalities, where the oxidative stress molecule GPX3 acts as a critical hub. Following IL-17Ai intervention, both skin lesions and early atherosclerosis markers significantly improved, accompanied by downregulation of the proinflammatory peripheral blood factor S100A9 and upregulation of anti-inflammatory lipid peroxidation metabolites (e.g., 17(R)-RVD1). This study systematically revealed the modular hierarchical structure of PV comorbidities at the network topology and molecular mechanism levels, confirming the central role of the IL-17 signaling pathway in driving the comorbidity network. This conclusion was further clinically validated by IL-17Ai intervention outcomes. This research provides theoretical and clinical evidence for early identification, prioritized management, and \"one drug, multiple targets\" therapeutic strategies for treating PV comorbidities.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1744789","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:36:47Z","timestamp":1776145007000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating clinical and multiomics evidence based on disease module theory: deciphering the comorbidity network of psoriasis vulgaris via the Ising model for mechanistic insights"],"prefix":"10.3389","volume":"17","author":[{"given":"Dongwen","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Dermatology, Air Force Medical Center, Air Force Medical University, PLA","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Luo","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Medicine, Air Force Medical Center, Air Force Medical University, PLA","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Air Force Medical Center, Air Force Medical University, PLA","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Air Force Medical Center, Air Force Medical University, PLA","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengmeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Air Force Medical Center, Air Force Medical University, PLA","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Air Force Medical Center, Air Force Medical University, PLA","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Air Force Medical Center, Air Force Medical University, PLA","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.339","article-title":"Global epidemiology of psoriasis: a systematic review of incidence and prevalence","volume":"133","author":"Parisi","year":"2013","journal-title":"J Invest Dermatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2018.5462","article-title":"Association of atherosclerosis prevalence with age, race, and traditional risk factors in patients with psoriasis","volume":"155","author":"Arnold","year":"2019","journal-title":"JAMA Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16029","article-title":"Psoriasis, cardiovascular risk factors and metabolic disorders: sex-specific findings of a population-based study","volume":"34","author":"Sondermann","year":"2020","journal-title":"J Eur Acad Dermatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.07.029","article-title":"Incidence and risk of inflammatory bowel disease in patients with psoriasis-a nationwide 20-year cohort study","volume":"139","author":"Egeberg","year":"2019","journal-title":"J Invest Dermatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-3864","article-title":"Effect modification by smoking status on the association between psoriasis and chronic obstructive pulmonary disease among adults in the USA","volume":"101","author":"Liu","year":"2021","journal-title":"Acta Derm Venereol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: a network-based approach to human disease","volume":"12","author":"Barab\u00e1si","year":"2011","journal-title":"Nat Rev Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology. 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