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While conventional therapies (colchicine, NSAIDs) remain first-line, their limitations in refractory cases have spurred the development of biologic agents targeting pro-inflammatory pathways. Clinical studies demonstrate that TNF-\u03b1 inhibitors (etanercept, infliximab), IL-6 blockade (tocilizumab), and autophagy modulators effectively reduce flares and inflammation in treatment-resistant GA. Emerging strategies, including combination therapies and biomarker-guided approaches, highlight the shift toward precision medicine in GA management. This review summarizes current insights into GA\u2019s immunopathogenesis and evaluates the therapeutic potential of immunomodulatory biologics.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1615914","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:12:33Z","timestamp":1750291953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["A systems immunology perspective on gout pathogenesis and its precision-targeted treatment strategies"],"prefix":"10.3389","volume":"16","author":[{"given":"Zilong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfei","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)00569-9","article-title":"Gout","volume":"397","author":"Gosling","year":"2021","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202308749","article-title":"Monosodium urate crystal-induced pyroptotic cell death in neutrophil and macrophage facilitates the pathological progress of gout","volume":"20","author":"Chen","year":"2024","journal-title":"Small"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2019.10.002","article-title":"Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis","volume":"15","author":"Ristic","year":"2020","journal-title":"Asian J Pharm Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.777522","article-title":"The anti-inflammatory and uric acid lowering effects of si-miao-san on gout","volume":"12","author":"Cao","year":"2022","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.311","article-title":"Modulation of the immunity and inflammation by autophagy","volume":"4","author":"Gan","year":"2023","journal-title":"MedComm"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118566","article-title":"Investigating the involvement of the NLRP3\/ASC\/caspase-1 and NF-\u03bab\/MAPK pathways in the pathogenesis of gouty arthritis: Insights from irradiated and non-irradiated Trifolium alexandrium L","volume":"334","author":"Mohammed","year":"2024","journal-title":"extracts some metabolites. 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