A systems immunology perspective on gout pathogenesis and its precision-targeted treatment strategies

Gouty arthritis (GA) is a sterile inflammatory disease driven by monosodium urate (MSU) crystal deposition, which activates innate and adaptive immune responses. Key mechanisms involve NLRP3 inflammasome activation, cytokine release (IL-1β, TNF-α, IL-6), and dysregulated autophagy, positioning GA at...

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Published inFrontiers in immunology Vol. 16; p. 1615914
Main Authors Chen, Zilong, Guo, Qian, Zhang, Yanzhao, Chen, Lulu, Li, Puyu, Cheng, Wenfei, Liu, Chuanxin, Jiang, Hongwei
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 19.06.2025
Subjects
Adaptive Immunity
Animals
autoimmune
Autophagy
Biomarkers
cytokine
Epigenesis, Genetic
Gout - drug therapy
Gout - immunology
gouty arthritis
Humans
Immunity, Innate
Immunology
immunotherapy
Microbiota
monosodium urate crystals
cytokine
autophagy
autoimmune
gouty arthritis
monosodium urate crystals
immunotherapy
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Summary:Gouty arthritis (GA) is a sterile inflammatory disease driven by monosodium urate (MSU) crystal deposition, which activates innate and adaptive immune responses. Key mechanisms involve NLRP3 inflammasome activation, cytokine release (IL-1β, TNF-α, IL-6), and dysregulated autophagy, positioning GA at the intersection of metabolic and autoimmune disorders. 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-α 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’s immunopathogenesis and evaluates the therapeutic potential of immunomodulatory biologics.
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Reviewed by: Ganchen Xiao, Guizhou University of Traditional Chinese Medicine, China
These authors have contributed equally to this work
Edited by: Yongfu Shao, Ningbo University, China
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2025.1615914