A Systems Immunology Perspective on Gout Pathogenesis and Its Precision-Targeted Treatment Strategies

Zilong Chen¹Qian Guo²Yanzhao Zhang¹Lulu Chen¹Puyu Li¹Wenfei Cheng¹Chuanxin Liu^1*Hongwei Jiang^1*

• ¹Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China, 471003, Luoyang, Henan Province, China
• ²Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China, Zhengzhou, Henan Province, China

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.