Review of neutrophil extracellular traps in patients with gout

Gout is an aseptic inflammatory disease caused by monosodium urate (MSU) crystal deposition. Its clinical signs go beyond the intense pain of acute arthritis to include structural damage such as chronic synovitis, bone erosion, and tophus formation. The long-term progression and recurring episodes of inflammation pose significant challenges in managing the disease. While hyperuricemia creates the metabolic basis, only a small percentage of patients develop gout, indicating that activation of the innate immune system is essential for its development. Recently, neutrophil extracellular traps (NETs) have become recognized as key mediators connecting metabolic issues to inflammatory responses, representing an important breakthrough in understanding gout pathogenesis. Initially, NETs are considered a host defense mechanism that protects against microbial invasion, where neutrophils release a web-like structure made of chromatin fibers and granular proteins to trap and eliminate microbes. However, in gout, a non-infectious disease, NETs have roles that extend beyond their traditional function, acting as a “double-edged sword”: they help limit acute inflammation but can also contribute to tissue damage and disease progression during the chronic phase, with their function changing according to the microenvironment. This review systematically discusses the mechanisms of NETs in gout development and examines their potential in diagnosing and treating the disease.