Background/Purpose: Chronic gouty arthritis (CGA) is different from acute gouty arthritis  (AGA), its main characteristics include repeated or even persistent joint symptoms, tophus and bone destruction. At present, there is a lack of attention to CGA and its related pathogenesis. Therefore, the purpose of this study was to explore whether interleukin-17, which is closely related to chronic inflammation, is involved in the pathogenesis of CGA.

Methods: 69 patients with gout and 30 healthy controls (HCs) were enrolled in this study. Transcriptome sequencing, Luminex multifactor detection and flow cytometry were used to detect the changes of the level of various cytokines and chemokines in serum, and the proportion of helper T cell 17 (Th17)/ regulatory T cell (Treg) in peripheral blood. The serum levels of bone destruction-related factors and the ability of osteoclast differentiation in CGA patients were detected. The effect of IL-17 on osteoclast differentiation in CGA patients was further explored by Transwell assay or application of anti-IL-17 antibody.

Results: Firstly, we compared various cytokine levels in the serum of AGA patients with CGA patients. we found that in CGA patients, it is characterized by persistent elevations of IL-6. Further comparison the levels of cytokines in both gout synovial fluid and serum showed that the level of IL-17 was increased in synovial fluid of patients with gout (Fig.1A).

Transcriptome sequencing indicated that IL-17 signaling pathway and osteoclast differentiation pathways were significantly up-regulated in CGA patients (Fig.1B). And the serum of CGA patients have higher expression of various chemokines, regulated by IL-17. And the level of IL-17 in PBMC supernatant of patients with CGA was significantly higher than that of HCs. Furthermore, it was found that the proportion of Th17 cells in peripheral blood of patients with CGA was abnormally higher than that of HCs, due to the higher differentiation ability from Naive T cells to Th17 cells in CGA patients (Fig.1C-D).

The serum levels of bone destruction-related factors in patients with CGA were also significantly increased, and the osteoclast differentiation ability of CGA patients was significantly enhanced compared with HCs (Fig.2A-B). In addition, the abnormally increased Th17 cells in CGA patients could promote osteoclast differentiation through secreting higher level of IL-17, and antagonizing IL-17 could inhibit osteoclast differentiation in CGA (Fig.2C-D).

Conclusion: IL-17 may be involved in immune disorders in CGA, and further participate in bone destruction, suggesting that IL-17 may be a therapeutic target in CGA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-17-participates-in-the-pathogenesis-of-chronic-gouty-arthritis/