Elevated serum IL-2 and Th17/Treg imbalance are associated with gout

Abstract

Gout is considered an auto-inflammatory disorder, and the immunological drivers have not been fully unraveled. This study compared the peripheral lymphocyte and CD4+T cell subsets, and cytokines in gout and healthy controls (HCs) to explore the contributions of T helper 17 (Th17) cells, T regulatory (Treg) cells and cytokines to the pathogenesis of gout. We enrolled 126 gout patients (53 early-onset gout with age of first presentation < 40 years, and 73 late-onset gout with age of first presentation ≥ 40 years) and 77 HCs. Percentage and absolute numbers of peripheral lymphocyte and CD4+T cell subpopulations in each group were detected by flow cytometry. The serum cytokine levels were determined by flow cytometric bead array. For circulating CD4+T cell subsets, Th17/Treg ratio was significantly higher in early-onset gout, late-onset gout and gout without tophus than HCs; Th17 cells were significantly elevated in early-onset gout and gout without tophus, while the percentage of Treg cells was significantly decreased in early-onset and late-onset gout. Additionally, gout patients had significantly higher cytokines levels (including IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α) than HCs; IL-2 levels were positively correlated with Treg cells and negatively correlated with ESR. ROC analysis showed that disease duration, CRP and fibrinogen, had moderate predictive performances for tophus in gout (the AUCs were 0.753, 0.703 and 0.701, respectively). Our study suggests that early-onset and late-onset gout differ in Th17/Treg imbalance, which in early-onset gout is due to elevated Th17 cells and in late-onset gout is due to decreased Treg cells. And increased serum cytokine levels, especially IL-2, may play an essential role in that. Restoring Th17/Treg balance may be a crucial way to improve the prognosis of gout patients.