The imbalance of Th17/Treg cells exists in asymptomatic hyperuricemia (the early stage of gout)

TL;DR

The study finds that an imbalance in Th17 and Treg immune cells occurs in asymptomatic hyperuricemia, a precursor to gout, suggesting early immune system changes.

Contribution

This study is the first to identify immune dysregulation in asymptomatic hyperuricemia through Th17/Treg cell imbalance, offering new insights into early gout development.

Findings

Th17 cells and Th17/Treg ratio are elevated in asymptomatic hyperuricemia and acute gout compared to healthy controls.

GGT levels and Th17 cell counts are positively associated with acute gout flare-ups.

Immune activation is observed in both asymptomatic hyperuricemia and gout patients, with distinct immunological differences between groups.

Abstract

Given that hyperuricemia is a metabolic condition with a prolonged asymptomatic period and strong associations with gout and various metabolic disorders, we investigated the role of lymphocyte subsets in asymptomatic hyperuricemia (aHUA) and explored their potential implications for immune regulation.

The study enrolled 59 male patients with aHUA, 29 with acute gout (AG), and 28 healthy male controls (HCs). Laboratory data, including blood cell counts, inflammatory markers, blood lipids, liver and renal function, and the percentage and absolute counts of lymphocytes and CD4 + T cell subpopulations in peripheral blood, were collected. We used flow cytometry to assess the peripheral blood lymphocyte subsets in these participants.

There were significant differences in GGT levels among all three groups, with the aHUA group showing the lowest value (AG vs. aHUA vs. HC, 69.00 vs. 23.00 vs. 35.50; P < 0.001). The lymphocyte subset data revealed a significant increase in the counts of helper T2 (Th2) (AG vs. aHUA vs. HC, 10.73 vs. 10.63 vs. 5.78; P < 0.001), Th17 (AG vs. aHUA vs. HC, 16.86 vs. 10.23 vs. 7.78; P < 0.001), and T suppressor (Ts) cells (AG vs. aHUA vs. HC, 669.32 vs. 655.00 vs. 488.84; P = 0.023), as well as the Th17/Treg ratio (AG vs. aHUA vs. HC, 0.44 vs. 0.37 vs. 0.26; P < 0.001) in both aHUA and AG groups. Furthermore, the increase in Th17 cells and the Th17/Treg ratio was more pronounced in the AG group. Total T cell levels were higher in both the aHUA and AG groups than in HCs, with the aHUA group showing the highest levels (statistically significant versus HCs) (AG vs. aHUA vs. HC, 1517.00 vs. 1620.00 vs. 1316.10; P < 0.001). Furthermore, the univariate regression analysis suggests that GGT [OR (95% CI) = 1.132 (1.069, 1.198), P < 0.001], Th17 [OR (95% CI) = 1.228 (1.104, 1.366), P < 0.001], and the Th17/Treg ratio [OR (95% CI) = 18.900 (1.892, 188.833), P = 0.012] are positively associated with acute gout flare. Multivariate regression analysis indicated that GGT [OR (95% CI) = 1.113 (1.049, 1.181), P < 0.001] and Th17 [OR (95% CI) = 1.235 (1.033, 1.476), P = 0.020] are positively correlated with acute gout flare.

Our study highlights significant alterations in lymphocyte subsets in aHUA, emphasizing their potential role in the immune response and providing insights for future therapeutic strategies.

Key Points• Th17 elevation and Th17/Treg imbalance in asymptomatic hyperuricemia (aHUA) suggest early immune dysregulation.• Th17 cell levels and GGT are positively associated with acute gout flares, serving as biomarkers of disease activity.• Both aHUA and gout patients show immune activation, while there were immunological differences across groups.

Key Points

• Th17 elevation and Th17/Treg imbalance in asymptomatic hyperuricemia (aHUA) suggest early immune dysregulation.

• Th17 cell levels and GGT are positively associated with acute gout flares, serving as biomarkers of disease activity.

• Both aHUA and gout patients show immune activation, while there were immunological differences across groups.

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