Background/Purpose: Background: Hyperuricemia, characterized by elevated serum uric acid levels, is often asymptomatic yet poses serious health risks. This study investigates how soluble monosodium urate (MSU) influences immune cell dynamics, uncovering potential immunological consequences of high uric acid levels.

Methods:

Methods: Leukocyte Reduction System (LRS) cells were cultured with or without soluble MSU at 100 μg/mL for 24 hours. Single-cell and bulk RNA sequencing was conducted to assess changes in immune cell populations, and enzyme-linked immunosorbent assays (ELISA) were utilized to measure cytokine production.

Results:

Results: MSU exposure led to significant alterations in immune cell profiles, decreasing CD8+ T cells including CD8+ TCM (T central memory), CD8+ TEM (T effector memory), and effective CD8+ T cells, monocytes and dendritic cells while increasing CD4+ T cells, Tregs, macrophages, mast cells. Importantly, MSU markedly elevated proinflammatory cytokines, including TNF-α, IL-1β. Additionally, upregulation of inhibitory immune checkpoint molecules such as CD274, PDCD1LG2, CD276, PDCD1, and ELISA showed the increased protein levels CD274 and CD276. These results indicated a shift toward an immunosuppressive state.

Conclusion: Conclusions: These findings reveal that MSU profoundly alters immune cell behavior, driving inflammation and activating immunosuppressive pathways. Asymptomatic hyperuricemia may compromise immune function, potentially diminishing cancer surveillance or inducing autoimmune conditions such as lupus. Proactive management of elevated uric acid levels is crucial for maintaining immune balance. Moreover, LRS cells serve as a valuable model for investigating immune interactions under stress, paving the way for future research into the health impacts of hyperuricemia.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-hidden-impact-of-hyperuricemia-on-immune-cell-dysfunction/