Single-cell RNA sequencing of immune cells in patients with acute gout

Abstract

Cell subpopulations in the blood and joint fluid of patients with gout are poorly understood. Single-cell RNA sequencing and bioinformatic tools were used to identify cell subsets and their gene signatures in blood and synovial fluid (SF) cells, determine their relationships, characterize the diversity, and evaluate interactions among specific cell types. We identified 34 subpopulations (5 types of B cells, 16 types of T and natural killer cells, 9 types of monocytes, and 4 other cell types) in the blood of five healthy subjects and seven patients with acute gouty, and the SF of three patients with acute gout. We found that naïve CD4 T cells and classical monocytes cell populations were enriched in patients with gout, whereas plasmacytoid dendritic cells and intermediate monocytes were more abundant in healthy subjects. SF was enriched in Th1/Th17 cells, effector memory CD8 T cells, mucosal-associated invariant T cells, and macrophages. Subclusters of these cell subpopulations showed different compositions between healthy subjects and those with acute gout, according to blood and SF samples. At the cellular level, the inflammation score of a subpopulation or subcluster was highest in SF, following by the blood of acute gout patients and healthy person, whereas energy score showed the opposite trend. We also detected specific cell–cell interactions for interleukin-1, tumor necrosis factor-α, and transforming growth factor-β1 expression in the cells of patients with acute gout. Our study reveals cellular and molecular insights on inflammatory responses to hyperuricemia or uric crystal and may provide therapeutic guidance to improve treatments for gout.

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

“…In gout, MSU crystals stimulate the macrophage by activating NLRP3 inflammasome, triggering the release of pro-inflammatory cytokines [ 10 , 34 ]. Although IL-1β plays a crucial role in the pathogenesis of the pathogenesis of gout flares, other cytokines such as IL-6, TNF-α, and TGF-β are also involved in that [ 16 , 31 , 35 ]. In the present study, the IL-6 levels were elevated in gout patients, and positively related to ESR, CRP, D-dimer, fibrinogen, neutrophils and monocytes.…”

“…The ROC curves showed that disease duration, CRP and fibrinogen had moderate predictive performances for tophus in gout, which indicated that tophus was chronic inflammatory tissue response and mostly the result of chronic recurrent gout attacks [ 48 ]. Further studies with the aid of single-cell RNA sequencing and other advanced new technologies may accurately explore the Th17/Treg imbalance in different disease states of gout [ 35 ].…”

Single-cell transcriptomics reveals variations in monocytes and Tregs between gout flare and remission

“…Several recent studies have examined single-cell–level differences in peripheral blood immune cells between patients with gout flares and healthy individuals ( 23 , 24 ). However, our work focused on investigating the gradual shift in the landscape of such cells during the transitional stages from gout flares to remission, which we believe offers valuable insights with considerable clinical therapeutic potential.…”

MAIT cells in immune‐mediated tissue injury and repair

“…In other forms of arthritis, such as ankylosing spondylitis, gout, and psoriasis arthritis, increased frequencies of MAIT cells in the inflamed joints have been observed, while peripheral MAIT cell numbers are generally reduced and show an exhausted phenotype [96,[103][104][105]. Similar to RA, blood MAIT cells may infiltrate the joints via the CCR6/CCL20 and CXCR6/CXCL16 axis [95], upregulate IL-23R, and produce IL-17 in the synovia [96,97,103,104].…”