Arthritis research & therapy · 2026
Differential gene expression of retrotransposons (LTR and non-LTR) in peripheral blood leukocytes of people with gout.
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Chang Ya-Sian, Hsu Ming-Hon, Chang Chieh-Min, Liu Ta-Chih, Chang Jan-Gowth
Аннотация
BACKGROUND: To investigate the expression profiles of retrotransposons in people with gout and their clinical significance.
METHODS: Peripheral blood leukocytes from 92 people with gout and 22 healthy controls were analyzed using Telescope and TEspeX to quantify human endogenous retroviruses (HERVs) and non-long terminal repeat (non-LTR). Gene Set Variation Analysis (GSVA) was used to assess the association of the alterations of HERV and viral related gene panels, and xCell to evaluate the changes of immune cell subpopulations. HEK293 and THP-1 cells were treated with uric acid (UA) and monosodium urate (MSU) to explore and confirm the mechanisms of retrotransposon changes.
RESULTS: A total of 238 HERVs and 49 non-LTR were differentially expressed in people with gout as compared to healthy controls. Notably, HERVs exhibited lower expression levels overall, whereas most non‑LTR retrotransposons showed higher expression in people with gout, suggesting distinct immunological triggers. Among 397 genes located near differentially expressed HERVs, several displayed altered expressions, indicating potential locus-specific co-regulation. GSVA revealed that gene panels related to HERV regulation, including nearby genes, KRAB zinc-finger proteins, and stemness-associated genes, were less enriched in gout patients compared to controls. xCell analysis revealed significant changes in immune cell composition, including reduced proportions of neutrophils and NK cells, and increased CD4 + memory T-cells and regulatory T cells, aligning with gout-related immune migration and modulation. Consistent with the transcriptomic data, our cell-based assays demonstrated that UA and MSU differentially modulate LTR and non-LTR retrotransposon expression across distinct cell types.
CONCLUSIONS: This study reveals a distinct and dynamic retrotransposon signature in gout, with potential implications priming, immune cell behavior, and gene regulation.
METHODS: Peripheral blood leukocytes from 92 people with gout and 22 healthy controls were analyzed using Telescope and TEspeX to quantify human endogenous retroviruses (HERVs) and non-long terminal repeat (non-LTR). Gene Set Variation Analysis (GSVA) was used to assess the association of the alterations of HERV and viral related gene panels, and xCell to evaluate the changes of immune cell subpopulations. HEK293 and THP-1 cells were treated with uric acid (UA) and monosodium urate (MSU) to explore and confirm the mechanisms of retrotransposon changes.
RESULTS: A total of 238 HERVs and 49 non-LTR were differentially expressed in people with gout as compared to healthy controls. Notably, HERVs exhibited lower expression levels overall, whereas most non‑LTR retrotransposons showed higher expression in people with gout, suggesting distinct immunological triggers. Among 397 genes located near differentially expressed HERVs, several displayed altered expressions, indicating potential locus-specific co-regulation. GSVA revealed that gene panels related to HERV regulation, including nearby genes, KRAB zinc-finger proteins, and stemness-associated genes, were less enriched in gout patients compared to controls. xCell analysis revealed significant changes in immune cell composition, including reduced proportions of neutrophils and NK cells, and increased CD4 + memory T-cells and regulatory T cells, aligning with gout-related immune migration and modulation. Consistent with the transcriptomic data, our cell-based assays demonstrated that UA and MSU differentially modulate LTR and non-LTR retrotransposon expression across distinct cell types.
CONCLUSIONS: This study reveals a distinct and dynamic retrotransposon signature in gout, with potential implications priming, immune cell behavior, and gene regulation.