Frontiers in immunology · 2026
Subclinical inflammation associated with monosodium urate crystal deposition: a cellular and proteomic study in synovial fluid.
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Andrés Mariano, Peral-Garrido María-Luisa, Ortuño-Miquel Samanta, Caño Rocío, Gómez-Sabater Silvia, Bermúdez-García Alejandra, Lozano Teresa, Perdiguero Miguel, Caro-Martínez Elena, Sánchez-Ortiga Ruth, Ruiz-García Carolina, Francés Rubén
Аннотация
BACKGROUND/PURPOSE: Subclinical inflammation linked to monosodium urate (MSU) crystals in gout and asymptomatic hyperuricemia (AH) remains poorly understood. We aimed to assess the cellular and inflammatory proteomic profiles in synovial fluid (SF) associated with MSU crystals, as observed by ultrasound or microscopy.
METHODS: 100 participants with AH or intercritical gout underwent clinical assessment, blood testing, musculoskeletal ultrasound, and SF aspiration. 81 samples were available for assessment. SF leukocyte counts and the inflammatory proteome from cell lysates were studied. Samples were compared based on ultrasound deposition (double-contour sign, tophi, or aggregates) and microcrystal deposition (MSU, CPP, no crystals). The analyses included protein expression comparisons, paired SF-serum correlations, and machine-learning predictive models development.
RESULTS: Leukocyte counts were higher in samples with MSU crystals [n=5] than in samples with CPP crystals [n=11] or no crystals [n=65]. A third of the MSU crystals were found intracellularly. MSU-containing samples showed several inflammatory proteins upregulated, including OSM, ADA, MCP3, CXCL-1, CXCL-6, and TNFSF14. CXCL-1 was preponderant in the predictive models. Ultrasound deposits were not associated with differences in leukocytes or proteome expression. Pro-inflammatory chemokines showed direct relationships at paired SF-sera correlations.
CONCLUSION: Despite its low prevalence in our sample, MSU crystal deposition was associated with subclinical inflammation characterized by elevated leukocyte counts and a distinctive inflammatory proteome in SF cells. Conversely, ultrasound deposits were not predictive of differences in SF inflammatory features. Most subclinical inflammation appears localized to the joint, but the parallel expression in the chemokine system requires further investigation to determine its relevance.
METHODS: 100 participants with AH or intercritical gout underwent clinical assessment, blood testing, musculoskeletal ultrasound, and SF aspiration. 81 samples were available for assessment. SF leukocyte counts and the inflammatory proteome from cell lysates were studied. Samples were compared based on ultrasound deposition (double-contour sign, tophi, or aggregates) and microcrystal deposition (MSU, CPP, no crystals). The analyses included protein expression comparisons, paired SF-serum correlations, and machine-learning predictive models development.
RESULTS: Leukocyte counts were higher in samples with MSU crystals [n=5] than in samples with CPP crystals [n=11] or no crystals [n=65]. A third of the MSU crystals were found intracellularly. MSU-containing samples showed several inflammatory proteins upregulated, including OSM, ADA, MCP3, CXCL-1, CXCL-6, and TNFSF14. CXCL-1 was preponderant in the predictive models. Ultrasound deposits were not associated with differences in leukocytes or proteome expression. Pro-inflammatory chemokines showed direct relationships at paired SF-sera correlations.
CONCLUSION: Despite its low prevalence in our sample, MSU crystal deposition was associated with subclinical inflammation characterized by elevated leukocyte counts and a distinctive inflammatory proteome in SF cells. Conversely, ultrasound deposits were not predictive of differences in SF inflammatory features. Most subclinical inflammation appears localized to the joint, but the parallel expression in the chemokine system requires further investigation to determine its relevance.