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Subclinical inflammation associated with monosodium urate crystal deposition: a cellular and proteomic study in
Mariano Andrés1,2, María-Luisa Peral-Garrido2,3, Samanta Ortuño-Miquel1
1Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain.
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.
Insights
Monosodium urate (MSU) crystal deposition in joints is linked to subclinical inflammation, with higher leukocyte counts and specific inflammatory proteins found in synovial fluid. Ultrasound findings did not predict these inflammatory changes.
Area of Science:
- Rheumatology
- Immunology
- Proteomics
Background:
- Subclinical inflammation in gout and asymptomatic hyperuricemia (AH) linked to monosodium urate (MSU) crystals is not well understood.
- Investigating cellular and proteomic profiles in synovial fluid (SF) associated with MSU crystals is crucial.
Purpose of the Study:
- To assess cellular and inflammatory proteomic profiles in SF related to MSU crystals.
- To compare these profiles based on ultrasound and microcrystal deposition.
Main Methods:
- 100 participants with AH or intercritical gout underwent clinical assessment, blood tests, ultrasound, and SF aspiration.
- SF leukocyte counts and proteomes were analyzed, comparing samples with MSU, CPP, or no crystals.
- Machine learning models were developed to predict inflammatory features.
Main Results:
- MSU crystal samples showed higher leukocyte counts and upregulated inflammatory proteins (e.g., OSM, ADA, MCP3, CXCL-1, CXCL-6, TNFSF14).
- CXCL-1 was a key predictor in developed models.
- Ultrasound deposition signs did not correlate with leukocyte counts or proteome differences in SF.
Conclusions:
- MSU crystal deposition is associated with subclinical inflammation in SF, characterized by elevated leukocytes and a distinct proteomic signature.
- Ultrasound findings were not predictive of SF inflammation.
- Further research is needed to understand the relevance of chemokine system expression in joint inflammation.
