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Monosodium urate crystals exposure is associated with limited transcriptional changes in primary human PBMCs Cover

Monosodium urate crystals exposure is associated with limited transcriptional changes in primary human PBMCs

Romanian Journal of Internal Medicine
AHEAD OF PRINT
By: Valentin Nica,  Medeea Badii,  Orsolya Gaal,  Georgiana Cabău,  Maartje Cleophas,  Akshayata Naidu,  Ioana Hotea,  Tim L. Jansen,  Cristina Pamfil,  Simona Rednic,  Radu A. Popp,  Yang Li,  Tania O. Crișan and  Leo A.B. Joosten  
Open Access
|Sep 2025

Figures & Tables

Figure 1.

IL-1β cytokine production in PBMCs after 24h stimulations. Cells were stimulated with MSU crystals (300 μg/mL), palmitate (50 μM) and the combination of both. Concentration of IL-1β were measured in supernatants by ELISA. The first cohort was split into (a) 181 normouricemic controls and (b) 123 gout patients. Similar analysis was performed in other cohorts which consist of (c) 132 healthy individuals and (d) 148 gout patients. Group differences were assessed by paired Wilcoxon test and the p values are reported.
IL-1β cytokine production in PBMCs after 24h stimulations. Cells were stimulated with MSU crystals (300 μg/mL), palmitate (50 μM) and the combination of both. Concentration of IL-1β were measured in supernatants by ELISA. The first cohort was split into (a) 181 normouricemic controls and (b) 123 gout patients. Similar analysis was performed in other cohorts which consist of (c) 132 healthy individuals and (d) 148 gout patients. Group differences were assessed by paired Wilcoxon test and the p values are reported.

Figure 2.

RNA-seq after 24h PBMC stimulation with MSU crystals. (a) Principal Component Analysis Biplots of the 3 experiments. The first experiment contains 2 replicates (gout patients, n=4 and n=3), where cells were stimulated with MSU crystals (300 μg/mL), palmitate (50 μM), palmitate+MSU, LPS (10 ng/mL) or LPS+MSU. The second experiment (healthy individuals, n=4) was independently performed in the same experimental conditions with MSU, palmitate and palmitate+MSU stimulations. Clustering along the PC1 can be observed based on the experimental conditions (MSU with Control, C16 with C16+MSU, LPS with LPS+MSU) showing similar transcriptomic signatures associated with each pair. (b) Volcano plots depicting the results of the Differential Expression Analysis comparing cells stimulated with MSU crystals and control. X axis represents the log2 Fold Change and y axis the p value for each analyzed mRNA.
RNA-seq after 24h PBMC stimulation with MSU crystals. (a) Principal Component Analysis Biplots of the 3 experiments. The first experiment contains 2 replicates (gout patients, n=4 and n=3), where cells were stimulated with MSU crystals (300 μg/mL), palmitate (50 μM), palmitate+MSU, LPS (10 ng/mL) or LPS+MSU. The second experiment (healthy individuals, n=4) was independently performed in the same experimental conditions with MSU, palmitate and palmitate+MSU stimulations. Clustering along the PC1 can be observed based on the experimental conditions (MSU with Control, C16 with C16+MSU, LPS with LPS+MSU) showing similar transcriptomic signatures associated with each pair. (b) Volcano plots depicting the results of the Differential Expression Analysis comparing cells stimulated with MSU crystals and control. X axis represents the log2 Fold Change and y axis the p value for each analyzed mRNA.

Figure 3.

RNA-seq after 24h PBMC stimulations with palmitate, LPS and MSU combinations. The first experiment contains 2 replicates (gout patients, n=4 and n=3), where cells were stimulated with MSU crystals (300 μg/mL), palmitate (50 μM), palmitate+MSU, LPS (10 ng/mL) or LPS+MSU. The second experiment (healthy individuals, n=4) was independently performed in the same experimental conditions with MSU, palmitate and palmitate+MSU stimulations. Volcano plots depicting the results of the Differential Expression Analysis comparing (a) palmitate vs control; (b) palmitate+MSU vs palmitate; (c) LPS vs RPMI and (d) LPS+MSU vs RPMI. X axis represents the log2 Fold Change and y axis the p value for each analyzed mRNA. (e) KEGG pathway enrichment analysis of the top upregulated pathways in all comparisons. Infectious disease terms were excluded.
RNA-seq after 24h PBMC stimulations with palmitate, LPS and MSU combinations. The first experiment contains 2 replicates (gout patients, n=4 and n=3), where cells were stimulated with MSU crystals (300 μg/mL), palmitate (50 μM), palmitate+MSU, LPS (10 ng/mL) or LPS+MSU. The second experiment (healthy individuals, n=4) was independently performed in the same experimental conditions with MSU, palmitate and palmitate+MSU stimulations. Volcano plots depicting the results of the Differential Expression Analysis comparing (a) palmitate vs control; (b) palmitate+MSU vs palmitate; (c) LPS vs RPMI and (d) LPS+MSU vs RPMI. X axis represents the log2 Fold Change and y axis the p value for each analyzed mRNA. (e) KEGG pathway enrichment analysis of the top upregulated pathways in all comparisons. Infectious disease terms were excluded.
DOI: https://doi.org/10.2478/rjim-2025-0019 | Journal eISSN: 2501-062X | Journal ISSN: 1220-4749
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Language: English
Submitted on: Aug 25, 2025
Published on: Sep 18, 2025
Published by: N.G. Lupu Internal Medicine Foundation
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
Gout,
Monosodium Urate,
Palmitate,
Peripheral Blood Human Mononuclear Cells,
Transcriptomics,
Cytokine
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Internal medicine, other,
Cardiology,
Gastroenterology,
Rheumatology

© 2025 Valentin Nica, Medeea Badii, Orsolya Gaal, Georgiana Cabău, Maartje Cleophas, Akshayata Naidu, Ioana Hotea, , Tim L. Jansen, Cristina Pamfil, Simona Rednic, Radu A. Popp, Yang Li, Tania O. Crișan, Leo A.B. Joosten, published by N.G. Lupu Internal Medicine Foundation
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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