Using label-free quantitative proteomics based on high-performance liquid chromatography (HPLC) tandem mass spectrometry (MS), 32 significantly differential proteins were found in patients with gout and 10 proteins were found in patients with gout with kidney damage, according to study results published in Separations. Researchers noted that these plasma proteins may act as potential biomarkers for gout.

Studies have shown that hyperuricemia can transform to gout and may result in chronic kidney disease; however, the underlying mechanism is not well understood. The objective of the current study was to determine the plasma protein profile in individuals with vs without gout, using HPLC-MS/MS.

The study sample included 16 patients (8 men) with gout from the Gout Department of Tianjin Medical University Metabolic Diseases Hospital, China, including 8 patients with gout alone and 8 patients with gout with kidney injury. The control group included 8 patients without gout, hyperuricemia, and kidney disease.


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Plasma samples from the control group, gout alone group, and gout with kidney injury group were tested using Human GS (gelsolin) enzyme-linked immunosorbent assay (ELISA) kit (Elabscience Biotechnology Co Ltd, Wuhan, China). The association between differential proteins and gout pathology was assessed using clinical data from patients with gout.

A total of 369 proteins were identified in all 3 groups, including 314 proteins in the control group, 303 proteins in the group of patients with gout, and 283 proteins in the group of patients with gout and kidney injury. The most common biological processes of these proteins were innate immune response, platelet degranulation, and complement activation.

Using HPLC-MS/MS, 32 differential proteins were identified in patients with. Compared with the control group, the gout patient group had a comprehensive effect on the blood plasma proteome profile, with 22 decreased and 10 increased protein levels.

The analysis also revealed 10 differential proteins in patients with gout and kidney disease. The expressions of plasma complement C4A, C4B, and SERPINF1 in patients with gout and kidney injury were significantly increased compared with those of patients with gout alone.

There were 5 inflammatory factors that most significantly correlated with serum uric acid: gelsolin, S100A8, S100A9, ORM2, and ANXA1.

To validate the accuracy of the HPLC-MS/MS results, a key protein, gelsolin, was selected by ELISA for further study, which confirmed the findings; the inflammatory factor was also validated in clinical samples.

“These results suggest that hyperuricemia can induce oxidative stress and inflammatory reaction in the cells of patients with gout by promoting oxidation. Our result provides promising candidates for a biomarker for gout,” the researchers concluded.

Reference

Shen L, Dong H, Guo Z, Zhai G, Zhang K. Identification of abnormal proteins in plasma from gout patients by LC-MS/MS. Seperations. Published online June 16, 2021. doi:10.3390/separations8060085