Identification of Abnormal Proteins in Plasma from Gout Patients by LC-MS/MS

Abstract

A high level of uric acid may cause hyperuricemia, which further develops into gout, eventually leading to chronic kidney disease. However, the pathogenic mechanism remains largely unknown. To investigate the cause and block the transformation of hyperuricemia to related diseases, it is important to discover the alterations in protein levels between gout patients and non-gout individuals. To date, human blood plasma is still the predominant matrices for clinical analysis. Due to the high abundance, the proteins of plasma samples have strong shielding effects on low abundance proteins, thus, the information on low abundance protein expression is always masked, while the low abundance proteins of human plasma are often of great significance for the diagnosis and treatment of diseases. Therefore, it is very important to separate and analyze the plasma proteins. High-performance liquid chromatography (LC) tandem mass spectrometry (MS)-based proteomics has been developed as a powerful tool to investigate changes in the human plasma proteome. Here, we used LC-MS/MS to detect the differential proteins in the plasmas from simple gout patients, gout with kidney damage patients, and non-gout individuals. We identified 32 obviously differential proteins between non-gout and gout subjects and 10 differential proteins between simple gout and gout with kidney damage patients. These differential proteins were further analyzed to characterize their localization and functions. Additionally, the correlation analysis showed multiple relationships between the abnormal plasma proteins and clinical biochemical indexes, particularly for the immune-inflammatory response proteins. Furthermore, inflammation factors gelsolin (GSN) were confirmed. Our results offer a view of plasma proteins for studying biomarkers of gout patients.

The biomarkers discovery of hyperuricemia and gout: proteomics and metabolomics

“…Recent proteomic studies show that gout and hyperuricemia trigger the complement system in the body. Shen et al (2021a) detected differential plasma proteins using label-free quantitative proteomics in simple gout patients, gout with renal damage patients, and non-gout patients. As mentioned earlier, these three groups of detected proteins are thought to be involved in natural immune responses, complement activation, etc .…”

“…The major difference between hyperuricemia and gout is the development of MSU crystals that cause gout attacks. The presence of significantly expressed inflammatory proteins in gout patients suggests that the inflammatory mechanism deserves our attention ( Shen et al, 2021a ; Qiu et al, 2021 ). As a final observation, patients with gout showed an even more profound association with complement and coagulation cascade pathways ( Shen et al, 2021a ; Chen et al, 2021a ; Huang et al, 2022 ).…”

“…The presence of significantly expressed inflammatory proteins in gout patients suggests that the inflammatory mechanism deserves our attention ( Shen et al, 2021a ; Qiu et al, 2021 ). As a final observation, patients with gout showed an even more profound association with complement and coagulation cascade pathways ( Shen et al, 2021a ; Chen et al, 2021a ; Huang et al, 2022 ). In summary, multiple biomarkers can provide insights into disease mechanisms based on their expression and functions through a holistic approach to identifying diseases.…”

“…Hypertriglyceridemia in patients with hyperuricemia may be associated with apolipoprotein C3 (APOC3). Furthermore, the plasma of gout patients also has abnormal levels of apolipoproteins (APOC4, APOD) ( Shen et al, 2021a ). As part of our investigations, we analyzed some proteomic studies about patients with metabolic abnormalities, diabetes, and obesity.…”

Analysis of Differentially Expressed Proteins and Modifications Induced by Formaldehyde Using LC-MS/MS

“…To understand the molecular mechanism of FA-induced damage to biological macromolecules, a variety of methods have been employed to determine the levels and effects of FA, including spectrophotometry, fluorescence, liquid chromatography (LC) and mass spectrometry (MS) [16][17][18][19][20][21]. At present, liquid chromatography tandem mass spectrometry (LC-MS/MS) is a powerful tool for proteomics analysis and protein modification identification [22,23], and thus can provide more detailed information regarding protein alterations induced by FA compared to traditional methods [24][25][26][27]. However, the effect of FA at the protein level remains to be explored.…”