Quantitative proteomics by iTRAQ-PRM based reveals the new characterization for gout

Abstract

Background Gout is a common and complex form of immunoreactive arthritis based on hyperuricemia, while the symptoms would turn to remission or even got worse. So, it is hard to early identify whether an asymptomatic hyperuricemia (AHU) patient will be susceptible to get acute gout attack and it is also hard to predict the process of gout remission to flare. Here, we report that the plasma proteins profile can distinguish among acute gout (AG), remission of gout (RG), AHU patients, and healthy controls. Methods We established an isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM) based method to measure the plasma proteins for AG group (n = 8), RG group (n = 7), AHU group (n = 7) and healthy controls (n = 8). Results Eleven differentially expressed proteins such as Histone H2A, Histone H2B, Thrombospondin-1 (THBS1), Myeloperoxidase (MPO), Complement C2, Complement component C8 beta chain (C8B), Alpha-1-acid glycoprotein 1 (ORM1), Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Carbonic anhydrase 1 (CA1), Serum albumin (ALB) and Multimerin-1 (MMRN1) were identified. Histone H2A, Histone H2B and THBS1 might be the strongest influential regulator to maintain the balance and stability of the gout process. The complement and coagulation cascades is one of the main functional pathways in the mechanism of gout process. Conclusions Histone H2A, Histone H2B and THBS1 are potential candidate genes for novel biomarkers in discriminating gout attack from AHU or RG, providing new theoretical insights for the prognosis, treatment, and management of gout process. Trial registration This study is not a clinical trial.

The biomarkers discovery of hyperuricemia and gout: proteomics and metabolomics

“…Gout patients may experience inflammatory episodes as a result of the upregulation of serum acute phase reaction protein. Compared to the AHU group, some proteins were expressed at lower levels in the AG group, multimerin-1 being the lowliest expressed ( Chen et al, 2021a ). According to the results of quantitative proteomics studies conducted in patients with gout and hyperuricemia, the expression of certain proteins is different when a single protein is targeted.…”

“…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.…”

“…Among the most widely used quantitative proteomics techniques are iTRAQ and TMT. Chen and co-workers developed an iTRAQ and parallel reaction monitoring method to analyze plasma protein profiles of AG, remission of gout (RG), and AHU patients ( Chen et al, 2021a ). Researchers found 11 essential proteins, most of which regulate cytokines or enhance inflammation in gout.…”

Urine inter‐alpha‐trypsin inhibitor family‐related proteins may serve as biomarkers for disease activity of lupus

“…Unfortunately, AMBP was difficult to identified because its peptide spectrum matches (PSM) is lower from DDA database (Only the best scoring peptide to spectrum match for each LC/MS spectrum is considered as the potential peptide identification and is taken to the subsequent statistical validation). 27 The results of PRM analysis are shown in Table 4 .…”

“…Therefore, we used a PRM assay to further quantitatively validate the six proteins related to the ITI family. Unfortunately, AMBP was difficult to identified because its peptide spectrum matches (PSM) is lower from DDA database (Only the best scoring peptide to spectrum match for each LC/MS spectrum is considered as the potential peptide identification and is taken to the subsequent statistical validation) 27 4.…”