Metabolic Pattern of Systemic Sclerosis: Association of Changes in Plasma Concentrations of Amino Acid-Related Compounds With Disease Presentation

Abstract

Objective: Amino acids (AA) and their derivatives play an integral role in the synthesis of structural and regulatory elements in human organisms and therefore pathologies such as systemic sclerosis that may alter the blood pattern of these compounds. This study aimed to evaluate changes in plasma concentrations of amino acid-related metabolites in systemic sclerosis in a search for potential biomarkers and mechanisms of the disease. Methods: Plasma samples from 42 patients diagnosed with systemic sclerosis (SSc) according to the 2013 American College of Rheumatology and European League Against Rheumatism ACR/EULAR classification criteria were compared to 27 matched healthy controls. Liquid chromatography/mass spectrometry was applied for the analysis of 36 amino acid-related metabolites. Results: The analysis of plasma AA metabolite patterns revealed the number of changes including an increase (20%) in concentrations of NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) in SSc vs. healthy subjects. Furthermore, SSc patients had higher glutamine, proline, betaine, 1-methylhistidine, and methylnicotinamide levels, while the concentration of tryptophan was lower. The specific metabolic pattern was identified for several aspects of disease presentation. Most interestingly NOS inhibitor L-NAME was elevated in patients with diffuse systemic sclerosis or telangiectasia. Conclusions: These results provide further evidence for the involvement of endothelium-dependent pathways in the mechanisms and presentation of SSc. Endothelial dysfunction biomarkers may be useful in the assessment of presentation and prognosis in SSc.

A systematic review and meta-analysis of the kynurenine pathway of tryptophan metabolism in rheumatic diseases

“…Thus, 24 studies were selected for analysis ( Table 1 ) ( 26 – 49 ). The risk of bias, presented in Supplementary Table 3 , was moderate in 14 studies ( 26 – 35 , 37 , 41 , 44 , 45 , 47 ), and low in the remaining 10 ( 34 , 36 , 38 – 40 , 42 , 43 , 46 , 48 , 49 ). The initial certainty of evidence was low for all studies (rating 2, ⊕⊕⊝⊝) given their cross-sectional design.…”

Effect of Hyperbaric Oxygenation on Blood Cytokines and Arginine Derivatives; No Evidence for Induction of Inflammation or Endothelial Injury

“…The concentrations of arginine metabolites were determined using liquid chromatography/ mass spectrometry (LC/MS) as we have described previously [ 19 ]. Firstly, an aliquot of serum (25 μL) was spiked with internal standards and deproteinized with 0.1 mL of acetonitrile.…”

Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review

“…The influence of amino acids is evident in a wide range of diseases, including cardiovascular diseases (acute ischemic stroke [ 134 ], systolic heart failure [ 135 ], coronary artery ectasia [ 93 ], among several others [ 136 ]); metabolic diseases (involving supplementation of ketogenic diet [ 137 , 138 ] and diabetes mellitus); neurodegenerative disorders [ 139 , 140 , 141 ]; psoriasis [ 142 ]; and autoimmune diseases (SLE, RA). Here, we briefly examine all the listed categories and their involvement in amino acid metabolism.…”

“…Another investigation highlighted several elements of arginine metabolism, including arginine, agmatine, creatine, and some others, as inflammation-related biomarkers. These compounds revealed metabolic abnormalities in the systemic inflammatory processes of myocardial infarction, ulcerative colitis, and ischemic heart disease [ 140 ]. The study provided a robust and rapid approach to characterizing inflammation and immune-related amino acid metabolites, which can be prospectively used in biomarker discovery to assess inflammation and immunity states in various pathological conditions.…”