Abstract
ObjectiveAmino 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.MethodsPlasma 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.ResultsThe 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.ConclusionsThese 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.
Highlights
Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by fibrosis of the tissues, preceded by microvascular alterations and immune dysfunction (Zanatta et al, 2019)
Many studies have shown that dcSSc characterized by rapid progression of skin thickness has been associated with earlier onset of heart, lung involvement, and with increased disease severity and mortality rates due to this organ involvement (Kumánovics et al, 2017)
The patients have higher concentration of glutamine (12% increase over control = IOC), proline (17% IOC), 1-methylhistidine (39% IOC), betaine (23% IOC), methylnicotinamide (MNA, 35% IOC) and asymmetric dimethylarginine (ADMA, 19% IOC)
Summary
Amino acids (AA) and their derivatives play an integral role in the synthesis of structural and regulatory elements in human organisms and 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
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