Background: Systemic sclerosis (SSc) is a chronic autoimmune disease with an unclear etiology. It is characterized by an unpredictable course, high morbidity, and an increased risk of mortality. According to recent studies, identifying altered metabolic pathways may be crucial to comprehend the physiopathology of the disease. Thus, metabolomics might play an important role in a better understanding of these pathogenic mechanisms and a possible tool to identify disease phenotypes. Objective: To evaluate the differences in the metabolomic profile from amino acid-derived metabolites measured in serum samples of SSc patients compared to healthy subjects and their association with the different disease phenotypes. Methodology: A case-control study was conducted. The serum concentration of amino acid-derived metabolites from SSc patients (n=38) compared to a control group (n=38) was measured. The metabolite differences in serum samples were analyzed using gas chromatography coupled to quadruple time-of-flight mass spectrometry (GC/MS-QTOF). Results: The analysis of serum samples of 13 AA-derived metabolites revealed a significant downregulation of N-ethylglycine in SSc patients compared to healthy controls (p= 0,048). Likewise, fold change >1 of L-cysteine, DL-isoleucine, Sarcosine, L-proline, L-leucine, L-valine, Hydroxy-L-proline, Ala-ala, L-alanine, and L-serine showed a downward trend in patients with SSc compared to healthy subjects; however, this change was not statistically significant. Furthermore, our results demonstrated a significant increase in Ala-Ala and L-serine (p= 0,032) metabolites in the diffuse cutaneous SSc subtype, and a significant decrease in DL-isoleucine, L-leucine, and L-valine in SSc-interstitial lung disease patients. Conclusion: These findings shed light on SSc patients' altered metabolic profiles and pathways, which may offer novel targets for SSc-directed therapies and diagnostics.
