Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis

Abstract

ObjectiveLiquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still’s disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome.MethodsSerum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites.ResultsEighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05).ConclusionThirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis.

Analytical tools for urocanic acid determination in human samples: A review

“…Recent studies have been proposed to identify metabolites in clinical research using LC‐MS to determine correlations with diseases. This technique is widely used for a sensitive and noninvasive diagnostic for metabolomic research [27,28,46].…”

“…Eighteen different expressed metabolites were identified in this disease by LC‐MS‐based analysis, of which 13 were validated by NMR/MS. One of such metabolites was UCA, which was found to have significantly lower serum levels [28].…”

“…[27] screened UCA as a biomarker of endometrial carcinoma (EOC) since it was one of the five biomarkers that are significantly changed in EOC patients. UCA was also investigated as a metabolite profile on Adult‐Onset Still's disease patients, and serum levels were significantly different [28]. Correale and Farez [25] found differences in cis ‐UCA levels in multiple sclerosis patients compared to healthy controls.…”

Reduced Glutamatergic Neurotransmission as Possible Indicator of Unfavorable Prognosis

“…[30] Among the analytical methods used in metabolomics research, liquid chromatography/ mass spectrometry (LC/MS) has been shown to be one of the best techniques in terms of selectivity, sensitivity, and reproducibility. [40,41] It provides the highest level of metabolite coverage, using a unified analytical technique. In LC-MS, limit of sensitivity is about 5nM to10nM and the number of detectable characteristics -from 5000 to 20000.…”

“…[42] Measuring the Glu concentration by MRS with the usual values of the magnetic field causes difficulty in distinguishing between Glu and Gln; for this reason, a composite index is often used. [43] Another aspect of modern metabolomic research is the application of multivariate statistical analysis [40] and the construction of predictive models. [30] Thus, the levels of metabolites in the blood plasma reflect the systemic reactions of the body and are considered as a body's response to the disease.…”