Plasma, urine and ligament tissue metabolite profiling reveals potential biomarkers of ankylosing spondylitis using NMR-based metabolic profiles

Abstract

BackgroundAnkylosing spondylitis (AS) is an autoimmune rheumatic disease mostly affecting the axial skeleton. Currently, anti-tumour necrosis factor α (anti-TNF-α) represents an effective treatment for AS that may delay the progression of the disease and alleviate the symptoms if the diagnosis can be made early. Unfortunately, effective diagnostic biomarkers for AS are still lacking; therefore, most patients with AS do not receive timely and effective treatment. The intent of this study was to determine several key metabolites as potential biomarkers of AS using metabolomic methods to facilitate the early diagnosis of AS.MethodsFirst, we collected samples of plasma, urine, and ligament tissue around the hip joint from AS and control groups. The samples were examined by nuclear magnetic resonance spectrometry, and multivariate data analysis was performed to find metabolites that differed between the groups. Subsequently, according to the correlation coefficients, variable importance for the projection (VIP) and P values of the metabolites obtained in the multivariate data analysis, the most crucial metabolites were selected as potential biomarkers of AS. Finally, metabolic pathways involving the potential biomarkers were determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the metabolic pathway map was drawn.ResultsForty-four patients with AS agreed to provide plasma and urine samples, and 30 provided ligament tissue samples. An equal number of volunteers were recruited for the control group. Multidimensional statistical analysis suggested significant differences between the patients with AS and control subjects, and the models exhibited good discrimination and predictive ability. A total of 20 different metabolites ultimately met the requirements for potential biomarkers. According to KEGG analysis, these marker metabolites were primarily related to fat metabolism, intestinal microbial metabolism, glucose metabolism and choline metabolism pathways, and they were also probably associated with immune regulation.ConclusionsOur work demonstrates that the potential biomarkers that were identified appeared to have diagnostic value for AS and deserve to be further investigated. In addition, this work also suggests that the metabolomic profiling approach is a promising screening tool for the diagnosis of patients with AS.

Nuclear magnetic resonance‐based metabolomics reveals similar metabolomics profiles in undifferentiated peripheral spondyloarthritis and reactive arthritis

“…The possible correlations of all metabolite and pathway perturbations found have been summarized in Table . Also in a study in AS, the ketones 3‐hydroxybutyrate and acetone were also increased, thereby hinting at a possible common pathway involved . This was the only common finding we had with other metabolomic studies in inflammatory arthritis.…”

“…Previous studies of metabolomics are present for RA and ankylosing spondylitis (AS) . Table summarizes the major metabolite disturbances reported in these studies as compared to our findings.…”

“…The more recent studies have used 1 H NMR‐based metabolomics . To the best of our knowledge, this is a novel exploration of metabolomics in patients with ReA and undifferentiated pSpA.…”

Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet’s Disease by Gas Chromatography/Time-of-Flight−Mass Spectrometry

“…Recently, metabolomics has been playing a significant role in identifying diagnostic biomarkers for various rheumatic diseases. Metabolomic studies using urine samples have been widely used to diagnose or predict treatment in a variety of rheumatic disease such as lupus nephritis, ankylosing spondylitis, or RA [ 7 , 8 , 9 , 10 , 11 , 12 ]. However, there are few metabolomic studies that investigate urine metabolites as diagnostic biomarkers of BD.…”

“…Metabolomic analysis can be performed using easily accessible biofluids such as urine, blood or cerebrospinal fluid and may permit the identification of disease-specific metabolite signatures that may be useful as disease biomarkers. Several metabolomic studies of BD, rheumatoid arthritis (RA), or lupus nephritis have been performed using various analytical platforms and biologic fluids [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ].…”