Serum Metabolomics Signatures Associated With Ankylosing Spondylitis and TNF Inhibitor Therapy

Abstract

Ankylosing spondylitis (AS) is a type of spondyloarthropathies, the diagnosis of which is often delayed. The lack of early diagnosis tools often delays the institution of appropriate therapy. This study aimed to investigate the systemic metabolic shifts associated with AS and TNF inhibitors treatment. Additionally, we aimed to define reliable serum biomarkers for the diagnosis. We employed an untargeted technique, ultra-performance liquid chromatography-mass spectroscopy (LC-MS), to analyze the serum metabolome of 32 AS individuals before and after 24-week TNF inhibitors treatment, as well as 40 health controls (HCs). Multivariate and univariate statistical analyses were used to profile the differential metabolites associated with AS and TNF inhibitors. A diagnostic panel was established with the least absolute shrinkage and selection operator (LASSO). The pathway analysis was also conducted. A total of 55 significantly differential metabolites were detected. We generated a diagnostic panel comprising five metabolites (L-glutamate, arachidonic acid, L-phenylalanine, PC (18:1(9Z)/18:1(9Z)), 1-palmitoylglycerol), capable of distinguishing HCs from AS with a high AUC of 0.998, (95%CI: 0.992–1.000). TNF inhibitors treatment could restore the equilibrium of 21 metabolites. The most involved pathways in AS were amino acid biosynthesis, glycolysis, glutaminolysis, fatty acids biosynthesis and choline metabolism. This study characterized the serum metabolomics signatures of AS and TNF inhibitor therapy. We developed a five-metabolites-based panel serving as a diagnostic tool to separate patients from HCs. This serum metabolomics study yielded new knowledge about the AS pathogenesis and the systemic effects of TNF inhibitors.

Disturbance of Gut Bacteria and Metabolites Are Associated with Disease Severity and Predict Outcome of NMDAR Encephalitis: A Prospective Case–Control Study

“…We identified phosphatidylserine (PS), phosphatidylethanolamine (PE), and lysoPA as differential serum metabolites in NMDAR encephalitis patients versus controls. According to most previous studies, these glycerolipids (glycerophosphocholines and glycerophosphoethanolamines) are the major pro-inflammatory glycerolipid derivatives that are absorbed into the bloodstream (53,54). Phosphocholines, which are low-density lipoprotein (LDL, "bad") cholesterol components, interact with C-reactive proteins in a pro-inflammatory and proatherosclerotic manner (55)(56)(57).…”

Metabolomics: An Emerging Approach to Understand Pathogenesis and to Assess Diagnosis and Response to Treatment in Spondyloarthritis

“…After treatment, the levels of 21 metabolites were found to be restored when comparing responders to healthy controls. The consequent conclusion is that effective treatment may revert an aberrant shift in metabolism in AS [34]. However, the observation deserves to be deeply studied in larger cohorts of patients, and it is worth emphasizing that the authors did not find any difference in the metabolic profile of responders versus non-responders before treatment, meaning that a signature predictive of response to therapy is still far from being discovered.…”

Glycolysis in Innate Immune Cells Contributes to Autoimmunity

“…Genetic factors (153) and environmental factors, including smoking and infection (154), are the main risk factors for AS development; however, the exact mechanisms underlying AS pathogenesis are unclear. Ou et al established a serum metabolism-associated diagnostic panel and found 55 metabolites that were significantly different between patients with AS before and after TNF inhibitor treatment (116). Healthy volunteers and patients with AS could be differentiated using five metabolites: L-glutamic acid, arachidonic acid, L-phenylalanine, phosphocholine [18:1(9Z)/ 18:1(9Z)], and 1-palmitoylglycerol (area under the curve 0.998, 95% confidence interval: 0.992-1.000) (116).…”

“…Ou et al established a serum metabolism-associated diagnostic panel and found 55 metabolites that were significantly different between patients with AS before and after TNF inhibitor treatment (116). Healthy volunteers and patients with AS could be differentiated using five metabolites: L-glutamic acid, arachidonic acid, L-phenylalanine, phosphocholine [18:1(9Z)/ 18:1(9Z)], and 1-palmitoylglycerol (area under the curve 0.998, 95% confidence interval: 0.992-1.000) (116). Pathway analysis showed that multiple pathways, including amino acid biosynthesis, glycolysis, glutaminolysis, fatty acid biosynthesis, and choline metabolism, were significantly active in patients with AS (116).…”