Serum Metabolomics Signatures Associated With Ankylosing Spondylitis and TNF Inhibitor Therapy

Jiayong Ou,Shuangyan Cao,Liudan Tu,Yefei Huang,Jieruo Gu,Qiujing Wei,Min Xiao,Zena Chen

doi:10.3389/fimmu.2021.630791

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.

Highlights

Ankylosing spondylitis (AS) belongs in the group of diseases called spondyloarthropathies, presenting with chronic back pain, which predominantly affects the spine and the sacroiliac joints
The treatment stage consisted of 32 follow-up patients who received 24-week tumor necrosis factor (TNF) inhibitors therapy
A significant reduction of BASDAI, BASFI, and ASDAS-CRP was observed (p

Summary

Introduction

Ankylosing spondylitis (AS) belongs in the group of diseases called spondyloarthropathies, presenting with chronic back pain, which predominantly affects the spine and the sacroiliac joints. AS is more common in males, presenting with inflammatory back pain, the onset of which typically occurs in the third or fourth decade of life. The disease progression may result in spinal deformity, limitations of spinal mobility and inevitably impaired quality of life. According to studies in twins, genetic factors are thought to account for over 90% of the risk for AS [1]. Despite the numerous disease-associated variants identified in AS with genome-wide association studies, they cumulatively explain only a small proportion (

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