Abstract
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diagnose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway.
Highlights
Systemic lupus erythematosus (SLE) is a chronic inflammatory systemic autoimmune disease affecting mostly females in childbearing ages
The first step in the multivariate analysis of the metabolic data was to investigate if the three different SLE phenotypes G1, G2 and G3 may be differentiated by their metabolic profiles
It is obvious that the metabolic profiles of the three phenotypes overlap
Summary
Systemic lupus erythematosus (SLE) is a chronic inflammatory systemic autoimmune disease affecting mostly females in childbearing ages. Most organ systems can be involved and symptoms from skin and joints are common but more severe disease with inflammation in kidneys and/or central nervous system (CNS) occur frequently, and there is an increased mortality in this disease. The prevalence in Sweden has been estimated to 68/100,000 and the annual incidence to approximately 5/100,000 [1]. The specific roles of these authors are articulated in the "author contributions" section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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