Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren's Syndrome and Systemic Sclerosis

PLoS One. 2016 Jul 21;11(7):e0159384. doi: 10.1371/journal.pone.0159384. eCollection 2016.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Case-Control Studies
  • Demography
  • Discriminant Analysis
  • Female
  • Humans
  • Least-Squares Analysis
  • Lupus Erythematosus, Systemic / metabolism*
  • Male
  • Metabolomics / methods*
  • Middle Aged
  • Phenotype
  • Principal Component Analysis
  • Scleroderma, Systemic / metabolism*
  • Sensitivity and Specificity
  • Sjogren's Syndrome / metabolism*
  • Young Adult

Grants and funding

This research was supported by Medical Faculty at Lund University (AB, DMW), The Craford Foundation (AB, DMW), Greta and Johan Kock’s Foundation (AB, DMW), King Gustaf V’s 80th Birthday Foundation (AB), Lund University Hospital (AB), the Swedish Rheumatism Association (AB), Österlund’s Foundation (AB), the Biology of Liver and Pancreatic Development and Disease (BOLD) Marie Curie Initial Training Network (MCITN) within EU’s FP7 program (TL, JT, SC), and Swedish Research Council grant no. 2011-6044 (JT, FT). AcureOmics AB and Leo Pharma A/S provided support in the form of salaries for authors MD and CJS. 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.