title: Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren's Syndrome and Systemic Sclerosis.
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.
authors.affiliation: Department of Rheumatology, University Hospital Lund, Lund, Sweden.
authors.forename: Anders A
authors.initials: AA
authors.lastname: Bengtsson
authors.affiliation: Computational Life Science Center (CLiC), Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Trygg
authors.affiliation: Department of Rheumatology, University Hospital Lund, Lund, Sweden.
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Wuttge
authors.affiliation: Department of Rheumatology, University Hospital Lund, Lund, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sturfelt
authors.affiliation: Department of Rheumatology, Skåne University Hospital Malmö, Lund University, Lund, Sweden.
authors.forename: Elke
authors.initials: E
authors.lastname: Theander
authors.affiliation: AcureOmics AB. Tvistevägen 48, Umeå, Sweden.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Donten
authors.affiliation: Swedish Metabolomics Centre, Swedish University of Agricultural Sciences, Umeå, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moritz
authors.affiliation: Leo Pharma A/S, 55 Industriparken, DK-2750 Ballerup, Denmark.
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Sennbro
authors.affiliation: Computational Life Science Center (CLiC), Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Frida
authors.initials: F
authors.lastname: Torell
authors.affiliation: Department of Rheumatology, University Hospital Lund, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Lood
authors.affiliation: Computational Life Science Center (CLiC), Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Izabella
authors.initials: I
authors.lastname: Surowiec
authors.affiliation: AcureOmics AB. Tvistevägen 48, Umeå, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rännar
authors.affiliation: AcureOmics AB. Tvistevägen 48, Umeå, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lundstedt
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003710:Demography; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010641:Phenotype; D025341:Principal Component Analysis; D012595:Scleroderma, Systemic / Q000378:metabolism*; D012680:Sensitivity and Specificity; D012859:Sjogren's Syndrome / Q000378:metabolism*; D055815:Young Adult