Proteomics and metabolomics in the classification of SLE subsets

• Background: Systemic autoimmune diseases (SAIDs) affect about 0.5–1% of Europeans with a remarkable female predominance (80–90%). Present diagnostic entities are vague and rely on fairly old and unspecific criteria that do not use state-of-the-art laboratory parameters. New diagnostic tools and therapeutic/prognostic biomarkers are needed. Systemic lupus erythematosus (SLE) is regarded as a prototype for SAIDs and we hypothesized that subgroups of patients with SLE may have different pathogenesis and should consequently be subject to different treatment strategies. Our aim was to find new biomarkers to be used for the identification of more homogeneous patient populations.Method: This study involved 320 SLE patients from the Karolinska lupus cohort and 320 age- and gender-matched controls. Plasma samples were analysed using an antibody Luminex assay with 367 antibodies targeting 281 unique selected proteins. Subsets of the SLE cohort and controls were also analysed for their sphingolipid content, as well as by a metabolomic and mass spectrometry-based proteomic approach.Results: The Luminex platform revealed 66 proteins found at higher or lower levels in SLE. Mass spectrometry-based proteomics has shown very promising data for the components of the complement and coagulation cascades. Metabolomics identified patterns of plasma metabolites that separate SLE from controls. Finally, analysis of >30 sphingolipids demonstrated a specific group of these lipids at significantly higher concentrations in SLE compared to controls. Following treatment, these differences were normalized.Conclusions: Preliminary data demonstrate the involvement of several distinct biochemical pathways in SLE that can be used for biomarker discovery and a better understanding of the pathophysiological events underlying the disease.

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NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

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