title: Metabolite and Lipid Profiling of Biobank Plasma Samples Collected Prior to Onset of Rheumatoid Arthritis.
abstract: OBJECTIVE
  The early diagnosis of rheumatoid arthritis (RA) is desirable to install treatment to prevent disease progression and joint destruction. Autoantibodies and immunological markers pre-date the onset of symptoms by years albeit not all patients will present these factors, even at disease onset. Additional biomarkers would be of high value to improve early diagnosis and understanding of the process, leading to disease development.
  
  
  METHODS
  Plasma samples donated before the onset of RA were identified in the Biobank of Northern Sweden, a collection within national health survey programs. Thirty samples from pre-symptomatic individuals and nineteen from controls were subjected to liquid chromatography-mass spectrometry (LCMS) metabolite and lipid profiling. Lipid and metabolite profiles discriminating samples from pre-symptomatic individuals from controls were identified after univariate and multivariate OPLS-DA based analyses.
  
  
  RESULTS
  The OPLS-DA models including pre-symptomatic individuals and controls identified profiles differentiating between the groups that was characterized by lower levels of acyl-carnitines and fatty acids, with higher levels of lysophospatidylcholines (LPCs) and metabolites from tryptophan metabolism in pre-symptomatic individuals compared with controls. Lipid profiling showed that the majority of phospholipids and sphingomyelins were at higher levels in pre-symptomatic individuals in comparison with controls.
  
  
  CONCLUSIONS
  Our LCMS based approach demonstrated that there are changes in small molecule and lipid profiles detectable in plasma samples collected from the pre-symptomatic individuals who subsequently developed RA, which point to an up-regulation of levels of lysophospatidylcholines, and of tryptophan metabolism, perturbation of fatty acid beta-oxidation and increased oxidative stress in pre-symptomatic individuals' years before onset of symptoms.
authors.affiliation: Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Izabella
authors.initials: I
authors.lastname: Surowiec
authors.affiliation: Department of Public Health and Clinical Medicine, Rheumatology, Umeå University Hospital, Umeå, Sweden.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Ärlestig
authors.affiliation: Department of Public Health and Clinical Medicine, Rheumatology, Umeå University Hospital, Umeå, Sweden.
authors.forename: Solbritt
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
authors.affiliation: Computational Life Science Cluster (CLiC), Department of Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Trygg
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000175:diagnosis*; D018070:Biological Specimen Banks; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D002331:Carnitine / Q000031:analogs & derivatives / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D016002:Discriminant Analysis; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008055:Lipids / Q000032:analysis*; D008244:Lysophosphatidylcholines / Q000032:analysis / Q000378:metabolism; D055432:Metabolomics; D008875:Middle Aged; D025341:Principal Component Analysis; D012372:ROC Curve; D014364:Tryptophan / Q000032:analysis
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D008055:Lipids; D008244:Lysophosphatidylcholines; C116917:acylcarnitine; D014364:Tryptophan; D002331:Carnitine