title: Characterization of rheumatoid arthritis subtypes using symptom profiles, clinical chemistry and metabolomics measurements.
abstract: OBJECTIVE
  The aim is to characterize subgroups or phenotypes of rheumatoid arthritis (RA) patients using a systems biology approach. The discovery of subtypes of rheumatoid arthritis patients is an essential research area for the improvement of response to therapy and the development of personalized medicine strategies.
  
  
  METHODS
  In this study, 39 RA patients are phenotyped using clinical chemistry measurements, urine and plasma metabolomics analysis and symptom profiles. In addition, a Chinese medicine expert classified each RA patient as a Cold or Heat type according to Chinese medicine theory. Multivariate data analysis techniques are employed to detect and validate biochemical and symptom relationships with the classification.
  
  
  RESULTS
  The questionnaire items 'Red joints', 'Swollen joints', 'Warm joints' suggest differences in the level of inflammation between the groups although c-reactive protein (CRP) and rheumatoid factor (RHF) levels were equal. Multivariate analysis of the urine metabolomics data revealed that the levels of 11 acylcarnitines were lower in the Cold RA than in the Heat RA patients, suggesting differences in muscle breakdown. Additionally, higher dehydroepiandrosterone sulfate (DHEAS) levels in Heat patients compared to Cold patients were found suggesting that the Cold RA group has a more suppressed hypothalamic-pituitary-adrenal (HPA) axis function.
  
  
  CONCLUSIONS
  Significant and relevant biochemical differences are found between Cold and Heat RA patients. Differences in immune function, HPA axis involvement and muscle breakdown point towards opportunities to tailor disease management strategies to each of the subgroups RA patient.
authors.affiliation: Division of Analytical Biosciences, LACDR, Leiden University, Leiden, The Netherlands. h.vanwietmarschen@lacdr.leidenuniv.nl
authors.forename: Herman A
authors.initials: HA
authors.lastname: van Wietmarschen
authors.forename: Weidong
authors.initials: W
authors.lastname: Dai
authors.forename: Anita J
authors.initials: AJ
authors.lastname: van der Kooij
authors.forename: Theo H
authors.initials: TH
authors.lastname: Reijmers
authors.forename: Yan
authors.initials: Y
authors.lastname: Schroën
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Xu
authors.forename: Xinchang
authors.initials: X
authors.lastname: Wang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Kong
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankemeier
authors.forename: Jacqueline J
authors.initials: JJ
authors.lastname: Meulman
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism*; D002097:C-Reactive Protein / Q000096:biosynthesis; D002624:Chemistry, Clinical / Q000379:methods; D003080:Cold Temperature; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008516:Medicine, Chinese Traditional; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D057285:Precision Medicine / Q000379:methods; D012217:Rheumatoid Factor / Q000097:blood; D012219:Rheumatology / Q000379:methods; D011795:Surveys and Questionnaires
chemical_list: D002097:C-Reactive Protein; D012217:Rheumatoid Factor