title: Systems biology guided by Chinese medicine reveals new markers for sub-typing rheumatoid arthritis patients.
abstract: BACKGROUND
  Complex chronic diseases such as rheumatoid arthritis have become a major challenge in medicine and for the pharmaceutical industry. New impulses for drug development are needed.
  
  
  OBJECTIVE
  : A systems biology approach is explored to find subtypes of rheumatoid arthritis patients enabling a development towards more personalized medicine.
  
  
  METHODS
  Blood samples of 33 rheumatoid arthritis (RA) patients and 16 healthy volunteers were collected. The RA patients were diagnosed according to Chinese medicine (CM) theory and divided into 2 groups, the RA Heat and RA Cold group. CD4 T-cells were used for a total gene expression analysis. Metabolite profiles were measured in plasma using gas chromatography/mass spectrometry. Multivariate statistics was employed to find potential biomarkers for the RA Heat and RA Cold phenotype. A comprehensive biologic interpretation of the results is discussed.
  
  
  RESULTS
  : The genomics and metabolomics analysis showed statistically relevant different gene expression and metabolite profiles between healthy controls and RA patients as well as between the RA Heat and RA Cold group. Differences were found in the regulation of apoptosis. In the RA Heat group caspase 8 activated apoptosis seems to be stimulated while in the RA Cold group apoptosis seems to be suppressed through the Nrf2 pathway.
  
  
  CONCLUSIONS
  RA patients could be divided in 2 groups according to CM theory. Molecular differences between the RA Cold and RA Heat groups were found which suggest differences in apoptotic activity. Subgrouping of patients according to CM diagnosis has the potential to provide opportunities for better treatment outcomes by targeting Western or CM treatment to specific groups of patients.
authors.affiliation: Division of Analytical Biosciences, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: van Wietmarschen
authors.forename: Kailong
authors.initials: K
authors.lastname: Yuan
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Jiangshan
authors.initials: J
authors.lastname: Wang
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiao
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yan
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Jan
authors.initials: J
authors.lastname: Schroën
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.forename: Guowang
authors.initials: G
authors.lastname: Xu
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
mesh_terms: D000328:Adult; D017209:Apoptosis; D018771:Arthralgia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000145:classification* / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D016022:Case-Control Studies; D053181:Caspase 8 / Q000097:blood; D003080:Cold Temperature; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008516:Medicine, Chinese Traditional / Q000379:methods*; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000097:blood; D049490:Systems Biology / Q000379:methods*
chemical_list: D015415:Biomarkers; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D053181:Caspase 8