期刊
JCR-JOURNAL OF CLINICAL RHEUMATOLOGY
卷 15, 期 7, 页码 330-337出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/RHU.0b013e3181ba3926
关键词
rheumatoid arthritis; systems biology; CM; genomics; apoptosis
类别
资金
- Netherlands Genomics Initiative
- Chinese Academy of Sciences, Ministry of Science and Technology (China)
- National Science Foundation of China [90209002, 90709007]
- Netherlands Metabolomics Center and the Osteo- and Rheumatoid Arthritis Foundation (NL)
- China International Science and Technology Cooperation Program [2007DFA31060, 2009DFA41250]
- National Key Project of Scientific and Technical Supporting Programs [2006BAK02A12]
- Ministry of Science and Technology of China
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.
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