Division of Analytical Biosciences, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
J Clin Rheumatol. 2009 Oct;15(7):330-7. doi: 10.1097/RHU.0b013e3181ba3926.
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.
: A systems biology approach is explored to find subtypes of rheumatoid arthritis patients enabling a development towards more personalized medicine.
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.
: 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.
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.
类风湿性关节炎等复杂的慢性疾病已成为医学和制药行业的重大挑战。需要为药物开发提供新的动力。
探索系统生物学方法，寻找类风湿关节炎患者的亚型，从而实现更个性化的医学。
收集了 33 名类风湿关节炎（RA）患者和 16 名健康志愿者的血液样本。根据中医理论对 RA 患者进行诊断，并将其分为 RA 热证组和 RA 寒证组。使用 CD4 T 细胞进行全基因表达分析。采用气相色谱/质谱法测量血浆中的代谢物谱。采用多元统计方法寻找 RA 热证和 RA 寒证表型的潜在生物标志物。对结果进行了全面的生物学解释。
基因组学和代谢组学分析表明，健康对照组与 RA 患者之间以及 RA 热证组和 RA 寒证组之间的基因表达和代谢谱存在统计学上的显著差异。在细胞凋亡的调节方面存在差异。在 RA 热证组中，caspase 8 激活的细胞凋亡似乎受到刺激，而在 RA 寒证组中，细胞凋亡似乎通过 Nrf2 途径受到抑制。
根据中医理论，RA 患者可分为两组。在 RA 寒证和 RA 热证组之间发现了分子差异，这表明细胞凋亡活性存在差异。根据 CM 诊断对患者进行分组有可能为特定患者群体提供更好的治疗效果的机会，即针对西方或 CM 治疗的特定患者群体。
