Abstract
ObjectiveThe 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.MethodsIn 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.ResultsThe 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.ConclusionSignificant 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.
Highlights
Discovering subtypes of rheumatoid arthritis (RA) patients is considered a key research area for the improvement of response to therapy [1,2]
Subjects In total 50 patients were enrolled in the study. Eleven of these patients did not fulfill the inclusion criteria and were removed from the analysis. Seven of those eleven patients were male and excluded, of two persons there was no RA diagnosis available, one patient was in the hospital for other reasons and excluded and one person was excluded from this analysis because the symptom questionnaire was not completed
In this study we find that the levels of a range of acylcarnitines are lower in the Cold RA group than in the Heat RA group
Summary
Discovering subtypes of rheumatoid arthritis (RA) patients is considered a key research area for the improvement of response to therapy [1,2]. Several subtypes of RA patients have been identified based on particular clinical and molecular features [6,7] Markers such as disease duration and age have been identified that predict response to treatment [8,9]. One reason is the difficulty to translate markers found in trial populations to routinely measurable and cost-effective predictors for individuals [10]. This indicates that there is a need to develop new robust and reliable clinically applicable tools to identify subtypes of patients
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