Characterization of Rheumatoid Arthritis Subtypes Using Symptom Profiles, Clinical Chemistry and Metabolomics Measurements

TLDR

Identifying rheumatoid arthritis subtypes is essential for improving therapeutic response and advancing personalized medicine. The study aims to characterize rheumatoid arthritis subgroups using a systems biology approach. The authors phenotyped 39 RA patients with clinical chemistry, urine and plasma metabolomics, and symptom profiles, classified them as Cold or Heat by a Chinese medicine expert, and applied multivariate analysis to uncover biochemical and symptom relationships. Multivariate analysis revealed distinct biochemical profiles between Cold and Heat RA patients, including lower acylcarnitines and higher DHEAS in Heat, indicating differences in muscle breakdown, HPA axis activity, and inflammation that could inform tailored disease management.

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. Conclusion 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.