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

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.

Lipid and Metabolic Changes in Rheumatoid Arthritis

“…A Dutch group looked at RA subtypes using clinical chemistry measurements, urine and plasma LC-MS metabolomics analysis and according to traditional Chinese medicine (TCM) theory. They showed that urine acylcarnitines could separate patients into heat and cold Chinese medicine RA subtypes and hypothesized that the acylcarnitines could be related to fatigue levels in the patients and suggested that carnitine and acylcarnitine supplementation might be beneficial in the cold patient subtypes [92]. Of note, recent metabolic phenotyping of atherosclerotic plaques showed perturbations in acylcarnitine metabolism which the authors suggest is related to dysregulation of fatty acid metabolism and mitochondrial dysfunction [93••].…”

Review of the regulations for clinical research in herbal medicines in USA

“…(56,57) These types of RCTs include patients according to their genotype rather than the traditional methods based on clinical diagnosis. This personalized medicine may be corresponding well to individualized diagnostic and individualized treatment concept of traditional Asia medicine, i.e., Van, et al (58)(59)(60) study showed that "heat" and "cold", two Chinese medicine diagnosis patterns, was associated with different underlying genomic and metabolomics profiles and different treatment outcomes. Thus sponsor and PI need to consider alternative therapeutic endpoint for RCTs design, redesigning RCTs may integrate traditional herbal medicinal approaches to conventional Western medicine.…”

Immune biomarkers in the spectrum of childhood noncommunicable diseases

“…This has revealed shared profiles of overexpressed miRNAs but it is the signature measurable in blood including miR-24, miR-125a-5p, and miR-451, amongst others, that holds the most promise as biomarkers [104][105][106][107][108][109] . Recent work provided evidence for the use of 14-3-3n serum antibodies in RA 110,111 , and a diagnostic blood panel (including ANA, anti-Ro, anti-La, rheumatoid factor, and novel SjS autoantibodies such as anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6) and anti-parotid secretory protein (PSP)) for Sjögren syndrome [112][113][114] .…”