Metabolite Space of Rheumatoid Arthritis
Herman van Wietmarschen *
Division of Analytical Biosciences, LACDR, Leiden University, Leiden, The Netherlands and Sino-Dutch centre for Preventive and Personalized Medicine, Zeist, The Netherlands
Jan van der Greef
Division of Analytical Biosciences, LACDR, Leiden University, Leiden, The Netherlands and Sino-Dutch centre for Preventive and Personalized Medicine, Zeist, The Netherlands and TNO, P.O. Box 360, 3700 AJ, Zeist, The Netherlands
*Author to whom correspondence should be addressed.
Abstract
Metabolites play numerous roles in the healthy and diseased body, ranging from regulating physiological processes to providing building blocks for the body. Therefore, understanding the role of metabolites is important in elucidating the etiology and pathology of diseases and finding targets for new treatment options. Rheumatoid arthritis is a complex chronic disease for which new disease management strategies are needed. The aim of this review is to bring together and integrate information about the various roles that metabolites have in rheumatoid arthritis.
An extensive PubMed search is conducted to collect the relevant manuscripts. The metabolites are discussed in relation to rheumatoid arthritis. Subsequently, the metabolites are organized according to levels of system organization. In the last section an integrated pathway analysis of the metabolites conducted with Ingenuity Pathway Analysis software is presented.
Literature search resulted in information about vitamins, eicosanoids, fatty acids, lipids, hormones and peptides. The metabolites could be related to metabolic processes, oxidative stress processes and inflammatory processes. Cell death, lipid metabolism and small molecule biochemistry were found by the pathway analysis to be the top functions, characterized by the metabolites arachidonic acid, ascorbic acid, beta-carotene, cholecalciferol, hydrocortisone, keratan sulfate, melatonin, palmitic acid and stearic acid. These nine metabolites are highly connected to a number of canonical pathways related to immune functions, the production of nitric oxygen and reactive oxygen species in macrophages and pathways involved in arthritis.
This review indicates groups of metabolites that could be interesting for metabolomics studies related to rheumatoid arthritis. Circadian rhythms of metabolite levels are found to be important for understanding and treating rheumatoid arthritis. In addition, some key processes and pathways are found by integrating the metabolite data. This might offer new ideas for studies into the mechanism of and possible treatment options for rheumatoid arthritis.
Keywords: Rheumatoid arthritis, metabolites, systems biology, health space, diagnosis