Immunometabolism Dysfunction in the Pathophysiology and Treatment of Rheumatoid Arthritis Publisher Pubmed



Masoumi M¹ ; Hashemi N² ; Moadab F^{3, 4, 5} ; Didehdar M⁶ ; Farahani R⁷ ; Khorramdelazad H^{4, 5, 8} ; Sahebkar A^{9, 10, 11} ; Johnston TP¹² ; Karami J¹³
Source: Current Medicinal Chemistry Published:2023

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and joint damage. Systemic complications and progressive disabili-ty are burdens that lead to a significant socio-economic costs in patients with RA. Current RA biomarkers used in predicting, diagnosing, and monitoring the treatment of the disease have not been very successful. Moreover, only 60% of patients show a satisfacto-ry response to current biological and conventional therapies. Studies on im-munometabolism have suggested that dysregulated enzymes, transcription factors, metabolites, and metabolic pathways could be considered potential therapeutic targets for the treatment of RA. Factors such as the high concentration of various intermediate molecules arising from metabolism, hypoxia, lack of nutrients, and other metabolic alterations affect local immune responses and preserve a state of chronic inflammation in syn-ovial tissues. Fortunately, in vitro and in vivo studies have shown that targeting specific metabolic pathways is associated with a decreased level of inflammation. Specifically, targeting metabolic intermediates, such as succinate or lactate, has shown promising clinical outcomes in RA treatment. These findings open an avenue for the identification of novel biomarkers for diagnosis, prognosis, and determining the success of various treat-ments in RA patients, as well as the discovery of new therapeutic targets. © 2023 Bentham Science Publishers.