Title:Immunometabolism Dysfunction in the Pathophysiology and Treatment
of Rheumatoid Arthritis
Volume: 30
Issue: 27
Author(s): Maryam Masoumi, Nader Hashemi, Fatemeh Moadab, Mojtaba Didehdar, Rahim Farahani, Hossein Khorramdelazad, Amirhossein Sahebkar*, Thomas P. Johnston and Jafar Karami*
Affiliation:
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences,
Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Biotechnology,
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Laboratory Sciences, Khomein University of
Medical Sciences, Khomein, Iran
Keywords:
Rheumatoid, arthritis, immunometabolism, autoimmune disease, synovial hyperplasia, RA biomarkers.
Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by
synovial hyperplasia and joint damage. Systemic complications and progressive disability
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 satisfactory
response to current biological and conventional therapies. Studies on immunometabolism
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 synovial
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 treatments
in RA patients, as well as the discovery of new therapeutic targets.