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.
Keywords:
Rheumatoid, Arthritis, Immunometabolism, Chronic, Inflammation, Treatment
[7]
Smolen, J.; Aletaha, D.; McInnes, I. Therapies for bone R. Lancet, 2016, 30173-30178.
[12]
Smolen, J.S.; Breedveld, F.C.; Burmester, G.R.; Bykerk, V.; Dougados, M.; Emery, P.; Kvien, T.K.; Navarro-Compán, M.V.; Oliver, S.; Schoels, M.; Scholte-Voshaar, M.; Stamm, T.; Stoffer, M.; Takeuchi, T.; Aletaha, D.; Andreu, J.L.; Aringer, M.; Bergman, M.; Betteridge, N.; Bijlsma, H.; Burkhardt, H.; Cardiel, M.; Combe, B.; Durez, P.; Fonseca, J.E.; Gibofsky, A.; Gomez-Reino, J.J.; Graninger, W.; Hannonen, P.; Haraoui, B.; Kouloumas, M.; Landewe, R.; Martin-Mola, E.; Nash, P.; Ostergaard, M.; Östör, A.; Richards, P.; Sokka-Isler, T.; Thorne, C.; Tzioufas, A.G.; van Vollenhoven, R.; de Wit, M.; van der Heijde, D. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force.
Ann. Rheum. Dis., 2016,
75(1), 3-15.
[
http://dx.doi.org/10.1136/annrheumdis-2015-207524] [PMID:
25969430]
[13]
Tsokos, GC Metabolic control of arthritis: Switch pathways to treat. Sci. Transl. Med., 2016, 8(331), 331fs8.
[26]
Pucino, V; Certo, M; Bulusu, V; Cucchi, D; Goldmann, K; Pontarini, E Lactate buildup at the site of chronic inflammation promotes disease by inducing CD4+ T cell metabolic rewiring. Cell metabolism, 2019, 30(6), 1055-74.
[76]
Contribution of metabolic reprogramming to macrophage plasticity and function. Seminars in immunology. Semin Immunol, 2015, 27(4), 267-75.
[103]
Forrest, C.M.; Kennedy, A.; Stone, T.W.; Stoy, N.; Darlington, L.G. Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis during drug treatment. In: Allegri, G., Costa, C.V.L., Ragazzi, E., Steinhart, H., Varesio, L. Eds., Developments in tryptophan and serotonin metabolism. Advances in experimental medicine and biology; Springer: Boston, MA, 2003; 527, pp. 287-295.
[117]
Yan, H; Zhou, H-f; Hu, Y; Pham, CT. Suppression of experimental arthritis through AMP-activated protein kinase activation and autophagy modulation. J. Rheum. Dis., 2015, 1(1), 5.
[119]
Son, H-J; Lee, J; Lee, S-Y; Kim, E-K; Park, M-J; Kim, K-W. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis. Mediat. Inflamm., 2014, 2014, 973986.