Background: Nuclear factor of activated T cells (NFAT) is a transcription factor family that plays a crucial role in physiological and immune processes, modulating intracellular and extracellular signaling pathways related with several diseases ^1,2 . In this regard, it has been involved in the pathogenesis of rheumatoid arthritis (RA) and in the development of cardiovascular (CV) disease ^3-5 . Given that CV disease is one of the main causes of morbidity and mortality in patients with RA ⁶ , functional studies focused on the implication of NFAT in CV disease in RA are of potential interest.

Objectives: To study the role of the gene expression of two members of the NFAT family, NFATc1 and NFATc2 , in the risk of developing CV disease in patients with RA.

Methods: A total of 79 disease-modifying antirheumatic drug-naïve patients with early RA ⁷ from Hospital Universitario Marqués de Valdecilla (Santander, Spain) were included in this study. The relative mRNA expression of NFATc1 and NFATc2 in peripheral blood was determined by qPCR. Carotid ultrasound data were used as surrogate markers of subclinical atherosclerosis. The association between NFATc1 and NFATc2 expression in RA patients and their clinical characteristics was evaluated. Results were adjusted by sex, age at the time of the study and traditional CV risk factors.

Results: A statistically significant increase of NFATc1 mRNA expression was found in women compared to men (fold change=+1.18, p=0.035). In addition, a higher NFATc1 mRNA expression was observed in patients with dyslipidemia compared to those with normal lipid profile (fold change=+1.18, p=0.006). With respect to this, we also disclosed a positive correlation between NFATc1 mRNA expression and low-density lipoprotein cholesterol levels (r=0.27, p=0.039). No significant associations were detected between NFATc2 mRNA expression and clinical characteristics of our RA patients. Carotid ultrasound findings were not related to NFATc1 and NFATc2 expression.

Conclusion: Our study suggests that a higher expression of NFATc1 in peripheral blood is associated with abnormalities in the lipid profile and, consequently, with an increased risk of CV disease in patients with early RA.

REFERENCES:

[1]Annu Rev Immunol.1997;15:707-747;

[2]Nat Rev Immunol.2005;5:472-484;

[3]Autoimmun Rev.2006;5:106-110;

[4]Immunol Rev. 2010;233:286-300;

[5]Front Cardiovasc Med. 2021;8:635172;

[6]Arthritis Rheumatol. 2019;71:351-360;

[7]Arthritis Rheum.2010;62:2569-2581.

Acknowledgements: Study supported by NVAL 19/18 awarded to SR-M (IDIVAL) and partially supported by PI18/00043 (ISCIII). Personal funds, SR-M: RD16/0012/0009 (ISCIII-ERDF); VP-C: PREVAL18/01 (IDIVAL); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).

Disclosure of Interests: Fernanda Genre: None declared, Verónica Pulito-Cueto: None declared, Alfonso Corrales: None declared, Virginia Portilla: None declared, Leticia Lera-Gómez: None declared, Belén Atienza-Mateo: None declared, Oreste Gualillo: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Iván Ferraz-Amaro: None declared, Santos Castañeda: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Grant/research support from: Abbvie, MSD, Janssen, and Roche, Sara Remuzgo-Martínez: None declared