0251: Nuclear Factor of Activated T Cells Cytoplasmic 1 as a Potential Biomarker of Increased Cardiovascular Risk in Patients with Early Rheumatoid Arthritis

Sara Remuzgo-Martinez¹, Fernanda Genre¹, Veronica Pulito-Cueto², Alfonso Corrales¹, Virgi Portilla¹, Leticia Lera-Gómez¹, Belén Atienza-Mateo¹, María Sebastián Mora-Gil¹, J Gonzalo Ocejo-Vinyals³, Oreste Gualillo⁴, Ricardo Blanco⁵, Ivan Ferraz Amaro⁶, Santos Castañeda⁷, Raquel Lopez Mejias² and Miguel Ángel González-Gay⁸, ¹Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL; and Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain, ²IDIVAL, Santander, Spain, ³Department of Immunology, Hospital Universitario Marqués de Valdecilla, Santander, Spain, ⁴Hospital Clínico Universitario de Santiago, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago de Compostela, Spain, ⁵Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain, ⁶Division of Rheumatology. Hospital Universitario de Canarias. Spain., Santa Cruz de Tenerife, Spain, ⁷Division of Rheumatology, Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Spain, ⁸Department of Medicine and Psychiatry, Universidad de Cantabria; Rheumatology Division, Hospital Universitario Marqués de Valdecilla; Research group on genetic epidemiology and atherosclerosis in systemic diseases and in metabolic diseases of the musculoskeletal system, IDIVAL, Santander, Spain. Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Background/Purpose: NFKB1, NKIRAS1, NFATc1, NFATc2 and MTHFR, inflammation and immune response-related genes, predispose to the increased risk of cardiovascular (CV) disease in patients with RA [1-2]. Nevertheless, the molecular mechanisms by which these genes exert this role remain to be elucidated. In this regard, the assessment of the expression of these genes is pivotal to explain their functional role. Accordingly, the aim of this study was to determine the expression of these relevant genes in a well-defined cohort of RA patients.

Methods: A total of 83 disease-modifying antirheumatic drug-naïve patients with early RA [3] from Hospital Universitario Marqués de Valdecilla (Santander, Spain) were included in this study. The relative mRNA expression of NFKB1, NKIRAS1, NFATc1, NFATc2 and MTHFR in peripheral blood was determined by qPCR. Carotid ultrasound data were used as surrogate markers of subclinical atherosclerosis. The association between the expression of these five genes 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 the other genes analyzed and clinical characteristics of our RA patients. Carotid ultrasound findings were not related with NFKB1, NKIRAS1, NFATc1, NFATc2 and MTHFR 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. Autoimmun Rev. 2016;15:1013-1030
2. Arthritis Rheumatol. 2019 Mar;71(3):351-360
3. 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 and VP-C: RD16/0012/0009 (ISCIII-ERDF); FG: RICORS Program RD21/0002/0025 (ISCIII-EU); RL-M: Miguel Servet type II CPII21/00004 (ISCIII-ESF).



Disclosures: S. Remuzgo-Martinez, None; F. Genre, None; V. Pulito-Cueto, None; A. Corrales, None; V. Portilla, None; L. Lera-Gómez, None; B. Atienza-Mateo, AbbVie/Abbott, Roche, Pfizer, Celgene, Novartis, Janssen, UCB, Eli Lilly; M. Sebastián Mora-Gil, None; J. Ocejo-Vinyals, None; O. Gualillo, None; R. Blanco, Eli Lilly, Pfizer, Roche, Janssen, MSD, AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Galapagos, Novartis, Sanofi; I. Ferraz Amaro, AbbVie/Abbott, Merck/MSD, Janssen, Roche, AbbVie/Abbott, Pfizer, Roche, Amgen, Celgene, Merck/MSD; S. Castañeda, Roche; R. Lopez Mejias, None; M. González-Gay, AbbVie/Abbott, Merck/MSD, Janssen, Roche, AbbVie/Abbott, Roche, Sanofi, Eli Lilly, Celgene, Sobi, Merck/MSD.