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Serum interleukin-2 levels associate with disease activity and cardiovascular risk in patients with rheumatoid arthritis

1, 2, 3, 4, 5, 6, 7, 8, 9, 10

 

  1. Division of Rheumatology, IIS-Fundación Jiménez Díaz, Madrid; and Department of Medicine and Psychiatry, University of Cantabria, Santander, Spain. miguelaggay@hotmail.com
  2. Division of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, Spain.
  3. Division of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, Spain.
  4. Division of Rheumatology, Hospital Doctor Negrín, Las Palmas de Gran Canaria, Spain.
  5. Department of Immunology, Hospital Ramón y Cajal, Madrid, Spain.
  6. Department of Immunology, Hospital Ramón y Cajal, Madrid, Spain.
  7. Fundación Jiménez Díaz School of Nursing, Autonomous University of Madrid, Spain.
  8. Department of Immunology, Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain.
  9. Joint and Bone Research Unit, Service of Rheumatology, IIS-Fundación Jiménez Díaz UAM, Madrid, Spain
  10. Department of Internal Medicine, University of La Laguna (ULL), Tenerife; and Division of Rheumatology, Hospital Universitario de Canarias, Tenerife, Spain. iferraza@ull.edu.es

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Received: 03/02/2026
Accepted : 04/05/2026
In Press: 22/06/2026

Abstract

OBJECTIVES:
Interleukin-2 (IL-2) plays anti-inflammatory and immunoregulatory roles and has been implicated in the pathogenesis of rheumatoid arthritis (RA). However, the relationship between its circulating serum levels and specific clinical features of the disease remains unclear. In this study, we aimed to investigate the association between serum IL-2 concentrations and a wide range of RA-related characteristics, including cardiovascular comorbidities.
METHODS:
216 RA patients underwent assessments of disease characteristics and activity indices. Lipid profile was obtained, insulin resistance indices were calculated, and metabolic syndrome criteria were applied. Carotid ultrasound examinations were performed to assess arterial stiffness, intima-media thickness, and the presence of carotid plaques. Cardiovascular risk was estimated using the SCORE2 tool. Serum IL-2 levels were measured using the Simoa (Single Molecule Array) technique. Finally, a multivariable linear regression analysis was conducted to explore the associations between disease characteristics and IL-2 levels.
RESULTS:
After multivariable adjustment, IL-2 was independently and positively associated with disease activity. Patients positive for rheumatoid factor and anti-citrullinated protein antibodies also exhibited significantly higher IL-2 levels than seronegative individuals. Furthermore, IL-2 showed a positive relationship with pancreatic beta-cell function. Notably, circulating IL-2 concentrations were significantly associated with increased cardiovascular risk as estimated by the SCORE2 algorithm.
CONCLUSIONS:
Circulating IL-2 levels are independently and positively associated with both disease activity and cardiovascular risk in patients with RA. These findings further emphasise the pivotal role of IL-2 in the pathophysiology of RA and its associated cardiovascular comorbidities, highlighting IL-2 as a potential biomarker and therapeutic target in this population.

Rheumatology Article