TOPLINE:

In adults with rheumatoid arthritis (RA), higher serum levels of interferon (IFN) alfa were linked to greater disease activity and autoantibody positivity; however, IFN-gamma showed no such link, and neither IFN was associated with cardiovascular or metabolic risk characteristics.

METHODOLOGY:

• Investigators conducted a cross‑sectional study to evaluate whether serum levels of IFN-alfa and IFN-gamma were associated with clinical and cardiovascular features in patients with RA.
• They included 216 adults (mean age, 59 years; 83% women) with RA from hospitals in Spain who had the disease for at least 1 year.
• Serum levels of IFN-alfa and IFN-gamma were measured using an ultrasensitive assay, and patients underwent detailed assessments of RA activity, autoantibody status, and inflammatory markers.
• Cardiovascular and metabolic assessments included lipid levels, insulin resistance, metabolic syndrome, and carotid ultrasound measures of plaque, artery thickness, and stiffness.

TAKEAWAY:

• The median serum level of IFN‑alfa and IFN‑gamma was 51 and 538 fg/mL, respectively. IFN-alfa levels were higher in patients positive for rheumatoid factor (beta-coefficient [β], 1.2; P < .001) or anti-citrullinated protein antibodies (β, 0.51; P = .037) and increased with disease activity across multiple activity scores (P < .05).
• IFN-gamma levels were not linked to most clinical manifestations of RA but were higher in patients with extra-articular manifestations (β, 0.5) and those on methotrexate (β, 0.3) or tocilizumab (β, 0.8) and lower in those using prednisone (β, -0.4; P < .05 for all).
• Serum levels of IFN-alfa and IFN-gamma had a modest positive correlation with each other (Pearson's correlation coefficient, 0.260; P < .001). IFN-gamma was associated with higher levels of interleukin (IL)-2 (β, 0.3) and IL-6 (β, 0.005), and IFN-alfa was associated with higher levels of IL-8 (β, 0.06; P < .01 for all).
• Neither IFN had meaningful associations with most cardiovascular or metabolic measures. The only notable lipid finding was a higher ratio of low- to high-density lipoprotein cholesterol with higher IFN‑alfa levels.

IN PRACTICE:

"Type I IFN-α [alfa], but not type II IFN-γ [gamma], is significantly associated with seropositivity and disease activity in RA. Accordingly, serum IFN-α levels may serve as a reliable biomarker for monitoring disease activity in this patient population," the authors of the study concluded.

SOURCE:

This study was led by Fuensanta Gómez-Bernal, Hospital Universitario de Canarias, Tenerife, Spain. It was published online on January 29, 2026, in Rheumatology.

LIMITATIONS:

The cross‑sectional design limited the ability to establish cause-and-effect relationships. The study lacked a control group with healthy control individuals. Researchers did not assess IFN gene expression signatures.

DISCLOSURES:

This study was funded by a grant from Instituto de Salud Carlos III and co-funded by the European Union. One author reported receiving research support from various sources, including the Spanish Ministry of Health, Spanish Red de Investigación RICORS, and the funding institute. Two authors reported receiving grants or research support and consultation fees from multiple pharmaceutical and healthcare companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.