Serum IL-2 levels are associated with disease activity and related to dyslipidaemia and the immunological profile in systemic lupus erythematosus

TL;DR

This study finds that IL-2 levels in lupus patients are linked to disease activity, inflammation, and lipid levels, suggesting a key role in lupus progression.

Contribution

The study establishes novel associations between serum IL-2 and specific autoantibodies, inflammation markers, and dyslipidaemia in SLE patients.

Findings

Serum IL-2 levels are positively associated with inflammatory markers like CRP and IL-6 in SLE patients.

Higher IL-2 levels correlate with disease activity and specific autoantibodies such as anti-DNA and anti-SSA/SSB.

Triglycerides are positively linked to IL-2, while HDL-cholesterol is inversely associated.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterised by multisystem involvement, frequently including cardiovascular manifestations. Interleukin 2 (IL-2), a key cytokine in immune regulation, plays a pivotal role in maintaining tolerance by promoting regulatory T cell function. The relationship between serum IL-2 levels and specific SLE features remains incompletely defined. The aim of our study was to investigate the associations between serum IL-2 concentrations and disease activity, inflammatory markers, autoantibody profiles as well as cardiovascular and metabolic parameters in a well-characterised cohort of patients with SLE.

In this cross-sectional study, 235 patients with SLE were recruited and characterised, including assessment of autoantibody profiles, disease activity indices (SLE Disease Activity Index-2000 (SLEDAI-2K)), Damage Index and remission status. Cardiovascular characteristics were evaluated, encompassing lipid profiles, insulin resistance indices and carotid ultrasound parameters such as plaque presence, intima-media thickness and arterial stiffness. Serum IL-2 concentrations were quantified using an ultrasensitive technique, the Single Molecule Array (Simoa). Multivariable linear regression was conducted to examine the associations between circulating IL-2 levels and clinical as well as cardiovascular manifestations of SLE.

In multivariable analyses, serum IL-2 levels showed significant positive associations with inflammatory markers including C reactive protein and IL-6. Disease activity, assessed by SLEDAI-2K, was positively correlated with IL-2 levels. Positive and significant associations were also noted, after adjustment for covariates, between IL-2 and specific autoantibodies, including anti-DNA, anti-Sjögren’s syndrome antigen A (SSA), anti-Sjögren’s syndrome antigen B (SSB), anti-Smith (Sm) and antiribosome. Regarding cardiovascular disease factors, triglycerides were positively associated with IL-2 whereas high-density lipoprotein-cholesterol exhibited an inverse relationship.

Significant correlations exist between serum IL-2 levels and markers of inflammation, lipid profile, disease activity and specific autoantibody profiles in patients with SLE. These findings underscore the pivotal role of IL-2 in SLE immunopathogenesis, reflecting its intricate involvement in modulating both inflammatory responses and metabolic pathways.

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