Ultrasensitive serum levels of interleukin 13 in systemic lupus erythematosus patients: a cross-sectional study

Systemic lupus erythematosus (SLE) is characterized by elevated levels of various cytokines. Interleukin (IL)-13 is a pleiotropic type 2 cytokine that plays a central role in allergic inflammation and tissue fibrosis. Until recently, serum measurement of IL-13 was not feasible because of its extremely low concentration. New highly sensitive techniques now allow its quantification at the femtogram level. In the present study, we aimed to evaluate the association between SLE-disease characteristics and ultrasensitive serum IL-13 levels. In this cross-sectional study, a comprehensive characterization of 313 patients with SLE was performed, including autoantibody profiles and indices of disease activity (SLE-DAS, SLEDAI-2 K, and LLDAS), damage (SLICC-DI), and remission (DORIS). In addition, the cohort was evaluated with complete hematological and lipid profiles, insulin resistance indices, and assessment of subclinical carotid atherosclerosis and carotid stiffness. Serum IL-13 levels were measured using the Simoa (Single Molecule Array) technique. Multivariable linear regression analyses were then conducted to examine the associations between these disease characteristics and circulating IL-13. In multivariable regression analyses demographic features, disease activity indices (SLEDAI-2 K, SLE-DAS, DORIS), damage scores, overall disease duration, autoantibodies and interferon or complement levels were not associated with IL-13. However, in the adjusted models, neutrophil and platelet counts showed an inverse association with IL-13. It was also the case for metabolic factors, as higher levels of HDL-cholesterol and apolipoprotein A1 were independently associated with lower IL-13 levels, while a higher LDL: HDL ratio, a higher ApoB: ApoA1 ratio, and a higher atherogenic index were associated with superior IL-13 levels. In contrast, augmentation index was inversely and independently associated with IL-13. Serum IL-13 levels are not associated with key SLE-related features such as disease activity or the autoantibodies profile. Since IL-13 was associated with an adverse lipid profile, its inverse relationship with augmentation index suggests that its cardiovascular effects may be at least partially independent of circulating lipids. These apparently divergent associations likely reflect distinct but interconnected pathways through which IL-13 influences cardiovascular risk in SLE.