Interleukin-22 reflects adverse cardiometabolic features in SLE

Interleukin-22 (IL-22), a member of the IL-10 cytokine family, primarily targets non-haematopoietic epithelial and stromal cells, contributing to maintenance of epithelial barrier integrity, antimicrobial immunity and tissue regeneration. In this study, we sought to evaluate the association between serum levels of IL-22, measured by an ultrasensitive assay, and disease characteristics in patients with SLE.

In this cross-sectional study, we thoroughly assessed 313 patients with SLE, collecting data on autoantibody status as well as disease activity indices (SLE Disease Activity Index-2000 and Lupus Low Disease Activity State), damage accrual (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-DI)) and remission status (Definitions of Remission in SLE). The cohort was also characterised in terms of haematological parameters, lipid profile, insulin resistance markers and measures of subclinical carotid atherosclerosis and arterial stiffness. Serum IL-22 concentrations were quantified using the Simoa (Single Molecule Array) platform. We then used multivariable linear regression to explore the associations between these clinical characteristics and circulating IL-22 levels.

After multivariable adjustment, serum IL-22 levels were independently linked to longer disease duration, cumulative damage (SLICC-DI >1) and inversely to methotrexate use. However, these associations did not remain significant after multiple comparison correction. Disease activity, autoantibody profile or complement and interferon levels did not show significant associations with IL-22 levels. Similarly, haematological parameters were not related to circulating IL-22. Regarding cardiovascular risk factors, IL-22 was inversely related to high-density lipoprotein-cholesterol and apolipoprotein A1 suggesting an adverse lipid profile. In addition, serum C-peptide levels were independently related to higher circulating IL-22 concentrations whereas the presence of metabolic syndrome was associated with increased IL-22 levels. Besides, carotid intima-media thickness was significantly correlated with superior IL-22 levels after adjustment for covariates although in this case this association did not withstand adjustment for multiple testing.

In patients with SLE, IL-22 identifies a phenotype of increased cardiovascular risk despite showing little relationship with current disease activity.