High-sensitivity serum interferon-α and interferon-γ as immunometabolic mediators of metabolic syndrome in systemic lupus erythematosus

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with a higher risk of metabolic syndrome compared with the general population. Interferon-alpha (IFN-α) and interferon-gamma (IFN-γ) have been implicated in the pathogenesis of SLE. However, their serum quantification has been challenging until the development of ultrasensitive detection techniques. In this study, we aimed to examine the relationship between IFN-α and IFN-γ values and lipid profile abnormalities as well as pancreatic β-cell dysfunction, both of which are linked to the metabolic syndrome observed in patients with SLE. METHODS: A total of 313 patients with SLE were recruited. A panel of cardiovascular characteristics was collected, including lipid profiles and indices of insulin resistance. Serum IFN-α and IFN-γ levels were measured using an innovative ultrasensitive technique (Single Molecule Array). Multivariable linear regression analysis was performed to examine the relationships between serum IFN-α and IFN-γ concentrations and both the lipid profile and insulin resistance indices. RESULTS: After multivariable adjustment for classical cardiovascular risk factors and SLE disease activity, IFN‑α and IFN‑γ levels were associated with an adverse lipid profile and insulin resistance indices. Specifically, IFN‑α showed significant positive associations with triglycerides, LDL‑cholesterol, lipoprotein (a), and the atherogenic index, and a negative association with HDL‑cholesterol. Remarkably, these associations remained significant after adjustment for IFN‑γ. Conversely, IFN‑γ was significantly and positively associated with triglycerides and pancreatic β‑cell dysfunction after adjustment for covariates, including serum IFN‑α levels. CONCLUSION: Serum IFN‑α and IFN‑γ are independently associated with key components of metabolic syndrome in SLE, including dyslipidaemia and pancreatic β‑cell dysfunction.