Improvement of High-Density Lipoprotein Atheroprotective Properties in Patients with Systemic Lupus Erythematosus after Belimumab Treatment

Objective Chronic inflammatory diseases, like Systemic Lupus Erythematosus (SLE), carry an increased risk for atherosclerosis and cardiovascular events, accompanied by impairment of atheroprotective properties of high-density lipoprotein (HDL). In SLE, serum B cell-activating factor (BAFF), a cytokine implicated in disease progression, has been correlated with subclinical atherosclerosis. We investigated the impact of treatment with belimumab -an anti-BAFF monoclonal antibody- on HDL atheroprotective properties and composition in SLE patients.Methods Serum samples were collected from 35 SLE patients with active disease despite conventional therapy, before and after 6-month add-on treatment with belimumab, and 26 matched healthy individuals. We measured cholesterol efflux and antioxidant capacities, paraoxonase-1 (PON1) activity, serum amyloid A1 (SAA1), myeloperoxidase (MPO) and lipid peroxidation product levels of HDL. LC-MS/MS was performed to analyse the HDL lipidome.Results Following treatment with belimumab, cholesterol efflux and antioxidant capacities of HDL were significantly increased in SLE patients and restored to levels of control subjects. HDL-associated PON1 activity was also increased, whereas lipid peroxidation products were decreased following treatment. HDL cholesterol efflux and antioxidant capacities correlated negatively with the disease activity. Changes were noted in the HDL lipidome of SLE patients following belimumab treatment, as well as between SLE patients and healthy individuals, and specific changes in lipid species correlated with functional parameters of HDL.Conclusions HDL of SLE patients with active disease displays impaired atheroprotective properties accompanied by distinct lipidomic signatures compared with controls. Belimumab treatment may improve the HDL atheroprotective properties and modify the HDL lipidomic signature in SLE patients, thus potentially mitigating atherosclerosis development. Graphical Abstract