Improvement of high-density lipoprotein atheroprotective properties in patients with systemic lupus erythematosus after belimumab treatment

Anastasia-Georgia Dedemadi; Christina Gkolfinopoulou; Dimitra Nikoleri; Myrto Nikoloudaki; Hanna Ruhanen; Minna Holopainen; Reijo Kakela; Georgia Christopoulou; Stavros Bournazos; Pantelis Constantoulakis; Prodromos Sidiropoulos; George Bertsias; Angeliki Chroni

doi:10.1093/rheumatology/keae192

Improvement of high-density lipoprotein atheroprotective properties in patients with systemic lupus erythematosus after belimumab treatment

Rheumatology (Oxford). 2024 Mar 21:keae192. doi: 10.1093/rheumatology/keae192. Online ahead of print.

Authors

Anastasia-Georgia Dedemadi^{1

2}, Christina Gkolfinopoulou¹, Dimitra Nikoleri^{3

4}, Myrto Nikoloudaki³, Hanna Ruhanen^{5

6}, Minna Holopainen^{5

6}, Reijo Kakela^{5

6}, Georgia Christopoulou⁷, Stavros Bournazos⁷, Pantelis Constantoulakis⁷, Prodromos Sidiropoulos^{3

4}, George Bertsias^{3

4}, Angeliki Chroni¹

Affiliations

¹ Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", Agia Paraskevi, Athens, Greece.
² Department of Chemistry, National and Kapodistrian University of Athens, Zografou, Athens, Greece.
³ Laboratory of Rheumatology, Autoimmunity and Inflammation, University of Crete Medical School, Heraklion, Greece.
⁴ Institute of Molecular Biology and Biotechnology, FORTH, Heraklion, Greece.
⁵ Helsinki University Lipidomics Unit, HiLIPID, Helsinki Institute of Life Science, HiLIFE, and Biocenter Finland, Helsinki, Finland.
⁶ Molecular and Integrative Biosciences Research Program, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
⁷ Genotypos-Science Labs, Athens, Greece.

PMID: 38514392
DOI: 10.1093/rheumatology/keae192

Abstract

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 BAFF (B cell-activating factor), 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 activity, serum amyloid A1, myeloperoxidase and lipid peroxidation product levels of HDL. LC-MS/MS was performed to analyze 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 controls. HDL-associated paraoxonase-1 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 signature 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.

Keywords: Biologicals; High-Density Lipoprotein; Systemic lupus erythematosus; atheroprotection; lipidomic profile.