Belimumab

Objectives: To explore the changes and significance of resolvin D1 (RvD1) in the treatment of systemic lupus erythematosus (SLE) with Belimumab. Methods: The clinical data from patients with moderate to severe disease activity SLE who received oral stable doses of glucocorticoids (≤10 mg/d) and/or immunosuppressants for more than 3 months at the outpatient or inpatient department of the First Affiliated Hospital of Soochow University from January 2022 to November, 2023 were retrospectively collected. All patients were treated with 10 mg/kg intravenous infusion of Belimumab. The medication was administered once on the 1st, 15th, and 29th days, and then every 4 weeks for a total of 24 weeks and 8 doses. Peripheral blood plasma before and after treatment were collected, and RvD1 levels before and after treatment were detected using enzyme-linked immunosorbent assay (ELISA). According to the guidelines, SLE patients were divided into kidney involvement group and kidney non-involvement group; the patients were further divided into a blood system involvement group and a blood system non-involvement group; according to the SLE Disease Activity Index (SLEDAI), the patients were divided into moderate activity group and severe activity group. After 24 weeks of treatment, the patients were divided into complete remission group, low disease activity group, and no remission group according the treatment effects. The changes in plasma RvD1 levels in each group before and after treatment with Belimumab were analyzed, and their correlation with various activity indicators of SLE was checked too. Results: A total of 81 patients were included, of which 15 were male and 66 were female, with an average age of (33.14±8.27) years. At baseline, plasma RvD1 levels in SLE patients were negatively correlated with SLEDAI scores (r=-0.642, P<0.001) and anti dsDNA antibody levels (r=-0.623, P=0.012). There was no significant difference in plasma RvD1 level [M(Q₁, Q₃)] between SLE patients with renal involvement (n=50) and those without renal involvement (n=31) [73.27 (45.16, 122.12) ng/L vs 58.32 (32.29, 94.33) ng/L, P=0.365]. There was no significant difference in plasma RvD1 level between SLE patients with hematological involvement (n=40) and those without hematological involvement (n=41) [74.78 (47.01, 121.67) ng/L vs 42.88 (30.05, 76.76) ng/L, P=0.277]. The plasma RvD1 level in the moderate activity group (n=51) was significantly higher than that in the severe activity group (n=30) [104.76 (65.65, 135.34) ng/L vs 55.86 (37.53, 81.35) ng/L, P=0.002]. After 24 weeks of treatment with Belimumab, plasma RvD1 levels in the complete remission group (n=10) were both significantly higher than those in the low disease activity group (n=61) and the non-remission group (n=10) [196.48 (123.08, 236.33) ng/L vs 98.87 (63.35, 110.23) ng/L and 77.68 (41.73, 128.55) ng/L, respectively, P=0.001]. After the treatment, the plasma RvD1 levels in both the complete remission group and the low disease activity group increased significantly when compared to those before the treatment [98.23 (40.45, 107.19) ng/L vs 176.48 (123.08, 226.33) ng/L and 65.27 (31.76, 94.35) ng/L vs 98.87 (63.35, 110.23) ng/L, both P<0.05]. Further analysis revealed that all the patients of complete remission group after treatment were from the moderate disease activity group before treatment, and the plasma RvD1 level in the complete remission group was significantly higher than that in the low disease activity group before the treatment [98.23 (40.45, 127.19) vs 65.27 (31.76, 94.35) ng/L] (P=0.022). Conclusions: The plasma RvD1 level significantly increased after treatment with Belimumab in SLE patients, patients with higher plasma RvD1 level before treatment have better efficacy with Belimumab.

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.

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.

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.

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.