Effects of belimumab on peripheral blood Breg cells and cytokines in childhood systemic lupus erythematosus.

Abstract

To evaluate the therapeutic effectiveness of belimumab (BLM) in childhood systemic lupus erythematosus (cSLE) by analyzing peripheral blood Breg cell subsets and related cytokines at multiple time points post-treatment, compared with conventional therapy. From January 2023 to August 2023, 36 cSLE patients receiving BLM plus standard therapy (BLM group) and 35 receiving standard therapy alone (conventional group) were enrolled. Thirty age- and sex-matched healthy children were included as controls. Flow cytometry was used to detect absolute counts and ratios of peripheral Breg cell subsets at baseline, 6 weeks, 6 months, and 1 year. Serum cytokine levels (IL-2, IL-10, IL-21, IL-35, and IFN-γ) were measured by ELISA. After 6 weeks, IL-2, IL-21, and IFN-γ levels decreased significantly in both groups (P > 0.05 between groups); however, after 6 months and 1 year, these cytokines remained lower in the BLM group (all P < 0.05). IL-10 and IL-35 levels increased in both groups from week 6, with a milder increase in the BLM group (all P < 0.05). CD3⁻CD19⁺ B cells declined in both groups, with significant intergroup differences (P < 0.001). The BLM group showed a higher proportion of CD27⁺CD24⁺ B cells at week 6 compared to the conventional group (P < 0.05), but this reversed at 1 year (P < 0.05). CD38⁺CD24⁺ B cells were significantly higher in the BLM group at 6 months and 1 year (P < 0.001), while the conventional group showed no significant change after 6 weeks (P > 0.05). At baseline, the relative proportion of CD38⁺CD19⁺ B cells was higher in the BLM group than in the conventional treatment group (all P < 0.05). With ongoing treatment, both groups showed a decreasing trend in B cell proportions, with statistically significant differences observed within each group (all P < 0.05). Moreover, the decline in the BLM group was more pronounced compared to the conventional group at corresponding time points (all P < 0.05). Belimumab may exert immunomodulatory effects in childhood systemic lupus erythematosus by influencing peripheral Breg cell subsets and cytokine profiles. Compared with conventional therapy, it appears to provide more sustained regulation of certain immune parameters over time. These findings suggest its potential as a complementary therapeutic option targeting B cell dysregulation in cSLE, although further studies are needed to confirm these observations and clarify the underlying mechanisms.