Management of hypogammaglobulinemia in pediatric patients with refractory lupus nephritis: a focus on belimumab.

Background: Although the use of belimumab in children with lupus nephritis (LN) has increased over the past few years, there are limited data on the safety of belimumab in such patients with hypogammaglobulinemia. There are scarce reports of an association between hypogammaglobulinemia and infection in patients with LN who are receiving belimumab treatment. Methods: We reviewed the cases of 27 patients with lupus nephritis and nephrotic-range proteinuria admitted to Hebei Children's Hospital from January 2019 to October 2022. Among the 27 patients, 12 received intravenous (IV) belimumab (at a dose of 10 mg per kilogram of body weight) plus the standard systemic lupus erythematosus therapy (SoC) (belimumab group) and the other 15 received the SoC (glucocorticoids plus cyclophosphamide or mycophenolate mofetil) (control group). Estimated Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score; total amount of protein in urine in 24 h; the serum levels of IgG, IgM, IgA, and C3; total B lymphocyte count (BLC); total white lymphocyte count (WBC); erythrocyte sedimentation rate (ESR); and C-reactive protein level were measured five times (at weeks 0, 4, 12, 24, and 52, respectively) in the two groups. Results: Hypogammaglobulinemia was observed in 22/27 (81.5%) participants with LN prior to initiating treatment. Participants developed hypogammaglobulinemia by week 4. There were no significant differences between the two groups in the total amount of protein in urine in 24 h, serum IgG level, and total B cell count at 0 weeks. Furthermore, no IgG replacement therapy was used in either group until week 15 of observation. However, five patients in the belimumab group and one patient in the control group, whose serum IgG level was below 4 g/L, received 1-2 intravenous immunoglobulin (IVIG) treatments in weeks 16-26 due to severe or recurrent infections. The incidence of infection in the belimumab group was significantly higher than that in the control group, and the IgG serum level in the belimumab group was significantly lower than that in the control group. We also found that the ESR in the belimumab group was significantly lower than that in the control group at weeks 12 and 24 ( Conclusions: Hypogammaglobulinemia is common in refractory LN. Belimumab treatment may increase the possibility of IgG reduction and the risk of infection. Pediatric patients with LN whose serum IgG levels are below 4 g/L always receive IVIG replacement therapy because of infection. In patients treated with belimumab, monitoring IgG levels is necessary, and IgG replacement therapy should be more aggressive.