Mangement of hypogammaglobulinemia in pediatric patients with refractory lupus nephritis: Focus on belimumab

Abstract

Background: Although the use of belimumab in children with lupus nephritis has increased over the past few years, there are limited data on the safety of belimumab in such patients with hypogammaglobulinemia. There are few reports of an association between hypogammaglobulinemia and infection in LN patients receiving belimumab treatment. Methods: We reviewed 27 patients with lupus nephritis and nephrotic-range proteinuria admitted to Hebei Children's Hospital from January 2019 to June 2022. In all 27 patients, 12 received intravenous (IV) belimumab (at a dose of 10 mg per kilogram of body weight) plus standard systemic lupus erythematosus (SLE) therapy (SoC) (belimumab group), and the other 15 received SoC (glucocorticoids plus cyclophosphamide or mycophenolate mofetil) (control group). Estimated SLEDAI-score, total amount of urine protein in 24 hours, the serum level of IgG, IgM, IgA and C3, total B lymphocyte count (BLC) , total white lymphocyte count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level were measured 5 times (at week 0, 4, 12, 24 and 52, respectively) in two groups. Results: Hypogammaglobulinemia was observed in 22/27 (81.5%) participants prior to initiatial treatment of LN patients with nephrotic range proteinuria. Participants developed hypogammaglobulinemia by week 4, 5 patients in the belimumab group and 1 patient in control group received 1-2 IVIG treatments at weeks 16-26 due to severe or recurrent infections. The incidence of infection was significantly higher in patients in the belimumab group than in the control group, and the IVIG serum level was significantly lower than the control group. However, infection rates and serum IgG levels were not significantly different between the two groups at weeks 24 and 52. We also found that CRP level of patients in the belimumab group was significantly lower than in the control group at week 4 and week 24 respectively (P<0.05), and ESR level of patients in the belimumab group was also significantly lower than in the control group at week 12 (P<0.05). At week 52, WBC of patients in the belimumab group was significantly higher than in the control group(P<0.05). Conclusions: Hypogammaglobulinemia is a complication of refractory LN，obtaining IgG level before initiating belimumab in pediatric patients with refractory lupus nephritis，and close monitoring of hypogammaglobulinemia after belimumab use in pediatric patients. Immunoglobulin replacement therapy should be initiated as soon as possible if patients develop recurrent infections.