Correlation of hypogammaglobulinaemia with proteinuria, and the relationship between hypogammaglobulinaemia and infection in active lupus nephritis

Objective To evaluate hypogammaglobulinaemia and risk of serious infectious adverse events in active lupus nephritis. Methods The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS) compared abatacept with placebo in participants with lupus nephritis undergoing treatment with Euro-Lupus Nephritis low-dose cyclophosphamide. Serum IgG levels were assessed prior to initiation of treatment and throughout the trial. Hypogammaglobulinaemia was defined as IgG <450 mg/dL. Results Hypogammaglobulinaemia was observed in 16/102 (15.7%) participants prior to initiation of induction therapy for active lupus nephritis. Participants with nephrotic range proteinuria were more likely to have hypogammaglobulinaemia, and serum IgG levels were inversely correlated with urine protein to creatinine ratio (r=-0.42, p<0.0001). Following initiation of treatment for active lupus nephritis, additional participants developed hypogammaglobulinaemia by weeks 2-4. Serum IgG levels then increased, and all but one participant had serum IgG ≥450 mg/dL at 24 weeks. Hypogammaglobulinaemia was not associated with an increased risk of serious infectious adverse events. Conclusions In active lupus nephritis in ACCESS, hypogammaglobulinaemia was common and inversely correlated with proteinuria. Serum IgG levels were lowest in the weeks immediately following initiation of induction therapy, and subsequently improved by 24 weeks. Hypogammaglobulinaemia was not associated with serious infectious adverse events. Trial registration