Rituximab-induced hypogammaglobulinemia associated with increased risk of infections in children

Published: April 13, 2021

Rituximab is a monoclonal antibody that targets B-cells and can therefore potentially affect the humoral immune system and immunoglobulin levels. There have not been large studies of the impact of rituximab use on the immune system in pediatric patients to date.

In a recent article in The Journal of Allergy and Clinical Immunology (JACI), Labrosse et al. examined the prevalence, risk factors, and clinical significance of hypogammaglobulinemia following rituximab therapy in children less than 18 years old in a multi-center, international, retrospective cohort study. Clinical and immunological data were extracted from the medical record at each of four tertiary care hospitals including immunoglobulin levels pre- and post-rituximab, occurrence of severe infections, use of immunosuppressive medications, and immune cell counts.

In this study of 207 patients, the authors reported an increase in the prevalence of hypogammaglobulinemia following rituximab. In these patients, rituximab was used mainly for malignancy and rheumatologic, autoimmune neurologic, immune mediated renal and autoimmune hematologic diseases. In those patients with both pre- and post-rituximab immunoglobulin levels measured, the prevalence of hypogammaglobulinemia increased significantly post-rituximab. Low IgG levels post-rituximab were associated with a high risk of serious infections defined as requiring either an emergency room visit or hospitalization, in the year following treatment. Persistent hypogammaglobulinemia, lasting more than 1 year, was observed in 27 percent of patients. Risk factors for long-lasting IgG hypogammaglobulinemia included low IgG and IgA levels before rituximab. Nine patients were subsequently diagnosed with an inborn error of immunity. In comparison to the rest of the cohort, many of those patients who were later diagnosed with an inborn error of immunity were younger at the time of rituximab initiation and had one or more autoimmune cytopenias.

Immunoglobulin levels should be assessed before and after rituximab initiation in pediatric patients in order to identify patients at higher risk for hypogammaglobulinemia and infections. These patients may benefit from close monitoring, immunoglobulin replacement, and/or antibiotic prophylaxis. Vigilance for immune deficiency in those patients with hypogammaglobulinemia may be warranted, particularly in those with multi-lineage autoimmune cytopenias.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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