Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients

J Allergy Clin Immunol. 2021 Aug;148(2):523-532.e8. doi: 10.1016/j.jaci.2021.03.041. Epub 2021 Apr 20.


Background: Rituximab is a B-cell depleting agent used in B-cell malignancies and autoimmune diseases. A subset of adult patients may develop prolonged and symptomatic hypogammaglobulinemia following rituximab treatment. However, this phenomenon has not been well delineated in the pediatric population.

Objectives: This study sought to determine the prevalence, risk factors, and clinical significance of hypogammaglobulinemia following rituximab therapy in children.

Methods: This was a multicenter, retrospective cohort study that extracted clinical and immunological data from pediatric patients who received rituximab.

Results: The cohort comprised 207 patients (median age, 12.0 years). Compared to baseline values, there was a significant increase in hypogammaglobulinemia post-rituximab therapy, with an increase in prevalence of hypo-IgG (28.7%-42.6%; P = .009), hypo-IgA (11.1%-20.4%; P = .02), and hypo-IgM (20.0%-62.0%; P < .0001). Additionally, low IgG levels at any time post-rituximab therapy were associated with a higher risk of serious infections (34.4% vs 18.9%; odds ratio, 2.3; 95% CI, 1.1-4.8; P = .03). Persistent IgG hypogammaglobulinemia was observed in 27 of 101 evaluable patients (26.7%). Significant risk factors for persistent IgG hypogammaglobulinemia included low IgG and IgA levels pre-rituximab therapy. Nine patients (4.3%) within the study were subsequently diagnosed with a primary immunodeficiency, 7 of which received rituximab for autoimmune cytopenias.

Conclusions: Hypogammaglobulinemia post-rituximab treatment is frequently diagnosed within the pediatric population. Low IgG levels are associated with a significant increase in serious infections, and underlying primary immunodeficiencies are relatively common in children receiving rituximab, thus highlighting the importance of immunologic monitoring both before and after rituximab therapy.

Keywords: B-cell depleting therapy; IgG; children; hypogammaglobulinemia; immunoglobulin; infection; pediatrics; primary immunodeficiency; rituximab; secondary immunodeficiency.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Agammaglobulinemia* / blood
  • Agammaglobulinemia* / chemically induced
  • Agammaglobulinemia* / epidemiology
  • Child
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Infections* / blood
  • Infections* / chemically induced
  • Infections* / epidemiology
  • Male
  • Prevalence
  • Retrospective Studies
  • Risk Factors
  • Rituximab / administration & dosage
  • Rituximab / adverse effects*


  • Immunoglobulin A
  • Immunoglobulin G
  • Rituximab