Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab

Int Rev Immunol. 2017 Nov 2;36(6):352-359. doi: 10.1080/08830185.2017.1346092. Epub 2017 Aug 11.


Rituximab (RTX) is a monoclonal antibody against CD20, commonly used in the treatment of hematological malignancies and autoimmune diseases. The use of RTX is related to the development of hypogammaglobulinemia and infections. Aim of this review is to summarize the evidence supporting the association of specific risk factors with the development of hypogammaglobulinemia and infections post-RTX. Immunological complications are more common in patients with malignant diseases as compared to non-malignant diseases. Moreover, the use of more than one dose of RTX, maintenance regimens, low pre-treatment basal immunoglobulin levels and the association with Mycophenolate and purine analogues represent risk factors for the development of hypogammaglobulinemia. The number of RTX courses, the evidence of low IgG levels for more than 6 months, the use of G-CSF, the occurrence of chronic lung disease, cardiac insufficiency, extra-articular involvement in patients with rheumatoid arthritis, low levels of IgG and older age have been correlated with a higher risk of infections. Even though the heterogeneity of the studies in terms of study population age and underlying disease, RTX schedules as well as differences in pre-treatment or concomitant therapy doesn't allow drawing definitive conclusions, the study of the literature highlight the association of specific risk factors with the occurrence of hypogammaglobulinemia and/or infections. A long term randomized controlled clinical trial could be useful to define a personalized evidence-based risk management plan for patients treated with RTX.

Keywords: Rituximab; hypogammaglobulinemia; infections; risk factor.

Publication types

  • Review

MeSH terms

  • Agammaglobulinemia / epidemiology*
  • Agammaglobulinemia / etiology
  • Age Factors*
  • Animals
  • Antigens, CD20 / immunology
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Humans
  • Infections / epidemiology*
  • Infections / etiology
  • Lung Diseases / epidemiology*
  • Risk Factors
  • Rituximab / adverse effects*
  • Rituximab / therapeutic use


  • Antigens, CD20
  • Rituximab