Post-rituximab immunoglobulin M (IgM) hypogammaglobulinemia

Autoimmun Rev. 2020 Mar;19(3):102466. doi: 10.1016/j.autrev.2020.102466. Epub 2020 Jan 7.


Rituximab is a B cell depleting monoclonal antibody that targets the B cell-specific cell surface antigen CD20 and is currently used to treat several autoimmune diseases. The elimination of mature CD20-positive B lymphocytes committed to differentiate into autoantibody-producing plasma cells is considered to be the major effect of rituximab, that makes it a beneficial biological agent in treating autoimmune diseases. Hypogammaglobulinemia has been reported after rituximab therapy in patients with lymphoma and rheumatoid arthritis. Similar data are scarce for other autoimmune diseases. Low immunoglobulin G (IgG) or hypogammaglobulinemia has attracted the most attention because of its significant role in protective immunity. However, the incidence and clinical implications of low immunoglobulin M (IgM) or hypogammaglobulinemia have not been studied in detail. This review will focus on the frequency and the clinical concerns of low IgM levels that result as a consequence of the administration of rituximab. The etiopathogenic mechanisms underlying post-rituximab IgM hypogammaglobulinemia and its implications are presented. The long-term consequences, if any, are not known or documented. Multiple factors may be involved in whether IgG or IgM decreases secondary to rituximab therapy. It is possible that the autoimmune disease itself may be one of the important factors. The dose, frequency and number of infusions appear to be important variables. Post-rituximab therapy immunoglobulin levels return to normal. During this process. IgM levels take a longer time to return to normal levels when compared to IgG or other immunoglobulins. IgM deficiency persists after B cell repopulation to normal levels has occurred. Laboratory animals and humans deficient in IgM can have multiple infections. Specific pharmacologic agents or biologic therapy that address and resolve IgM deficiency are currently unavailable. If the clinical situation so warrants, then prophylactic antibiotics may be indicated and perhaps helpful. Research in this iatrogenic phenomenon will provide a better understanding of not only the biology of IgM, but also the factor(s) that control its production and regulation, besides its influence if any, on rituximab therapy.

Keywords: Autoimmune diseases; Decreased IgG; Decreased IgM; Hypogammaglobulinemia; Post-rituximab; Rituximab.

Publication types

  • Review

MeSH terms

  • Agammaglobulinemia / chemically induced*
  • Animals
  • Humans
  • Immunoglobulin M / blood
  • Immunoglobulin M / deficiency*
  • Rituximab / adverse effects*


  • Immunoglobulin M
  • Rituximab