The hyper IgM syndromes

Nashmia Qamar, Ramsay L Fuleihan*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

93 Scopus citations


The hyper IgM syndromes are a group of rare inherited immune deficiency disorders characterized by impairment of immunoglobulin isotype switching resulting from defects in the CD40 ligand/CD40 signaling pathway. X-linked forms of hyper IgM are caused by defects in the CD40 ligand gene or NF-κB essential modulator, while autosomal recessive forms of hyper IgM are caused by defects in CD40 or downstream signaling molecules including activation-induced cytidine deaminase, uracil N glycosylase or postmeiotic segregation increased 2. The loss of interaction between CD40 and its ligand results in an impairment of T cell function, of B cell differentiation and of monocyte function while only B cell differentiation appears to be affected in defects of sinaling molecules downstream of CD40 with the exception of defects of the NF-κB complex, which mediates signaling via multiple receptor pathways. With many genetic defects in the hyper IgM syndrome identified, it is possible to diagnose patients definitively, to perform genetic screening, and to delineate the clinical manifestations of the different diseases in this syndrome. Stem cell transplantation is an available therapeutic option for defects that result in a combined immunodeficiency while antibody replacement appears sufficient for the strictly humoral immunodeficiencies.

Original languageEnglish (US)
Pages (from-to)120-130
Number of pages11
JournalClinical Reviews in Allergy and Immunology
Issue number2
StatePublished - Jan 1 2014


  • CD40
  • CD40 ligand
  • Cryptosporidium
  • Ectodermal dysplasia with immunodeficiency
  • Gene therapy
  • Hyper IgM syndrome
  • Immunoglobulin isotype switching
  • Immunoglobulin replacement therapy
  • Opportunistic infection
  • Pneumocystis jiroveci
  • Registry
  • Stem cell transplantation
  • Switched memory B cells
  • sclerosing cholangitis

ASJC Scopus subject areas

  • Immunology and Allergy


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