Clinical Reviews in Allergy & Immunology

, Volume 46, Issue 2, pp 120–130

The Hyper IgM Syndromes


DOI: 10.1007/s12016-013-8378-7

Cite this article as:
Qamar, N. & Fuleihan, R.L. Clinic Rev Allerg Immunol (2014) 46: 120. doi:10.1007/s12016-013-8378-7


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.


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

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Allergy and Immunology, Ann & Robert H. Lurie Children’s Hospital of ChicagoNorthwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Division of Allergy and ImmunologyAnn & Robert H. Lurie Children’s Hospital of ChicagoChicagoUSA

Personalised recommendations