Hyper IgM syndrome
|Hyper IgM syndrome|
|Classification and external resources|
|NCI||Hyper IgM syndrome|
|Patient UK||Hyper IgM syndrome|
Hyper IgM syndrome is a family of genetic disorders in which the level of Immunoglobulin M (IgM) antibodies is relatively high. The most common type is a result of a defect in a Th2 cell protein (CD40 ligand). The disorder causes immunodeficiencies, including a higher than normal susceptibility to various types of infections. Individuals with hyper-IgM syndrome typically also have a low number of neutrophils and platelets.
IgM is the form of antibody that all B cells produce initially, before they undergo class switching due to exposure to a recognized antigen. Healthy B cells efficiently switch to other types of antibodies as needed to attack invading bacteria, viruses, and other pathogens. Generally, in people with hyper IgM syndromes, the B cells keep making IgM antibodies because they can't switch to a different kind of antibody. This results in an overproduction of IgM antibodies and an underproduction of all other types, IgA, IgG, and IgE.
Five types have been characterized:
- Hyper-IgM syndrome type 1 (X-linked), characterized by mutations of the CD40LG gene. In this type, T cells cannot tell B cells to switch classes.
- Hyper-IgM syndrome type 2 (autosomal recessive), characterized by mutations of the AICDA gene. In this type, B cells cannot recombine genetic material to change heavy chain production, which is a required step in switching classes.
- Hyper-IgM syndrome type 3, characterized by mutations of the CD40 gene. In this type, B cells cannot receive the signal from T cells to switch classes.
- Hyper-IgM syndrome type 4, which is a defect in class switch recombination downstream of the AICDA gene that does not impair Somatic Hyper Mutation.
Infections with Pneumocystis pneumonia are common in infants with Hyper IgM syndrome.
- GeneReviews/NCBI/NIH/UW entry on X-Linked Hyper IgM Syndrome or Immunodeficiency with Hyper-IgM, Type 1
- Lougaris V, Badolato R, Ferrari S, Plebani A (2005). "Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features". Immunol. Rev. 203: 48–66. PMID 15661021. doi:10.1111/j.0105-2896.2005.00229.x.