Hyper IgM syndrome

Hyper IgM syndrome
Immunoglobulin M
Classification and external resources
Specialty
ICD-10	D80.5
ICD-9-CM	279.05
eMedicine	ped/2457
Patient UK	Hyper IgM syndrome
MeSH	D053306

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.

Pathophysiology

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.

Types

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.

• Hyper-IgM syndrome type 5, characterized by mutations of the UNG gene.

Pneumocystis pneumonia

Infections with Pneumocystis pneumonia are common in infants with Hyper IgM syndrome.

External links

• GeneReviews/NCBI/NIH/UW entry on X-Linked Hyper IgM Syndrome or Immunodeficiency with Hyper-IgM, Type 1