Hyper IgM syndrome

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

Hyper IgM Syndromes is a group of primary immune deficiency disorders characterized by defective CD40 signaling by B cells affecting class switch recombination and somatic hypermutation. Immunoglobulin (Ig) class switch recombination deficiencies (CSR-Ds, which were previously named "dysgammaglobulinemia" and then "hyper-IgM syndromes") are characterized by elevated (or sometimes normal) serum Immunoglobulin M (IgM) levels and a considerable decrease in (or the absence of) Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin E (IgE) – suggesting defective CSR. As a consequence, patients with HIGM have decreased concentrations of serum IgG and IgA and normal or elevated IgM, leading to increased susceptibility to infections. The most common HIGM syndrome is X-linked and due to mutations of CD40 ligand (CD40L) expressed by activated CD4+ T lymphocytes.^[1]

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 Hypermutation.^[2]
• 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. Pneumocystis carinii Pneumonia (PJP or PCP) is a serious illness caused by the fungus Pneumocystis jirovecii. PJP is one of the most frequent and severe opportunistic infections in people with weakened immune systems. Many CD40 Ligand Deficiency are first diagnosed after having PJP in their first year of life. The fungus is common and is present in over 70% of healthy people’s lungs, however, Hyper IgM patients are not able to fight it off without the administration of Bactrim (Trimethoprim and Sulfamethoxazole).

External links

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

• About Hyper IgM Syndrome - The Hyper IgM Foundation

References

1. Ochs, Hans (4 February 2004). "Dr.". Pediatric Research (56). Retrieved 31 March 2016.
2. 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. doi:10.1111/j.0105-2896.2005.00229.x. PMID 15661021.