Hyper IgM syndrome

Hyper IgM syndrome describes a group of primary immune deficiency disorders characterized by defective CD40 signaling; via B cells affecting class switch recombination (CSR) and somatic hypermutation. Immunoglobulin (Ig) class switch recombination deficiencies are characterized by elevated serum Immunoglobulin M (IgM) levels and a considerable deficiency in Immunoglobulins G (IgG), A (IgA) and E (IgE). As a consequence, people with HIGM have decreased concentrations of serum IgG and IgA and normal or elevated IgM, leading to increased susceptibility to infections.[8][7][9]

Hyper IgM syndrome
Immunoglobulin M
SpecialtyImmunology 
SymptomsChronic diarrhea[1]
TypesHyper-IgM syndrome type 1,2,3,4 and 5[2][3][4][5][6]
Diagnostic methodMRI, Chest radiography[1]
TreatmentAllogeneic hematopoietic cell transplantation[7]

Signs and symptoms

Among the presentation consistent with hyper IgM syndrome are the following:[1][10]

Pneumocystis pneumonia
  • Infection/Pneumocystis pneumonia (PCP), which is common in infants with hyper IgM syndrome, is a serious illness.[8] PCP 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 PCP 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)
  • Hepatitis (Hepatitis C)
  • Chronic diarrhea
  • Hypothyroidism
  • Neutropenia
  • Arthritis
  • Encephalopathy (degenerative)

Cause
Class switch recombination

Different genetic defects cause HIgM syndrome, the vast majority are inherited as an X-linked recessive genetic trait and most sufferers are male.[7]

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. In people with hyper IgM syndromes, the B cells keep making IgM antibodies because they can't switch to a different antibody. This results in an overproduction of IgM antibodies and an underproduction of IgA, IgG, and IgE.[11][7]

Pathophysiology

CD40 is a co-stimulatory receptor on B cells that, when bound to CD40 ligand (CD40L), sends a signal to the B-cell receptor.[12] When there is a defect in CD40, this leads to defective T-cell interaction with B cells. Consequently, humoral immune response is affected. Certain insults, usually from encapsulated bacteria and toxin, then have a greater opportunity to damage the body.[1]

Diagnosis

The diagnosis of hyper IgM syndrome can be done via the following methods and tests:[1]

Types

Five types of hyper IgM syndrome have been characterized:

Treatment

In terms of treatment for hyper IgM syndrome, there is the use of allogeneic hematopoietic cell transplantation. Additionally, anti-microbial therapy, use of granulocyte colony-stimulating factor, immunosuppressants, as well as other treatments, may be needed.[7]

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See also

References
  1. "X-linked Immunodeficiency With Hyper IgM Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 27 November 2016.
  2. "OMIM Entry - # 308230 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1". www.omim.org. Retrieved 16 November 2016.
  3. "OMIM Entry - # 605258 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 2; HIGM2". omim.org. Retrieved 16 November 2016.
  4. "OMIM Entry - # 606843 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 3; HIGM3". www.omim.org. Retrieved 16 November 2016.
  5. "OMIM Entry - # 608106 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 5; HIGM5". omim.org. Retrieved 16 November 2016.
  6. "OMIM Entry - 608184 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 4; HIGM4". www.omim.org. Retrieved 2 January 2018.
  7. Johnson, Judith; Filipovich, Alexandra H.; Zhang, Kejian (1 January 1993). "X-Linked Hyper IgM Syndrome". GeneReviews. Retrieved 12 November 2016.update 2013
  8. Etzioni, Amos; Ochs, Hans D. (1 October 2004). "The Hyper IgM Syndrome—An Evolving Story". Pediatric Research. 56 (4): 519–525. doi:10.1203/01.PDR.0000139318.65842.4A. ISSN 0031-3998. PMID 15319456.
  9. "Hyper-Immunoglobulin M (Hyper-IgM) Syndromes | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 27 November 2016.
  10. Davies, E Graham; Thrasher, Adrian J (27 November 2016). "Update on the hyper immunoglobulin M syndromes". British Journal of Haematology. 149 (2): 167–180. doi:10.1111/j.1365-2141.2010.08077.x. ISSN 0007-1048. PMC 2855828. PMID 20180797.
  11. Reference, Genetics Home. "X-linked hyper IgM syndrome". Genetics Home Reference. Retrieved 27 November 2016.
  12. Reference, Genetics Home. "CD40 gene". Genetics Home Reference. Retrieved 27 November 2016.
  13. 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.subscription needed

Further reading
Classification
External resources
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