Hyper IgM syndrome

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Hyper IgM syndrome
IgM scheme.svg
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; 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.[1][2][3]


Five types of hyper IgM syndrome have been characterized:


Among the presentation consistent with hyper IgM syndrome are the following:[9][10]

Pneumocystis pneumonia
  • Infection/Pneumocystis pneumonia (common in infants with hyper IgM syndrome, Pneumocystis carinii pneumonia (PJP or PCP) is a serious illness.[1] 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[medical citation needed])
  • Hepatitis (Hepatitis C)
  • Chronic diarrhea
  • Hypothyroidism
  • Neutropenia
  • Arthritis
  • Encephalopathy (degenerative)


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.[2]

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][2]


In the mechanism one sees that CD40, protein is a receptor for cells of the human immune system, furthermore, is important in immune and inflammatory response.[12] When CD40L is not working properly, this then leads to defective T-cell interaction with monocytes. Consequently, resulting cell-mediated immune response is affected, therefore certain infections have a greater opportunity to invade the human body.[9]


The diagnosis of hyper IgM syndrome can be done via the following methods and tests:[9]


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.[2]

See also[edit]


  1. ^ a b 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. 
  2. ^ a b c d Johnson, Judith; Filipovich, Alexandra H.; Zhang, Kejian (1 January 1993). "X-Linked Hyper IgM Syndrome". GeneReviews(®). University of Washington, Seattle. Retrieved 12 November 2016. update 2013
  3. ^ "Hyper-Immunoglobulin M (Hyper-IgM) Syndromes | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 27 November 2016. 
  4. ^ "OMIM Entry - # 308230 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1". www.omim.org. Retrieved 16 November 2016. 
  5. ^ "OMIM Entry - # 605258 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 2; HIGM2". omim.org. Retrieved 16 November 2016. 
  6. ^ "OMIM Entry - # 606843 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 3; HIGM3". www.omim.org. Retrieved 16 November 2016. 
  7. ^ 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
  8. ^ "OMIM Entry - # 608106 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 5; HIGM5". omim.org. Retrieved 16 November 2016. 
  9. ^ a b c "X-linked Immunodeficiency With Hyper IgM Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. 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 2855828Freely accessible. 
  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. 

Further reading[edit]