Medicine:Hyper-IgM syndrome type 3

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Short description: Primary immune deficiency disorder


Hyper IgM syndrome type 3
IgM scheme.svg
Immunoglobulin M
TypesHyper-IgM syndrome type 1,2,3,4 and 5[1][2][3][4][5]
Diagnostic methodMRI, Chest radiography and genetic testing[6]
TreatmentAllogeneic hematopoietic cell transplantation[7]

Hyper-IgM syndrome type 3 is a form of hyper IgM syndrome characterized by mutations of the CD40 gene.[8] In this type, Immature B cells cannot receive signal 2 from helper T cells which is necessary to mature into mature B cells.

Hyper IgM syndromes

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 IgM levels and a considerable deficiency in Immunoglobulins G (IgG), A (IgA) and E (IgE). As a consequence, people with HIGM have an increased susceptibility to infections.[9][7][10]

Signs and symptoms

Hyper IgM syndrome can have the following syndromes:[6][11]

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][1][2][3][12][4]

IgM is the form of antibody that all B cells produce initially before they undergo class switching. 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 can not switch to a different antibody. This results in an overproduction of IgM antibodies and an underproduction of IgA, IgG, and IgE.[13][7]

Pathophysiology

CD40 is a costimulatory receptor on B cells that, when bound to CD40 ligand (CD40L), sends a signal to the B-cell receptor.[14] When there is a defect in CD40, this leads to defective T-cell interaction with B cells. Consequently, humoral immune response is affected. Patients are more susceptible to infection.[6]

Diagnosis

The diagnosis of hyper IgM syndrome can be done via the following methods and tests:[6]

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]

References

  1. 1.0 1.1 "OMIM Entry – # 308230 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1". http://www.omim.org/entry/308230. 
  2. 2.0 2.1 "OMIM Entry – # 605258 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 2; HIGM2". http://omim.org/entry/605258. 
  3. 3.0 3.1 "OMIM Entry – # 606843 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 3; HIGM3". http://www.omim.org/entry/606843. 
  4. 4.0 4.1 "OMIM Entry – # 608106 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 5; HIGM5". http://omim.org/entry/608106. 
  5. "OMIM Entry – 608184 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 4; HIGM4" (in en-us). https://www.omim.org/entry/608184. 
  6. 6.0 6.1 6.2 6.3 "X-linked Immunodeficiency With Hyper IgM Clinical Presentation: History, Physical, Causes". http://emedicine.medscape.com/article/889104-clinical. 
  7. 7.0 7.1 7.2 7.3 7.4 Johnson, Judith; Filipovich, Alexandra H.; Zhang, Kejian (1 January 1993). "X-Linked Hyper IgM Syndrome". GeneReviews. PMID 20301576. https://www.ncbi.nlm.nih.gov/books/NBK1402/. Retrieved 12 November 2016. update 2013
  8. "OMIM Entry- # 606843 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 3; HIGM3" (in en-us). https://omim.org/entry/606843. 
  9. 9.0 9.1 Etzioni, Amos; Ochs, Hans D. (1 October 2004). "The Hyper IgM Syndrome—An Evolving Story" (in en). Pediatric Research 56 (4): 519–525. doi:10.1203/01.PDR.0000139318.65842.4A. ISSN 0031-3998. PMID 15319456. 
  10. "Hyper-Immunoglobulin M (Hyper-IgM) Syndromes | NIH: National Institute of Allergy and Infectious Diseases". https://www.niaid.nih.gov/diseases-conditions/hyper-immunoglobulin-m-hyper-igm-syndromes. 
  11. 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. PMID 20180797. 
  12. "Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features". Immunol. Rev. 203: 48–66. 2005. doi:10.1111/j.0105-2896.2005.00229.x. PMID 15661021. subscription needed
  13. Reference, Genetics Home. "X-linked hyper IgM syndrome". https://ghr.nlm.nih.gov/condition/x-linked-hyper-igm-syndrome#. 
  14. Reference, Genetics Home. "CD40 gene". https://ghr.nlm.nih.gov/gene/CD40. 
Classification
External resources