Hyper-IgM syndrome type 3

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 syndrome type 3
Immunoglobulin M
SpecialtyHematology 
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 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. "OMIM Entry - # 308230 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1". www.omim.org. Retrieved 16 November 2016.
  2. "OMIM Entry - # 605258 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 2; HIGM2". omim.org. Retrieved 16 November 2016.
  3. "OMIM Entry - # 606843 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 3; HIGM3". www.omim.org. Retrieved 16 November 2016.
  4. "OMIM Entry - # 608106 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 5; HIGM5". omim.org. Retrieved 16 November 2016.
  5. "OMIM Entry - 608184 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 4; HIGM4". www.omim.org. Retrieved 2 January 2018.
  6. "X-linked Immunodeficiency With Hyper IgM Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 27 November 2016.
  7. Johnson, Judith; Filipovich, Alexandra H.; Zhang, Kejian (1 January 1993). "X-Linked Hyper IgM Syndrome". GeneReviews. Retrieved 12 November 2016.update 2013
  8. "OMIM Entry- # 606843 - IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 3; HIGM3". omim.org. Retrieved 23 February 2018.
  9. 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.
  10. "Hyper-Immunoglobulin M (Hyper-IgM) Syndromes | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 27 November 2016.
  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. PMC 2855828. PMID 20180797.
  12. 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
  13. Reference, Genetics Home. "X-linked hyper IgM syndrome". Genetics Home Reference. Retrieved 27 November 2016.
  14. Reference, Genetics Home. "CD40 gene". Genetics Home Reference. Retrieved 27 November 2016.
Classification
External resources
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