Hyper-IgM syndrome type 4 explained

Hyper IgM syndrome type 4
Types:Hyper-IgM syndrome type 1,2,3,4 and 5[1]
Diagnosis:MRI, Chest radiography and genetic testing
Treatment:Allogeneic hematopoietic cell transplantation

Hyper-IgM syndrome type 4 is a form of Hyper IgM syndrome which is a defect in class switch recombination downstream of the AICDA gene that does not impair somatic hypermutation.[2]

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.[3] [4]

Signs and symptoms

Hyper IgM syndrome can have the following syndromes:[5] [6]

Cause

Different genetic defects cause HIgM syndrome, the vast majority are inherited as an X-linked recessive genetic trait and most sufferers are male.[3] [8] [9] [10] [11] [12]

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] [3]

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.[5]

Diagnosis

The diagnosis of hyper IgM syndrome can be done via the following methods and tests:[5]

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.[3]

Notes and References

  1. Web site: OMIM Entry – 608184 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 4; HIGM4. omim.org. 2 January 2018. en-us.
  2. Lougaris V, Badolato R, Ferrari S, Plebani A . Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features . Immunol. Rev. . 203 . 48–66 . 2005 . 15661021 . 10.1111/j.0105-2896.2005.00229.x . 6678540 . free .
  3. Johnson. Judith. Filipovich. Alexandra H.. Zhang. Kejian. X-Linked Hyper IgM Syndrome. GeneReviews. 1 January 1993. 20301576 . 12 November 2016. update 2013
  4. Web site: Hyper-Immunoglobulin M (Hyper-IgM) Syndromes NIH: National Institute of Allergy and Infectious Diseases. niaid.nih.gov. 27 November 2016.
  5. Web site: X-linked Immunodeficiency With Hyper IgM Clinical Presentation: History, Physical, Causes. emedicine.medscape.com. 27 November 2016.
  6. Davies. E Graham. Thrasher. Adrian J. Update on the hyper immunoglobulin M syndromes. British Journal of Haematology. 27 November 2016. 149. 2. 167–180. 10.1111/j.1365-2141.2010.08077.x. 2855828. 0007-1048. 20180797.
  7. Etzioni. Amos. Ochs. Hans D.. The Hyper IgM Syndrome—An Evolving Story. Pediatric Research. 1 October 2004. 56. 4. 519–525. 10.1203/01.PDR.0000139318.65842.4A. 15319456. en. 0031-3998. free.
  8. Web site: OMIM Entry – # 308230 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1. omim.org. 16 November 2016.
  9. Web site: OMIM Entry – # 605258 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 2; HIGM2. omim.org. 16 November 2016.
  10. Web site: OMIM Entry – # 606843 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 3; HIGM3. omim.org. 16 November 2016.
  11. Lougaris V, Badolato R, Ferrari S, Plebani A . Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features . Immunol. Rev. . 203 . 48–66 . 2005 . 15661021 . 10.1111/j.0105-2896.2005.00229.x . 6678540 . free . subscription needed
  12. Web site: OMIM Entry – # 608106 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 5; HIGM5. omim.org. 16 November 2016.
  13. Web site: Reference. Genetics Home. X-linked hyper IgM syndrome. Genetics Home Reference. 27 November 2016.
  14. Web site: Reference. Genetics Home. CD40 gene. Genetics Home Reference. 27 November 2016.

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