Hyper-IgM syndrome type 4

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.

Signs and symptoms

Hyper IgM syndrome can have the following syndromes:

• Infection/Pneumocystis pneumonia (PCP), which is common in infants with hyper IgM syndrome, is a serious illness. PCP is one of the most frequent and severe opportunistic infections in people with weakened immune systems.
• Hepatitis (Hepatitis C)
• Chronic diarrhea
• Hypothyroidism
• Neutropenia
• Arthritis
• Encephalopathy (degenerative)

Cause

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

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.

Pathophysiology

CD40 is a costimulatory receptor on B cells that, when bound to CD40 ligand (CD40L), sends a signal to the B-cell receptor. 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.

Diagnosis

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

• MRI
• Chest radiography
• Pulmonary function test
• Lymph node test
• Laboratory test (to measure CD40)

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.

References

References

1. "OMIM Entry – 608184 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 4; HIGM4".
2. (2005). "Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features". Immunol. Rev..
3. (1 January 1993). "X-Linked Hyper IgM Syndrome". GeneReviews.
4. "Hyper-Immunoglobulin M (Hyper-IgM) Syndromes {{!}} NIH: National Institute of Allergy and Infectious Diseases".
5. "X-linked Immunodeficiency With Hyper IgM Clinical Presentation: History, Physical, Causes".
6. (27 November 2016). "Update on the hyper immunoglobulin M syndromes". British Journal of Haematology.
7. (1 October 2004). "The Hyper IgM Syndrome—An Evolving Story". Pediatric Research.
8. "OMIM Entry – # 308230 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 1; HIGM1".
9. "OMIM Entry – # 605258 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 2; HIGM2".
10. "OMIM Entry – # 606843 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 3; HIGM3".
11. (2005). "Hyper immunoglobulin M syndrome due to CD40 deficiency: clinical, molecular, and immunological features". Immunol. Rev..
12. "OMIM Entry – # 608106 – IMMUNODEFICIENCY WITH HYPER-IgM, TYPE 5; HIGM5".
13. "X-linked hyper IgM syndrome".
14. "CD40 gene".