Hyper IgM syndrome type 5 | |
---|---|
Immunoglobulin M | |
Symptoms | Chronic diarrhea [1] |
Types | Hyper-IgM syndrome type 1,2,3,4 and 5 [2] [3] [4] [5] [6] |
Diagnostic method | MRI, Chest radiography and genetic testing [1] |
Treatment | Allogeneic hematopoietic cell transplantation [7] |
The fifth type of hyper-IgM syndrome has been characterized in three patients from France and Japan. The symptoms are similar to hyper IgM syndrome type 2, but the AICDA gene is intact. [8]
These three patients instead had mutations in the catalytic domain of uracil-DNA glycosylase, an enzyme that removes uracil from DNA. In hyper-IgM syndromes, patients are deficient in the immunoglobulins, IgG, IgE and IgA types since the antibody producing B cells can not carry out the gene recombination steps necessary to class switch from immunoglobulin M (IgM) to the other three immunoglobulins types.
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]
Hyper IgM syndrome can have the following syndromes: [1] [11]
Different genetic defects cause HIgM syndrome, the vast majority are inherited as an X-linked recessive genetic trait and most with the condition are male. [7] [2] [3] [4] [12] [5]
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]
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. [1]
The diagnosis of hyper IgM syndrome can be done via the following methods and tests: [1]
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]