Hyper-IgM syndrome type 3


Hyper-IgM syndrome type 3 is a form of hyper IgM syndrome characterized by mutations of the CD40 gene. 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 and somatic hypermutation. Immunoglobulin class switch recombination deficiencies are characterized by elevated serum IgM levels and a considerable deficiency in Immunoglobulins G, A and E. As a consequence, people with HIGM have an increased susceptibility to infections.

Signs and symptoms

Hyper IgM syndrome can have the following syndromes:
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, 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:
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.