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 Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the ''AICDA'' gene. It creates mutations in DNA by deamination of cytosine base, which t ...

gene is intact. 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 Hyper IgM syndrome describes 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 rec ...

, patients are deficient in the immunoglobulins,

IgG Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...

, IgE and

IgA Iga may refer to: Arts and entertainment * Ambush at Iga Pass, a 1958 Japanese film * Iga no Kagemaru, Japanese manga series * Iga, a set of characters from the Japanese novel '' The Kouga Ninja Scrolls'' Biology * ''Iga'' (beetle), a gen ...

types since the antibody producing

B cell B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

s can not carry out the gene recombination steps necessary to

class switch Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the ...

from

immunoglobulin M Immunoglobulin M (IgM) is one of several isotypes of antibody (also known as immunoglobulin) that are produced by vertebrates. IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antig ...

(IgM) to the other three immunoglobulins types.

Hyper IgM syndromes

Hyper IgM syndromes is a group of primary immune deficiency disorders characterized by defective CD40 signaling; ''via''

s affecting class switch recombination (CSR) and

somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM dive ...

Immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

(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.update 2013

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 Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...

Neutropenia Neutropenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria ...

Arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

* Encephalopathy (degenerative)

Cause

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. 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

, 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 Humoral immunity is the aspect of immunity that is mediated by macromolecules - including secreted antibodies, complement proteins, and certain antimicrobial peptides - located in extracellular fluids. Humoral immunity is named so because it in ...

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 A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

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 Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into ...

, as well as other treatments, may be needed.

References

{{DEFAULTSORT:Hyper Igm Syndrome Immune system disorders Rare syndromes