Hyper-IgM syndrome type 3 is a form of

hyper IgM syndrome 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 reco ...

characterized by mutations of the ''

CD40 Cluster of differentiation 40, CD40 is a costimulatory protein found on antigen-presenting cells and is required for their activation. The binding of CD154 ( CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of d ...

'' 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

signaling; ''via''

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 o ...

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 ...

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 th ...

(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 An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...

/ ''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 is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...

(Hepatitis C) * Chronic

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

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 ...

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 bacteri ...

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 Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...

(degenerative)

Cause

Different genetic defects cause HIgM syndrome, the vast majority are inherited as an

X-linked Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...

recessive genetic trait and most sufferers are male. IgM is the form of

antibody 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 t ...

that all B cells produce initially before they undergo

class switching 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 ...

. Healthy

B cells 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 o ...

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 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 g ...

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 an ...

, and IgE.

Pathophysiology

CD40 is a costimulatory receptor on B cells that, when bound to CD40 ligand (

CD40L CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells (APC), which leads to many effects dependin ...

), sends a signal to the

B-cell receptor The B cell receptor (BCR) is a transmembrane protein on the surface of a B cell. A B cell receptor is composed of a membrane-bound immunoglobulin molecule and a signal transduction moiety. The former forms a type 1 transmembrane receptor protein, ...

. 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 Radiography is an imaging technique using X-rays, gamma rays, or similar ionizing radiation and non-ionizing radiation to view the internal form of an object. Applications of radiography include medical radiography ("diagnostic" and "therapeu ...

Pulmonary function test Pulmonary function testing (PFT) is a complete evaluation of the respiratory system including patient history, physical examinations, and tests of pulmonary function. The primary purpose of pulmonary function testing is to identify the severity ...

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 includ ...

test * Laboratory test (to measure CD40)

Treatment

In terms of treatment for hyper IgM syndrome, there is the use of allogeneic

hematopoietic cell A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), ...

transplantation. Additionally, anti-microbial therapy, use of

granulocyte colony-stimulating factor Granulocyte colony-stimulating factor (G-CSF or GCSF), also known as colony-stimulating factor 3 (CSF 3), is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. Functiona ...

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 in ...

, as well as other treatments, may be needed.

References

{{Immune disorders Immune system disorders Rare syndromes