Hyper-Immunoglobulin M (Hyper-IgM) Syndromes

Hyper-IgM syndromes are conditions in which the immune system fails to produce normal levels of immunoglobulin A (IgA), IgG, and IgE antibodies but can produce normal or elevated levels of IgM. Various gene defects can cause hyper-IgM syndromes.

Why Is the Study of Hyper-Immunoglobulin M (Hyper-IgM) Syndromes a Priority for NIAID?

Hyper-IgM syndromes are rare genetic diseases that may be chronic, debilitating, and costly. By learning more about these diseases and their effects on the body, scientists gain a greater understanding of immune function that can inform multiple areas of research.

How Is NIAID Addressing This Critical Topic?

Researchers at the NIH are studying the genes involved in hyper-IgM syndromes to understand how different patients are affected by these diseases.

Hyper-IgM syndromes are a primary immune deficiency diseases (PIDD). For more information on PIDD research and patient care at NIAID, visit the NIAID PIDD site

Photo of Section of lung tissue with Pneumocystis jiroveci cysts
Credit: CDC

Section of lung tissue with Pneumocystis jiroveci cysts.

Causes

Hyper-IgM syndromes are caused by problems in communication between T cells and antibody-producing B cells. This leads to B cells that do not mature properly and only produce IgM antibodies because  production of other antibody types, such as IgA, IgG, and IgE, requires normal T and B cell interaction. Scientists have identified mutations in six genes that can result in hyper-IgM syndromes. Four forms of hyper-IgM syndrome are autosomal recessive, and two are X-linked.

Symptoms & Diagnosis

Infants with a hyper-IgM syndrome usually develop severe respiratory infections within the first year of life. Some people with a hyper-IgM syndrome may have low levels of white blood cells called neutrophils (a condition called neutropenia) and an increased risk of unusual infections, such as Pneumocystis jiroveci pneumonia or chronic diarrhea caused by infection with the parasite Cryptosporidium. People with X-linked hyper-IgM syndrome also may experience bone loss. Unusual infections and low antibody levels may indicate hyper-IgM syndrome. Normal numbers of T and B cells but elevated levels of IgM are very suggestive of this condition.

Treatment

People with a hyper-IgM syndrome must receive regular intravenous or subcutaneous antibody replacement therapy. Hyper-IgM patients with neutropenia also may take a drug called granulocyte-colony stimulating factor (G-CSF) to stimulate the body to produce more white blood cells. Some patients also may take anti-fungal medications to prevent pneumonia caused by the fungus Pneumocystis jiroveci.

Depending on the genetic defect that causes their particular form of hyper-IgM syndrome, some people can be treated with a bone marrow transplant from a healthy donor, which can reset and replenish the immune system

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Content last reviewed on June 24, 2016