Hyper-Immunoglobulin M (Hyper-IgM) Syndromes
Section of lung tissue (green) with Pneumocystis jirovecicysts (dark spheres) stained with methenamine silver stain.
Hyper-IgM syndromes are conditions in which the immune system fails to produce normal immunoglobulin A (IgA), IgG, and IgE antibodies but can produce normal or elevated IgM. Various gene defects can cause hyper-IgM syndromes. Researchers at the National Institutes of Health are studying the genes involved in hyper-IgM syndromes to understand how different patients are affected by the disease.
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. 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 result in hyper-IgM syndromes. Four forms of hyper-IgM syndrome are autosomal recessive, and two are X-linked.
Signs and Symptoms
Infants with a hyper-IgM syndrome usually develop severe respiratory infections within the first year of life. Some people may have low levels of white blood cells called neutrophils (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 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.
People with a hyper-IgM syndrome receive regular treatments of intravenous (through the vein) immunoglobulin or subcutaneous (under the skin) immunoglobulin. Those with neutropenia may take a drug called granulocyte-colony stimulating factor (G-CSF) to stimulate the body to produce more white blood cells. Some also may take medications to prevent pneumonia caused by the fungusPneumocystis jiroveci.
Depending on the genetic defect that causes their disease, some people with hyper-IgM syndrome can be treated with a bone marrow transplant, which re-sets and replenishes the immune system.