Hyper-Immunoglobulin M Syndromes are antibody disorders inhibiting the sufferer’s ability to fight infections. Immunoglobulins, as the name suggests, are antibodies involved in the immune response. These cells help to recognise invading viruses and bacteria. Once they have done so, they bind to them and destroy them, preventing them from causing sickness and disease.
However, if anything goes wrong, such as in those individuals with Hyper-Immunoglobulin M Syndromes, then viruses and bacteria are allowed to invade the body and multiply without being properly attacked by the body’s immune defence system.
A common feature of Hyper-Immunoglobulin M Syndromes is a deficiency in immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin E (IgE) antibodies. These deficiencies make it hard for the body to fight off invading pathogens and viruses, and this places sufferers at increased risk of serious illness from common infectious diseases.
Symptoms are highly dependent on what form of hyper IgM an individual goes on to develop. The severity of the syndrome differs as well, but infants with the most common form of the illness, which is known as X-Linked Hyper-Immunoglobulin M Syndrome, can fail to thrive, and frequent infections such as ear infections, sinus infections, and pneumonia can also be experienced.
Diarrhoea and weight loss may also exist along with an increased risk of developing lymphoma.
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Severe Combined Immunodeficiency (SCID)
STAT3 Dominant Negative Disease (STAT3DN)
STAT3 Gain-Of-Function Disease (STAT3 GOF)
Warts, Hypogammaglobulinemia, Infections, And Myelokathexis (WHIM) Syndrome
Wiskott-Aldrich Syndrome (WAS)
X-Linked Agammaglobulinemia (XLA)
X-Linked Lymphoproliferative Disease (XLP)
Immunodeficiency Disease Medications
There are different forms of hyper IgM syndromes, and all are the result of genetic defects involving the interaction between T-cells and B-cells. These gene mutations and defects result in failure to produce the full range of different antibodies needed for a healthy immune system.
The risk factors are genetic, and most forms of this disease are inherited in an autosomal recessive pattern, which means that an individual must inherit two variants in a gene for the same trait, and one variant must come from each parent.
However, X-Linked Hyper-Immunoglobulin M Syndrome is expressed in boys who have one X chromosome. Problems that occur in the CD40LG gene lead to abnormal production of a protein called CD40 ligand which is needed to attach to receptors on B cells. Otherwise, antibodies cannot be produced. The gene associated with this fault is located on the X chromosome.
Diagnosis is usually made from a physical examination. The symptoms experienced blood tests to examine immune cell development and serum Ig levels. Genetic testing for faults in the genes behind this disease can also help confirm the disorder’s presence.
Treatment for this syndrome includes antibiotics to treat frequent infections and regular immunoglobulin replacement therapy, which helps to restore immunoglobulin levels in the blood.
The only possible cure for some forms of this disease is to perform an allogeneic hematopoietic stem cell transplant which replaces the cells of the syndrome sufferer with healthy cells that can produce all the various types of antibodies needed to build a healthy immune system. This involves a bone marrow transplant.
Genetic testing can identify those with the highest risk of having children that will go on to develop the syndrome, and this is the best way of preventing the disease.