Immune and Autoimmune Issues in Kabuki Syndrome

We all get exposed every day to many things that can cause infections, and we all know how easy it is to catch a cold if a family member or co-worker is sick. The body relies on the immune system to fight infections from germs such as viruses, bacteria, or fungi. But if the body’s immune system is not working well, a person can get infections more often and have a harder time getting better.

Many children with Kabuki syndrome get an increased number of infections. Although not all of these children have a problem with the immune system, some children with KS do have an immune system that is not working completely properly. For example, an immune problem, or immunodeficiency, can be a cause of more frequent and/or more serious infections. The extent and severity of the infections depends on the degree to which the immune system is affected. There are medications that can be given if a child is found to have an immunodeficiency.

A number of doctors have seen that there can be immune problems in children with KS, and in children that we have evaluated at The Children’s Hospital of Philadelphia, many have decreased antibody levels. Antibodies (also called immunoglobulins) are made by immune cells and are found in the blood. Antibodies are critical for the body to handle infections effectively. If the antibody levels fall very low, there is a much greater chance that a person will get an infection, and it will be harder for the body to fight off the infection. There are several different types, or classes, of antibodies. The major classes are IgG, IgM, IgA, and IgE. When the antibody levels are low, usually only some, not all, of the antibody classes are decreased. The severity of infections will depend on which of these classes are low, and how low the levels are. The levels of each class of antibody can be easily measured with a blood test. We do not know exactly why the immune problems happen in KS, although it is probably due to a change in a genei that is different in individuals with KS.

We also know that autoimmune conditions seem to occur more often in children with KS. However, most children with KS do not develop an autoimmune condition. An autoimmune condition is a disease in which the body’s immune system causes damage to its own cells and tissues. Autoimmune conditions that have been seen in children with KS include those that affect the thyroid, the skin (vitiligoi, a localized decrease in skin pigment), and blood cells (anemiai, low plateletsi). The fact that autoimmune problems occur more often in people with KS is probably related to the fact that immune problems may also be seen in children with KS, although a person does not have to have a known immune problem to have an autoimmune diseasei.

In order for the immune system to work properly, it has to be able to detect an infection and send the right cells into action to fight off that particular infection. That is, the immune system is regulated in a very precise way. The immune system is also regulated so that it does not attack the body. So, problems with regulation of the immune system can cause the immune system to not function properly, either by not responding well to infections or by failing to ensure that the immune system does not attack the body. Therefore, it is likely that suboptimal regulation of the immune system underlies the immune and autoimmune issues that can be seen in children with KS.

Checking of antibody levels should be considered for children with KS who are more than one year old or if there are symptoms of an immunodeficiency. If there are any deficiencies, the child should be seen by a pediatric immunologist. Also, if a child seems to be having more infections or more serious infections than most children, the immune system should be checked. It should be remembered that if the antibody levels are only mildly low, there may not be any problems with fighting infections. However, this is still good information to know because it will be important to have an immunologist follow the antibody levels over time in case the antibody levels get lower. Also, the immunologist will be alert about infections so that the proper treatment and immune diagnosis can be given quickly.

Jeffrey E. Ming, MD, PhD, is in the Division of Human Genetics at the Children’s Hospital of Philadelphia. He has seen over 35 children with KS and has written medical articles on immune issues and other aspects of KS. He is also conducting research studies in order to understand the genesi that cause KS.

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