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Autoimmune Lymphoproliferative Syndrome (ALPS)

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ALPS and the Immune System

To understand ALPS, it helps to understand how the immune system responds to an infection. For example, when a person has the flu, cells in the nose and throat instruct the immune system to start making more lymphocytes, a major class of white blood cells comprising T cells and B cells. New troops of lymphocytes come to the nose and throat to seek out and destroy the cells infected with the flu virus. Once the virus is conquered, the lymphocytes get a message that their job is done and that they are no longer needed. At this point, it is normal for most of the fighter cells to disintegrate through a process called apoptosis.

While immune systems of people with ALPS are efficient in fighting germs and other agents, the problems begin after an infection is gone. In ALPS, apoptosis does not work as well as it should. In other words, the lymphocytes don't hear the message that the war is over. As a result, excess T cells and B cells gather in the lymph nodes, liver, and spleen, causing them to become enlarged.

Fas Gene

One reason the blood cells don’t get the message to disintegrate is the mutation of a gene called Fas. Under normal circumstances, the Fas gene produces Fas protein, which controls the life span of certain cells, including lymphocytes. The mutated Fas gene, however, produces abnormal Fas protein, which is unable to give the cells the message that it is time to die. Although most ALPS patients have one normal and one mutated copy of the Fas gene, the abnormal protein is able to interfere with the function of the normal one.

It is not completely understood how an abnormal Fas protein leads to ALPS, but it clearly does. However, Fas mutations do not explain all cases of ALPS. Approximately 30 percent of people with ALPS do not have a Fas mutation. Some of them have alterations in other proteins. In some ALPS patients, a genetic alteration has not yet been found. Also, there are many relatives of ALPS patients who have a Fas mutation and do not have symptoms of ALPS. Scientists believe that other genes and environmental factors also play a role in determining which people get ALPS.

T Cells and B Cells

In general, the accumulation of extra T cells in people with ALPS does not cause a problem. Sometimes, however, the proliferation of extra B cells can prompt the immune system to attack the body. B cells produce antibodies, which are custom-fit to stick to a specific germ or other microbe. Instead of custom-designing antibodies against microbes, the ALPS B cells make antibodies against platelets, which help the blood form clots; red blood cells, which help transport oxygen to body tissues; or neutrophils, which help fight infection.

This causes autoimmune problems as the antibodies become stuck to the platelets and red blood cells, which then get stuck in the spleen. As a result, excess T cells and B cells gather in the lymph nodes, liver, and spleen, causing them to become enlarged.

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Last Updated October 06, 2008