Autoimmune Lymphoproliferative Syndrome (ALPS)

Illustration of fas protein.

The Fas protein—which can be missing or defective in people with ALPS—spans the cell membrane and helps facilitate apoptosis, or programmed cell death. Without normal apoptosis, some cells can build up, thereby disrupting the immune system.

Credit: NIAID

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of the immune system first described by NIH scientists in the mid-1990s that affects both children and adults. In ALPS, unusually high numbers of white blood cells called lymphocytes accumulate in the lymph nodes, liver, and spleen and can lead to enlargement of these organs. ALPS can also cause anemia (low level of red blood cells), thrombocytopenia (low level of platelets), and neutropenia (low level of neutrophils, the most common type of white blood cell in humans). These problems can increase the risk of infection and hemorrhage.

Why Is the Study of Autoimmune Lymphoproliferative Syndrome (ALPS) a Priority for NIAID?

ALPS can cause debilitating symptoms and put those affected at an increased risk for developing serious health conditions, including autoimmune diseases and lymphoma. Researchers at NIAID are working to develop safe and effective treatments targeting the genetic defects in people with ALPS and related disorders.

How Is NIAID Addressing This Critical Topic?

Researchers at NIAID focus on gaining a better understanding of the clinical and genetic characteristics of people with ALPS and related disorders. By identifying the genes responsible for ALPS symptoms, NIAID researchers not only help affected families but also increase understanding of how the immune system works.

To learn about resources for the diagnosis and management of ALPS and sources of support and advocacy, visit the National Library of Medicine, Genetics Home Reference autoimmune lymphoproliferative syndrome site.

Causes

Most cases of ALPS are caused by mutations in the FAS gene. FAS produces a receptor that, when activated, leads to programmed cell death, or apoptosis. This programmed death is an important part of the normal cell lifecycle. When cells do not receive the message that it is time for them to die, an abnormal buildup of cells can result. In the case of ALPS, mutations in FAS cause an abnormal buildup of white blood cells.

Symptoms & Diagnosis

The major clinical symptoms of ALPS, including fatigue, nosebleeds, and infections, result from a proliferation of lymphocytes and autoimmune destruction of other blood cells. The diagnosis of ALPS is based on clinical findings, laboratory findings, and identification of genetic mutations.

Treatment

There currently is no standard cure for ALPS. The disorder can be managed by treating low blood-cell counts and autoimmune diseases that occur in people with ALPS, as well as by monitoring for and treating the proliferation of immune cells, enlarged spleen, and lymphoma.

Related Information for Researchers

NIAID offers resources, information about funding, and ways to connect to other scientists researching autoimmune diseases diseases including ALPS.

Content last reviewed on April 19, 2019