Autoimmune Lymphoproliferative Syndrome (ALPS)

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder of the immune system 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, which can lead to enlargement of these organs. ALPS can cause numerous autoimmune problems such as anemia (low count of red blood cells), thrombocytopenia (low count of platelets), and neutropenia (low count of neutrophils, the most common type of white blood cell in humans).

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 of developing autoimmune diseases and lymphoma. Researchers at NIAID hope to develop safe and effective treatments targeting the genetic defects in children with ALPS and related disorders.

How Is NIAID Addressing This Critical Topic?

Researchers at NIAID focus on gaining better understanding of the clinical and genetic characteristics of people with ALPS and related disorders. By identifying the genes responsible for symptoms in these people, NIAID researchers not only help affected families but also increase understanding of how the immune system works. Whole genome sequencing is one of the tools the investigators are using to address these research questions. 

ALPS is a primary immune deficiency disease (PIDD). For more information on PIDD research and patient care at NIAID, visit the NIAID PIDD site.

To learn about risk factors for ALPS and current management and treatment strategies visit the National Library of Medicine, Genetics Home Reference autoimmune lymphoproliferative syndrome site.

Illustration of fas protein.
Credit: NIAID

The Fas protein spans the cell membrane, with part of the protein located outside the cell (blue) and part within the cell (grey). When Fas interacts with an immune system protein called Fas ligand, it signals proteins within the cell to begin the pathway

Causes

Most cases of ALPS are caused by mutations in the FAS gene. The FAS gene 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 the FAS gene 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 mutations in genes.

Treatment

There currently is no standard cure for ALPS. The disorder can be managed by treating cytopenias (low blood cell count) and autoimmune diseases that occur in people with ALPS, as well as monitoring for and treating lymphoproliferation, an enlarged spleen, and lymphoma.

Related Autoimmune Research

More than 80 diseases occur as a result of the immune system attacking the body’s own organs, tissues, and cells. Some of the more common autoimmune diseases include type 1 diabetes, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel diseases (IBD). ALPS also falls under this category of diseases.

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