The autoimmune lymphoproliferative syndrome (ALPS) is a recently described syndrome with ties to autoimmune disease. As its name implies, ALPS is a disorder in which there is an increased proliferation and consequent overabundance of lymphocytes. Lymphocytes are white blood cells with a key role in the immune system. There are two major subtypes of lymphocytes, T cells and B cells. In addition, there are other lymphocytes known as killer cells and natural killer cells that are capable of destroying other cells.
B lymphocyte cells respond to foreign threats by producing antibodies. In autoimmune disorders, they produce autoantibodies. There are two subsets of T lymphocyte cells, helper cells and suppressor cells. While the T cells defend the body and guard against foreign antigens, the suppressor cells destroy cells that become carcinogen and cells that react with self antigens. A decreased number of T suppressor cells and an increased number of B lymphocytes set the stage for autoimmune disease.
And while all of the body’s cells have a programmed time of death known as apoptosis, individuals with ALPS have lymphocytes that defy apoptosis. They live far longer than intended. This results in an expansion of lymphocytes and an enlargement in the tissues where lymphocytes are normally found, such as the lymph nodes and spleen. APLS is caused by a polymorphism in the Fas ligand gene.
A defect in lymphocyte apoptosis, resulting in the decreased number of T suppressor cells typically seen, has also long been suspected as being associated with the development of certain autoimmune disorders. Without the control of apoptosis, lymphocytes that react with self antigens persist. Normally these auto-reactive lymphocytes would be programmed during their maturation in the thymus to die when this happened. Normally, auto-reactive cells would die before they went on to produce autoantibodies and autoimmune disease. It’s suspected that a number of patients with autoimmune disease also have ALPS. In fact, patients with Graves’ disease also have altered levels of soluble Fas, suggesting a genetic connection.
Individuals with ALPS also have an increased risk, approximately 15-50 times more than normal individuals, of developing lymphoma, which is a cancer of the lymphoid tissues. Like patients with the autoimmune disorder celiac disease, individuals with ALPS generally develop lymphoma many years after their initial diagnosis.
While the risk of developing lymphoma is increased in individuals with ALPS, the risk is still rare. In a recent NIH study, of 130 patients diagnosed with ALPS, only 10 patients developed lymphoma. The discovery of this syndrome suggests that therapies directed at the genes that control apoptosis would work for both ALPS and some forms of autoimmune disease.
