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Autoimmune lymphoproliferative syndrome (ALPS): Clinical features and diagnosis

Jack JH Bleesing, MD, PhD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS


Autoimmune lymphoproliferative syndrome (ALPS) is characterized by dysregulation of the immune system, due to an inability to regulate lymphocyte homeostasis through the process of lymphocyte apoptosis (a form of programmed cell death). The consequences of this include lymphoproliferative disease, manifested by lymphadenopathy, hepatomegaly, splenomegaly, and an increased risk of lymphoma, as well as autoimmune disease, typically involving blood cells.

The signature laboratory abnormalities that facilitate diagnosis of ALPS include an expansion of T cells that express the alpha/beta T cell receptor but lack both CD4 and CD8 (alpha/beta double-negative T [DNT] cells) in peripheral blood and tissue specimens, elevated levels of interleukin-10 (IL-10) in blood, increased levels of vitamin B12, and defective Fas-mediated apoptosis in vitro.

This topic reviews the clinical features and diagnosis of ALPS. The epidemiology, genetics, pathogenesis, management, and prognosis of ALPS are discussed separately. (See "Autoimmune lymphoproliferative syndrome (ALPS): Epidemiology and pathogenesis" and "Autoimmune lymphoproliferative syndrome (ALPS): Management and prognosis".)


In the two largest cohorts of patients with ALPS, the French cohort and National Institutes of Health (NIH) cohort, disease onset was most commonly defined by lymphoproliferative disease, with a median age of disease onset of 2.7 to 3 years of age [1,2]. Patients with later disease onset often presented with autoimmune disease rather than lymphoproliferative disease.

Autoimmune lymphoproliferative syndrome due to mutations in the FAS gene that encodes an apoptosis-associated antigen (ALPS-FAS) is the most common and best-characterized type of ALPS. The following are the main consequences of perturbed lymphocyte homeostasis in ALPS-FAS.


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Literature review current through: Sep 2016. | This topic last updated: Oct 15, 2014.
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