Autoimmune lymphoproliferative syndrome: an update and review of the literature

Curr Allergy Asthma Rep. 2014 Sep;14(9):462. doi: 10.1007/s11882-014-0462-4.


Autoimmune lymphoproliferative syndrome (ALPS) is characterized by immune dysregulation due to a defect in lymphocyte apoptosis. The clinical manifestations may be noted in multiple family members and include lymphadenopathy, splenomegaly, increased risk of lymphoma, and autoimmune disease, which typically involves hematopoietic cell lines manifesting as multilineage cytopenias. Since the disease was first characterized in the early 1990s, there have been many advances in the diagnosis and management of this syndrome. The inherited genetic defect of many ALPS patients has involved (FAS) pathway signaling proteins, but there remain those patients who carry undefined genetic defects. Despite ALPS having historically been considered a primary immune defect presenting in early childhood, adult onset presentation is increasingly becoming recognized and more so in genetically undefined patients and those with somatic FAS mutations. Thus, future research may identify novel pathways and/or regulatory proteins important in lymphocyte activation and apoptosis.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Apoptosis
  • Autoimmune Lymphoproliferative Syndrome* / complications
  • Autoimmune Lymphoproliferative Syndrome* / diagnosis
  • Autoimmune Lymphoproliferative Syndrome* / drug therapy
  • Autoimmune Lymphoproliferative Syndrome* / genetics
  • Diagnosis, Differential
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Activation / immunology
  • Signal Transduction
  • Splenomegaly / etiology
  • T-Lymphocytes / immunology
  • fas Receptor / genetics*
  • fas Receptor / physiology


  • Anti-Inflammatory Agents
  • Immunosuppressive Agents
  • fas Receptor