The Autoimmune Lymphoproliferative Syndrome with Defective FAS or FAS-Ligand Functions

J Clin Immunol. 2018 Jul;38(5):558-568. doi: 10.1007/s10875-018-0523-x. Epub 2018 Jun 17.


The autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant and non-infectious uncontrolled proliferation of lymphocytes accompanied by autoimmune cytopenia. The genetic etiology of the ALPS was described in 1995 by the discovery of the FAS gene mutations. The related apoptosis defect accounts for the accumulation of autoreactive lymphocytes as well as for specific clinical and biological features that distinguish the ALPS-FAS from other monogenic defects of this apoptosis pathway, such as FADD and CASPASE 8 deficiencies. The ALPS-FAS was the first description of a monogenic cause of autoimmunity, but its non-Mendelian expression remained elusive until the description of somatic and germline mutations in ALPS patients. The recognition of these genetic diseases brought new information on the role of this apoptotic pathway in controlling the adaptive immune response in humans.

Keywords: FAS; FASLG; apoptosis; autoimmunity; lymphoproliferation.

Publication types

  • Review

MeSH terms

  • Alleles
  • Animals
  • Autoimmune Lymphoproliferative Syndrome / diagnosis
  • Autoimmune Lymphoproliferative Syndrome / etiology*
  • Autoimmune Lymphoproliferative Syndrome / metabolism*
  • Autoimmune Lymphoproliferative Syndrome / therapy
  • Disease Management
  • Disease Susceptibility
  • Fas Ligand Protein / genetics*
  • Fas Ligand Protein / metabolism*
  • Genetic Association Studies
  • Genotype
  • Humans
  • Mutation
  • Phenotype
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • fas Receptor / genetics*
  • fas Receptor / metabolism*


  • FASLG protein, human
  • Fas Ligand Protein
  • fas Receptor