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Excerpted from the GeneReview: Autoimmune Lymphoproliferative Syndrome
Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age; Autoimmune disease, mostly directed toward blood cells; and Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases in many affected individuals. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS is characterized by severe lymphoproliferation before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (α/β-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, keeping in mind that those with somatic pathogenic variants need to be better characterized, particularly with regard to the risk for lymphoma.

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Practice guidelines

  • NIH, 2009
    Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop

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