Revised Diagnostic Criteria for Autoimmune Lymphoproliferative Syndrome (ALPS)

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited syndrome characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis. This failure leads to the clinical manifestations of non-infectious and non-malignant lymphadenopathy, splenomegaly, and autoimmune pathology, most commonly, autoimmune cytopenias.

Revised Diagnostic Criteria for ALPS


  1. Chronic (> 6 months), nonmalignant, noninfectious lymphadenopathy or splenomegaly or both
  2. Elevated CD3+TCRαβ+CD4−CD8− DNT cells (≥ 1.5% of total lymphocytes or 2.5% of CD3+ lymphocytes) in the setting of normal or elevated lymphocyte counts


  1. Primary
    1. Defective lymphocyte apoptosis (in 2 separate assays)
    2. Somatic or germline pathogenic mutation in FAS, FASLG, or CASP10
  2. Secondary
    1. Elevated plasma sFASL levels (>200 pg/mL) OR elevated plasma interleukin-10 levels (>20 pg/mL) OR elevated serum or plasma vitamin B12 levels (> 1500 ng/L) OR elevated plasma interleukin-18 levels > 500 pg/mL
    2. Typical immunohistological findings as reviewed by an experienced hematopathologist
    3. Autoimmune cytopenias (hemolytic anemia, thrombocytopenia, or neutropenia) AND elevated immunoglobulin G levels (polyclonal hypergammaglobulinemia)
    4. Family history of a nonmalignant/noninfectious lymphoproliferation with or without autoimmunity

A definitive diagnosis is based on the presence of both required criteria plus one primary accessory criterion. A probable diagnosis is based on the presence of both required criteria plus one secondary accessory criterion.

Abbreviations: TCR, T-cell receptor; DNTs, double-negative T cells




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Created: Sep 12, 2019