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

Required

  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

Accessory

  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

 

 

References:

  1. Bride K, Teachey D. Autoimmune lymphoproliferative syndrome: more than a FAScinating disease. F1000Res. 2017 Nov 1;6:1928. [Medline]
  2. Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ, Rieux-Laucat F, Siegel RM, Su HC, Teachey DT, Rao VK. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood. 2010 Oct 7;116(14):e35-40. [Medline]
  3. Teachey DT, Manno CS, Axsom KM, Andrews T, Choi JK, Greenbaum BH, McMann JM, Sullivan KE, Travis SF, Grupp SA. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS). Blood. 2005 Mar 15;105(6):2443-8. [Medline]
  4. Bleesing JJ, Straus SE, Fleisher TA. Autoimmune lymphoproliferative syndrome: a human disorder of abnormal lymphocyte survival. Pediatr Clin North Am. 2000;47: 1291-1310. [Medline]

Created: Sep 12, 2019

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