Diagnostic Criteria for Autoimmune Lymphoproliferative Syndrome (ALPS)

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by dysregulation of the immune system due to an inability to regulate lymphocyte homeostasis through the process of lymphocyte apoptosis (a form of programmed cell death). The consequences of this include lymphoproliferative disease, manifested by lymphadenopathy, hepatomegaly, splenomegaly, and an increased risk of lymphoma, as well as autoimmune disease, typically involving blood cells.

Diagnostic criteria for ALPS

Required

1. Chronic nonmalignant lymphoproliferation
2. Defective in vitro Fas-mediated lymphocyte apoptosis
3. At least 1% TCR {alpha}/{beta}+, CD3+, CD4-, CD8- cells (DNTs) in peripheral blood or lymphoid tissue

Supporting

1. Autoimmune antibodies
2. Mutations in Fas gene, Fas ligand gene, or caspase 8 or 10 genes

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

 

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

Primary

1. Defective lymphocyte apoptosis (in 2 separate assays)
2. Somatic or germline pathogenic mutation in FAS, FASLG, or CASP10

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.

 

References:

1. 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]
2. 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]
3. Oliveira JB, Bleesing JJ, Dianzani U, et al. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood. 2010;116(14):e35–e40. [Medline]

 

Created: Oct 20, 2009
Update Feb 05, 2020