Table 1.

Diagnostic criteria for ALPS defined by 2009 NIH consensus (20).

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, FASL, or CASP10
Secondary
1. Elevated plasma sFASL levels (>200 pg/mL) OR elevated plasma IL-10 levels (>20 pg/mL) OR elevated serum or plasma vitamin B12 levels (>1,500 ng/L) OR elevated plasma IL-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

Definitive diagnosis: required criteria plus one primary accessory criterion.

Probable diagnosis: required criteria plus one secondary criterion.

CASP10 caspase 10, DNT double-negative T cell, FASL Fas-ligand, Ig immunoglobulin, IL interleukin, NIH National Institutes of Health, sFasL soluble Fas ligand.