Table 2.

Diagnostic Criteria for Autoimmune Lymphoproliferative Syndrome

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 two 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 (>1,500 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.

CASP10, caspase 10; DNT, double-negative T; FAS, first apoptosis signal; FASLG, FAS ligand; sFASL, soluble FAS ligand.