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 |
| 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.