From the Guidelines
Autoimmune Lymphoproliferative Syndrome (ALPS) is diagnosed based on required and supportive criteria, including chronic non-malignant lymphadenopathy or splenomegaly lasting over 6 months, elevated CD3+TCRαβ+CD4-CD8- double-negative T cells (DNTs) ≥1.5% of total lymphocytes, and normal or elevated lymphocyte counts, as outlined in the revised diagnostic criteria and classification for ALPS reported in the 2009 NIH International Workshop 1. The required criteria for ALPS diagnosis include:
- Chronic non-malignant lymphadenopathy or splenomegaly lasting over 6 months
- Elevated CD3+TCRαβ+CD4-CD8- double-negative T cells (DNTs) ≥1.5% of total lymphocytes, or 2.5% of CD3 lymphocytes, in the setting of normal or elevated lymphocyte counts, as specified in the revised criteria 1 The accessory criteria are subdivided into primary and secondary criteria, with primary criteria including:
- Defective lymphocyte apoptosis, which can be assessed through assays such as direct FAS activation or TCR restimulation, with a test considered abnormal if the patient’s cells show consistently 50% or less of the cell death observed in the control 1
- Somatic or germline pathogenic mutation in FAS, FASLG, or CASP10, which can be identified through genetic testing The secondary criteria include:
- 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) 1
- Typical immunohistological findings, as reviewed by an experienced hematopathologist
- Autoimmune cytopenias (hemolytic anemia, thrombocytopenia, or neutropenia) and elevated immunoglobulin G levels (polyclonal hypergammaglobulinemia)
- Family history of a nonmalignant/noninfectious lymphoproliferation with or without autoimmunity A definitive diagnosis of ALPS is based on the presence of both required criteria plus one primary accessory criterion, while a probable diagnosis is based on the presence of both required criteria plus one secondary accessory criterion, as outlined in the revised criteria 1. Management of ALPS begins with observation for mild cases, and first-line therapy for significant cytopenias includes corticosteroids and mycophenolate mofetil, with sirolimus and rituximab considered for refractory cases, and splenectomy reserved for severe refractory cytopenias, as discussed in the context of ALPS management 1.
From the Research
Diagnostic Criteria for Autoimmune Lymphoproliferative Syndrome (ALPS)
The diagnostic criteria for ALPS include:
- Clinical manifestations such as unexplained lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias, and elevated number of double-negative T (DNT) cells 2, 3, 4
- Laboratory findings including abnormal in vitro apoptosis function, elevated soluble FAS ligand (sFASL), interleukin 10 (IL-10), and IL-18 3
- Molecular genetic diagnosis with mutations in genes affecting the extrinsic apoptotic pathway, such as FAS, FASL, and CASP10 3, 4
Management Options for ALPS
The management options for ALPS include:
- Immunosuppressive therapies such as mycophenolate mofetil, sirolimus, and pentostatin 2, 5
- Glucocorticoids, immunoglobulin G, and rituximab to manage symptoms 4
- Bone marrow transplant as a curative therapy, although rarely done due to complications 4
- Sirolimus as a first-line corticosteroid-sparing therapy for patients in need of chronic treatment 5
Key Diagnostic Markers for ALPS
The key diagnostic markers for ALPS include: