Autoimmune lymphoproliferative syndrome criteria

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; David Teachey, MD [2] Associate Editor(s)-in-Chief: Sharmi Biswas, M.B.B.S

Following the international conference in 2009, a revised set of diagnostic criteria was published in 2010. According to this set of criteria, to reach a definitive diagnosis it is mandatory to have the presence of two required criteria and one primary accessory criteria. The presence of two required criteria and one secondary criterion together indicates the probable diagnosis.

Old criteria^[1]

• Required
  • Chronic non-malignant lymphoproliferation
  • Elevated peripheral blood Double Negative T cells (DNTs)
  • Defective in vitro Fas mediated apoptosis

New criteria^[2]

• Required
  • Chronic non-malignant lymphoproliferation (>6 months lymphadenopathy and/or splenomegaly)
  • Elevated peripheral blood DNTs
• Accessory
  • Primary Accessory
    • Defective in vitro Fas mediated apoptosis
    • Somatic or germline mutation in ALPS causative gene (FAS, FASL, CASP10)
  • Secondary Accessory
    • Elevated biomarkers
      • Plasma sFASL >200pg/ml
      • Plasma IL-10 >20pg/ml
      • Plasma or serum vitamin B12 >1500ng/L
      • Plasma IL-18 >500pg/ml
    • Immunohistochemical findings on biopsy consistent with ALPS as determined by experienced hematopathologist
    • Autoimmune cytopenias and polyclonal hypergammaglobulinemia
    • Family history of ALPS or non-malignant lymphoproliferation
• Definitive diagnosis: Required plus one primary accessory criteria
• Probable diagnosis: Required plus one secondary accessory criteria
• Definitive and Probable ALPS should be TREATED THE SAME and patients counseled that they have ALPS if definitive or probable