Autoimmune Lymphoproliferative Syndrome Type IIB (ALPS IIB)

Autoimmune lymphoproliferative syndrome (all types) generally presents in early childhood, and is characterized by chronic, non-malignant lymphadenopathy, usually with autoimmunity. The underlying cause is a defect in lymphocyte apoptosis, or programmed cell death, leading to persistence of mature T and B cells, including the usually rare CD4/CD8-double-negative T (DNT) cell. The formal diagnostic triad for ALPS is elevated DNT cells, hepato/splenomegaly, and defective in vitro lymphocyte apoptosis. Autoimmunity may be present, most often directed against erythrocytes, platelets and neutrophils. In some patients, skin rashes, glomerulonephritis, arthritis, Guillan-Barré syndrome and autoimmune hepatitis may occur. The disorder can vary significantly in severity, even within families. Some individuals have only positive laboratory findings, typically including DNT cells, autoantibodies (such as Coombs positivity), hypergammaglobulinemia (IgG, IgM, IgA), elevated serum IL-10, and elevated serum vitamin B12. The majority of ALPS patients have mutations in the FAS (TNFRSF6) gene and are referred to as Type IA. ALPS cases associated with CASP8 and CASP10 mutations are extremely rare and less well understood. ALPS2B has been called Caspase-8 Deficiency State (CEDS) because the two published siblings have immunodeficiency in addition to ALPS.

Tests Available

Forms and Documents

Test Details

CASP8
  • Confirmation of the clinical diagnosis
  • Differentiation from malignant forms of lymphoproliferation and from other sub-types of ALPS
  • Development of an appropriate treatment plan for affected individuals
  • Development of an appropriate medical surveillance plan for relatives at risk of lymphoma
  • Capillary Sequencing Reflex to Exon Array

Ordering

2612
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 283 Acquired hemolytic anemias
  • 202.x Malignant neoplasms of lymphoid and histiocytic tissue, specific decimal required
  • 238.7 Other lymphatic and hematopoietic tissues
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References

  1. Zhu, S. et al., Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome, Human Genetics 119:284-294, 2006.
  2. Cerutti E. et al, Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome. BMC Immunol 8:22, 2007.
  3. Chun, H., et al., Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419: 395-399, 2002.
  4. Wang, J., et al., Inherited caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell 47-58, 1999
  5. Su H et al, Genetic Defects of Apoptosis and Primary Immunodeficiency. Immunol Allergy Clin N Am, 28:329, 2008.