KEGG   DISEASE: H00108Help
Entry
H00108                      Disease                                

Name
Autoimmune lymphoproliferative syndromes (ALPS), including the following five diseases:
CD95 (Fas) defect, ALPS type 1a;
CD95L (Fas ligand) defect, ALPS type 1b;
Caspase 10 defect, ALPS type 2a;
Caspase 8 defext, ALPS type 2b;
Activaing N-Ras defect, N-Ras ALPS
Description
Autoimmune lymphoproliferative syndrome (ALPS) is an autosomal dominant disorder with clinical features of various autoimmune manifestations that predominantly involve polyclonal accumulation of lymphocytes in the spleen and lymph nodes with lymphadenopathy and/or splenomegaly, and expansion of double-negative (DN) T cells in the peripheral blood. Central to the cellular pathogenesis is defective FAS-induced apoptosis, which in turn leads to dysregulation of lymphocyte homeostasis. ALPS caused by heterozygous mutations in the Fas gene (ALPS Type Ia) make up the majority of identified cases. However, other mutations, namely of the FasL gene (ALPS Type Ib) and the caspase 8 and 10 gene (ALPS Type II) are occasionally detected, whereas some patients do not present any known mutations (ALPS-III). Recently, mutations of the NRAS gene have been suggested to cause ALPS Type IV.
Category
Primary immunodeficiency
BRITE hierarchy
Pathway
hsa04210 Apoptosis  
 
Gene
TNFRSF6 (Fas) [HSA:8771] [KO:K05143]
TNFSF6 (Fas ligand) [HSA:356] [KO:K04389]
Caspase 10 [HSA:843] [KO:K04400]
Caspase 8 [HSA:841] [KO:K04398]
N-Ras [HSA:4893] [KO:K07828]
Other DBs
Reference
PMID:17999750 (description, gene)
  Authors
Cerutti E, Campagnoli MF, Ferretti M, Garelli E, Crescenzio N, Rosolen A, Chiocchetti A, Lenardo MJ, Ramenghi U, Dianzani U
  Title
Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome.
  Journal
BMC Immunol 8:28 (2007)
Reference
PMID:16611303 (gene)
  Authors
Worth A, Thrasher AJ, Gaspar HB
  Title
Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical  phenotype.
  Journal
Br J Haematol 133:124-40 (2006)
Reference
PMID:17162365 (gene)
  Authors
Kumar A, Teuber SS, Gershwin ME.
  Title
Current perspectives on primary immunodeficiency diseases.
  Journal
Clin Dev Immunol 13:223-59 (2006)
Reference
PMID:18424339 (gene)
  Authors
Morra M, Geigenmuller U, Curran J, Rainville IR, Brennan T, Curtis J, Reichert V, Hovhannisyan H, Majzoub J, Miller DT.
  Title
Genetic diagnosis of primary immune deficiencies.
  Journal
Immunol Allergy Clin North Am 28:387-412, x (2008)
Reference
PMID:17952897 (gene)
  Authors
Geha RS, Notarangelo LD, Casanova JL, Chapel H, Conley ME, Fischer A, Hammarstrom L, Nonoyama S, Ochs HD, Puck JM, Roifman C, Seger R, Wedgwood J.
  Title
Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee.
  Journal
J Allergy Clin Immunol 120:776-94 (2007)

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