| H00108 | |
| H number | H00108 |
| Name | Autoimmune lymphoproliferative syndromes |
| Description | Autoimmune lymphoproliferative syndromes (ALPS) are autosomal dominant disorders 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 genes (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 |
| Network | nt06524(H00108) Apoptosis nt06527(H00108) Necroptosis |
| Gene | (ALPS1A) FAS [HSA:355] [KO:K04390] (ALPS1B) FASLG [HSA:356] [KO:K04389] (ALPS2A) CASP10 [HSA:843] [KO:K04400] (ALPS2B) CASP8 [HSA:841] [KO:K04398] (ALPS3) PRKCD [HSA:5580] [KO:K06068] (ALPS4) NRAS [HSA:4893] [KO:K07828] (ALPS5) CTLA4 [HSA:1493] [KO:K06538] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 4A01.22 ICD-10: D47.9 MeSH: D056735 OMIM: 601859 603909 614470 615559 607271 616100 |
| Reference | PMID:16611303 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) DOI:10.1111/j.1365-2141.2006.05993.x PMID:17952897 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) DOI:10.1016/j.jaci.2007.08.053 PMID:17999750 (ALPS1_2) 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) DOI:10.1186/1471-2172-8-28 PMID:23666743 (ALPS3) AUTHORS Belot A, Kasher PR, Trotter EW, Foray AP, Debaud AL, Rice GI, Szynkiewicz M, Zabot MT, Rouvet I, Bhaskar SS, Daly SB, Dickerson JE, Mayer J, O'Sullivan J, Juillard L, Urquhart JE, Fawdar S, Marusiak AA, Stephenson N, Waszkowycz B, W Beresford M, Biesecker LG, C M Black G, Rene C, Eliaou JF, Fabien N, Ranchin B, Cochat P, Gaffney PM, Rozenberg F, Lebon P, Malcus C, Crow YJ, Brognard J, Bonnefoy N TITLE Protein kinase cdelta deficiency causes mendelian systemic lupus erythematosus with B cell-defective apoptosis and hyperproliferation. JOURNAL Arthritis Rheum 65:2161-71 (2013) DOI:10.1002/art.38008 PMID:17517660 (ALPS4) AUTHORS Oliveira JB, Bidere N, Niemela JE, Zheng L, Sakai K, Nix CP, Danner RL, Barb J, Munson PJ, Puck JM, Dale J, Straus SE, Fleisher TA, Lenardo MJ TITLE NRAS mutation causes a human autoimmune lymphoproliferative syndrome. JOURNAL Proc Natl Acad Sci U S A 104:8953-8 (2007) DOI:10.1073/pnas.0702975104 PMID:25213377 (ALPS5) AUTHORS Kuehn HS, Ouyang W, Lo B, Deenick EK, Niemela JE, Avery DT, Schickel JN, Tran DQ, Stoddard J, Zhang Y, Frucht DM, Dumitriu B, Scheinberg P, Folio LR, Frein CA, Price S, Koh C, Heller T, Seroogy CM, Huttenlocher A, Rao VK, Su HC, Kleiner D, Notarangelo LD, Rampertaap Y, Olivier KN, McElwee J, Hughes J, Pittaluga S, Oliveira JB, Meffre E, Fleisher TA, Holland SM, Lenardo MJ, Tangye SG, Uzel G TITLE Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. JOURNAL Science 345:1623-1627 (2014) DOI:10.1126/science.1255904 |