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. 2010 Mar 26;32(3):291-5.
doi: 10.1016/j.immuni.2010.03.013.

ALPS-ten lessons from an international workshop on a genetic disease of apoptosis

Michael J Lenardo  1 , João B Oliveira, Lixin Zheng, V Koneti Rao
Affiliations

ALPS-ten lessons from an international workshop on a genetic disease of apoptosis

Michael J Lenardo et al. Immunity. .

Abstract

An international group of researchers investigating the molecular, cellular, immunological, and clinical aspects of the autoimmune lymphoproliferative syndrome (ALPS) met in Bethesda, Maryland on September 21-22, 2009 to discuss advances made over the past 15 years. Their discussions yielded ten broad messages applicable to genetic and immunological investigations of human disease.

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Figures

Figure 1
Figure 1. Molecular Basis for ALPS Genetic Mutations and Clinical Classification
Molecules involved in canonical Fas signaling are illustrated on top and the normal signaling pathway on the left. Membrane-bound Fas ligand binds the pre-associated trimeric Fas and triggers formation of the death-inducing signaling complex (DISC) by recruiting adaptor FADD (Fas-associated death domain) protein, caspase-8 (Casp8) and/or caspase-10 (Casp10). On the right, the identified gene mutations in ALPS and ALPS-like patients are linked to their clinical classifications. The percentage incidence for each type is shown in parenthesis. Mutations for ALPS: Type-Ia: Fas; Type-Ib: Fas ligand; Type-Im: somatic mutation of Fas; Type-II: Casp-10; Type-III: unknown genetic defect; Type-IV: N-Ras (neuroblastoma Ras, a molecule involved in the regulation of cytokine-withdrawal apoptosis); CEDS (Caspase-8 deficiency state): Casp8 homozygous gene defect. Bim stands for BCL-2-interacting mediator of cell death.
See this image and copyright information in PMC

References

    1. Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson TP, Straus SE, Lenardo MJ. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002;419:395–399. - PubMed
    1. Clementi R, Chiocchetti A, Cappellano G, Cerutti E, Ferretti M, Orilieri E, Dianzani I, Ferrarini M, Bregni M, Danesino C, Bozzi V, Putti MC, Cerutti F, Cometa A, Locatelli F, Maccario R, Ramenghi U, Dianzani U. Variations of the perforin gene in patients with autoimmunity/ lymphoproliferation and defective Fas function. Blood. 2006;108:3079–3084. - PubMed
    1. Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, Strober W, Lenardo MJ, Puck JM. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995;81:935–946. - PubMed
    1. Garibyan L, Lobito AA, Siegel RM, Call ME, Wucherpfenning KW, Geha RS. Dominant-negative effect of the heterozygous C104R TACI mutation in common variable immunodeficiency (CVID) J. Clin. Invest. 2007;117:1550–1557. - PMC - PubMed
    1. Holzelova E, Vonarbourg C, Stolzenberg MC, Arkwright PD, Selz F, Prieur AM, Blanche S, Bartunkova J, Vilmer E, Fischer A, Le Deist F, Rieux-Laucat F. Autoimmune lymphoproliferative syndrome with somatic Fas mutations. N Engl J Med. 2004;351:1409–1418. - PubMed

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