The Autoimmune Lymphoproliferative Syndrome with Defective FAS or FAS-Ligand Functions

Abstract

The autoimmune lymphoproliferative syndrome (ALPS) is a non-malignant and non-infectious uncontrolled proliferation of lymphocytes accompanied by autoimmune cytopenia. The genetic etiology of the ALPS was described in 1995 by the discovery of the FAS gene mutations. The related apoptosis defect accounts for the accumulation of autoreactive lymphocytes as well as for specific clinical and biological features that distinguish the ALPS-FAS from other monogenic defects of this apoptosis pathway, such as FADD and CASPASE 8 deficiencies. The ALPS-FAS was the first description of a monogenic cause of autoimmunity, but its non-Mendelian expression remained elusive until the description of somatic and germline mutations in ALPS patients. The recognition of these genetic diseases brought new information on the role of this apoptotic pathway in controlling the adaptive immune response in humans.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

References

  1. 1.

    Canale VC, Smith CH. Chronic lymphadenopathy simulating malignant lymphoma. J Pediatr. 1967;70(6):891–9.

    Article  PubMed  CAS  Google Scholar 

  2. 2.

    Lavrik IN, Krammer PH. Regulation of CD95/Fas signaling at the DISC. Cell Death Differ. 2012;19(1):36–41. https://doi.org/10.1038/cdd.2011.155.

    Article  PubMed  CAS  Google Scholar 

  3. 3.

    Schleich K, Krammer PH, Lavrik IN. The chains of death: a new view on caspase-8 activation at the DISC. Cell Cycle. 2013;12(2):193–4. https://doi.org/10.4161/cc.23464.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. 4.

    Rieux-Laucat F, Fischer A, Deist FL. Cell-death signaling and human disease. Curr Opin Immunol. 2003;15(3):325–31.

    Article  PubMed  CAS  Google Scholar 

  5. 5.

    Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defect in Fas antigen that mediates apoptosis. Nature. 1992;356:314–7.

    Article  PubMed  CAS  Google Scholar 

  6. 6.

    Yonehara S, Ishii A, Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med. 1989;169(5):1747–56.

    Article  PubMed  CAS  Google Scholar 

  7. 7.

    Trauth B, Klas C, Peters A, Matzku S, Möller P, Falk W, et al. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 1989;245:301–4.

    Article  PubMed  CAS  Google Scholar 

  8. 8.

    Andrews BS, Eisenberg RA, Theofilopoulos AN, Izui S, Wilson CB, McConahey PJ, et al. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978;148(5):1198–215.

    Article  PubMed  CAS  Google Scholar 

  9. 9.

    Takei F. Unique surface phenotype of T cells in lymphoproliferative autoimmune MRL/Mp-lpr/lpr mice. J Immunol. 1984;133(4):1951–4.

    PubMed  CAS  Google Scholar 

  10. 10.

    Nagata S, Suda T. Fas and Fas ligand: lpr and gld mutations. Immunol Today. 1995;16(1):39–43.

    Article  PubMed  CAS  Google Scholar 

  11. 11.

    Shi X, Xie C, Kreska D, Richardson JA, Mohan C. Genetic dissection of SLE: SLE1 and FAS impact alternate pathways leading to lymphoproliferative autoimmunity. J Exp Med. 2002;196(3):281–92.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. 12.

    Vidal S, Kono DH, Theofilopoulos AN. Loci predisposing to autoimmunity in MRL-Fas lpr and C57BL/6-Faslpr mice. J Clin Invest. 1998;101(3):696–702.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. 13.

    Adachi M, Suematsu S, Suda T, Watanabe D, Fukuyama H, Ogasawara J, et al. Enhanced and accelerated lymphoproliferation in Fas-null mice. Proc Natl Acad Sci U S A. 1996;93(5):2131–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. 14.

    Karray S, Kress C, Cuvellier S, Hue-Beauvais C, Damotte D, Babinet C, et al. Complete loss of Fas ligand gene causes massive lymphoproliferation and early death, indicating a residual activity of gld allele. J Immunol. 2004;172(4):2118–25.

    Article  PubMed  CAS  Google Scholar 

  15. 15.

    Matsuzawa A, Moriyama T, Kaneko T, Tanaka M, Kimura M, Ikeda H, et al. A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse. J Exp Med. 1990;171(2):519–31.

    Article  PubMed  CAS  Google Scholar 

  16. 16.

    Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995;81(6):935–46.

    Article  PubMed  CAS  Google Scholar 

  17. 17.

    Rieux-Laucat F, Le Deist F, Hivroz C, Roberts I, Debatin K, Fischer A, et al. Mutations in fas associated with human lymphoproliferative syndrome and autoimmunity. Science. 1995;268:1347–9.

    Article  PubMed  CAS  Google Scholar 

  18. 18.

    Le Deist F, Emile JF, Rieux-Laucat F, Benkerrou M, Roberts I, Brousse N, et al. Clinical, immunological, and pathological consequences of Fas-deficient conditions. Lancet. 1996;348(9029):719–23. https://doi.org/10.1016/S0140-6736(96)02293-3.

    Article  PubMed  Google Scholar 

  19. 19.

    Bettinardi A, Brugnoni D, Quiros-Roldan E, Malagoli A, La Grutta S, Correra A, et al. Missense mutations in the Fas gene resulting in autoimmune lymphoproliferative syndrome: a molecular and immunological analysis. Blood. 1997;89(3):902–9.

    PubMed  CAS  Google Scholar 

  20. 20.

    Holzelova E, Vonarbourg C, Stolzenberg MC, Arkwright PD, Selz F, Prieur AM, et al. Autoimmune lymphoproliferative syndrome with somatic Fas mutations. N Engl J Med. 2004;351(14):1409–18. https://doi.org/10.1056/NEJMoa040036.

    Article  PubMed  CAS  Google Scholar 

  21. 21.

    Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB, et al. Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. Blood. 2010;115(25):5164–9. https://doi.org/10.1182/blood-2010-01-263145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. 22.

    Savic S, Dickie LJ, Battellino M, McDermott MF. Familial Mediterranean fever and related periodic fever syndromes/autoinflammatory diseases. Curr Opin Rheumatol. 2012;24(1):103–12. https://doi.org/10.1097/BOR.0b013e32834dd2d5.

    Article  PubMed  CAS  Google Scholar 

  23. 23.

    Ma CA, Xi L, Cauff B, DeZure A, Freeman AF, Hambleton S, et al. Somatic STAT5b gain-of-function mutations in early onset nonclonal eosinophilia, urticaria, dermatitis, and diarrhea. Blood. 2017;129(5):650–3. https://doi.org/10.1182/blood-2016-09-737817.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. 24.

    Magerus-Chatinet A, Neven B, Stolzenberg MC, Daussy C, Arkwright PD, Lanzarotti N, et al. Onset of autoimmune lymphoproliferative syndrome (ALPS) in humans as a consequence of genetic defect accumulation. J Clin Invest. 2011;121(1):106–12. https://doi.org/10.1172/JCI43752.

    Article  PubMed  CAS  Google Scholar 

  25. 25.

    Martinez-Feito A, Melero J, Mora-Diaz S, Rodriguez-Vigil C, Elduayen R, Gonzalez-Granado LI, et al. Autoimmune lymphoproliferative syndrome due to somatic FAS mutation (ALPS-sFAS) combined with a germline caspase-10 (CASP10) variation. Immunobiology. 2016;221(1):40–7. https://doi.org/10.1016/j.imbio.2015.08.004.

    Article  PubMed  CAS  Google Scholar 

  26. 26.

    van der Burg M, de Groot R, Comans-Bitter WM, den Hollander JC, Hooijkaas H, Neijens HJ, et al. Autoimmune lymphoproliferative syndrome (ALPS) in a child from consanguineous parents: a dominant or recessive disease? Pediatr Res. 2000;47(3):336–43.

    Article  PubMed  Google Scholar 

  27. 27.

    Kasahara Y, Wada T, Niida Y, Yachie A, Seki H, Ishida Y, et al. Novel Fas (CD95/APO-1) mutations in infants with a lymphoproliferative disorder. Int Immunol. 1998;10(2):195–202.

    Article  PubMed  CAS  Google Scholar 

  28. 28.

    Del-Rey M, Ruiz-Contreras J, Bosque A, Calleja S, Gomez-Rial J, Roldan E, et al. A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome. Blood. 2006;108(4):1306–12. https://doi.org/10.1182/blood-2006-04-015776.

    Article  PubMed  CAS  Google Scholar 

  29. 29.

    Magerus-Chatinet A, Stolzenberg MC, Lanzarotti N, Neven B, Daussy C, Picard C, et al. Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand (FASLG) mutation. J Allergy Clin Immunol. 2013;131(2):486–90. https://doi.org/10.1016/j.jaci.2012.06.011.

    Article  PubMed  CAS  Google Scholar 

  30. 30.

    Sobh A, Crestani E, Cangemi B, Kane J, Chou J, Pai SY, et al. Autoimmune lymphoproliferative syndrome caused by a homozygous FasL mutation that disrupts FasL assembly. J Allergy Clin Immunol. 2015;137:324–327.e2. https://doi.org/10.1016/j.jaci.2015.08.025.

    Article  PubMed  Google Scholar 

  31. 31.

    Nabhani S, Honscheid A, Oommen PT, Fleckenstein B, Schaper J, Kuhlen M, et al. A novel homozygous Fas ligand mutation leads to early protein truncation, abrogation of death receptor and reverse signaling and a severe form of the autoimmune lymphoproliferative syndrome. Clin Immunol. 2014;155(2):231–7. https://doi.org/10.1016/j.clim.2014.10.006.

    Article  PubMed  CAS  Google Scholar 

  32. 32.

    Suzuki I, Fink PJ. Maximal proliferation of cytotoxic T lymphocytes requires reverse signaling through Fas ligand. J Exp Med. 1998;187(1):123–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. 33.

    Luckerath K, Kirkin V, Melzer IM, Thalheimer FB, Siele D, Milani W, et al. Immune modulation by Fas ligand reverse signaling: lymphocyte proliferation is attenuated by the intracellular Fas ligand domain. Blood. 2011;117(2):519–29. https://doi.org/10.1182/blood-2010-07-292722.

    Article  PubMed  CAS  Google Scholar 

  34. 34.

    Paulsen M, Mathew B, Qian J, Lettau M, Kabelitz D, Janssen O. FasL cross-linking inhibits activation of human peripheral T cells. Int Immunol. 2009;21(5):587–98. https://doi.org/10.1093/intimm/dxp028.

    Article  PubMed  CAS  Google Scholar 

  35. 35.

    Desbarats J, Duke RC, Newell MK. Newly discovered role for Fas ligand in the cell-cycle arrest of CD4+ T cells. Nat Med. 1998;4(12):1377–82. https://doi.org/10.1038/3965.

    Article  PubMed  CAS  Google Scholar 

  36. 36.

    Malleter M, Tauzin S, Bessede A, Castellano R, Goubard A, Godey F, et al. CD95L cell surface cleavage triggers a prometastatic signaling pathway in triple-negative breast cancer. Cancer Res. 2013;73(22):6711–21. https://doi.org/10.1158/0008-5472.CAN-13-1794.

    Article  PubMed  CAS  Google Scholar 

  37. 37.

    Kleber S, Sancho-Martinez I, Wiestler B, Beisel A, Gieffers C, Hill O, et al. Yes and PI3K bind CD95 to signal invasion of glioblastoma. Cancer Cell. 2008;13(3):235–48. https://doi.org/10.1016/j.ccr.2008.02.003.

    Article  PubMed  CAS  Google Scholar 

  38. 38.

    Poissonnier A, Sanseau D, Le Gallo M, Malleter M, Levoin N, Viel R, et al. CD95-mediated calcium signaling promotes T helper 17 trafficking to inflamed organs in lupus-prone mice. Immunity. 2016;45(1):209–23. https://doi.org/10.1016/j.immuni.2016.06.028.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. 39.

    Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995;270(5239):1189–92.

    Article  PubMed  CAS  Google Scholar 

  40. 40.

    Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC. A role for CD95 ligand in preventing graft rejection. Nature. 1995;377(6550):630–2. https://doi.org/10.1038/377630a0.

    Article  PubMed  CAS  Google Scholar 

  41. 41.

    O'Connell J. Fas ligand and the fate of antitumour cytotoxic T lymphocytes. Immunology. 2002;105(3):263–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. 42.

    Kang SM, Schneider DB, Lin Z, Hanahan D, Dichek DA, Stock PG, et al. Fas ligand expression in islets of Langerhans does not confer immune privilege and instead targets them for rapid destruction. Nat Med. 1997;3(7):738–43.

    Article  PubMed  CAS  Google Scholar 

  43. 43.

    Dupont PJ, Warrens AN. Fas ligand exerts its pro-inflammatory effects via neutrophil recruitment but not activation. Immunology. 2007;120(1):133–9. https://doi.org/10.1111/j.1365-2567.2006.02504.x.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. 44.

    Ferguson TA, Griffith TS. A vision of cell death: Fas ligand and immune privilege 10 years later. Immunol Rev. 2006;213:228–38. https://doi.org/10.1111/j.1600-065X.2006.00430.x.

    Article  PubMed  CAS  Google Scholar 

  45. 45.

    Wu JG, Wilson J, He J, Xiang LB, Schur PH, Mountz JD. Fas ligand mutation in a patient with systemic lupus erythematosus and lymphoproliferative disease. J Clin Investig. 1996;98(5):1107–13.

    Article  PubMed  CAS  Google Scholar 

  46. 46.

    Bi LL, Pan G, Atkinson TP, Zheng L, Dale JK, Makris C, et al. Dominant inhibition of Fas ligand-mediated apoptosis due to a heterozygous mutation associated with autoimmune lymphoproliferative syndrome (ALPS) type Ib. BMC Med Genet. 2007;8:41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. 47.

    Bolze A, Byun M, McDonald D, Morgan NV, Abhyankar A, Premkumar L, et al. Whole-exome-sequencing-based discovery of human FADD deficiency. Am J Hum Genet. 2010;87(6):873–81. https://doi.org/10.1016/j.ajhg.2010.10.028.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. 48.

    Zhang J, Cado D, Chen A, Kabra NH, Winoto A. Fas-mediated apoptosis and activation-induced T-cell proliferation are defective in mice lacking FADD/Mort1. Nature. 1998;392(6673):296–300.

    Article  PubMed  CAS  Google Scholar 

  49. 49.

    Zhu S, Hsu AP, Vacek MM, Zheng L, Schaffer AA, Dale JK, et al. Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome. Hum Genet. 2006;119(3):284–94. https://doi.org/10.1007/s00439-006-0138-9.

    Article  PubMed  CAS  Google Scholar 

  50. 50.

    Campagnoli MF, Garbarini L, Quarello P, Garelli E, Carando A, Baravalle V, et al. The broad spectrum of autoimmune lymphoproliferative disease: molecular bases, clinical features and long-term follow-up in 31 patients. Haematologica. 2006;91(4):538–41.

    PubMed  CAS  Google Scholar 

  51. 51.

    Puck JM, Zhu S. Immune disorders caused by defects in the caspase cascade. Curr Allergy Asthma Rep. 2003;3(5):378–84.

    Article  PubMed  Google Scholar 

  52. 52.

    Wang J, Zheng L, Lobito A, Chan FK, Dale J, Sneller M, et al. Inherited human caspase 10 mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome type II. Cell. 1999;98(1):47–58. https://doi.org/10.1016/S0092-8674(00)80605-4.

    Article  PubMed  CAS  Google Scholar 

  53. 53.

    Cerutti E, Campagnoli MF, Ferretti M, Garelli E, Crescenzio N, Rosolen A, et al. Co-inherited mutations of Fas and caspase-10 in development of the autoimmune lymphoproliferative syndrome. BMC Immunol. 2007;8:28.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. 54.

    Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002;419(6905):395–9. https://doi.org/10.1038/nature01063.

    Article  PubMed  CAS  Google Scholar 

  55. 55.

    Niemela J, Kuehn HS, Kelly C, Zhang M, Davies J, Melendez J, et al. Caspase-8 deficiency presenting as late-onset multi-organ lymphocytic infiltration with granulomas in two adult siblings. J Clin Immunol. 2015;35(4):348–55. https://doi.org/10.1007/s10875-015-0150-8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. 56.

    Salmena L, Hakem R. Caspase-8 deficiency in T cells leads to a lethal lymphoinfiltrative immune disorder. J Exp Med. 2005;202(6):727–32. https://doi.org/10.1084/jem.20050683.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. 57.

    Kataoka T, Budd RC, Holler N, Thome M, Martinon F, Irmler M, et al. The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways. Curr Biol. 2000;10(11):640–8.

    Article  PubMed  CAS  Google Scholar 

  58. 58.

    Shah S, Wu E, Rao VK, Tarrant TK. Autoimmune lymphoproliferative syndrome: an update and review of the literature. Curr Allergy Asthma Rep. 2014;14(9):462. https://doi.org/10.1007/s11882-014-0462-4.

    Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ, et al. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome: report from the 2009 NIH International Workshop. Blood. 2010;116:e35–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. 60.

    Rensing-Ehl A, Volkl S, Speckmann C, Lorenz MR, Ritter J, Janda A, et al. Abnormally differentiated CD4+ or CD8+ T cells with phenotypic and genetic features of double negative T cells in human Fas deficiency. Blood. 2014;124(6):851–60. https://doi.org/10.1182/blood-2014-03-564286.

    Article  PubMed  CAS  Google Scholar 

  61. 61.

    Magerus-Chatinet A, Stolzenberg MC, Loffredo MS, Neven B, Schaffner C, Ducrot N, et al. FAS-L, IL-10, and double-negative CD4− CD8− TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoproliferative syndrome (ALPS) associated with FAS loss of function. Blood. 2009;113(13):3027–30. https://doi.org/10.1182/blood-2008-09-179630.

    Article  PubMed  CAS  Google Scholar 

  62. 62.

    Neven B, Bruneau J, Stolzenberg MC, Meyts I, Magerus-Chatinet A, Moens L, et al. Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patients. Blood. 2014;124(10):1597–609. https://doi.org/10.1182/blood-2014-02-553834.

    Article  PubMed  CAS  Google Scholar 

  63. 63.

    van den Berg A, Tamminga R, de Jong D, Maggio E, Kamps W, Poppema S. FAS gene mutation in a case of autoimmune lymphoproliferative syndrome type IA with accumulation of gammadelta+ T cells. Am J Surg Pathol. 2003;27(4):546–53.

    Article  PubMed  Google Scholar 

  64. 64.

    Neven B, Magerus-Chatinet A, Florkin B, Gobert D, Lambotte O, De Somer L, et al. A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. Blood. 2011;118(18):4798–807. https://doi.org/10.1182/blood-2011-04-347641.

    Article  PubMed  CAS  Google Scholar 

  65. 65.

    Rensing-Ehl A, Warnatz K, Fuchs S, Schlesier M, Salzer U, Draeger R, et al. Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency. Clin Immunol. 2010;137(3):357–65. https://doi.org/10.1016/j.clim.2010.08.008.

    Article  PubMed  CAS  Google Scholar 

  66. 66.

    Roberts CA, Ayers L, Bateman EA, Sadler R, Magerus-Chatinet A, Rieux-Laucat F, et al. Investigation of common variable immunodeficiency patients and healthy individuals using autoimmune lymphoproliferative syndrome biomarkers. Hum Immunol. 2013;74(12):1531–5. https://doi.org/10.1016/j.humimm.2013.08.266.

    Article  PubMed  CAS  Google Scholar 

  67. 67.

    Sriram S, Joshi AY, Rodriguez V, Kumar S. Autoimmune lymphoproliferative syndrome: a rare cause of disappearing HDL syndrome. Case Rep Immunol. 2016;2016:7945953. https://doi.org/10.1155/2016/7945953.

    Article  Google Scholar 

  68. 68.

    Muppidi JR, Siegel RM. Ligand-independent redistribution of Fas (CD95) into lipid rafts mediates clonotypic T cell death. Nat Immunol. 2004;5(2):182–9. https://doi.org/10.1038/ni1024.

    Article  PubMed  CAS  Google Scholar 

  69. 69.

    Caminha I, Fleisher TA, Hornung RL, Dale JK, Niemela JE, Price S, et al. Using biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome. J Allergy Clin Immunol. 2010;125(4):946–9 e6. https://doi.org/10.1016/j.jaci.2009.12.983.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. 70.

    Lambotte O, Neven B, Galicier L, Magerus-Chatinet A, Schleinitz N, Hermine O, et al. Diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency in adults. Haematologica. 2013;98(3):389–92. https://doi.org/10.3324/haematol.2012.067488.

    Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Teachey DT, Manno CS, Axsom KM, Andrews T, Choi JK, Greenbaum BH, et al. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS). Blood. 2005;105(6):2443–8. https://doi.org/10.1182/blood-2004-09-3542.

    Article  PubMed  CAS  Google Scholar 

  72. 72.

    Lo B, Abdel-Motal UM. Lessons from CTLA-4 deficiency and checkpoint inhibition. Curr Opin Immunol. 2017;49:14–9. https://doi.org/10.1016/j.coi.2017.07.014.

    Article  PubMed  CAS  Google Scholar 

  73. 73.

    Janda A, Schwarz K, van der Burg M, Vach W, Ijspeert H, Lorenz MR, et al. Disturbed B-lymphocyte selection in autoimmune lymphoproliferative syndrome. Blood. 2016;127(18):2193–202. https://doi.org/10.1182/blood-2015-04-642488.

    Article  PubMed  CAS  Google Scholar 

  74. 74.

    Boulanger E, Rieux-Laucat F, Picard C, Legall M, Sigaux F, Clauvel JP, et al. Diffuse large B-cell non-Hodgkin’s lymphoma in a patient with autoimmune lymphoproliferative syndrome. Br J Haematol. 2001;113(2):432–4.

    Article  PubMed  CAS  Google Scholar 

  75. 75.

    Straus SE, Jaffe ES, Puck JM, Dale JK, Elkon KB, Rosen-Wolff A, et al. The development of lymphomas in families with autoimmune lymphoproliferative syndrome with germline Fas mutations and defective lymphocyte apoptosis. Blood. 2001;98(1):194–200.

    Article  PubMed  CAS  Google Scholar 

  76. 76.

    Price S, Shaw PA, Seitz A, Joshi G, Davis J, Niemela JE, et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014;123(13):1989–99. https://doi.org/10.1182/blood-2013-10-535393.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. 77.

    Rao VK, Oliveira JB. How I treat autoimmune lymphoproliferative syndrome. Blood. 2011;118(22):5741–51. https://doi.org/10.1182/blood-2011-07-325217.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. 78.

    Klemann C, Esquivel M, Magerus-Chatinet A, Lorenz MR, Fuchs I, Neveux N, et al. Evolution of disease activity and biomarkers on and off rapamycin in 28 patients with autoimmune lymphoproliferative syndrome. Haematologica. 2017;102(2):e52–e6. https://doi.org/10.3324/haematol.2016.153411.

    Article  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Sleight BJ, Prasad VS, DeLaat C, Steele P, Ballard E, Arceci RJ, et al. Correction of autoimmune lymphoproliferative syndrome by bone marrow transplantation. Bone Marrow Transplant. 1998;22(4):375–80. https://doi.org/10.1038/sj.bmt.1701306.

    Article  PubMed  CAS  Google Scholar 

  80. 80.

    Benkerrou M, Le Deist F, de Villartay J, Caillat-Zuckman S, Rieux-Laucat F, Jabado N, et al. Correction of fas (CD95) deficiency by haploidentical bone marrow transplantation. Eur J Immunol. 1997;27:2043–7.

    Article  PubMed  CAS  Google Scholar 

  81. 81.

    Rieux-Laucat F, Immunology CJL. Autoimmunity by haploinsufficiency. Science. 2014;345(6204):1560–1. https://doi.org/10.1126/science.1260791.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Frédéric Rieux-Laucat.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rieux-Laucat, F., Magérus-Chatinet, A. & Neven, B. The Autoimmune Lymphoproliferative Syndrome with Defective FAS or FAS-Ligand Functions. J Clin Immunol 38, 558–568 (2018). https://doi.org/10.1007/s10875-018-0523-x

Download citation

Keywords

  • FAS
  • FASLG
  • apoptosis
  • lymphoproliferation
  • autoimmunity