nach oben

Journal of Clinical Immunology

Erschienen in:

30.10.2017 | CME Review

Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome

verfasst von: Fabio Candotti

Erschienen in: Journal of Clinical Immunology | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

The Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder originally described by Dr. Alfred Wiskott in 1937 and Dr. Robert Aldrich in 1954 as a familial disease characterized by infections, bleeding tendency, and eczema. Today, it is well recognized that the syndrome has a wide clinical spectrum ranging from mild, isolated thrombocytopenia to full-blown presentation that can be complicated by life-threatening hemorrhages, immunodeficiency, atopy, autoimmunity, and cancer. The pathophysiology of classic and emerging features is being elucidated by clinical studies, but remains incompletely defined, which hinders the application of targeted therapies. At the same time, progress of hematopoietic stem cell transplantation and gene therapy offer optimistic prospects for treatment options aimed at the replacement of the defective lymphohematopoietic system that have the potential to provide a cure for this rare and polymorphic disease.

Wiskott A. Familiärer, angeborener Morbus Werlhofii? Monatsschr Kinderheilkd. 1937;68:212–6.

Aldrich RA, Steinberg AG, Campbell DC. Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea. Pediatrics. 1954;13(2):133–9.PubMed

Kwan SP, Sandkuyl LA, Blaese M, Kunkel LM, Bruns G, Parmley R, et al. Genetic mapping of the Wiskott-Aldrich syndrome with two highly-linked polymorphic DNA markers. Genomics. 1988;3(1):39–43.PubMedCrossRef

de Saint Basile G, Arveiler B, Fraser NJ, Boyd Y, Graig IW, Griscelli G, et al. Close linkage of hypervariable marker DXS255 to disease locus of Wiskott-Aldrich syndrome. Lancet. 1989;2(8675):1319–21.PubMedCrossRef

Derry JM, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell. 1994;78(4):635–44.PubMedCrossRef

Perry GS III, Spector BD, Schuman LM, Mandel JS, Anderson VE, McHugh RB, et al. The Wiskott-Aldrich syndrome in the United States and Canada (1892-1979). J Pediatr. 1980;97(1):72–8.PubMedCrossRef

Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA. A multiinstitutional survey of the Wiskott-Aldrich syndrome. J Pediatr. 1994;125(6 Pt 1):876–85.PubMedCrossRef

Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, et al. Clinical course of patients with WASP gene mutations. Blood. 2004;103(2):456–64. https://doi.org/10.1182/blood-2003-05-1480.PubMedCrossRef

Mahlaoui N, Pellier I, Mignot C, Jais JP, Bilhou-Nabera C, Moshous D, et al. Characteristics and outcome of early-onset, severe forms of Wiskott-Aldrich syndrome. Blood. 2013;121(9):1510–6. https://doi.org/10.1182/blood-2012-08-448118.PubMedCrossRef

10.

Zhu Q, Zhang M, Blaese RM, Derry JM, Junker A, Francke U, et al. The Wiskott-Aldrich syndrome and X-linked congenital thrombocytopenia are caused by mutations of the same gene. Blood. 1995;86(10):3797–804.PubMed

11.

Ochs HD, Filipovich AH, Veys P, Cowan MJ, Kapoor N. Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment. Biol Blood Marrow Transplant. 2009;15(1 Suppl):84–90. https://doi.org/10.1016/j.bbmt.2008.10.007. PubMedCrossRef

12.

Villa A, Notarangelo L, Macchi P, Mantuano E, Cavagni G, Brugnoni D, et al. X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nat Genet. 1995;9(4):414–7.PubMedCrossRef

13.

Albert MH, Bittner TC, Nonoyama S, Notarangelo LD, Burns S, Imai K, et al. X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options. Blood. 2010;115(16):3231–8. https://doi.org/10.1182/blood-2009-09-239087.PubMedCrossRef

14.

Liu DW, Zhang ZY, Zhao Q, Jiang LP, Liu W, Tu WW, et al. Wiskott-Aldrich syndrome/X-linked thrombocytopenia in China: clinical characteristic and genotype-phenotype correlation. Pediatr Blood Cancer. 2015;62(9):1601–8. https://doi.org/10.1002/pbc.25559.PubMedCrossRef

15.

Patel PD, Samanich JM, Mitchell WB, Manwani D. A unique presentation of Wiskott-Aldrich syndrome in relation to platelet size. Pediatr Blood Cancer. 2011;56(7):1127–9. https://doi.org/10.1002/pbc.22920.PubMedCrossRef

16.

Mantadakis E, Sawalle-Belohradsky J, Tzanoudaki M, Kanariou M, Chatzimichael A, Albert MH. X-linked thrombocytopenia in three males with normal sized platelets due to novel WAS gene mutations. Pediatr Blood Cancer. 2014;61(12):2305–6. https://doi.org/10.1002/pbc.25196.PubMedCrossRef

17.

Sokolic R, Oden N, Candotti F. Assessment of immature platelet fraction in the diagnosis of Wiskott-Aldrich syndrome. Front Pediatr. 2015;3:49. https://doi.org/10.3389/fped.2015.00049.PubMedPubMedCentralCrossRef

18.

Baharin MF, Dhaliwal JS, Sarachandran SV, Idris SZ, Yeoh SL. A rare case of Wiskott-Aldrich syndrome with normal platelet size: a case report. J Med Case Rep. 2016;10(1):188. https://doi.org/10.1186/s13256-016-0944-1. PubMedPubMedCentralCrossRef

19.

Bastida JM, Del Rey M, Revilla N, Benito R, Perez-Andres M, Gonzalez B, et al. Wiskott-Aldrich syndrome in a child presenting with macrothrombocytopenia. Platelets. 2017;28(4):417–20. https://doi.org/10.1080/09537104.2016.1246715.PubMedCrossRef

20.

Haddad E, Cramer E, Riviere C, Rameau P, Louache F, Guichard J, et al. The thrombocytopenia of Wiskott Aldrich syndrome is not related to a defect in proplatelet formation. Blood. 1999;94(2):509–18.PubMed

21.

Ochs HD, Slichter SJ, Harker LA, Von Behrens WE, Clark RA, Wedgwood RJ. The Wiskott-Aldrich syndrome: studies of lymphocytes, granulocytes, and platelets. Blood. 1980;55(2):243–52.PubMed

22.

Semple JW, Siminovitch KA, Mody M, Milev Y, Lazarus AH, Wright JF, et al. Flow cytometric analysis of platelets from children with the Wiskott- Aldrich syndrome reveals defects in platelet development, activation and structure. Br J Haematol. 1997;97(4):747–54.PubMedCrossRef

23.

Prislovsky A, Zeng X, Sokolic RA, Garabedian EN, Anur P, Candotti F, et al. Platelets from WAS patients show an increased susceptibility to ex vivo phagocytosis. Platelets. 2013;24(4):288–96. https://doi.org/10.3109/09537104.2012.693991.PubMedCrossRef

24.

Gerrits AJ, Leven EA, Frelinger AL III, Brigstocke SL, Berny-Lang MA, Mitchell WB, et al. Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia. Blood. 2015;126(11):1367–78. https://doi.org/10.1182/blood-2014-09-602573.PubMedPubMedCentralCrossRef

25.

Ingrungruanglert P, Amarinthnukrowh P, Rungsiwiwut R, Maneesri-le Grand S, Sosothikul D, Suphapeetiporn K, et al. Wiskott-Aldrich syndrome iPS cells produce megakaryocytes with defects in cytoskeletal rearrangement and proplatelet formation. Thromb Haemost. 2015;113(4):792–805. https://doi.org/10.1160/TH14-06-0503. PubMedCrossRef

26.

Mullen CA, Anderson KD, Blaese RM. Splenectomy and/or bone marrow transplantation in the management of the Wiskott-Aldrich syndrome: long-term follow-up of 62 cases. Blood. 1993;82(10):2961–6.PubMed

27.

Litzman J, Jones A, Hann I, Chapel H, Strobel S, Morgan G. Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome. Arch Dis Child. 1996;75(5):436–9.PubMedPubMedCentralCrossRef

28.

Grottum KA, Hovig T, Holmsen H, Abrahamsen AF, Jeremic M, Seip M. Wiskott-Aldrich syndrome: qualitative platelet defects and short platelet survival. Br J Haematol. 1969;17(4):373–88.PubMedCrossRef

29.

Baldini MG. Nature of the platelet defect in the Wiskott-Aldrich syndrome. Ann N Y Acad Sci. 1972;201:437–44.PubMedCrossRef

30.

Zhang ZY, Xiao HQ, Jiang LP, Zhou Y, Zhao Q, Yu J, et al. Analysis of clinical and molecular characteristics of Wiskott-Aldrich syndrome in 24 patients from 23 unrelated Chinese families. Pediatr Allergy Immunol. 2010;21(3):522–32. https://doi.org/10.1111/j.1399-3038.2010.00996.x.PubMedCrossRef

31.

Badolato R, Sozzani S, Malacarne F, Bresciani S, Fiorini M, Borsatti A, et al. Monocytes from Wiskott-Aldrich patients display reduced chemotaxis and lack of cell polarization in response to monocyte chemoattractant protein-1 and formyl-methionyl-leucyl-phenylalanine. J Immunol. 1998;161(2):1026–33.PubMed

32.

Zicha D, Allen WE, Brickell PM, Kinnon C, Dunn GA, Jones GE, et al. Chemotaxis of macrophages is abolished in the Wiskott-Aldrich syndrome. Br J Haematol. 1998;101(4):659–65.PubMedCrossRef

33.

Linder S, Nelson D, Weiss M, Aepfelbacher M. Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages. Proc Natl Acad Sci U S A. 1999;96(17):9648–53.PubMedPubMedCentralCrossRef

34.

Lorenzi R, Brickell PM, Katz DR, Kinnon C, Thrasher AJ. Wiskott-Aldrich syndrome protein is necessary for efficient IgG-mediated phagocytosis. Blood. 2000;95(9):2943–6.PubMed

35.

Zhang H, Schaff UY, Green CE, Chen H, Sarantos MR, Hu Y, et al. Impaired integrin-dependent function in Wiskott-Aldrich syndrome protein-deficient murine and human neutrophils. Immunity. 2006;25(2):285–95. https://doi.org/10.1016/j.immuni.2006.06.014.PubMedPubMedCentralCrossRef

36.

Binks M, Jones GE, Brickell PM, Kinnon C, Katz DR, Thrasher AJ. Intrinsic dendritic cell abnormalities in Wiskott-Aldrich syndrome. Eur J Immunol. 1998;28(10):3259–67. https://doi.org/10.1002/(SICI)1521-4141(199810)28:10<3259::AID-IMMU3259>3.0.CO;2-B.PubMedCrossRef

37.

Pulecio J, Tagliani E, Scholer A, Prete F, Fetler L, Burrone OR, et al. Expression of Wiskott-Aldrich syndrome protein in dendritic cells regulates synapse formation and activation of naive CD8+ T cells. J Immunol. 2008;181(2):1135–42.PubMedCrossRef

38.

Bouma G, Mendoza-Naranjo A, Blundell MP, de Falco E, Parsley KL, Burns SO, et al. Cytoskeletal remodeling mediated by WASp in dendritic cells is necessary for normal immune synapse formation and T-cell priming. Blood. 2011;118(9):2492–501. https://doi.org/10.1182/blood-2011-03-340265.PubMedCrossRef

39.

Stabile H, Carlino C, Mazza C, Giliani S, Morrone S, Notarangelo LD, et al. Impaired NK-cell migration in WAS/XLT patients: role of Cdc42/WASp pathway in the control of chemokine-induced beta2 integrin high-affinity state. Blood. 2010;115(14):2818–26. https://doi.org/10.1182/blood-2009-07-235804.PubMedPubMedCentralCrossRef

40.

Orange JS, Ramesh N, Remold-O'Donnell E, Sasahara Y, Koopman L, Byrne M, et al. Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses. Proc Natl Acad Sci U S A. 2002;99(17):11351–6. https://doi.org/10.1073/pnas.162376099.PubMedPubMedCentralCrossRef

41.

Huang W, Ochs HD, Dupont B, Vyas YM. The Wiskott-Aldrich syndrome protein regulates nuclear translocation of NFAT2 and NF-kappa B (RelA) independently of its role in filamentous actin polymerization and actin cytoskeletal rearrangement. J Immunol. 2005;174(5):2602–11.PubMedCrossRef

42.

Gismondi A, Cifaldi L, Mazza C, Giliani S, Parolini S, Morrone S, et al. Impaired natural and CD16-mediated NK cell cytotoxicity in patients with WAS and XLT: ability of IL-2 to correct NK cell functional defect. Blood. 2004;104(2):436–43. https://doi.org/10.1182/blood-2003-07-2621.PubMedCrossRef

43.

Park JY, Kob M, Prodeus AP, Rosen FS, Shcherbina A, Remold-O’Donnell E. Early deficit of lymphocytes in Wiskott-Aldrich syndrome: possible role of WASP in human lymphocyte maturation. Clin Exp Immunol. 2004;136(1):104–10.PubMedPubMedCentralCrossRef

44.

Rawlings SL, Crooks GM, Bockstoce D, Barsky LW, Parkman R, Weinberg KI. Spontaneous apoptosis in lymphocytes from patients with Wiskott-Aldrich syndrome: correlation of accelerated cell death and attenuated bcl-2 expression. Blood. 1999;94(11):3872–82.PubMed

45.

Wada T, Schurman SH, Garabedian EK, Yachie A, Candotti F. Analysis of T-cell repertoire diversity in Wiskott-Aldrich syndrome. Blood. 2005;106(12):3895–7. https://doi.org/10.1182/blood-2005-06-2336.PubMedPubMedCentralCrossRef

46.

Wu J, Liu D, Tu W, Song W, Zhao X. T-cell receptor diversity is selectively skewed in T-cell populations of patients with Wiskott-Aldrich syndrome. J Allergy Clin Immunol. 2015;135(1):209–16. https://doi.org/10.1016/j.jaci.2014.06.025.PubMedCrossRef

47.

O'Connell AE, Volpi S, Dobbs K, Fiorini C, Tsitsikov E, de Boer H, et al. Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with Wiskott-Aldrich syndrome. Front Immunol. 2014;5:340. https://doi.org/10.3389/fimmu.2014.00340.PubMedPubMedCentral

48.

Molina IJ, Kenney DM, Rosen FS, Remold ODE. T cell lines characterize events in the pathogenesis of the Wiskott-Aldrich syndrome. J Exp Med. 1992;176(3):867–74.PubMedCrossRef

49.

Molina IJ, Sancho J, Terhorst C, Rosen FS, Remold ODE. T cells of patients with the Wiskott-Aldrich syndrome have a restricted defect in proliferative responses. J Immunol. 1993;151(8):4383–90.PubMed

50.

Haddad E, Zugaza JL, Louache F, Debili N, Crouin C, Schwarz K, et al. The interaction between Cdc42 and WASP is required for SDF-1-induced T- lymphocyte chemotaxis. Blood. 2001;97(1):33–8.PubMedCrossRef

51.

Dupre L, Aiuti A, Trifari S, Martino S, Saracco P, Bordignon C, et al. Wiskott-Aldrich syndrome protein regulates lipid raft dynamics during immunological synapse formation. Immunity. 2002;17(2):157–66.PubMedCrossRef

52.

Calvez R, Lafouresse F, De Meester J, Galy A, Valitutti S, Dupre L. The Wiskott-Aldrich syndrome protein permits assembly of a focused immunological synapse enabling sustained T-cell receptor signaling. Haematologica. 2011;96(10):1415–23. https://doi.org/10.3324/haematol.2011.040204.PubMedPubMedCentralCrossRef

53.

Zhang X, Dai R, Li W, Zhao H, Zhang Y, Zhou L, et al. Abnormalities of follicular helper T-cell number and function in Wiskott-Aldrich syndrome. Blood. 2016;127(25):3180–91. https://doi.org/10.1182/blood-2015-06-652636.PubMedPubMedCentralCrossRef

54.

Castiello MC, Bosticardo M, Pala F, Catucci M, Chamberlain N, van Zelm MC, et al. Wiskott-Aldrich syndrome protein deficiency perturbs the homeostasis of B-cell compartment in humans. J Autoimmun. 2014;50:42–50. https://doi.org/10.1016/j.jaut.2013.10.006. PubMedPubMedCentralCrossRef

55.

Park JY, Shcherbina A, Rosen FS, Prodeus AP, Remold-O’Donnell E. Phenotypic perturbation of B cells in the Wiskott-Aldrich syndrome. Clin Exp Immunol. 2005;139(2):297–305. https://doi.org/10.1111/j.1365-2249.2005.02693.x.PubMedPubMedCentralCrossRef

56.

Simon KL, Anderson SM, Garabedian EK, Moratto D, Sokolic RA, Candotti F. Molecular and phenotypic abnormalities of B lymphocytes in patients with Wiskott-Aldrich syndrome. J Allergy Clin Immunol. 2014;133(3):896–899 e4. https://doi.org/10.1016/j.jaci.2013.08.050.PubMedCrossRef

57.

Dupuis-Girod S, Medioni J, Haddad E, Quartier P, Cavazzana-Calvo M, Le Deist F, et al. Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients. Pediatrics. 2003;111(5 Pt 1):e622–7.PubMedCrossRef

58.

Ozsahin H, Cavazzana-Calvo M, Notarangelo LD, Schulz A, Thrasher AJ, Mazzolari E, et al. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood. 2008;111(1):439–45. https://doi.org/10.1182/blood-2007-03-076679.PubMedCrossRef

59.

Moratto D, Giliani S, Bonfim C, Mazzolari E, Fischer A, Ochs HD, et al. Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980-2009: an international collaborative study. Blood. 2011;118(6):1675–84. https://doi.org/10.1182/blood-2010-11-319376.PubMedPubMedCentralCrossRef

60.

Schurman SH, Candotti F. Autoimmunity in Wiskott-Aldrich syndrome. Curr Opin Rheumatol. 2003;15(4):446–53.PubMedCrossRef

61.

Chen N, Zhang ZY, Liu DW, Liu W, Tang XM, Zhao XD. The clinical features of autoimmunity in 53 patients with Wiskott-Aldrich syndrome in China: a single-center study. Eur J Pediatr. 2015;174(10):1311–8. https://doi.org/10.1007/s00431-015-2527-3.PubMedCrossRef

62.

Adriani M, Aoki J, Horai R, Thornton AM, Konno A, Kirby M, et al. Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich syndrome. Clin Immunol. 2007;124(1):41–8. https://doi.org/10.1016/j.clim.2007.02.001.PubMedPubMedCentralCrossRef

63.

Marangoni F, Trifari S, Scaramuzza S, Panaroni C, Martino S, Notarangelo LD, et al. WASP regulates suppressor activity of human and murine CD4(+)CD25(+)FOXP3(+) natural regulatory T cells. J Exp Med. 2007;204(2):369–80. https://doi.org/10.1084/jem.20061334.PubMedPubMedCentralCrossRef

64.

Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G. Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med. 2001;193(11):1303–10.PubMedPubMedCentralCrossRef

65.

Baecher-Allan C, Hafler DA. Human regulatory T cells and their role in autoimmune disease. Immunol Rev. 2006;212:203–16. https://doi.org/10.1111/j.0105-2896.2006.00417.x.PubMedCrossRef

66.

Bouma G, Carter NA, Recher M, Malinova D, Adriani M, Notarangelo LD, et al. Exacerbated experimental arthritis in Wiskott-Aldrich syndrome protein deficiency: modulatory role of regulatory B cells. Eur J Immunol. 2014;44(9):2692–702. https://doi.org/10.1002/eji.201344245.PubMedPubMedCentralCrossRef

67.

Du HQ, Zhang X, An YF, Ding Y, Zhao XD. Effects of Wiskott-Aldrich syndrome protein deficiency on IL-10-producing regulatory B cells in humans and mice. Scand J Immunol. 2015;81(6):483–93. https://doi.org/10.1111/sji.12282.PubMedCrossRef

68.

Crestani E, Volpi S, Candotti F, Giliani S, Notarangelo LD, Chu J, et al. Broad spectrum of autoantibodies in patients with Wiskott-Aldrich syndrome and X-linked thrombocytopenia. J Allergy Clin Immunol. 2015;136(5):1401–1404 e1–3. https://doi.org/10.1016/j.jaci.2015.08.010.PubMedPubMedCentralCrossRef

69.

Pala F, Morbach H, Castiello MC, Schickel JN, Scaramuzza S, Chamberlain N, et al. Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients. J Clin Invest. 2015;125(10):3941–51. https://doi.org/10.1172/JCI82249.PubMedPubMedCentralCrossRef

70.

Kolhatkar NS, Brahmandam A, Thouvenel CD, Becker-Herman S, Jacobs HM, Schwartz MA, et al. Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome. J Exp Med. 2015;212(10):1663–77. https://doi.org/10.1084/jem.20150585.PubMedPubMedCentralCrossRef

71.

Kinnunen T, Chamberlain N, Morbach H, Choi J, Kim S, Craft J, et al. Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells. Blood. 2013;121(9):1595–603. https://doi.org/10.1182/blood-2012-09-457465.PubMedPubMedCentralCrossRef

72.

Shimizu M, Kanegane H, Wada T, Motoyoshi Y, Morio T, Candotti F, et al. Aberrant glycosylation of IgA in Wiskott-Aldrich syndrome and X-linked thrombocytopenia. J Allergy Clin Immunol. 2013;131(2):587–590 e1–3. https://doi.org/10.1016/j.jaci.2012.08.040.PubMedCrossRef

73.

Tomana M, Novak J, Julian BA, Matousovic K, Konecny K, Mestecky J. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactose-deficient hinge region and antiglycan antibodies. J Clin Invest. 1999;104(1):73–81. https://doi.org/10.1172/JCI5535.PubMedPubMedCentralCrossRef

74.

Chintalacharuvu SR, Yamashita M, Bagheri N, Blanchard TG, Nedrud JG, Lamm ME, et al. T cell cytokine polarity as a determinant of immunoglobulin A (IgA) glycosylation and the severity of experimental IgA nephropathy. Clin Exp Immunol. 2008;153(3):456–62. https://doi.org/10.1111/j.1365-2249.2008.03703.x.PubMedPubMedCentralCrossRef

75.

Taylor MD, Sadhukhan S, Kottangada P, Ramgopal A, Sarkar K, D'Silva S, et al. Nuclear role of WASp in the pathogenesis of dysregulated TH1 immunity in human Wiskott-Aldrich syndrome. Sci Transl Med. 2010;2(37):37ra44. https://doi.org/10.1126/scitranslmed.3000813.PubMedPubMedCentralCrossRef

76.

Lexmond WS, Goettel JA, Lyons JJ, Jacobse J, Deken MM, Lawrence MG, et al. FOXP3+ Tregs require WASP to restrain Th2-mediated food allergy. J Clin Invest. 2016;126(10):4030–44. https://doi.org/10.1172/JCI85129.PubMedPubMedCentralCrossRef

77.

Trifari S, Sitia G, Aiuti A, Scaramuzza S, Marangoni F, Guidotti LG, et al. Defective Th1 cytokine gene transcription in CD4+ and CD8+ T cells from Wiskott-Aldrich syndrome patients. J Immunol. 2006;177(10):7451–61.PubMedCrossRef

78.

Peng W, Novak N. Pathogenesis of atopic dermatitis. Clin Exp Allergy. 2015;45(3):566–74. https://doi.org/10.1111/cea.12495.PubMedCrossRef

79.

Tuano KS, Orange JS, Sullivan K, Cunningham-Rundles C, Bonilla FA, Davis CM. Food allergy in patients with primary immunodeficiency diseases: prevalence within the US Immunodeficiency Network (USIDNET). J Allergy Clin Immunol. 2015;135(1):273–5. https://doi.org/10.1016/j.jaci.2014.09.024.PubMedCrossRef

80.

Cotelingam JD, Witebsky FG, Hsu SM, Blaese RM, Jaffe ES. Malignant lymphoma in patients with the Wiskott-Aldrich syndrome. Cancer Investig. 1985;3(6):515–22.CrossRef

81.

Picard C, Mellouli F, Duprez R, Chedeville G, Neven B, Fraitag S, et al. Kaposi’s sarcoma in a child with Wiskott-Aldrich syndrome. Eur J Pediatr. 2006;165(7):453–7. https://doi.org/10.1007/s00431-006-0107-2.PubMedCrossRef

82.

Yoshimi A, Kamachi Y, Imai K, Watanabe N, Nakadate H, Kanazawa T, et al. Wiskott-Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia. Pediatr Blood Cancer. 2013;60(5):836–41. https://doi.org/10.1002/pbc.24359.PubMedCrossRef

83.

De Meester J, Calvez R, Valitutti S, Dupre L. The Wiskott-Aldrich syndrome protein regulates CTL cytotoxicity and is required for efficient killing of B cell lymphoma targets. J Leukoc Biol. 2010;88(5):1031–40. https://doi.org/10.1189/jlb.0410197.PubMedCrossRef

84.

Moratto D, Giliani S, Notarangelo LD, Mazza C, Mazzolari E, Notarangelo LD. The Wiskott-Aldrich syndrome: from genotype-phenotype correlation to treatment. Expert Rev Clin Immunol. 2007;3(5):813–24. https://doi.org/10.1586/1744666X.3.5.813.PubMedCrossRef

85.

Jin Y, Mazza C, Christie JR, Giliani S, Fiorini M, Mella P, et al. Mutations of the Wiskott-Aldrich syndrome protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood. 2004;104(13):4010–9.PubMedCrossRef

86.

Shcherbina A, Candotti F, Rosen FS, Remold-O’Donnell E. High incidence of lymphomas in a subgroup of Wiskott-Aldrich syndrome patients. Br J Haematol. 2003;121(3):529–30.PubMedCrossRef

87.

Thrasher AJ, Burns SO. WASP: a key immunological multitasker. Nat Rev Immunol. 2010;10(3):182–92. https://doi.org/10.1038/nri2724.PubMedCrossRef

88.

Matalon O, Reicher B, Barda-Saad M. Wiskott-Aldrich syndrome protein—dynamic regulation of actin homeostasis: from activation through function and signal termination in T lymphocytes. Immunol Rev. 2013;256(1):10–29. https://doi.org/10.1111/imr.12112.PubMedCrossRef

89.

Sadhukhan S, Sarkar K, Taylor M, Candotti F, Vyas YM. Nuclear role of WASp in gene transcription is uncoupled from its ARP2/3-dependent cytoplasmic role in actin polymerization. J Immunol. 2014;193(1):150–60. https://doi.org/10.4049/jimmunol.1302923.PubMedPubMedCentralCrossRef

90.

Ariga T, Kondoh T, Yamaguchi K, Yamada M, Sasaki S, Nelson DL, et al. Spontaneous in vivo reversion of an inherited mutation in the Wiskott-Aldrich syndrome. J Immunol. 2001;166(8):5245–9.PubMedCrossRef

91.

Wada T, Schurman SH, Otsu M, Garabedian EK, Ochs HD, Nelson DL, et al. Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism. Proc Natl Acad Sci U S A. 2001;98(15):8697–702. https://doi.org/10.1073/pnas.151260498.PubMedPubMedCentralCrossRef

92.

Lutskiy MI, Rosen FS, Remold-O’Donnell E. Spontaneous correction of the T-cell defect in patients with the Wiskott-Aldrich syndrome. Blood. 2002;100(11):1802.

93.

Wada T, Konno A, Schurman SH, Garabedian EK, Anderson SM, Kirby M, et al. Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings. J Clin Invest. 2003;111(9):1389–97. https://doi.org/10.1172/JCI15485.PubMedPubMedCentralCrossRef

94.

Konno A, Wada T, Schurman SH, Garabedian EK, Kirby M, Anderson SM, et al. Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T- and B-cell lineages. Blood. 2004;103(2):676–8. https://doi.org/10.1182/blood-2003-05-1739.PubMedCrossRef

95.

Wada T, Schurman SH, Jagadeesh GJ, Garabedian EK, Nelson DL, Candotti F. Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family. Blood. 2004;104(5):1270–2. https://doi.org/10.1182/blood-2004-03-0846.PubMedCrossRef

96.

Lutskiy MI, Beardsley DS, Rosen FS, Remold-O’Donnell E. Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome. Blood. 2005;106(8):2815–7.PubMedPubMedCentralCrossRef

97.

Du W, Kumaki S, Uchiyama T, Yachie A, Yeng Looi C, Kawai S, et al. A second-site mutation in the initiation codon of WAS (WASP) results in expansion of subsets of lymphocytes in an Wiskott-Aldrich syndrome patient. Hum Mutat. 2006;27(4):370–5. https://doi.org/10.1002/humu.20308.PubMedCrossRef

98.

Boztug K, Baumann U, Ballmaier M, Webster D, Sandrock I, Jacobs R, et al. Large granular lymphocyte proliferation and revertant mosaicism: two rare events in a Wiskott-Aldrich syndrome patient. Haematologica. 2007;92(3):e43–5.PubMedCrossRef

99.

Stewart DM, Candotti F, Nelson DL. The phenomenon of spontaneous genetic reversions in the Wiskott-Aldrich syndrome: a report of the workshop of the ESID Genetics Working Party at the XIIth Meeting of the European Society for Immunodeficiencies (ESID). Budapest, Hungary October 4-7, 2006. J Clin Immunol. 2007;27(6):634–9. https://doi.org/10.1007/s10875-007-9121-z.PubMedCrossRef

100.

Davis BR, Dicola MJ, Prokopishyn NL, Rosenberg JB, Moratto D, Muul LM, et al. Unprecedented diversity of genotypic revertants in lymphocytes of a patient with Wiskott-Aldrich syndrome. Blood. 2008;111(10):5064–7. https://doi.org/10.1182/blood-2007-06-095299.PubMedPubMedCentralCrossRef

101.

Boztug K, Germeshausen M, Avedillo Diez I, Gulacsy V, Diestelhorst J, Ballmaier M, et al. Multiple independent second-site mutations in two siblings with somatic mosaicism for Wiskott-Aldrich syndrome. Clin Genet. 2008;74(1):68–74. https://doi.org/10.1111/j.1399-0004.2008.01019.x.PubMedCrossRef

102.

Lutskiy MI, Park JY, Remold SK, Remold-O'Donnell E. Evolution of highly polymorphic T cell populations in siblings with the Wiskott-Aldrich syndrome. PLoS One. 2008;3(10):e3444. https://doi.org/10.1371/journal.pone.0003444.PubMedPubMedCentralCrossRef

103.

Davis BR, Candotti F. Revertant somatic mosaicism in the Wiskott-Aldrich syndrome. Immunol Res. 2009;44(1–3):127–31. https://doi.org/10.1007/s12026-008-8091-4.PubMedCrossRef

104.

Davis BR, Yan Q, Bui JH, Felix K, Moratto D, Muul LM, et al. Somatic mosaicism in the Wiskott-Aldrich syndrome: molecular and functional characterization of genotypic revertants. Clin Immunol. 2010;135(1):72–83. https://doi.org/10.1016/j.clim.2009.12.011.PubMedCrossRef

105.

Trifari S, Scaramuzza S, Catucci M, Ponzoni M, Mollica L, Chiesa R, et al. Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: analysis of function and distribution in lymphoid organs. J Allergy Clin Immunol. 2010;125(2):439–448 e8. https://doi.org/10.1016/j.jaci.2009.11.034.PubMedCrossRef

106.

Xie JW, Zhang ZY, Wu JF, Liu DW, Liu W, Zhao Y, et al. In vivo reversion of an inherited mutation in a Chinese patient with Wiskott-Aldrich syndrome. Hum Immunol. 2015;76(6):406–13. https://doi.org/10.1016/j.humimm.2015.04.001.PubMedCrossRef

107.

Notarangelo LD, Mazza C, Giliani S, D'Aria C, Gandellini F, Ravelli C, et al. Missense mutations of the WASP gene cause intermittent X-linked thrombocytopenia. Blood. 2002;99(6):2268–9.PubMedCrossRef

108.

Medina SS, Siqueira LH, Colella MP, Yamaguti-Hayakawa GG, Duarte BKL, Dos Santos Vilela MM, et al. Intermittent low platelet counts hampering diagnosis of X-linked thrombocytopenia in children: report of two unrelated cases and a novel mutation in the gene coding for the Wiskott-Aldrich syndrome protein. BMC Pediatr. 2017;17(1):151. https://doi.org/10.1186/s12887-017-0897-6. PubMedPubMedCentralCrossRef

109.

Briggs C. Quality counts: new parameters in blood cell counting. Int J Lab Hematol. 2009;31(3):277–97.PubMedCrossRef

110.

Zhou L, Li W, Zhang X, Liu D, Ding Y, Dai R, et al. Abnormal distribution of distinct lymphocyte subsets in children with Wiskott-Aldrich syndrome. Hum Immunol. 2017; https://doi.org/10.1016/j.humimm.2017.05.004.

111.

Borte S, Fasth A, von Dobeln U, Winiarski J, Hammarstrom L. Newborn screening for severe T and B cell lymphopenia identifies a fraction of patients with Wiskott-Aldrich syndrome. Clin Immunol. 2014;155(1):74–8. https://doi.org/10.1016/j.clim.2014.09.003.PubMedCrossRef

112.

Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014;312(7):729–38. https://doi.org/10.1001/jama.2014.9132.PubMedPubMedCentralCrossRef

113.

Lanzi G, Moratto D, Vairo D, Masneri S, Delmonte O, Paganini T, et al. A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP. J Exp Med. 2012;209(1):29–34. https://doi.org/10.1084/jem.20110896.PubMedPubMedCentralCrossRef

114.

Gabelli M, Marzollo A, Notarangelo LD, Basso G, Putti MC. Eltrombopag use in a patient with Wiskott-Aldrich syndrome. Pediatr Blood Cancer. 2017; https://doi.org/10.1002/pbc.26692.

115.

Oshima K, Imai K, Albert MH, Bittner TC, Strauss G, Filipovich AH, et al. Hematopoietic stem cell transplantation for X-linked thrombocytopenia with mutations in the WAS gene. J Clin Immunol. 2015;35(1):15–21. https://doi.org/10.1007/s10875-014-0105-5.PubMedCrossRef

116.

Young G, Angiolillo AL. Long-term treatment of refractory thrombocytopenia in a patient with Wiskott-Aldrich syndrome with vincristine, immunoglobulin, and methylprednisolone. Am J Hematol. 1999;62(3):183–5.PubMedCrossRef

117.

Kim JJ, Thrasher AJ, Jones AM, Davies EG, Cale CM. Rituximab for the treatment of autoimmune cytopenias in children with immune deficiency. Br J Haematol. 2007;138(1):94–6. https://doi.org/10.1111/j.1365-2141.2007.06616.x.PubMedCrossRef

118.

Huang JT, Rademaker A, Paller AS. Dilute bleach baths for Staphylococcus aureus colonization in atopic dermatitis to decrease disease severity. Arch Dermatol. 2011;147(2):246–7. https://doi.org/10.1001/archdermatol.2010.434.PubMedCrossRef

119.

Jyonouchi S, Gwafila B, Gwalani LA, Ahmad M, Moertel C, Holbert C, et al. Phase I trial of low-dose interleukin 2 therapy in patients with Wiskott-Aldrich syndrome. Clin Immunol. 2017; https://doi.org/10.1016/j.clim.2017.02.001.

120.

Bach FH, Albertini RJ, Joo P, Anderson JL, Bortin MM. Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome. Lancet. 1968;2(583):1364–6.PubMedCrossRef

121.

Parkman R, Rappeport J, Geha R, Belli J, Cassady R, Levey R, et al. Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation. N Engl J Med. 1978;298(17):921–7. https://doi.org/10.1056/NEJM197804272981701.PubMedCrossRef

122.

Friedrich W, Schutz C, Schulz A, Benninghoff U, Honig M. Results and long-term outcome in 39 patients with Wiskott-Aldrich syndrome transplanted from HLA-matched and -mismatched donors. Immunol Res. 2009;44(1–3):18–24. https://doi.org/10.1007/s12026-008-8063-8.PubMedCrossRef

123.

Shin CR, Kim MO, Li D, Bleesing JJ, Harris R, Mehta P, et al. Outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome. Bone Marrow Transplant. 2012;47(11):1428–35. https://doi.org/10.1038/bmt.2012.31.PubMedCrossRef

124.

Kobayashi R, Ariga T, Nonoyama S, Kanegane H, Tsuchiya S, Morio T, et al. Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan. Br J Haematol. 2006;135(3):362–6. https://doi.org/10.1111/j.1365-2141.2006.06297.x.PubMedCrossRef

125.

Shekhovtsova Z, Bonfim C, Ruggeri A, Nichele S, Page K, AlSeraihy A, et al. A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome. Haematologica. 2017; https://doi.org/10.3324/haematol.2016.158808.

126.

Kharya G, Nademi Z, Leahy TR, Dunn J, Barge D, Schulz A, et al. Haploidentical T-cell alpha beta receptor and CD19-depleted stem cell transplant for Wiskott-Aldrich syndrome. J Allergy Clin Immunol. 2014;134(5):1199–201. https://doi.org/10.1016/j.jaci.2014.04.041.PubMedCrossRef

127.

Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Diez IA, Dewey RA, et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med. 2010;363(20):1918–27. https://doi.org/10.1056/NEJMoa1003548.PubMedPubMedCentralCrossRef

128.

Braun CJ, Boztug K, Paruzynski A, Witzel M, Schwarzer A, Rothe M, et al. Gene therapy for Wiskott-Aldrich syndrome—long-term efficacy and genotoxicity. Sci Transl Med. 2014;6(227):227ra33. https://doi.org/10.1126/scitranslmed.3007280.PubMedCrossRef

129.

Dupre L, Trifari S, Follenzi A, Marangoni F, Lain de Lera T, Bernad A, et al. Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction. Mol Ther. 2004;10(5):903–15.PubMedCrossRef

130.

Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science. 2013; https://doi.org/10.1126/science.1233151.

131.

Ferrua F, Cicalese MP, Galimberti S, Scaramuzza S, Giannelli S, Pajno R, et al. Safety and clinical benefit of lentiviral hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Blood. 2015;126(23):3.

132.

Castiello MC, Scaramuzza S, Pala F, Ferrua F, Uva P, Brigida I, et al. B-cell reconstitution after lentiviral vector-mediated gene therapy in patients with Wiskott-Aldrich syndrome. J Allergy Clin Immunol. 2015;136(3):692–702 e2. https://doi.org/10.1016/j.jaci.2015.01.035.PubMedPubMedCentralCrossRef

133.

Hacein-Bey Abina S, Gaspar HB, Blondeau J, Caccavelli L, Charrier S, Buckland K, et al. Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome. JAMA. 2015;313(15):1550–63. https://doi.org/10.1001/jama.2015.3253.PubMedCrossRef

134.

Chu JI, Henderson LA, Armant M, Male F, Dansereau CH, MacKinnon B, et al. Gene therapy using a self-inactivating lentiviral vector improves clinical and laboratory manifestations of Wiskott-Aldrich syndrome. Blood. 2015;126(23):260.

135.

Koldej RM, Carney G, Wielgosz MM, Zhou S, Zhan J, Sorrentino BP, et al. Comparison of insulators and promoters for expression of the Wiskott-Aldrich syndrome protein using lentiviral vectors. Hum Gene Ther Clin Dev. 2013;24(2):77–85. https://doi.org/10.1089/humc.2012.244.PubMedPubMedCentralCrossRef

136.

Wielgosz MM, Kim YS, Carney GG, Zhan J, Reddivari M, Coop T, et al. Generation of a lentiviral vector producer cell clone for human Wiskott-Aldrich syndrome gene therapy. Mol Ther Methods Clin Dev. 2015;2:14063. https://doi.org/10.1038/mtm.2014.63. PubMedPubMedCentralCrossRef

137.

Uchiyama T, Adriani M, Jagadeesh GJ, Paine A, Candotti F. Foamy virus vector-mediated gene correction of a mouse model of Wiskott-Aldrich syndrome. Mol Ther. 2012;20(6):1270–9. https://doi.org/10.1038/mt.2011.282.PubMedPubMedCentralCrossRef

138.

Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Shearer WT, et al. Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol. 2016;138(2):375–85. https://doi.org/10.1016/j.jaci.2016.01.051.PubMedPubMedCentralCrossRef

139.

Glasmacher JS, Bittner TC, Ochs HD, Aiuti A, Arkwright PD, Balashov D, et al. Wiskott-Aldrich syndrome: a retrospective study on 575 patients analyzing the impact of splenectomy, stem cell transplantation, or no definitive treatment on frequency of disease-related complications and physician-perceived quality of life. Blood. 2016;128(22):366.

140.

Laskowski TJ, Van Caeneghem Y, Pourebrahim R, Ma C, Ni Z, Garate Z, et al. Gene correction of iPSCs from a Wiskott-Aldrich syndrome patient normalizes the lymphoid developmental and functional defects. Stem Cell Rep. 2016;7(2):139–48. https://doi.org/10.1016/j.stemcr.2016.06.003.CrossRef

Titel: Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome
verfasst von: Fabio Candotti
Publikationsdatum: 30.10.2017
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 1/2018
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-017-0453-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

19.04.2024 | Vorhofflimmern | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2018

DOCK2 Deficiency in a Patient with Hyper IgM Phenotype

Modulation of the Interleukin-21 Pathway with Interleukin-4 Distinguishes Common Variable Immunodeficiency Patients with More Non-infectious Clinical Complications

Allogeneic Transplant for Mycosis Fungoides in Patient with Wiskott-Aldrich Syndrome

A Severe Anaphylactic Reaction Associated with IgM-Class Anti-Human IgG Antibodies in a Hyper-IgM Syndrome Type 2 Patient

Newborn Screening for Primary Immunodeficiency Diseases: History, Current and Future Practice

Trichohepatoenteric Syndrome Presenting with Severe Infection and Later Onset Diarrhoea

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin