Severe Food Allergy as a Variant of IPEX Syndrome Caused by a Deletion in a Noncoding Region of the FOXP3 Gene

Gastroenterology

Volumn 132, Issue 5, 2007, Pages 1705-1717

  Torgerson, Troy R ^a   Linane, Avriel ^a   Moes, Nicolette ^b,c   Anover, Stephanie ^a   Mateo, Véronique ^c   Rieux Laucat, Frédéric ^c   Hermine, Olivier ^c   Vijay, Shashi ^a   Gambineri, Eleonora ^d   Cerf Bensussan, Nadine ^c   Fischer, Alain ^b,c   Ochs, Hans D ^a   Goulet, Olivier ^b,c   Ruemmele, Frank M ^b,c  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b HÔPITAL NECKER ENFANTS MALADES   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d UNIVERSITY OF FLORENCE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

MESSENGER RNA; TRANSCRIPTION FACTOR FOXP3;

ARTICLE; ATOPIC DERMATITIS; AUTOIMMUNITY; CD4+ CD25+ T LYMPHOCYTE; CELL FUNCTION; COCULTURE; CONTROLLED STUDY; ENTEROPATHY; EOSINOPHILIA; EXON; FLOW CYTOMETRY; FOOD ALLERGY; GENE DELETION; GENE EXPRESSION; GENE IDENTIFICATION; GENE SEQUENCE; HUMAN; HUMAN CELL; INTESTINE MUCOSA; INTRON; PERIPHERAL LYMPHOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; REGULATORY T LYMPHOCYTE; RNA SPLICING; STAINING; X CHROMOSOME LINKED DISORDER;

EID: 34247862225     PISSN: 00165085     EISSN: None     Source Type: Journal    
DOI: 10.1053/j.gastro.2007.02.044     Document Type: Article

References (66)

1. Green D.R., Flood P.M., and Gershon R.K. Immunoregulatory T-cell pathways. Annu Rev Immunol 1 (1983) 439-463
2. Waldmann T.A., Blaese R.M., Broder S., and Krakauer R.S. Disorders of suppressor immunoregulatory cells in the pathogenesis of immunodeficiency and autoimmunity. Ann Intern Med 88 (1978) 226-238
3. Chatila T.A., Blaeser F., Ho N., Lederman H.M., Voulgaropoulos C., Helms C., and Bowcock A.M. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 106 (2000) R75-R81
4. Wildin R.S., Ramsdell F., Peake J., Faravelli F., Casanova J.L., Buist N., Levy-Lahad E., Mazzella M., Goulet O., Perroni L., Bricarelli F.D., Byrne G., McEuen M., Proll S., Appleby M., and Brunkow M.E. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat Genet 27 (2001) 18-20
5. Bennett C.L., Christie J., Ramsdell F., Brunkow M.E., Ferguson P.J., Whitesell L., Kelly T.E., Saulsbury F.T., Chance P.F., and Ochs H.D. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27 (2001) 20-21
6. Fontenot J.D., Gavin M.A., and Rudensky A.Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4 (2003) 330-336
7. Hori S., Nomura T., and Sakaguchi S. Control of regulatory T-cell development by the transcription factor Foxp3. Science 299 (2003) 1057-1061
8. Khattri R., Cox T., Yasayko S.A., and Ramsdell F. An essential role for scurfin in CD4+CD25+ T-regulatory cells. Nat Immunol 4 (2003) 337-342
9. Bacchetta R., Gregori S., and Roncarolo M.G. CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmun Rev 4 (2005) 491-496
10. Randolph D.A., and Fathman C.G. Cd4+Cd25+ regulatory T cells and their therapeutic potential. Annu Rev Med 57 (2006) 381-402
11. Karlsson M.R., Rugtveit J., and Brandtzaeg P. Allergen-responsive CD4+CD25+ regulatory T cells in children who have outgrown cow's milk allergy. J Exp Med 199 (2004) 1679-1688
12. Agardh D., Lynch K., Brundin C., Ivarsson S.A., Lernmark A., and Cilio C.M. Reduction of tissue transglutaminase autoantibody levels by gluten-free diet is associated with changes in subsets of peripheral blood lymphocytes in children with newly diagnosed celiac disease. Clin Exp Immunol 144 (2006) 67-75
13. Brunkow M.E., Jeffery E.W., Hjerrild K.A., Paeper B., Clark L.B., Yasayko S.A., Wilkinson J.E., Galas D., Ziegler S.F., and Ramsdell F. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 27 (2001) 68-73
14. Schubert L.A., Jeffery E., Zhang Y., Ramsdell F., and Ziegler S.F. Scurfin (FOXP3) acts as a repressor of transcription and regulates T-cell activation. J Biol Chem 276 (2001) 37672-37679
15. Lopes J.E., Torgerson T.R., Schubert L.A., Anover S.D., Ocheltree E.L., Ochs H.D., and Ziegler S.F. Analysis of FOXP3 reveals multiple domains required for its function as a transcriptional repressor. J Immunol 177 (2006) 3133-3142
16. Wu Y., Borde M., Heissmeyer V., Feuerer M., Lapan A.D., Stroud J.C., Bates D.L., Guo L., Han A., Ziegler S.F., Mathis D., Benoist C., Chen L., and Rao A. FOXP3 controls regulatory T-cell function through cooperation with NFAT. Cell 126 (2006) 375-387
17. Powell B.R., Buist N.R., and Stenzel P. An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy. J Pediatr 100 (1982) 731-737
18. Wildin R.S., Smyk-Pearson S., and Filipovich A.H. Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J Med Genet 39 (2002) 537-545
19. Gambineri E., Torgerson T.R., and Ochs H.D. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr Opin Rheumatol 15 (2003) 430-435
20. Ruemmele F.M., Brousse N., and Goulet O. Autoimmune enteropathy: molecular concepts. Curr Opin Gastroenterol 20 (2004) 587-591
21. Bousvaros A., Leichtner A.M., Book L., Shigeoka A., Bilodeau J., Semeao E., Ruchelli E., and Mulberg A.E. Treatment of pediatric autoimmune enteropathy with tacrolimus (FK506). Gastroenterology 111 (1996) 237-243
22. Bindl L., Torgerson T., Perroni L., Youssef N., Ochs H.D., Goulet O., and Ruemmele F.M. Successful use of the new immune-suppressor sirolimus in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). J Pediatr 147 (2005) 256-259
23. McGinness J.L., Bivens M.M., Greer K.E., Patterson J.W., and Saulsbury F.T. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) associated with pemphigoid nodularis: a case report and review of the literature. J Am Acad Dermatol 55 (2006) 143-148
24. Baud O., Goulet O., Canioni D., Le Deist F., Radford I., Rieu D., Dupuis-Girod S., Cerf-Bensussan N., Cavazzana-Calvo M., Brousse N., Fischer A., and Casanova J.L. Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) by allogeneic bone marrow transplantation. N Engl J Med 344 (2001) 1758-1762
25. Mazzolari E., Forino C., Fontana M., D'Ippolito C., Lanfranchi A., Gambineri E., Ochs H., Badolato R., and Notarangelo L.D. A new case of IPEX receiving bone marrow transplantation. Bone Marrow Transplant 35 (2005) 1033-1034
26. Rao A., Kamani N., Filipovich A., Lee S.M., Davies S., Dalal J., and Shenoy S. Successful bone marrow transplantation for IPEX syndrome following reduced intensity conditioning. Blood 109 (2007) 383-385
27. Kobayashi I., Imamura K., Yamada M., Okano M., Yara A., Ikema S., and Ishikawa N. A 75-kD autoantigen recognized by sera from patients with X-linked autoimmune enteropathy associated with nephropathy. Clin Exp Immunol 111 (1998) 527-531
28. Kobayashi I., Shiari R., Yamada M., Kawamura N., Okano M., Yara A., Iguchi A., Ishikawa N., Ariga T., Sakiyama Y., Ochs H.D., and Kobayashi K. Novel mutations of FOXP3 in two Japanese patients with immune dysregulation, polyendocrinopathy, enteropathy, X linked syndrome (IPEX). J Med Genet 38 (2001) 874-876
29. Pfaffl M.W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29 (2001) e45
30. Takahashi T., Kuniyasu Y., Toda M., Sakaguchi N., Itoh M., Iwata M., Shimizu J., and Sakaguchi S. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 10 (1998) 1969-1980
31. Bennett C.L., Brunkow M.E., Ramsdell F., O'Briant K.C., Zhu Q., Fuleihan R.L., Shigeoka A.O., Ochs H.D., and Chance P.F. A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA→AAUGAA) leads to the IPEX syndrome. Immunogenetics 53 (2001) 435-439
32. Gavin M.A., Torgerson T.R., Houston E., DeRoos P., Ho W.Y., Stray-Pedersen A., Ocheltree E.L., Greenberg P.D., Ochs H.D., and Rudensky A.Y. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T-cell development. Proc Natl Acad Sci U S A 103 (2006) 6659-6664
33. Walker M.R., Kasprowicz D.J., Gersuk V.H., Benard A., Van Landeghen M., Buckner J.H., and Ziegler S.F. Induction of FOXP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J Clin Invest 112 (2003) 1437-1443
34. Pillai V., Ortega S.B., Wang C.K., and Karandikar N.J. Transient regulatory T-cells: a state attained by all activated human T-cells. Clin Immunol 123 (2007) 18-29
35. Wang J., Ioan-Facsinay A., van der Voort E.I., Huizinga T.W., and Toes R.E. Transient expression of FOXP3 in human activated nonregulatory CD4(+) T cells. Eur J Immunol 37 (2007) 129-138
36. den Dunnen J.T., and Antonarakis S.E. Nomenclature for the description of human sequence variations. Hum Genet 109 (2001) 121-124
37. Lejeune F., and Maquat L.E. Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells. Curr Opin Cell Biol 17 (2005) 309-315
38. Jackson R.J. Alternative mechanisms of initiating translation of mammalian mRNAs. Biochem Soc Trans 33 (2005) 1231-1241
39. Allan S.E., Passerini L., Bacchetta R., Crellin N., Dai M., Orban P.C., Ziegler S.F., Roncarolo M.G., and Levings M.K. The role of 2 FOXP3 isoforms in the generation of human CD4+ Tregs. J Clin Invest 115 (2005) 3276-3284
40. Roncador G., Brown P.J., Maestre L., Hue S., Martinez-Torrecuadrada J.L., Ling K.L., Pratap S., Toms C., Fox B.C., Cerundolo V., Powrie F., and Banham A.H. Analysis of FOXP3 protein expression in human CD4(+)CD25(+) regulatory T cells at the single-cell level. Eur J Immunol 35 (2005) 1681-1691
41. Bacchetta R., Passerini L., Gambineri E., Dai M., Allan S.E., Perroni L., Dagna-Bricarelli F., Sartirana C., Matthes-Martin S., Lawitschka A., Azzari C., Ziegler S.F., Levings M.K., and Roncarolo M.G. Defective regulatory and effector T-cell functions in patients with FOXP3 mutations. J Clin Invest 116 (2006) 1713-1722
42. De Benedetti F., Insalaco A., Diamanti A., Cortis E., Muratori F., Lamioni A., Carsetti R., Cusano R., De Vito R., Perroni L., Gambarara M., Castro M., Bottazzo G.F., and Ugazio A.G. Mechanistic associations of a mild phenotype of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome. Clin Gastroenterol Hepatol 4 (2006) 653-659
43. Tommasini A., Ferrari S., Moratto D., Badolato R., Boniotto M., Pirulli D., Notarangelo L.D., and Andolina M. X-chromosome inactivation analysis in a female carrier of FOXP3 mutation. Clin Exp Immunol 130 (2002) 127-130
44. Izcue A., Coombes J.L., and Powrie F. Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol Rev 212 (2006) 256-271
45. Sakaguchi S. Naturally arising FOXP3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6 (2005) 345-352
46. Mattingly J.A., and Waksman B.H. Immunologic suppression after oral administration of antigen. I. Specific suppressor cells formed in rat Peyer's patches after oral administration of sheep erythrocytes and their systemic migration. J Immunol 121 (1978) 1878-1883
47. Richman L.K., Chiller J.M., Brown W.R., Hanson D.G., and Vaz N.M. Enterically induced immunologic tolerance. I. Induction of suppressor T lymphoyctes by intragastric administration of soluble proteins. J Immunol 121 (1978) 2429-2434
48. Fowler S., and Powrie F. CTLA-4 expression on antigen-specific cells but not IL-10 secretion is required for oral tolerance. Eur J Immunol 32 (2002) 2997-3006
49. Dubois B., Chapat L., Goubier A., Papiernik M., Nicolas J.F., and Kaiserlian D. Innate CD4+CD25+ regulatory T cells are required for oral tolerance and inhibition of CD8+ T cells mediating skin inflammation. Blood 102 (2003) 3295-3301
50. Thorstenson K.M., and Khoruts A. Generation of anergic and potentially immunoregulatory CD25+CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen. J Immunol 167 (2001) 188-195
51. Hauet-Broere F., Unger W.W., Garssen J., Hoijer M.A., Kraal G., and Samsom J.N. Functional CD25- and CD25+ mucosal regulatory T cells are induced in gut-draining lymphoid tissue within 48 hours after oral antigen application. Eur J Immunol 33 (2003) 2801-2810
52. Zhang X., Izikson L., Liu L., and Weiner H.L. Activation of CD25(+)CD4(+) regulatory T cells by oral antigen administration. J Immunol 167 (2001) 4245-4253
53. Mucida D., Kutchukhidze N., Erazo A., Russo M., Lafaille J.J., and Curotto de Lafaille M.A. Oral tolerance in the absence of naturally occurring Tregs. J Clin Invest 115 (2005) 1923-1933
54. Cuenod B., Brousse N., Goulet O., De Potter S., Mougenot J.F., Ricour C., Guy-Grand D., and Cerf-Bensussan N. Classification of intractable diarrhea in infancy using clinical and immunohistological criteria. Gastroenterology 99 (1990) 1037-1043
55. Kutlu T., Brousse N., Rambaud C., Le Deist F., Schmitz J., and Cerf-Bensussan N. Numbers of T-cell receptor (TCR) αβ+ but not of TcR γδ+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet. Gut 34 (1993) 208-214
56. Murch S.H., Fertleman C.R., Rodrigues C., Morgan G., Klein N.J., Meadows N., Savidge T.C., Phillips A.D., and Walker-Smith J.A. Autoimmune enteropathy with distinct mucosal features in T-cell activation deficiency: the contribution of T cells to the mucosal lesion. J Pediatr Gastroenterol Nutr 28 (1999) 393-399
57. Halstensen T.S., Scott H., and Brandtzaeg P. Intraepithelial T cells of the TcR γ/δ+ CD8- and V δ 1/J δ 1+ phenotypes are increased in celiac disease. Scand J Immunol 30 (1989) 665-672
58. Jonas M.M., Bell M.D., Eidson M.S., Koutouby R., and Hensley G.T. Congenital diabetes mellitus and fatal secretory diarrhea in two infants. J Pediatr Gastroenterol Nutr 13 (1991) 415-425
59. Russo P.A., Brochu P., Seidman E.G., and Roy C.C. Autoimmune enteropathy. Pediatr Dev Pathol 2 (1999) 65-71
60. Mitton S.G., Mirakion R., Larcher V.F., Dillon M.J., and Walker-Smith J.A. Enteropathy and renal involvement in an infant with evidence of widespread autoimmune disturbance. J Pediatr Gastroenterol Nutr 8 (1989) 397-400
61. Walker-Smith J.A., Unsworth D.J., Hutchins P., Phillips A.D., and Holborow E.J. Auto-antibodies against gut epithelium in child with small-intestinal enteropathy. Lancet 1 (1982) 566-567
62. Kobayashi I., Imamura K., Kubota M., Ishikawa S., Yamada M., Tonoki H., Okano M., Storch W.B., Moriuchi T., Sakiyama Y., and Kobayashi K. Identification of an autoimmune enteropathy-related 75-kilodalton antigen. Gastroenterology 117 (1999) 823-830
63. Scanlan M.J., Chen Y.T., Williamson B., Gure A.O., Stockert E., Gordan J.D., Tureci O., Sahin U., Pfreundschuh M., and Old L.J. Characterization of human colon cancer antigens recognized by autologous antibodies. Int J Cancer 76 (1998) 652-658
64. Zahorsky-Reeves J.L., and Wilkinson J.E. A transgenic mouse strain with antigen-specific T cells (RAG1KO/sf/OVA) demonstrates that the scurfy (sf) mutation causes a defect in T-cell tolerization. Comp Med 52 (2002) 58-62
65. Caramalho I., Lopes-Carvalho T., Ostler D., Zelenay S., Haury M., and Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide. J Exp Med 197 (2003) 403-411
66. Liu H., Komai-Koma M., Xu D., and Liew F.Y. Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T cells. Proc Natl Acad Sci U S A 103 (2006) 7048-7053