Understanding eosinophilic esophagitis: The cellular and molecular mechanisms of an emerging disease

Mucosal Immunology

Volumn 4, Issue 2, 2011, Pages 139-147

  Mulder, D J ^a   Justinich, C J ^a  

^a QUEEN S UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFLAMMATORY AGENT; CHEMOKINE RECEPTOR CCR3; CROMOGLYCATE DISODIUM; EOTAXIN; EOTAXIN 2; EOTAXIN 3; FIBROBLAST GROWTH FACTOR 9; FLUTICASONE; FLUTICASONE PROPIONATE; FOOD ALLERGEN; GLUCOCORTICOID; IMMUNOGLOBULIN E; INFLIXIMAB; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 5; LEUKOTRIENE; MEPOLIZUMAB; OC 000459; OMALIZUMAB; PLACEBO; QAX 576; RESLIZUMAB; THYMIC STROMAL LYMPHOPOIETIN; TRALOKINUMAB; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; ATOPY; B LYMPHOCYTE ACTIVATION; BASAL CELL; CELL HYPERPLASIA; CYTOTOXIC T LYMPHOCYTE; DELAYED HYPERSENSITIVITY; DISEASE ASSOCIATION; DRUG EFFICACY; DRUG TARGETING; EOSINOPHILIC ESOPHAGITIS; EPITHELIUM CELL; ESOPHAGUS MUCOSA; FIBROBLAST CULTURE; FIBROSIS; GENETIC ASSOCIATION; HUMAN; LEUKOCYTE AGGREGATION; MAST CELL DEGRANULATION; MICROARRAY ANALYSIS; MOLECULAR DYNAMICS; MOLECULARLY TARGETED THERAPY; NONHUMAN; PATCH DYNAMICS; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; T LYMPHOCYTE ACTIVATION; TH2 CELL; TREATMENT DURATION;

EID: 79951939344     PISSN: 19330219     EISSN: None     Source Type: Journal    
DOI: 10.1038/mi.2010.88     Document Type: Review

References (103)

1. Furuta G. T. et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 133 1342-1363 ( 2007 ).
2. Odze R. D. Pathology of eosinophilic esophagitis: what the clinician needs to know. Am. J. Gastroenterol. 104 485-490 ( 2009 ).
3. Wang F. Y. Gupta S. K. & Fitzgerald J. F. Is there a seasonal variation in the incidence or intensity of allergic eosinophilic esophagitis in newly diagnosed children? J. Clin. Gastroenterol. 41 451-453 ( 2007 ). (Pubitemid 46642529)
4. Almansa C. et al. Seasonal distribution in newly diagnosed cases of eosinophilic esophagitis in adults. Am. J. Gastroenterol. 104 828-833 ( 2009 ).
5. Noel R. J. Putnam P. E. & Rothenberg M. E. Eosinophilic esophagitis. N. Engl. J. Med. 351 940-941 ( 2004 ).
6. Straumann A. & Simon H. U. Eosinophilic esophagitis: escalating epidemiology? J. Allergy Clin. Immunol.115 418-419 ( 2005 ).
7. Cherian S. Smith N. M. & Forbes D. A. Rapidly increasing prevalence of eosinophilic oesophagitis in Western Australia. Arch. Dis. Child 91 1000-1004 ( 2006 ). (Pubitemid 44863138)
8. Croese J. et al. Clinical and endoscopic features of eosinophilic esophagitis in adults. Gastrointest. Endosc. 58 516-522 ( 2003 ). (Pubitemid 37205763)
9. Dalby K. et al. Eosinophilic oesophagitis in infants and children in the region of southern Denmark: a prospective study of prevalence and clinical presentation. J. Pediatr. Gastroenterol. Nutr. 51 ( 2010 ).
10. Prasad G. A. et al. Epidemiology of eosinophilic esophagitis over three decades in Olmsted County, Minnesota. Clin. Gastroenterol. Hepatol. 7 1055-1061 ( 2009 ).
11. Bach J. F. The effect of infections on susceptibility to autoimmune and allergic diseases. N. Engl. J. Med. 347 911-920 ( 2002 ).
12. Rosenberg H. F. Phipps S. & Foster P. S. Eosinophil traffi cking in allergy and asthma. J. Allergy Clin. Immunol.119 1303-1310 ( 2007 ). (Pubitemid 46855872)
13. Stone K. D. Prussin C. & Metcalfe D. D. IgE, mast cells, basophils, and eosinophils. J. Allergy Clin. Immunol.125 S73 - S80 ( 2010 ).
14. Lim L. H. Burdick M. M. Hudson S. A. Mustafa F. B. Konstantopoulos K. & Bochner B. S. Stimulation of human endothelium with IL-3 induces selective basophil accumulation in vitro. J. Immunol.176 5346-5353 ( 2006 ).
15. Simon H. U. Yousefi S. Schranz C. Schapowal A. Bachert C. & Blaser K. Direct demonstration of delayed eosinophil apoptosis as a mechanism causing tissue eosinophilia. J. Immunol.158 3902-3908 ( 1997 ). (Pubitemid 127488750)
16. Okigami H. et al. Inhibition of eosinophilia in vivo by a small molecule inhibitor of very late antigen (VLA)-4. Eur. J. Pharmacol. 559 202-209 ( 2007 ). (Pubitemid 46295402)
17. Edwards B. S. Curry M. S. Tsuji H. Brown D. Larson R. S. & Sklar L. A. Expression of P-selectin at low site density promotes selective attachment of eosinophils over neutrophils. J. Immunol.165 404-410 ( 2000 ). (Pubitemid 30429533)
18. Barthel S. R. Johansson M. W. McNamee D. M. & Mosher D. F. Roles of integrin activation in eosinophil function and the eosinophilic infl ammation of asthma. J. Leukoc. Biol. 83 1-12 ( 2008 ).
19. Afshar K. Vucinic V. & Sharma O. P. Eosinophil cell: pray tell us what you do!. Curr. Opin. Pulm. Med. 13 414-421 ( 2007 ). (Pubitemid 47472304)
20. Plager D. A. Stuart S. & Gleich G. J. Human eosinophil granule major basic protein and its novel homolog. Allergy 53 33-40 ( 1998 ). (Pubitemid 28446496)
21. Hogan S. P. et al. Eosinophils: biological properties and role in health and disease. Clin. Exp. Allergy 38 709-750 ( 2008 ). (Pubitemid 351550670)
22. Spergel J. M. et al. 14 years of eosinophilic esophagitis: clinical features and prognosis. J. Pediatr. Gastroenterol. Nutr. 48 30-36 ( 2009 ).
23. Straumann A. The natural history and complications of eosinophilic esophagitis. Gastrointest. Endosc. Clin. N. Am. 18 99-118 ( 2008 ). (Pubitemid 350176666)
24. Justinich C. J. Ricci A. Jr. Kalafus D. A. Treem W. R. Hyams J. S. & Kreutzer D. L. Activated eosinophils in esophagitis in children: a transmission electron microscopic study. J. Pediatr. Gastroenterol. Nutr. 25 194-198 ( 1997 ). (Pubitemid 27311383)
25. Blanchard C. et al. Eotaxin-3 and a uniquely conserved geneexpression profi le in eosinophilic esophagitis. J. Clin. Invest. 116 536-547 ( 2006 ). (Pubitemid 43228372)
26. Konikoff M. R. et al. Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis. Clin. Gastroenterol. Hepatol. 4 1328-1336 ( 2006 ). (Pubitemid 44716743)
27. Bhattacharya B. et al. Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal refl ux disease. Hum. Pathol. 38 1744-1753 ( 2007 ). (Pubitemid 350179935)
28. Gupta S. K. Fitzgerald J. F. Kondratyuk T. & HogenEsch H. Cytokine expression in normal and infl amed esophageal mucosa: A study into the pathogenesis of allergic eosinophilic esophagitis 42 22-26 ( 2006 ). (Pubitemid 43061005)
29. Aceves S. S. Newbury R. O. Dohil R. Bastian J. F. & Broide D. H. Esophageal remodeling in pediatric eosinophilic esophagitis. J. Allergy Clin. Immunol.119 206-212 ( 2007 ). (Pubitemid 46037819)
30. Zhu X. et al. Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice. Gastroenterology 139 182 - 193 ( 2010 ).
31. Lucendo A. J. De Rezende L. Comas C. Caballero T. & Bellon T. Treatment with topical steroids downregulates IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression in eosinophilic esophagitis. Am. J. Gastroenterol. 103 2184-2193 ( 2008 ).
32. Mishra A. & Rothenberg M. E. Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism. Gastroenterology 125 1419-1427 ( 2003 ). (Pubitemid 37409762)
33. Neilsen C. V. & Bryce P. J. Interleukin-13 directly promotes oesophagus production of CCL11 and CCL24 and the migration of eosinophils. Clin. Exp. Allergy 40 427 - 434 ( 2010 ).
34. Rayapudi M. et al. Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice. J. Leukoc. Biol. 88 337 - 346 ( 2010 ).
35. Erin E. M. Williams T. J. Barnes P. J. & Hansel T. T. Eotaxin receptor (CCR3) antagonism in asthma and allergic disease. Curr. Drug Targets Infl amm. Allergy 1 201-214 ( 2002 ).
36. Bullock J. Z. et al. Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 45 22-31 ( 2007 ). (Pubitemid 47012327)
37. Straumann A. Bauer M. Fischer B. Blaser K. & Simon H. U. Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic infl ammatory response. J. Allergy Clin. Immunol.108 954-961 ( 2001 ). (Pubitemid 33151548)
38. Kephart G. M. et al. Marked deposition of eosinophil-derived neurotoxin in adult patients with eosinophilic esophagitis. Am. J. Gastroenterol. 105 298 - 307 ( 2010 ).
39. Mueller S. Neureiter D. Aigner T. & Stolte M. Comparison of histological parameters for the diagnosis of eosinophilic oesophagitis versus gastro-oesophageal refl ux disease on oesophageal biopsy material. Histopathology 53 676-684 ( 2008 ). (Pubitemid 352768719)
40. Ooi C. Y. Day A. S. Jackson R. Bohane T. D. Tobias V. & Lemberg D. A. Eosinophilic esophagitis in children with celiac disease. J. Gastroenterol. Hepatol. 23 1144-1148 ( 2008 ). (Pubitemid 352019370)
41. Aceves S. S. & Ackerman S. J. Relationships between eosinophilic infl ammation, tissue remodeling, and fi brosis in eosinophilic esophagitis. Immunol.Allergy Clin. North Am. 29 197-211 ( 2009 ).
42. Mulder D. J. et al. FGF9-induced proliferative response to eosinophilic infl ammation in oesophagitis. Gut 58 166-173 ( 2009 ).
43. Lewis C. J. Lamb C. A. Kanakala V. Pritchard S. Armstrong G. R. & Attwood S. E. Is the etiology of eosinophilic esophagitis in adults a response to allergy or refl ux injury? Study of cellular proliferation markers. Dis. Esophagus 22 249-255 ( 2009 ).
44. Gupta S. K. et al. Cysteinyl leukotriene levels in esophageal mucosal biopsies of children with eosinophilic infl ammation: are they all the same? Am. J. Gastroenterol. 101 1125-1128 ( 2006 ). (Pubitemid 43725330)
45. Okayama Y. & Kawakami T. Development, migration, and survival of mast cells. Immunol.Res. 34 97-115 ( 2006 ). (Pubitemid 43997964)
46. Caughey G. H. Mast cell tryptases and chymases in infl ammation and host defense. Immunol.Rev. 217 141-154 ( 2007 ). (Pubitemid 46718143)
47. Hallgren J. & Gurish M. F. Pathways of murine mast cell development and traffi cking: tracking the roots and routes of the mast cell. Immunol.Rev. 217 8-18 ( 2007 ). (Pubitemid 46718137)
48. Minai-Fleminger Y. & Levi-Schaffer F. Mast cells and eosinophils: the two key effector cells in allergic infl ammation. Infl amm. Res. 58 631-638 ( 2009 ).
49. Collins M. H. Histopathologic features of eosinophilic esophagitis. Gastrointest. Endosc. Clin. N. Am. 18 59-71 ( 2008 ). (Pubitemid 350176667)
50. Lucendo A. J. et al. Immunophenotypic characterization and quantifi cation of the epithelial infl ammatory infi ltrate in eosinophilic esophagitis through stereology: an analysis of the cellular mechanisms of the disease and the immunologic capacity of the esophagus. Am. J. Surg. Pathol. 31 598-606 ( 2007 ). (Pubitemid 46569045)
51. Kirsch R. Bokhary R. Marcon M. A. & Cutz E. Activated mucosal mast cells differentiate eosinophilic (allergic) esophagitis from gastroesophageal refl ux disease. J. Pediatr. Gastroenterol. Nutr. 44 20-26 ( 2007 ). (Pubitemid 46071787)
52. Yu S. Stahl E. Li Q. & Ouyang A. Antigen inhalation induces mast cells and eosinophils infi ltration in the guinea pig esophageal epithelium involving histamine-mediated pathway. Life Sci. 82 324-330 ( 2008 ).
53. Kung T. T. et al. Mast cells modulate allergic pulmonary eosinophilia in mice. Am. J. Respir. Cell Mol. Biol. 12 404-409 ( 1995 ).
54. Yu S. Kollarik M. Ouyang A. Myers A. C. & Undem B. J. Mast cellmediated long-lasting increases in excitability of vagal C fi bers in guinea pig esophagus. Am. J. Physiol. Gastrointest. Liver Physiol. 293 G850 - 856 ( 2007 ). (Pubitemid 47605931)
55. Vicario M. et al. Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis. Gut 59 12 - 20 ( 2010 ).
56. Abonia J. P. et al. Involvement of mast cells in eosinophilic esophagitis. J. Allergy Clin. Immunol.126 140 - 149 ( 2010 ).
57. Chehade M. Sampson H. A. Morotti R. A. & Magid M. S. Esophageal subepithelial fi brosis in children with eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 45 319-328 ( 2007 ). (Pubitemid 47415083)
58. Morganstern J. A. Wang M. Y. & Wershil B. K. Direct evidence of mast cell participation in acute acid-induced esophageal infl ammation in mice. J. Pediatr. Gastroenterol. Nutr. 46 134-138 ( 2008 ). (Pubitemid 351161118)
59. Muller-Stover I. Richter J. & Haussinger D. Infection with gnathostoma spinigerum as a cause of eosinophilic oesophagitis. Dtsch. Med. Wochenschr 129 1973-1975 ( 2004 ). (Pubitemid 39303394)
60. Wolfsen H. C. Hemminger L. L. & Achem S. R. Eosinophilic esophagitis and Barretts esophagus with dysplasia. Clin. Gastroenterol. Hepatol. 5 A18 ( 2007 ). (Pubitemid 350181605)
61. Konikoff M. R. et al. A randomized, double-blind, placebo-controlled trial of fl uticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology 131 1381-1391 ( 2006 ). (Pubitemid 44780861)
62. Liacouras C. A. et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin. Gastroenterol. Hepatol. 3 1198-1206 ( 2005 ). (Pubitemid 41797671)
63. Straumann A. et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 59 21 - 30 ( 2010 ).
64. Schroeder H. W. Jr. & Cavacini L. Structure and function of immunoglobulins. J. Allergy Clin. Immunol.125 S41 - S52 ( 2010 ).
65. Cambier J. C. & Getahun A. B cell activation versus anergy; the antigen receptor as a molecular switch. Immunol.Lett. 128 6 - 7 ( 2010 ).
66. Mishra A. Schlotman J. Wang M. & Rothenberg M. E. Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J. Leukoc. Biol. 81 916-924 ( 2007 ). (Pubitemid 46495640)
67. Simon D. Marti H. Heer P. Simon H. U. Braathen L. R. & Straumann A. Eosinophilic esophagitis is frequently associated with IgE-mediated allergic airway diseases. J. Allergy Clin. Immunol.115 1090-1092 ( 2005 ). (Pubitemid 40616230)
68. Akei H. S. Mishra A. Blanchard C. & Rothenberg M. E. Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice. Gastroenterology 129 985-994 ( 2005 ). (Pubitemid 41242689)
69. Teitelbaum J. E. et al. Eosinophilic esophagitis in children: immunopathological analysis and response to fl uticasone propionate. Gastroenterology 122 1216-1225 ( 2002 ). (Pubitemid 34465163)
70. Yamazaki K. et al. Allergen-specifi c in vitro cytokine production in adult patients with eosinophilic esophagitis. Dig. Dis. Sci. 51 1934-1941 ( 2006 ). (Pubitemid 44832570)
71. Prussin C. Lee J. & Foster B. Eosinophilic gastrointestinal disease and peanut allergy are alternatively associated with IL-5+ and IL-5- Th2 responses. J. Allergy Clin. Immunol.124 1326-1332 ( 2009 ).
72. Bullock J. Z. et al. Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 45 22-31 ( 2007 ). (Pubitemid 47012327)
73. Straumann A. Bauer M. Fischer B. Blaser K. & Simon H. U. Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic infl ammatory response. J. Allergy Clin. Immunol.108 954-961 ( 2001 ). (Pubitemid 33151548)
74. Mulder D. J. Pooni A. Mak N. Hurlbut D. J. Basta S. & Justinich C. J. Antigen presentation and MHC class II expression by human esophageal epithelial cells: Role in eosinophilic esophagitis. Am. J. Pathol in press ( 2011 ).
75. Paul W. E. & Zhu J. How are T(H)2-type immune responses initiated and amplifi ed? Nat. Rev. Immunol.10 225 - 235 ( 2010 ).
76. Gupta S. K. Fitzgerald J. F. Kondratyuk T. & HogenEsch H. Cytokine expression in normal and infl amed esophageal mucosa: a study into the pathogenesis of allergic eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 42 22-26 ( 2006 ). (Pubitemid 43061005)
77. Mishra A. Hogan S. P. Brandt E. B. & Rothenberg M. E. IL-5 promotes eosinophil traffi cking to the esophagus. J. Immunol.168 2464-2469 ( 2002 ). (Pubitemid 34171851)
78. Lucendo A. J. De Rezende L. Comas C. Caballero T. & Bellon T. Treatment with topical steroids downregulates IL-5, eotaxin-1/CCL11, and eotaxin-3/CCL26 gene expression in eosinophilic esophagitis. Am. J. Gastroenterol. 103 2184-2193 ( 2008 ).
79. Blanchard C. et al. IL-13 involvement in eosinophilic esophagitis: Transcriptome analysis and reversibility with glucocorticoids. J. Allergy Clin. Immunol.120 1292-1300 ( 2007 ). (Pubitemid 350225686)
80. Blanchard C. et al. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J. Immunol.184 4033 - 4041 ( 2010 ).
81. Neilsen C. V. & Bryce P. J. Interleukin-13 directly promotes oesophagus production of CCL11 and CCL24 and the migration of eosinophils. Clin. Exp. Allergy 40 427 - 434 ( 2010 ).
82. Blanchard C. Mishra A. Saito-Akei H. Monk P. Anderson I. & Rothenberg M. E. Inhibition of human interleukin-13-induced respiratory and oesophageal infl ammation by anti-human-interleukin-13 antibody (CAT-354). Clin. Exp. Allergy 35 1096-1103 ( 2005 ). (Pubitemid 41603145)
83. Schmid-Grendelmeier P. et al. Eosinophils express functional IL-13 in eosinophilic infl ammatory diseases. J. Immunol.169 1021-1027 ( 2002 ). (Pubitemid 34753462)
84. Noel R. J. et al. Clinical and immunopathologic effects of swallowed fl uticasone for eosinophilic esophagitis. Clin. Gastroenterol. Hepatol. 2 568-575 ( 2004 ). (Pubitemid 38834041)
85. Maloy K. J. & Powrie F. Regulatory T cells in the control of immune pathology. Nat. Immunol.2 816-822 ( 2001 ).
86. Zhu X. Wang M. Crump C. H. & Mishra A. An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 297 G550-G558 ( 2009 ).
87. Milner J. D. Ward J. M. Keane-Myers A. & Paul W. E. Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated infl ammatory disease. Proc. Natl. Acad. Sci. USA 104 576-581 ( 2007 ). (Pubitemid 46123067)
88. Tantibhaedhyangkul U. Tatevian N. Gilger M. A. Major A. M. & Davis C. M. Increased esophageal regulatory T cells and eosinophil characteristics in children with eosinophilic esophagitis and gastroesophageal refl ux disease. Ann. Clin. Lab. Sci. 39 99-107 ( 2009 ).
89. Fuhlbrigge R. C. Kieffer J. D. Armerding D. & Kupper T. S. Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skinhoming T cells. Nature 389 978-981 ( 1997 ). (Pubitemid 27485690)
90. Clark R. A. et al. The vast majority of CLA+ T cells are resident in normal skin. J. Immunol.176 4431-4439 ( 2006 ). (Pubitemid 44264423)
91. Steiner S. J. Kernek K. M. & Fitzgerald J. F. Severity of basal cell hyperplasia differs in refl ux versus eosinophilic esophagitis. J. Pediatr. Gastroenterol. Nutr. 42 506-509 ( 2006 ). (Pubitemid 43804727)
92. Mishra A. Hogan S. P. Brandt E. B. & Rothenberg M. E. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J. Clin. Invest. 107 83-90 ( 2001 ). (Pubitemid 32047417)
93. Mishra A. et al. Esophageal remodeling develops as a consequence of tissue specifi c IL-5-induced eosinophilia. Gastroenterology 134 204-214 ( 2008 ). (Pubitemid 350309313)
94. Blanchard C. et al. Periostin facilitates eosinophil tissue infi ltration in allergic lung and esophageal responses 1 289-296 ( 2008 ).
95. Zuo L. et al. IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R alpha2-inhibited pathway. J. Immunol.185 660 - 669 ( 2010 ).
96. Caldwell J. M. et al. Glucocorticoid-regulated genes in eosinophilic esophagitis: a role for FKBP51. J. Allergy Clin. Immunol.125 879 - 888 ( 2010 ).
97. Aceves S. S. et al. Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids. Allergy 65 109 - 116 ( 2010 ).
98. Basseri B. et al. Redefi ning the role of lymphocytes in gastroesophageal refl ux disease and eosinophilic esophagitis. Dis. Esophagus. 23 368 - 376 ( 2010 ).
99. Rothenberg M. E. et al. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat. Genet. 42 289 - 291 ( 2010 ).
100. Ardizzone S. & Bianchi Porro G. Biologic therapy for infl amatory bowel disease. Drugs 65 2253-2286 ( 2005 ). (Pubitemid 41571985)
101. Walsh G. M. Mepolizumab and eosinophil-mediated disease. Curr. Med. Chem. 16 4774-4778 ( 2009 ).
102. Walsh G. M. Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated infl ammatory conditions. Curr. Opin. Mol. Ther. 11 329-336 ( 2009 ).
103. Straumann A. Bussmann C. Conus S. Beglinger C. & Simon H. U. Anti-TNF-alpha (infl iximab) therapy for severe adult eosinophilic esophagitis. J. Allergy Clin. Immunol.122 425-427 ( 2008 ).