Celiac disease: An overview from pathophysiology to treatment

Minerva Pediatrica

Volumn 64, Issue 3, 2012, Pages 271-287

  Mubarak, A ^a   Houwen, R H J ^a   Wolters, V M ^a  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

Autoimmune diseases; Celiac disease; Gluten

Indexed keywords

ADAPTIVE IMMUNITY; CELIAC DISEASE; GLUTEN FREE DIET; GOLD STANDARD; INFLAMMATORY DISEASE; INNATE IMMUNITY; INTESTINE BIOPSY; MALABSORPTION; PATHOPHYSIOLOGY; REVIEW; SERODIAGNOSIS;

BIOPSY; CELIAC DISEASE; DIET, GLUTEN-FREE; GLIADIN; GLUTENS; HISTOCOMPATIBILITY ANTIGENS CLASS II; HISTOCOMPATIBILITY TESTING; HUMANS; INCIDENCE; PREVALENCE; RISK ASSESSMENT; RISK FACTORS; SEROLOGIC TESTS; TREATMENT OUTCOME; WORLD HEALTH;

EID: 84862584991     PISSN: 00264946     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (182)

1. Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R et al. ESPGHAN Working Group on Coeliac Disease Diagnosis; ESPGHAN Gastroenterology Committee. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136-60.
2. Adams F. The Extant Works of Aretaeus the Cappadocian. London: The Sydenham Society; 1856.
3. Gee SJ, St. Bartholomew's Hospital Reports, 1888, 24, 17.
4. Herter CA. On infantilism from chronic intestinal infection, characterized by the overgrowth and persistence of flora of the nursling period. A study of the clinical course, bacteriology, chemistry and therapeutics of arrested development in infancy. New York, NY: Macmillan; 1908.
5. Sauer LW. Celiac disease (chronic intestinal indigestion). Am J Dis Child 1925;34:934-9.
6. Still GF. The Lumelian lectures on celiac disease. Lancet 1918;2:163-6.
7. Dicke WK. Sample dietary treatment for the syndrome of Gee-Herter. Ned Tijdsh Geneesk 1941;85:1715-6.
8. Dicke WK. Coeliac disease. Investigation of the harmful effects of certain types of cereal on patients with celiac disease (thesis). University of Utrecht, the Netherlands; 1950.
9. Van der Kamer JH, Weijers HA, Dicke WK. Coeliac disease iv. An investigation into the injurious constituents of wheat in connection with their action on patients with coeliac disease. Acta Paediatr Scand 1953;43:223-31.
10. Paulley JW. Observation on the aetiology of idiopathic steatorrhoea; jejunal and lymph-node biopsies. Br Med J 1954;2:1318-21.
11. Rubin CE. Celiac disease and idiopathic sprue. Some reflections on reversibility, gluten, and the intestine. Gastroenterology 1960;39:260-1.
12. Davidson LSP, Fountain JR. Incidence of sprue syndrome with some observation on the natural history. Br Med J 1950;1:1157-61.
13. Meeuwisse GW. Diagnostic criteria in coeliac disease. Acta Paediatr Scand 1970;59:461-3.
14. Mylotte M, Egan-Mitchell B, McCarthy CF, McNicholl B. Incidence of coeliac disease in the west of Ireland. Br Med J 1973;703-5.
15. Logan RFA, Rifking EA, Busuttil A, Gilmous HM, Ferguson A. Prevalence and 'incidence' of celiac disease in Edinburgh and the Lothian region of Scotland. Gastroenterology 1986;90:334-42.
16. Van Stirum J, Baerlocher K, Fanconi A, Gugler E, Shmerling DH. The incidence of coeliac disease in children in Switzerland. Helv Paediatr Acta 1982;37:421-30.
17. Stenhammar L, Johansson CG. The incidence of coeliac disease in children in south-east Sweden. Acta Paediatr Scand 1981;70:379-81.
18. Greco L, Maki M, Di Donato F, Visakorpi JK. Epidemiology of coeliac disease in Europe and the Mediterranean area. In: Auricchio S, Visakorpi JK, editors. Common food intolerances I: epidemiology of coeliac disease. Basel: Karger; 1992. p. 25-44.
19. Kowlessar OD, Phillips LD. Celiac disease. Med Clin North Am 1970;54:647-56.
20. Cooke WT, Holmes GKT. Definition and epidemiology. In: Celiac Disease. Edinburgh: Churchill Livingstone; 1984. p. 11-22.
21. Lohi S, Mustalahti K, Kaukinen K, Laurila K, Collin P, Rissanen H et al. Increasing prevalence of coeliac disease over time. Aliment Pharmacol Ther 2007;26:1217-25.
22. Bingley PJ, Williams AJ, Norcross AJ, Unsworth DJ, Lock RJ, Ness AR et al. Undiagnosed coeliac disease at age seven: population based prospective birth cohort study. BMJ 2004;328:322-3.
23. West J, Logan RF, Hill PG, Lloyd A, Lewis S, Hubbard R et al. Seroprevalence, correlates, and characteristics of undetected coeliac disease in England. Gut 2003;52:960-5.
24. Mustalahti K, Catassi C, Reunanen A, Fabiani E, Heier M, McMillan S et al. The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med 2010;42:587-95.
25. Fasano A, Berti I, Gerarduzzi T, Not T, Colletti RB, Drago S et al. Prevalence of celiac disease in at-risk and not-at-risk groups in the United States: a large multicenter study. Arch Intern Med 2003;163:286-92.
26. Cataldo F, Montalto G. Celiac disease in the developing countries: a new and challenging public health problem. World J Gastroenterol 2007;13:2153-9.
27. Barada K, Bitar A, Mokadem MA, Hashash JG, Green P. Celiac disease in Middle Eastern and North African countries: a new burden? World J Gastroenterol 2010;16:1449-57.
28. Alarida K, Harown J, Ahmaida A, Marinelli L, Venturini C, Kodermaz G et al. Coeliac disease in Libyan children: a screening study based on the rapid determination of anti-transglutaminase antibodies. Dig Liver Dis 2011;43:688-91.
29. Oliveira RP, Sdepanian VL, Barreto JA, Cortez AJ, Carvalho FO et al. High prevalence of celiac disease in Brazilian blood donor volunteers based on screening by IgA antitissue transglutaminase antibody. Eur J Gastroenterol Hepatol 2007;19:43-9.
30. Jiang LL, Zhang BL, Liu YS. Is adult celiac disease really uncommon in Chinese? J Zhejiang Univ Sci B 2009;10:168-71.
31. Cummins AG, Roberts-Thomson IC. Prevalence of celiac disease in the Asia-Pacific region. J Gastroenterol Hepatol 2009;24:1347-51.
32. Wang XQ, Liu W, Xu CD, Mei H, Gao Y, Peng HM et al. Celiac disease in children with diarrhea in 4 cities in China. J Pediatr Gastroenterol Nutr 2011;53:368-70.
33. Catassi C, Rätsch IM, Gandolfi L, Pratesi R, Fabiani E, El Asmar R, Frijia M et al. Why is coeliac disease endemic in the people of the Sahara? Lancet 1999;354:647-8.
34. Roma E, Panayiotou J, Karantana H, Constantinidou C, Siakavellas SI, Krini M et al. Changing pattern in the clinical presentation of pediatric celiac disease: a 30-year study. Digestion 2009;80:185-91.
35. Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G et al. Selective IgA deficiency in autoimmune diseases. Mol Med 2011;17:1383-96.
36. Ludvigsson JF, Lindelöf B, Zingone F, Ciacci C.Psoriasis in a nationwide cohort study of patients with celiac disease. J Invest Dermatol 2011;131:2010-6.
37. Yang A, Chen Y, Scherl E, Neugut AI, Bhagat G, Green PH. Inflammatory bowel disease in patients with celiac disease. Inflamm Bowel Dis 2005;11:528-32.
38. Virta LJ, Kolho KL. The risk of contracting pediatric inflammatory bowel disease in children with celiac disease, epilepsy, juvenile arthritis and type 1 diabetes-a nationwide study. J Crohns Colitis 2012 [Epub ahead of print].
39. Walkowiak J, Blask-Osipa A, Lisowska A, Oralewska B, Pogorzelski A, Cichy W et al. Cystic fibrosis is a risk factor for celiac disease. Acta Biochim Pol 2010;57:115-8.
40. Pavone L, Fiumara A, Bottaro G, Mazzone D, Coleman M. Autism and celiac disease: failure to validate the hypothesis that a link might exist. Biol Psychiatry 19971;42:72-5.
41. Chen SJ, Chao YL, Chen CY, Chang CM, Wu EC, Wu CS et al. Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study. Br J Psychiatry 2012 [Epub ahead of print].
42. Wieser H. Chemistry of gluten proteins. Food Microbiol 2007;24:115-9.
43. Challacombe DN, Mecrow IK, Elliott K, Clarke FJ, Wheeler EE. Changing infant feeding practices and declining incidence of coeliac disease in West Somerset. Arch Dis Child 1997;77:206-9.
44. Agostoni C, Decsi T, Fewtrell M, Goulet O, Kolacek S, Koletzko B et al. Complementary feeding: a commentary by the ESPGHAN committee on nutrition. J Pediatr Gastroenterol Nutr 2008;461:99-110.
45. Akobeng AK , Ramanan AV , Buchan I, Heller RF. Effect of breast feeding on risk of coeliac disease: a systematic review and meta-analysis of observational studies. Arch Dis Child 2006;91:39-43.
46. Ivarsson A, Persson LA, Nyström L, Ascher H, Cavell B, Danielsson L et al. Epidemic of coeliac disease in Swedish children. Acta Paediatr 2000;89:165-71.
47. Myléus A, Ivarsson A, Webb C, Danielsson L, Hernell O, Högberg L et al. Celiac disease revealed in 3% of Swedish 12-year-olds born during an J Pediatr Gastroenterol Nutr 2009;49:170-6.
48. Carlsson A, Agardh D, Borulf S, Grodzinsky E, Axelsson I, Ivarsson SA. Prevalence of celiac disease: before and after a national change in feeding recommendations. Scand J Gastroenterol 2006;41:553-558.
49. Stene LC, Honeyman MC, Hoffenberg EJ, Haas JE, Sokol RJ, Emery L et al. Rotavirus infection frequency and risk of celiac disease autoimmunity in early childhood: a longitudinal study. Am J Gastroenterol 2006;101:2333-40.
50. Pinier M, Fuhrmann G, Verdu EF, Leroux JC. Prevention measures and exploratory pharmacological treatments of celiac disease. Am J Gastroenterol 2010;105:2551-61.
51. Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 2000;355:1518-9.
52. Elli L, Bergamini CM , Bardella MT, Schuppan D. Transglutaminases in inflammation and fibrosis of the gastrointestinal tract and the liver. Dig Liv Dis 2009;4:541-50.
53. Zanoni G, Navone R, Lunardi C, Tridente G, Bason C, Sivori S et al. In celiac disease a subset of autoantibodies against transglutaminase binds toll-like receptor 4 and induces activation of monocytes. PLoS Med 2006;3:e358.
54. Schippa S, Iebba V, Barbato M, Di Nardo G, Totino V, Checchi MP et al. A distinctive 'microbial signature' in celiac pediatric patients. BMC Microbiol 2010;10:175.
55. Nadal I, Donat E, Ribes-Koninckx C, Sanz Y. Imbalance in the composition of the duodenal microbiota of children with coeliac disease. J Med Microbiol 2007;56:1669-74.
56. Collado MC, Donat E, Ribes-Koninckx C, Sanz Y. Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. J Clin Pathol 2009;623:264-9.
57. Sellitto M, Bai G, Serena G, Fricke WF, Sturgeon C, Gajer P et al. Proof of concept of microbiome-metabolome analysis and delayed gluten exposure on celiac disease autoimmunity in genetically at-risk infants. PLoS One 2012;7:e33387.
58. Greco L, Romino R, Coto I, Di Cosmo N, Percopo S, Maglio M et al. The first large population based twin study in celiac disease. Gut 2002;50:624-8.
59. Nisticò L, Fagnani C, Coto I, Percopo S, Cotichini R, Limongelli MG et al. Concordance, disease progression, and heritability of coeliac disease in Italian twins. Gut 2006;55:803-8.
60. Petronzelli F, Bonamico M, Ferrante P, Grillo R, Mora B, Mariani P et al. Genetic contribution of the HLA region to the familial clustering of coeliac disease. Ann Hum Genet 1997;61:307-17.
61. Sollid L, Markussen M. Evidence of a primary association of celiac disease to a paticular HLA-DQ x/x heterodimer. J Exp Med 1989;169:345-50.
62. Sollid LM. Molecular basis of celiac disease. Annu Rev Immunol 2000;18:53-81.
63. Sollid LM, Thorsby E. HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis. Gastroenterology 1993;105:910-22.
64. Spurkland A, Sollid LM, Polanco I, Vandal F, Thorsby E. HLA-DR and -DQ genotypes of celiac disease patients serologically typed to be non-DR3 or non-DR5/7. Hum Immunol 1992;35:188-92.
65. Polvi A, Arranz E, Fernandez-Arquero M, Collin P, Mäki M, Sanz A et al. HLA-DQ2-negative celiac disease in Finland and Spain. Hum Immunol 1998;59:169-75.
66. Mearin ML, Biemond I, Peña AS, Polanco I, Vazquez C, Schreuder GT et al. HLA-DR phenotypes in Spanish coeliac children: their contribution to the understanding of the genetics of the disease. Gut 1983;24:532-27.
67. Wolters WM, Wijmenga C. Genetic background of celiac disease and its clinical implications. Am J Gastroentrol 2008;103:190-5.
68. Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterology 1992;102:330-54.
69. Ferguson A, MacDonald TT, McClure JP, Holden RJ. Cell-mediated immunity to gliadin within the small-intestinal mucosa in coeliac disease. Lancet 1975;1:895-7.
70. Lundin KE, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O et al. Gliadin-specific, HLA-DQ(a1*0501,b1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med 1993;178:187-96.
71. Lundin KA, Scott H, Fausa O, Thorsby E, Sollid LM. T cells from the small intestinal mucosa of a DR4, DQ7/DR4, DQ8 celiac-disease patient preferentially recognize gliadin when presented by DQ8. Hum Immunol 1994;41:285-91.
72. Korponay-Szabó IR, Laurila K, Szondy Z, Halttunen T, Szalai Z, Dahlbom I et al. Missing endomysial and reticulin binding of coeliac antibodies in transglutaminase 2 knockout tissues. Gut 2003;52:199-204
73. Mäki M, Hällström O, Marttinen A. Reaction of human non-collagenous polypeptides with coeliac disease autoantibodies.Lancet 1991;338:724-5.
74. Dieterich W, Ehnis T, Bauer M, Donner P, Volta U, Riecken EO et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801.
75. van de Wal Y, Kooy Y, van Veelen P, Pena S, Mearin L, Papadopoulos G et al. Cutting edge: selective deamidation by tissue transglutaminase strongly enhances gliadin-specific T cell reactivity. J Immunol 1998;161:1585-8.
76. Molberg O, Mcadam SN, Körner R, Quarsten H, Kristiansen C, Madsen L et al. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med 1998;4:713-7.
77. Osman AA, Gunnel T, Dietl A, Uhlig HH, Amin M, Fleckenstein B et al. B-cell epitopes of gliadin. Clin Exp Immunol 2000;121:248-54.
78. Aleanzi M, Demonte AM, Esper C, Garcilazo S, Waggener M. Celiac disease: antibody recognition against native and selectively deamidated gliadin peptides. Clin Chem 2001;47:2023-8.
79. Arentz-Hansen H, Körner R, Molberg O, Quarsten H, Vader W, Kooy YM et al. The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med 2000;191:603-12.
80. Vader LW, de Ru A, van der Wal Y, Kooy YM, Benckhuijsen W et al. Specificity of tissue transglutaminase explains cereal toxicity in celiac disease.J Exp Med 2002;195:643-9.
81. Vader W, Stepniak D, Kooy Y, Mearin L, Thompson A, van Rood JJ et al. The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses. Proc Natl Acad Sci U S A 2003;100:12390-5.
82. Al-Toma A, Goerres MS, Meijer JW, Peña AS, Crusius JB, Mulder CJ. Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma. Clin Gastroenterol Hepatol 2006;4:315-9.
83. Drago S, El Asmar R, Di Pierro M, Grazia Clemente M, Tripathi A, Sapone A et al. Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol 2006;41:408-19.
84. Matysiak-Budnik T, Moura IC, Arcos-Fajardo M, Lebreton C, Menard S, Candalh C et al. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J Exp Med 2008;205:143-54.
85. Ménard S, Lebreton C, Schumann M, Matysiak-Budnik T, Dugave C, Bouhnik Y et al. Paracellular versus transcellular intestinal permeability to gliadin peptides in active celiac disease. Am J Pathol 2012;180:608-15.
86. Esposito C, Paparo F, Caputo I, Porta R, Salvati VM, Mazzarella G et al. Expression and enzymatic activity of small intestinal tissue transglutaminase in celiac disease. Am J Gastroenterol 2003;98:1813-20.
87. Vader W, Kooy Y, Van Veelen P, De Ru A, Harris D, Benckhuijsen W et al. The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. Gastroenterology 2002;122:1729-37.
88. Tjon JM, van Bergen J, Koning F. Celiac disease: how complicated can it get? Immunogenetics. 2010;62:641-51.
89. Olaussen RW, Johansen FE, Lundin KE, Jahnsen J, Brandtzaeg P, Farstad IN. Interferon-gamma-secreting T cells localize to the epithelium in coeliac disease. Scand J Immunol 2002;56:652-64.
90. Garrote JA, Gómez-González E, Bernardo D, Arranz E, Chirdo F. Celiac disease pathogenesis: the proinflammatory cytokine network. J Pediatr Gastroenterol Nutr 2008;47:S27-32.
91. Maiuri L, Ciacci C, Ricciardelli I, Vacca L, Raia V, Auricchio S et al. Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease. Lancet 2003;362:30-7.
92. Di Sabatino A, Ciccocioppo R, Cupelli F, Cinque B, Millimaggi D, Clarkson MM et al. Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease. Gut 2006 ;55:469-77.
93. Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN et al. Coordinated Induction by IL15 of a TCR-Independent NKG2D signaling pathway converts CTL into Lymphokine-activated killer cells in celiac disease. Immunity 2004;21:357-66.
94. León AJ, Garrote JA, Blanco-Quirós A, Calvo C, Fernández-Salazar L, Del Villar A et al. Interleukin 18 maintains a long-standing inflammation in coeliac disease patients. Clin Exp Immunol 2006;146:479-85.
95. Mäki M, Collin P. Coeliac disease. Lancet 1997;349:1755-9.
96. Perri F, Pastore M, Zicolella A, Annese V, Quitadamo M, Andriulli A. Gastric emptying of solids is delayed in celiac disease and normalizes after gluten withdrawal. Acta Paediatr 2000;89:921-5.
97. Cheng J, Malahias T, Brar P, Minaya MT, Green PH. The association between celiac disease, dental enamel defects, and aphthous ulcers in a United States cohort. J Clin Gastroenterol 2010;44:191-4.
98. Ludvigsson JF, Olsson T, Ekbom A, Montgomery SM. A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases. Aliment Pharmacol Ther 2007;25:1317-27.
99. Choi JM, Lebwohl B, Wang J, Lee SK, Murray JA, Sauer MV et al. Increased prevalence of celiac disease in patients with unexplained infertility in the United States. J Reprod Med 2011;56:199-203.
100. Caproni M, Antiga E, Melani L, Fabbri P; Italian Group for Cutaneous Immunopathology. Guidelines for the diagnosis and treatment of dermatitis herpetiformis. J Eur Acad Dermatol Venereol 2009;23:633-8.
101. Cellier C, Delabesse E, Helmer C, Patey N, Matuchansky C, Jabri B et al. Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. Lancet 2000;356:203-8.
102. Bonamico M, Ferri M, Mariani P, Nenna R, Thanasi E, Luparia RP et al. Serologic and genetic markers of celiac disease: a sequential study in the screening of first degree relatives. J Pediatr Gastroenterol Nutr 2006;42:150-4.
103. Johnston SD, Watson RG, McMillan SA, Evans AE, Love AH. Serological markers for coeliac disease: changes with time and relationship to enteropathy. Eur J Gastroenterol Hepatol 1998;10:259-64.
104. Liu E, Bao F, Barriga K, Miao D, Yu L, Erlich HA et al. Fluctuating transglutaminase autoantibodies are related to histologic features of celiac disease. Clin Gastroenterol Hepatol 2003;1:356-62.
105. Simell S, Kupila A, Hoppu S, Hekkala A, Simell T, Ståhlberg MR et al. Natural history of transglutaminase autoantibodies and mucosal changes in children carrying HLA-conferred celiac disease susceptibility. Scand J Gastroenterol 2005;40:1182-91.
106. Hogen Esch CE, Csizmadia GD, van Hoogstraten IM, Schreurs MW, Mearin ML, von Blomberg BM. Childhood coeliac disease: towards an improved serological mass screening strategy. Aliment Pharmacol Ther 2010;31:760-6.
107. Tosco A, Salvati VM, Auricchio R, Maglio M, Borrelli M, Coruzzo A et al. Natural history of potential celiac disease in children. Clin Gastroenterol Hepatol 2011;9:320-5.
108. Waisbourd-Zinman O, Hojsak I, Rosenbach Y, MozerGlassberg Y, Shalitin S, Phillip M et al. Spontaneous Normalization of Anti-Tissue Transglutaminase Antibody Levels Is Common in Children with Type 1 Diabetes Mellitus. Dig Dis Sci 2011 [Epub ahead of print].
109. Sperandeo MP, Tosco A, Izzo V, Tucci F, Troncone R, Auricchio R et al. Potential celiac patients: a model of celiac disease pathogenesis. PLoS One 2011;6:e21281.
110. Congia M, Cucca F, Frau F, Lampis R, Melis L, Clemente MG et al. A gene dosage effect of the DQA1*0501/DQB1*0201 allelic combination influences the clinical heterogeneity of celiac disease. Hum Immunol 1994;40:138-42.
111. Karinen H, Kärkkäinen P, Pihlajamäki J, Janatuinen E, Heikkinen M, Julkunen R et al. Gene dose effect of the DQB1*0201 allele contributes to severity of coeliac disease. Scand J Gastroenterol 2006;41:191-9.
112. Zubillaga P, Vidales MC, Zubillaga I, Ormaechea V, García- Urkía N, Vitoria JC. HLA-DQA1 and HLA-DQB1 genetic markers and clinical presentation in celiac disease. J Pediatr Gastroenterol Nutr 2002;34:548-54.
113. Vermeulen BA, Hogen Esch CE, Yuksel Z, Koning F, Verduijn W, Doxiadis II et al. Phenotypic variance in childhood coeliac disease and the HLA-DQ/DR dose effect. Scand J Gastroenterol 2009;44:40-5.
114. Mustalahti K, Holopainen P, Karell K, Mäki M, Partanen J. Genetic dissection between silent and clinically diagnosed symptomatic forms of coeliac disease in multiplex families. Dig Liver Dis 2002;34:842-5.
115. Jores RD, Frau F, Cucca F, Grazia Clemente M, Orrù S, Rais M, De Virgiliis S et al. HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease. Scand J Gastroenterol 2007;42:48-53.
116. Greco L, Percopo S, Clot F, Bouguerra F, Babron MC, Eliaou JF et al. Lack of correlation between genotype and phenotype in celiac disease. J Pediatr Gastroenterol Nutr 1998;26:286-90.
117. McNeish AS, Harms HK, Rey J, Shmerling DH, Visakorpi JK, Walker-Smith JA. The diagnosis of coeliac disease. A commentary on the current practices of members of the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN). Arch Dis Child 1979;54:783-6.
118. Walker-Smith JA, Guandalini S, Schmitz J, Shmerling DH, Visakorpi JK. Revised criteria for diagnosis of coeliac disease. Arch Dis Child 1990; 65:909-11.
119. Mubarak A, Nikkeis P, Houwen R, Ten Kate F. Reproducibility of the histological diagnosis of celiac disease. Scand J Gastroenterol 2011;46:1065-73.
120. Kaukinen K, Mäki M, Partanen J, Sievänen H, Collin P. Celiac disease without villous atrophy: revision of criteria called for. Dig Dis Sci 2011;46:879-87.
121. Tursi A, Brandimarte G. The symptomatic and histologic response to a gluten-free diet in patients with borderline enteropathy. J Clin Gastoenterol 2003;36:13-7.
122. Paparo F, Petrone E, Tosco A, Maglio M, Borrelli M, Salvati VM et al. Clinical, HLA, and small bowel immunohistochemical features of children with positive serum antiendomysium antibodies and architecturally normal small intestinal mucosa. Am J Gastroenterol 2005;100:2294-8.
123. Ferguson A, Avanz E, O'Mahony S. Clinical and pathological spectrum of celiac disease: active, silent, latent, potential. Gut 1993;34:150-1.
124. Bonamico M, Thanasi E, Mariani P, Nenna R, Luparia RP, Barbera C, Morra I, Lerro P, Guariso G et al. Duodenal bulb biopsies in celiac disease: a multicenter study. J Pediatr Gastroenterol Nutr 2008;47: 618-22.
125. Collin P, Wahab PJ, Murray JA. Intraepithelial lymphocytes and coeliac disease. Best Pract Res Clin Gastroenterol 2005;19:341-50.
126. Karell K, Louka AS, Moodie SJ, Ascher H, Clot F, Greco L et al. HLA types in celiac disease patients not carrying the DQA1x05-DQB1x02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease. HumImmunol 2003,64:469-77.
127. Berger E, Buergin-Wolff A, Freudenberg E. Diagnostic value of the demonstration of gliadin antibodies in celiac disease. Klin Wochenschr 1964;42:788-90.
128. Rostom A, Dube C, Cranney A, Saloojee N, Sy R, Garritty C et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology 2005;128:S38-46.
129. Seah PP, Fry L, Rossiter MA, Hoffbrand AV, Holborow EJ. Anti-reticulin antibodies in childhood coeliac disease. Lancet 1971;2:681-2.
130. Chorzelski TP, Beutner EH, Sulej J, Tchorzewska H, Jablonska S, Kumar V et al. IgA anti-endomysium antibody. A new immunological marker of dermatitis herpetiformis and coeliac disease. Br J Dermatol 1984;111:395-402.
131. Parizade M, Bujanover Y, Weiss B, Nachmias V, Shainberg B. Performance of serology assays for diagnosing celiac disease in a clinical setting. Clin Vacc Imm 2009;16:1576-82.
132. Wolters V, Vooijs-Moulaert AF, Burger H, Brooimans R, De Schryver J, Rijkers G et al. Human tissue transglutaminase enzyme linked immunosorbent assay outperforms both the guinea pig based tissue transglutaminase assay and anti-endomysium antibodies when screening for coeliac disease. Eur J Pediatr 2002;161:284-7.
133. Korponay-Szabó IR, Dahlbom I, Laurila K, Laurila K, Koskinen S, Woolley N, Partanen J et al. Elevation of IgG antibodies against tissue transglutaminase as a diagnostic tool for coeliac disease in selective IgA deficiency. Gut 2003;52:1567-71.
134. Barker CC, Mitton C, Jevon G, Mock T. Can tissue transglutaminase antibody titers replace smallbowel biopsy to diagnose celiac disease in select pediatric populations? Pediatrics 2005;115:1341-6.
135. Donaldson MR, Firth SD, Wimpee H, Leiferman KM, Zone JJ, Horsley W et al. Correlation of duodenal histology with tissue transglutaminase and endomysial antibody levels in pediatric celiac disease. Clin Gastroentrol Hepatol 2007;5:567-73.
136. Donaldson MR, Book LS, LeifermanKM, Zone JJ Neuhausen SL. Strongly positive tissue transglutaminase antibodies are associated with Marsh 3 histopathology in adult and pediatric celiac disease. J Clin Gastroenterol 2008; 42:256-60.
137. Mubarak A, Wolters VM, Gerritsen SA, Gmelig-Meyling FH, Ten Kate FJ, Houwen RH. A biopsy is not always necessary to diagnose celiac disease. J Pediatr Gastroenterol Nutr 2011;52:554-47.
138. Baudon JJ, Johanet C, Absalon YB, Cabrol S, Mougenot JF. Diagnosing celiac disease: a comparison of human tissue transglutaminase antibodies with antigliadin and antiendomysium antibodies. Arch Pediatr Adolesc Med 2004;158:584-8.
139. Burgin-Wolff A, Gaze H, Hadziselimovic F, Huber H, Lentze MJ, Nussle D et al. Antigliadin and antiendomysium antibody determination for coeliac dis- ease. Arch Dis Child 1991;66:941-7.
140. Lagerqvist C, Dahlbom I, Hansson T, Jidell E, Juto P, Olcen P et al. Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age. J Pediatr Gastroenterol Nutr 2008;47:428-35.
141. Maglio M, Tosco A, Paparo F, Auricchio R, Granata V, Colicchio B et al. Serum and intestinal celiac disease-associated antibodies in children with celiac disease younger than 2 years of age. J Pediatr Gastroenterol Nutr 2010;50:43-8.
142. Basso D, Guariso G, Fogar P, Meneghel A, Zambon CF, Navaglia F et al. Antibodies against synthetic deamidated gliadin peptides for celiac disease diagnosis and follow-up in children. Clin Chem 2009;55:150-7.
143. Prause C, Ritter M, Probst C, Daehnrich C, Schlumberger W, Komorowski L et al. Antibodies against deamidated gliadin as new and accurate biomarkers of childhood coeliac disease. J Pediatr Gastroenterol Nutr 2009;49:52-8.
144. Mubarak A, Gmelig-Meyling FH, Wolters VM, Ten Kate FJ, Houwen RH. Immunoglobulin G antibodies against deamidated-gliadin-peptides outperform anti-endomysium and tissue transglutaminase antibodies in children <2 years age. APMIS 2011;119:894-900.
145. Tonutti E, Visentini D, Picierno A, Bizzaro N, Villalta D, Tozzoli R et al. Diagnostic efficacy of the ELISA test for the detection of deamidated anti-gliadin peptide antibodies in the diagnosis and monitoring of celiac disease. J Clin Lab Anal 2009;23:165-71.
146. Villalta D, Tonutti E, Prause C, Koletzko S, Uhlig HH, Vermeersch P et al. IgG antibodies against deamidated gliadin peptides for diagnosis of celiac disease in patients with IgA deficiency. Clin Chem 2010;56:464-8.
147. Dutta AK, Chacko A, Avinash B. Suboptimal performance of IgG anti-tissue transglutaminase in the diagnosis of celiac disease in a tropical country. Dig Dis Sci 2010;55:698-702.
148. Vreugdenhil AC, Wolters VM, Adriaanse MP, Van den Neucker AM, van Bijnen AA, Houwen R et al. Additional value of serum I-FABP levels for evaluating celiac disease activity in children. Scand J Gastroenterol 2011;46:1435-41.
149. Ioannou HP, Fotoulaki M, Pavlitou A, Efstratiou I, Augoustides-Sawopoulou P. Plasma citrulline levels in paediatric patients with celiac disease and the effect of a gluten-free diet. Eur J Gastroenterol Hepatol 2011;23:245-9.
150. Brottveit M, Ráki M, Bergseng E, Fallang LE, Simonsen B, Løvik A et al. Assessing possible celiac disease by an HLA-DQ2-gliadin Tetramer Test. Am J Gastroenterol 2011;106:1318-24.
151. Akobeng AK, Thomas AG. Systematic review: tolerable amount of gluten for people with coeliac disease. Aliment Pharmacol Ther 2008;27:1044-52.
152. Gibert A, Espadaler M, Angel Canela M, Sánchez A, Vaqué C, Rafecas M. Consumption of gluten-free products: should the threshold value for trace amounts of gluten be at 20, 100 or 200 p.p.m.? Eur J Gastroenterol Hepatol 2006;18:1187-95.
153. Thompson T, Dennis M, Higgins LA, Lee AR, Sharrett MK. Gluten-free diet survey: are Americans with coeliac disease consuming recommended amounts of fibre, iron, calcium and grain foods? J Hum Nutr Diet 2005;18:163-9.
154. Hogen Esch CE, Wolters VM, Gerritsen SA, Putter H, von Blomberg BM, van Hoogstraten IM et al. Specific celiac disease antibodies in children on a gluten-free diet. Pediatrics 2011;128:547-52.
155. Chow MA, Lebwohl B, Reilly NR, Green PH. Immunoglobulin a deficiency in celiac disease. J Clin Gastroenterol 2012 [Epub ahead of print].
156. Comino I, Real A, Vivas S, Síglez MA, Caminero A, Nistal E et al. Monitoring of gluten-free diet compliance in celiac patients by assessment of gliadin 33-mer equivalent epitopes in feces. Am J Clin Nutr 2012;95:670-7.
157. Olsson C, Hörnell A, Ivarsson A, Sydner YM. The everyday life of adolescent coeliacs: issues of importance for compliance with the gluten-free diet. J Hum Nutr Diet 2008;21:359-67.
158. Casellas F, Rodrigo L, Lopez Vivancos J, riestra S, Pantiga S et al. Factors that impact health-related quality of life in adults with celiac disease: A multicenter study. World J Gastroenterol 2008;14:46-52.
159. Häuser W, Gold J, Stein J, Caspary WF, Stallmach A. Health-related quality of life in adult coeliac disease in Germany: results of a national survey. 2006. Eur J Gastroenterol Hepatol 2011;18:747-54.
160. Zarkadas M, Cranney A, Case S, Molloy M, Switzer C, Graham ID et al. The impact of a gluten-free diet on adults with coeliac disease: results of a national survey. J Hum Nutr Diet 2006;19:41-9.
161. Mustalahti K, Lohiniemi S, Collin P, Vuolteenaho N, Laippala P, Mäk M. Gluten-free diet and quality of life in patients with screen-detected celiac disease. Eff Clin Pract 2002;5:105-13.
162. Johnston SD, Rodgers C, Watson RG. Quality of life in screen-detected and typical coeliac disease and the effect of excluding dietary gluten. Eur J Gastroenterol Hepatol 2004;16:1281-6.
163. Nachman F, Mauriño E, Vázquez H, Sfoggia C, Gonzalez A, Gonzalez V et al. Quality of life in celiac disease patients. Prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment. Dig Liver Dis 2009;41:15-25.
164. van Koppen EJ, Schweizer JJ, Csizmadia CG, Krom Y, Hylkema HB, van Geel AM, Koopman HM et al. Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study. Pediatrics 2009;123:e582-8.
165. Viljamaa M, Collin P, Huhtala H, Sievanen H, Mak M, Kaukinen K. Is coeliac disease screening in risk groups justified? A fourteen-year follow-up with special focus on compliance and quality of life. Aliment Pharmacol Ther 2005;22:317-24.
166. Whitaker JK, West J, Holmes GK, Logan RF. Patient perceptions of the burden of coeliac disease and its treatment in the UK. Aliment Pharmacol Ther 2009;29: 1131-6.
167. Nachman F, Mauriño E, Vázquez H, Sfoggia C, Gonzalez A, Gonzalez V et al. Quality of life in celiac disease patients: prospective analysis on the importance of clinical severity at diagnosis and the impact of treatment. Dig Liver Dis 2009;41:15-25.
168. Tontini GE, Rondonotti E, Saladino V, Saibeni S, de Franchis R, Vecchi M. Impact of gluten withdrawal on health-related quality of life in celiac subjects: an observational case-control study. Digestion 2010;9:221-8.
169. Ukkola A, Maki M, Kurppa K, Collin P, Huhtala H, Kekkonen L et al. Diet improves perception of health and well-being in symptomatic, but not asymptomatic, patients with celiac disease. Clin Gastroenterol Hepatol 2011;118-123 e111.
170. Metzger MH, Heier M, Maki M, Bravi E, Schneider A, Lowel H et al. Mortality excess in individuals with elevated IgA anti-transglutaminase antibodies: the KORA/MONICA Augsburg cohort study 1989-1998. Eur J Epidemiol 2006;21:359-65.
171. Rubio-Tapia A, Kyle RA, Kaplan EL, Johnson DR, Page W, Erdtmann F et al. Increased prevalence and mortality in undiagnosed celiac disease. Gastroenterology 2009;137: 88-93.
172. Ludvigsson JF, Montgomery SM, Ekbom A, Brandt L, Granath F. Small-intestinal histopathology and mortality risk in celiac disease. JAMA 2009;302:1171-8.
173. West J, Logan RF, Smith CJ, Hubbard RB, Card TR Malignancy and mortality in people with coeliac disease: population based cohort study. BMJ 2004;329:716-9.
174. Holmes GK, Prior P, Lane MR, Pope D, Allan RN. Malignancy in coeliac disease - effect of a gluten free diet. Gut 1989;30:333-8.
175. Holmes GK, Stokes PL, Sorahan TM, Prior P, Waterhouse JA, Cooke WT. Coeliac disease, gluten-free diet, and malignancy. Gut 1976;17: 612-9.
176. Goldacre MJ, Wotton CJ, Yeates D, Seagroatt V, Jewell D. Cancer in patients with ulcerative colitis, Crohn's disease and coeliac disease: record linkage study. Eur J Gastroenterol Hepatol 2008;20:297-304.
177. Toscano V, Conti FG, Anastasi E, Mariani P, Tiberti C, Poggi M et al. Importance of gluten in the induction of endocrine autoantibodies and organ dysfunction in adolescent celiac patients. Am J Gastroenterol 2000;95:1742-8.
178. Cosnes J, Cellier C, Viola S, Colombel JF, Michaud L, Sarles J et al. Incidence of autoimmune diseases in celiac disease: protective effect of the gluten-free diet. Clin Gastroenterol.Hepatol 2008,6:753-8.
179. Ventura A, Magazzù G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Gastroenterology 1999;117:297-303.
180. Sategna Guidetti C, Solerio E, Scaglione N, Mengozzi G. Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders. Gut 2001;49:502-4.
181. Viljamaa M, Kaukinen K, Huhtala H, Rasmussen M, Collin P. Coeliac disease, autoimmune diseases and gluten exposure. Scand J Gastroenterol 2005;40:437-43.
182. Guariso G, Conte S, Presotto F, Basso D, Brotto F, Visonà Dalla Pozza L. Clinical, subclinical and potential autoimmune diseases in an Italian population of children with coeliac disease. Aliment Pharmacol Ther 2007;26:1409-17.