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Italian Journal of Pediatrics
Published in: Italian Journal of Pediatrics 1/2017

Open Access 01-12-2017 | Case report

Coeliac disease in infants: antibodies to deamidated gliadin peptide come first!

Authors: Michele Arigliani, Francesca Rech Morassutti, Martina Fabris, Paola Melli, Elio Tonutti, Paola Cogo

Published in: Italian Journal of Pediatrics | Issue 1/2017

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Abstract

Background

The onset of coeliac disease (CD) in the first year of life is uncommon and the diagnosis can be challenging due to the suboptimal sensitivity of tissue transglutaminase antibodies (tTG) at this age and the many other possible causes of malabsorption in infants. Antibodies to deamidated gliadin peptides (anti-DGPs), especially IgG, may appear earlier than IgA anti-tTG in very young children with CD.

Case presentation

We report here on an 8-month-old child who was evaluated for failure to thrive, constipation and developmental delay. The symptoms started following gluten introduction in the diet. Laboratory tests showed high fecal elastase concentration, normal serum IgA levels with positive IgG and IgA anti-DGPs, whereas anti-tTG were not detected. The duodenal biopsy revealed a complete villous atrophy (Marsh-Oberhuber 3C). The culture of biopsy fragments in the presence of gliadin peptides did not stimulate the production of IgA anti-endomysial antibodies. Genetic testing proved the child was positive for HLA-DQ2 (DQA1*05; DQB1*02) and HLA-DQ8 (DQA1*03, DQB1*0302). Having initiated the gluten-free diet, the symptoms disappeared and the infant experienced rapid catch-up growth with normalization of psychomotor development.

Conclusions

This case report highlights the utility of anti-DGPs for screening infants with suspected CD. The pattern with positivity for IgG and IgA anti-DGPs only is rare in IgA-competent children with biopsy-proven CD. It could be explained in infancy as immaturity of the adaptive immune system.
Literature
1.
2.
Garnier-Lengliné H, Cerf-Bensussan N, Ruemmele FM. Celiac disease in children. Clin Res Hepatol Gastroenterol. 2015;39:544–51.CrossRefPubMed
3.
Snyder J, Butzner JD, DeFelice AR, Fasano A, Guandalini S, Liu E, et al. Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children. Pediatrics. 2016;138:e20153147.CrossRefPubMed
4.
Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, et al. Introduction of Gluten, HLA Status, and the Risk of Celiac Disease in Children. N Engl J Med. 2014;371:1295–303.CrossRefPubMed
5.
Saari A, Harju S, Mäkitie O, Saha M-T, Dunkel L, Sankilampi U. Systematic growth monitoring for the early detection of celiac disease in children. JAMA Pediatr. 2015;169:e1525.CrossRefPubMed
6.
Tanpowpong P, Broder-Fingert S, Katz AJ, Camargo CA. Age-Related Patterns in Clinical Presentations and Gluten-Related Issues Among Children and Adolescents With Celiac Disease. Clin Transl Gastroenterol. 2012;3:e9.CrossRefPubMedPubMedCentral
7.
8.
Di Sabatino A, Corazza GR. Coeliac disease. Lancet Lond Engl. 2009;373:1480–93.CrossRef
9.
10.
Gianfrani C, Auricchio S, Troncone R. Adaptive and innate immune responses in celiac disease. Immunol Lett. 2005;99:141–5.CrossRefPubMed
11.
Lagerqvist C, Dahlbom I, Hansson T, Jidell E, Juto P, Olcén 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.CrossRefPubMed
12.
Leffler DA, Schuppan D. Update on serologic testing in celiac disease. Am J Gastroenterol. 2010;105:2520–4.CrossRefPubMed
13.
Giersiepen K, Lelgemann M, Stuhldreher N, Ronfani L, Husby S, Koletzko S, et al. Accuracy of diagnostic antibody tests for coeliac disease in children: summary of an evidence report. J Pediatr Gastroenterol Nutr. 2012;54:229–41.CrossRefPubMed
14.
Simell S, Hoppu S, Hekkala A, Simell T, Ståhlberg M-R, Viander M, et al. Fate of five celiac disease-associated antibodies during normal diet in genetically at-risk children observed from birth in a natural history study. Am J Gastroenterol. 2007;102:2026–35.CrossRefPubMed
15.
Vermeersch P, Geboes K, Mariën G, Hoffman I, Hiele M, Bossuyt X. Diagnostic performance of IgG anti-deamidated gliadin peptide antibody assays is comparable to IgA anti-tTG in celiac disease. Clin Chim Acta Int J Clin Chem. 2010;411:931–5.CrossRef
16.
Basso D, Guariso G, Fogar P, Meneghel A, Zambon C-F, 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.CrossRefPubMed
17.
Volta U, Granito A, Parisi C, Fabbri A, Fiorini E, Piscaglia M, et al. Deamidated gliadin peptide antibodies as a routine test for celiac disease: a prospective analysis. J Clin Gastroenterol. 2010;44:186–90.CrossRefPubMed
18.
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.CrossRefPubMed
19.
Lammi A, Arikoski P, Simell S, Kinnunen T, Simell V, Paavanen-Huhtala S, et al. Antibodies to deamidated gliadin peptide in diagnosis of celiac disease in children. J Pediatr Gastroenterol Nutr. 2015;60:626–31.CrossRefPubMed
20.
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.CrossRefPubMed
21.
Mozo L, Gómez J, Escanlar E, Bousoño C, Gutiérrez C. Diagnostic value of anti-deamidated gliadin peptide IgG antibodies for celiac disease in children and IgA-deficient patients. J Pediatr Gastroenterol Nutr 2012;55:50–5.
22.
Pallav K, Xu H, Leffler DA, Kabbani T, Kelly CP. Immunoglobulin A deficiency in celiac disease in the United States. J Gastroenterol Hepatol. 2016;31:133–7.CrossRefPubMedPubMedCentral
23.
Wolf J, Hasenclever D, Petroff D, Richter T, Uhlig HH, Laaβ MW, et al. Antibodies in the Diagnosis of Coeliac Disease: A Biopsy-Controlled, International, Multicentre Study of 376 Children with Coeliac Disease and 695 Controls. PLoS One. 2014;9:e97853.CrossRefPubMedPubMedCentral
24.
Kaukinen K, Collin P, Laurila K, Kaartinen T, Partanen J, Mäki M. Resurrection of gliadin antibodies in coeliac disease. Deamidated gliadin peptide antibody test provides additional diagnostic benefit. Scand J Gastroenterol. 2007;42:1428–33.CrossRefPubMed
25.
de Chaisemartin L, Meatchi T, Malamut G, Fernani-Oukil F, Hosking F, Rault D, et al. Application of Deamidated Gliadin Antibodies in the Follow-Up of Treated Celiac Disease. PLoS One. 2015;10:e0136745.CrossRefPubMedPubMedCentral
26.
Monzani A, Rapa A, Fonio P, Tognato E, Panigati L, Oderda G. Use of deamidated gliadin peptide antibodies to monitor diet compliance in childhood celiac disease. J Pediatr Gastroenterol Nutr. 2011;53:55–60.CrossRefPubMed
27.
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.CrossRefPubMed
28.
Oberhuber G, Granditsch G, Vogelsang H. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol. 1999;11:1185–94.CrossRefPubMed
29.
Agardh D, Lee H-S, Kurppa K, Simell V, Aronsson CA, Jörneus O, et al. Clinical Features of Celiac Disease: A Prospective Birth Cohort. Pediatrics. 2015;135:627–34.CrossRefPubMedPubMedCentral
30.
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. Gastroenterol. Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2007;5:567–73.CrossRef
31.
Alessio MG, Tonutti E, Brusca I, Radice A, Licini L, Sonzogni A, et al. Correlation between IgA tissue transglutaminase antibody ratio and histological finding in celiac disease. J Pediatr Gastroenterol Nutr. 2012;55:44–9.CrossRefPubMed
32.
Amarri S, Alvisi P, De Giorgio R, Gelli MC, Cicola R, Tovoli F, et al. Antibodies to deamidated gliadin peptides: an accurate predictor of coeliac disease in infancy. J Clin Immunol. 2013;33:1027–30.CrossRefPubMed
33.
34.
35.
Hestvik E, Tumwine JK, Tylleskar T, Grahnquist L, Ndeezi G, Kaddu-Mulindwa DH, et al. Faecal calprotectin concentrations in apparently healthy children aged 0-12 years in urban Kampala. Uganda: a community-based survey BMC Pediatr. 2011;11:9.PubMed
36.
Carroccio A, Iacono G, D’Amico D, Cavataio F, Teresi S, Caruso C, et al. Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness in coeliac disease diagnosis. Scand J Gastroenterol. 2002;37:32–8.CrossRefPubMed
37.
Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. 2013;108:656–76.CrossRefPubMedPubMedCentral
38.
Liu E, Li M, Emery L, Taki I, Barriga K, Tiberti C, et al. Natural history of antibodies to deamidated gliadin peptides and transglutaminase in early childhood celiac disease. J Pediatr Gastroenterol Nutr. 2007;45:293–300.CrossRefPubMed
39.
Castillo NE, Theethira TG, Leffler DA. The present and the future in the diagnosis and management of celiac disease. Gastroenterol Rep. 2015;3:3–11.CrossRef
40.
Lammi A, Arikoski P, Hakulinen A, Schwab U, Uusitupa M, Heinonen S, et al. Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease. Scand J Gastroenterol. 2016;51:168–77.CrossRefPubMed
41.
Haller MJ, Schatz DA. The DIPP project: 20 years of discovery in type 1 diabetes. Pediatr Diabetes. 2016;17:5–7.CrossRefPubMed
42.
Parizade M, Shainberg B. Positive Deamidated Gliadin Peptide Antibodies and Negative Tissue Transglutaminase IgA Antibodies in a Pediatric Population: To Biopsy or Not To Biopsy. Clin Vaccine Immunol CVI. 2010;17:884–6.CrossRefPubMed
43.
Olen O, Gudjónsdóttir AH, Browaldh L, Hessami M, Elvin K, Liedberg A-S, et al. Antibodies against deamidated gliadin peptides and tissue transglutaminase for diagnosis of pediatric celiac disease. J Pediatr Gastroenterol Nutr. 2012;55:695–700.CrossRefPubMed
44.
Barbato M, Maiella G, Di Camillo C, Guida S, Valitutti F, Lastrucci G, et al. The anti-deamidated gliadin peptide antibodies unmask celiac disease in small children with chronic diarrhoea. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2011;43:465–9.
45.
Megiorni F, Mora B, Bonamico M, Barbato M, Nenna R, Maiella G, et al. HLA-DQ and risk gradient for celiac disease. Hum Immunol. 2009;70:55–9.CrossRefPubMed
46.
Carroccio A, Iacono G, Montalto G, Cavataio F, Di Marco C, Balsamo V, et al. Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. Gut. 1991;32:796–9.CrossRefPubMedPubMedCentral
47.
Nousia-Arvanitakis S, Fotoulaki M, Tendzidou K, Vassilaki C, Agguridaki C, Karamouzis M. Subclinical Exocrine Pancreatic Dysfunction Resulting From Decreased Cholecystokinin Secretion in the Presence of Intestinal Villous Atrophy: J. Pediatr Gastroenterol Nutr. 2006;43:307–12.CrossRef
48.
Nousia-Arvanitakis S, Karagiozoglou-Lamboudes T, Aggouridaki C, Malaka-Lambrellis E, Galli-Tsinopoulou A, Xefteri M. Influence of Jejunal Morphology Changes on Exocrine Pancreatic Function in Celiac Disease. J Pediatr Gastroenterol. 1999;29:81–5.CrossRef
49.
Kelly T, Buxbaum J. Gastrointestinal Manifestations of Cystic Fibrosis. Dig Dis Sci. 2015;60:1903–13.CrossRefPubMed
50.
51.
Rana SS, Dambalkar A, Chhabra P, Sharma R, Nada R, Sharma V, et al. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma? Ann. Gastroenterol Q Publ Hell Soc Gastroenterol. 2016;29:363–6.
52.
Zelnik N. Neurologic Disorders in Patients With Celiac Disease: Are They Mediated by Brain Perfusion Changes?: In Reply. Pediatrics. 2004;114:1734.CrossRef
53.
Black MM. The evidence linking zinc deficiency with children’s cognitive and motor functioning. J Nutr. 2003;133:1473S–6S.PubMedPubMedCentral
54.
Aronsson CA, Lee H-S, Liu E, Uusitalo U, Hummel S, Yang J, et al. Age at Gluten Introduction and Risk of Celiac Disease. Pediatrics. 2015;peds:2014–1787.
Metadata
Title
Coeliac disease in infants: antibodies to deamidated gliadin peptide come first!
Authors
Michele Arigliani
Francesca Rech Morassutti
Martina Fabris
Paola Melli
Elio Tonutti
Paola Cogo
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Italian Journal of Pediatrics / Issue 1/2017
Electronic ISSN: 1824-7288
DOI
https://doi.org/10.1186/s13052-017-0392-6

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