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Celiac Disease Screening Assays for Children Younger than 3 Years of Age: The Performance of Three Serological Tests

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Abstract

Background and Aims

The optimum serological test for celiac disease (CD) in young children is not known. The objective of our study was to compare the performance of three serological tests (IgA + IgG DGP, IgA TTG, and IgA + IgG EMA) for children younger than 3 years of age.

Methods

We identified all subjects younger than 3 years of age (n = 6,074) that were tested for CD serology and included those with biopsy data. Patients were classified as group 1 (n = 47): patients with confirmed CD or group 2 (n = 12): patients with normal biopsy findings.

Results

There was statistically significant difference between group 1 and group 2 with regard to number of patients with positive IgA TTG (97.87% vs. 50%, P < 0.001), IgA + IgG DGP (100% vs. 77.78%, P = 0.007), and IgA + IgG EMA (95.65% vs. 9.09%, P < 0.001). There was a significantly positive correlation between Marsh–Oberhuber score on the small duodenal biopsies and all tests. Analysis of sensitivity and specificity showed that manufacturer’s levels had high sensitivity for all tests (IgA TTG 97%, IgA + IgG DGP 100%, IgA + IgG EMA 96%), however specificity was low for IgA + IgG DGP (44%) and IgA TTG (50%) but not for IgA + IgG EMA (91%).

Conclusions

For children younger than 3 years of age, IgA + IgG EMA is highly sensitive and specific. Use of IgA + IgG DGP or IgA TTG as a single serological marker is insufficient for definite diagnosis of CD in this age group. Based on our results, it might be reasonable to postpone the biopsy for asymptomatic children with negative EMA.

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Abbreviations

CD:

Celiac disease

EMA:

Anti-endomesial antibody

TTG:

Anti-tissue transglutaminase

AGA:

Antigliadin antibodies

DGP:

Anti deamidated gliadin peptide antibodies

References

  1. Di Sabatino A, Corazza GR. Coeliac disease. Lancet. 2009;373:1480–1493.

    Article  PubMed  Google Scholar 

  2. Maki M, Mustalahti K, Kokkonen J, et al. Prevalence of celiac disease among children in Finland. N Engl J Med. 2003;348:2517–2524.

    Article  PubMed  Google Scholar 

  3. Hoffenberg EJ, MacKenzie T, Barriga KJ, et al. A prospective study of the incidence of childhood celiac disease. J Pediatr. 2003;143:308–314.

    Article  PubMed  Google Scholar 

  4. Castano L, Blarduni E, Ortiz L, et al. Prospective population screening for celiac disease: high prevalence in the first 3 years of life. J Pediatr Gastroenterol Nutr. 2004;39:80–84.

    Article  PubMed  Google Scholar 

  5. Ludvigsson JF, Montgomery SM, Ekbom A, et al. Small-intestinal histopathology and mortality risk in celiac disease. JAMA. 2009;302:1171–1178.

    Article  PubMed  CAS  Google Scholar 

  6. Solaymani-Dodaran M, West J, Logan RF. Long-term mortality in people with celiac disease diagnosed in childhood compared with adulthood: a population-based cohort study. Am J Gastroenterol. 2007;102:864–870.

    Article  PubMed  Google Scholar 

  7. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American society for pediatric gastroenterology, hepatology and nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1–19.

    Article  PubMed  Google Scholar 

  8. Shamaly H, Hartman C, Pollack S, et al. Tissue transglutaminase antibodies are a useful serological marker for the diagnosis of celiac disease in patients with Down syndrome. J Pediatr Gastroenterol Nutr. 2007;44:583–586.

    Article  PubMed  CAS  Google Scholar 

  9. Leach ST, Aurangzeb B, Day AS. Coeliac disease screening in children: assessment of a novel anti-gliadin antibody assay. J Clin Lab Anal. 2008;22:327–333.

    Article  PubMed  Google Scholar 

  10. Rostom A, Dube C, Cranney A, et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology. 2005;128:S38–S46.

    Article  PubMed  Google Scholar 

  11. Shamir R, Eliakim R, Lahat N, et al. ELISA of anti-endomysial antibodies in the diagnosis of celiac disease: comparison with immunofluorescence assay of anti-endomysial antibodies and tissue transglutaminase antibodies. Isr Med Assoc J. 2002;4:594–596.

    PubMed  CAS  Google Scholar 

  12. Lewis NR, Scott BB. Meta-analysis: deaminidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for celiac disease. Aliment Pharmacol Ther. 2010;31:73–81.

    Article  PubMed  CAS  Google Scholar 

  13. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Revised criteria for diagnosis of coeliac disease. Arch Dis Child 1990;65:909–911.

    Google Scholar 

  14. Simell S, Kupila A, Hoppu S, et al. Natural history of transglutaminase autoantibodies and mucosal changes in children carrying HLA-conferred celiac disease susceptibility. Scand J Gastroenterol. 2005;40:1182–1191.

    Article  PubMed  CAS  Google Scholar 

  15. Sorensen RU, Moore C. Antibody deficiency syndromes. Pediatr Clin North Am. 2000;47:1225–1252.

    Article  PubMed  CAS  Google Scholar 

  16. Oberhuber G, Granditsch G, Vogelsang H. The histopathology of coeliac disease: time for a standardized report scheme for pathologists. Eur J Gastroenterol Hepatol. 1999;11:1185–1194.

    Article  PubMed  CAS  Google Scholar 

  17. Hill PG, Holmes GK. Coeliac disease: a biopsy is not always necessary for diagnosis. Aliment Pharmacol Ther. 2008;27:572–577.

    Article  PubMed  CAS  Google Scholar 

  18. Westerbeek E, Mouat S, Wesley A, et al. Coeliac disease diagnosed at Starship Children’s Hospital: 1999–2002. N Z Med J 2005;118:U1613.

    Google Scholar 

  19. Wolters VM, van de Nadort C, Gerritsen SA, et al. Is gluten challenge really necessary for the diagnosis of coeliac disease in children younger than age 2 years? J Pediatr Gastroenterol Nutr. 2009;48:566–570.

    Article  PubMed  CAS  Google Scholar 

  20. Agardh D, Carlsson A, Lynch K, et al. Using radioligand-binding assays to measure tissue transglutaminase autoantibodies in young children. Acta Paediatr. 2004;93:1046–1051.

    Article  PubMed  CAS  Google Scholar 

  21. Burgin-Wolff A, Gaze H, Hadziselimovic F, et al. Antigliadin and antiendomysium antibody determination for coeliac disease. Arch Dis Child. 1991;66:941–947.

    Article  PubMed  CAS  Google Scholar 

  22. Parizade M, Bujanover Y, Weiss B, et al. Performance of serology assays for diagnosing celiac disease in a clinical setting. Clin Vaccine Immunol. 2009;16:1576–1582.

    Article  PubMed  CAS  Google Scholar 

  23. Barker CC, Mitton C, Jevon G, et al. Can tissue transglutaminase antibody titers replace small bowel biopsy to diagnose celiac disease in select pediatric populations? Pediatrics. 2005;115:1341–1346.

    Article  PubMed  Google Scholar 

  24. Vivas SJ, Ruiz de Morales M, Fernandez M, et al. Age-related clinical, serological, and histopathological features of celiac disease. Am J Gastroenterol. 2008;103:2360–2365.

    Article  PubMed  Google Scholar 

  25. McGowan KE, Castiglione DA, Butzner JD. The changing face of childhood celiac disease in North America: impact of serological testing. Pediatrics. 2009;124:1572–1578.

    Article  PubMed  Google Scholar 

  26. Tonutti E, Visentini D, Bizzarro N, et al. The role of antitissue transglutaminase assay for the diagnosis and monitoring of coeliac disease: a French-Italian multicentre study. J Clin Pathol. 2003;56:389–393.

    Article  PubMed  CAS  Google Scholar 

  27. Liu E, Li M, Emery L, 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.

    Article  PubMed  CAS  Google Scholar 

  28. Lagerqvist C, Dahlbom I, Hansson T, et al. Antigliadin immunoglobulin a best in finding celiac disease in children younger than 18 months of age. J Pediatr Gastroenterol Nutr. 2008;47:428–435.

    Article  PubMed  CAS  Google Scholar 

  29. Basso D, Guariso G, Fogar P, et al. Antibodies against synthetic deamidated gliadin peptides for celiac disease diagnosis and follow-up in children. Clin Chem. 2009;55:150–157.

    Article  PubMed  CAS  Google Scholar 

  30. Hogen Esch CE, Csizmadia GD, van Hoogstraten IM, et al. Childhood coeliac disease: towards an improved serological mass screening strategy. Aliment Pharmacol Ther. 2010;31:760–766.

    Article  PubMed  CAS  Google Scholar 

  31. Kurppa K, Ashorn M, Iltanen S, et al. Celiac disease without villous atrophy in children: a prospective study. J Pediatr. 2010;157:373–380.

    Article  PubMed  Google Scholar 

  32. Paparo F, Petrone E, Tosco A, 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;100:2294–2298.

    Article  PubMed  Google Scholar 

  33. Lahdeaho M, Kaukinen K, Collin P, et al. Celiac disease: from inflammation to atrophy: a long-term follow-up study. J Pediatr Gastroenterol Nutr. 2005;41:44–48.

    Article  PubMed  Google Scholar 

  34. 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. 2010;17:884–886.

    Article  PubMed  CAS  Google Scholar 

  35. Donaldson MR, Firth SD, Wimpee H, et al. Correlation of duodenal histology with tissue transglutaminase and endomysial antibody levels in pediatric celiac disease. Clin Gastroenterol Hepatol. 2007;5:567–573.

    Article  PubMed  CAS  Google Scholar 

  36. Dahlbom I, Korponay-Szabó IR, Kovács JB, et al. Prediction of clinical and mucosal severity of coeliac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase. J Pediatr Gastroenterol Nutr. 2010;50:140–146.

    Article  PubMed  CAS  Google Scholar 

  37. Lurz E, Scheidegger U, Spalinger J, et al. Clinical presentation of celiac disease and the diagnostic accuracy of serologic markers in children. Eur J Pediatr. 2009;168:839–845.

    Article  PubMed  Google Scholar 

  38. Van Meensel B, Hiele M, Hoffman I, et al. Diagnostic accuracy of ten second-generation (human) tissue transglutaminase antibody assays in celiac disease. Clin Chem. 2004;50:2125–2135.

    Article  PubMed  Google Scholar 

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Conflict of interest

All authors have stated that they have no conflict of interest.

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Authors and Affiliations

  1. Institute of Gastroenterology, Nutrition, and Liver Disease, Schneider Children’s Medical Center of Israel, 14 Kaplan St., 49202, Petach Tikva, Israel

    Iva Hojsak, Yael Mozer-Glassberg, Corina Hartman & Raanan Shamir

  2. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Corina Hartman & Raanan Shamir

  3. Central Laboratory, Clalit Health Services, Tel Aviv, Israel

    Netta Segal Gilboa & Ronit Weinberger

  4. Referral Center for Pediatric Gastroenterology and Nutrition, Children’s Hospital Zagreb, University Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia

    Iva Hojsak

Authors
  1. Iva Hojsak
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  2. Yael Mozer-Glassberg
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  3. Netta Segal Gilboa
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  4. Ronit Weinberger
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  5. Corina Hartman
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  6. Raanan Shamir
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Correspondence to Yael Mozer-Glassberg.

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Hojsak, I., Mozer-Glassberg, Y., Segal Gilboa, N. et al. Celiac Disease Screening Assays for Children Younger than 3 Years of Age: The Performance of Three Serological Tests. Dig Dis Sci 57, 127–132 (2012). https://doi.org/10.1007/s10620-011-1857-x

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  • DOI: https://doi.org/10.1007/s10620-011-1857-x

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