Skip to main content

Advertisement

SpringerLink
Log in

Immune Phenotype of Children with Newly Diagnosed and Gluten-Free Diet-Treated Celiac Disease

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Background

Recent data suggest the involvement of both the adaptive and the innate immune system in celiac disease (CD). However, little is known about the immune phenotype of children with CD and its alteration upon dietary intervention.

Aims

We characterized the prevalence of major interacting members of the adaptive and innate immune system in peripheral blood of newly diagnosed children with CD and tested its alteration with the improvement of clinical signs after the introduction of gluten-free diet (GFD).

Methods

Peripheral blood was taken from ten children with biopsy-proven CD at the time of diagnosis and after the resolution of clinical symptoms following GFD. As controls, 15 children with functional abdominal pain were enrolled. The prevalence of the cells of adaptive and innate immunity was measured with labeled antibodies against surface markers and intracellular FoxP3 using a flow cytometer.

Results

Patients with CD were found to have lower T helper, Th1 and natural killer (NK), NKT and invariant NKT cell prevalence and with higher prevalence of activated CD4+ cells, myeloid dendritic cells (DC) and Toll-like receptor (TLR) 2 and TLR-4 positive DCs and monocytes compared to controls. After resolution of symptoms on GFD, the majority of these changes normalized, although the prevalence of NK and NKT cell, DC and TLR-2 expressing DCs and monocytes remained abnormal.

Conclusions

The immune phenotype in childhood CD indicates the implication of both adaptive and innate immune system. The normalization of immune abnormalities occurs on GFD, but the kinetics of this process probably differs among different cell types.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology. 2009;137:1912–1933.

    Article  CAS  PubMed  Google Scholar 

  2. Bardella MT, Fredella C, Saladino V, et al. Gluten intolerance: gender- and age-related differences in symptoms. Scand J Gastroenterol. 2005;40:15–19.

    Article  PubMed  Google Scholar 

  3. Thomson AB, Keelan M, Thiesen A, Clandinin MT, Ropeleski M, Wild GE. Small bowel review: diseases of the small intestine. Dig Dis Sci. 2001;46:2555–2566.

    Article  CAS  PubMed  Google Scholar 

  4. Ciccocioppo R, Di Sabatino A, Corazza GR. The immune recognition of gluten in celiac disease. Clin Exp Immunol. 2005;140:408–416.

    Article  CAS  PubMed  Google Scholar 

  5. Maiuri L, Ciacci C, Ricciardelli I, et al. Association between innate response to gliadin and activation of pathogenic T cells in celiac disease. Lancet. 2003;362:30–37.

    Article  CAS  PubMed  Google Scholar 

  6. Koning F. Celiac disease: sandwiched between innate and adaptive immune responses induced by gluten. J Pediatr Gastroenterol Nutr. 2008;46:E8–E9.

    Article  PubMed  Google Scholar 

  7. Di Sabatino A, Bertrandi E, Casadei Maldini M, Pennese F, Proietti F, Corazza GR. Phenotyping of peripheral blood lymphocytes in adult celiac disease. Immunology. 1998;95:572–576.

    Article  CAS  PubMed  Google Scholar 

  8. Camarero C, Leon F, Sanchez L, Asensio A, Roy G. Age-related variation of intraepithelial lymphocytes subsets in normal human duodenal mucosa. Dig Dis Sci. 2007;52:685–691.

    Article  CAS  PubMed  Google Scholar 

  9. León F, Sánchez L, Camarero C, Roy G. Cytokine production by intestinal intraepithelial lymphocyte subsets in celiac disease. Dig Dis Sci. 2005;50:593–600.

    Article  PubMed  Google Scholar 

  10. O’Keeffe J, Mills K, Jackson J, Feighery C. T cell proliferation, MHC class II restriction and cytokine products of gliadin-stimulated peripheral blood mononuclear cells (PBMC). Clin Exp Immunol. 1999;117:269–276.

    Article  PubMed  Google Scholar 

  11. Kerttula TO, Hällström O, Mäki M. Phenotypical characterization of peripheral blood T cells in patients with celiac disease: elevation of antigen-primed CD45RO + T lymphocytes. Immunology. 1995;86:104–109.

    CAS  PubMed  Google Scholar 

  12. Penttila IA, Gibson CE, Forrest BD, Cummins AG, LaBrooy JT. Lymphocyte activation as measured by interleukin-2 receptor expression to gluten fraction 111 in celiac disease. Immunol Cell Biol. 1990;68:155–160.

    Article  PubMed  Google Scholar 

  13. Perticarari S, Prodan M, Fragonas E, Canova S, Presani G. CD69 expression on alpha-gliadin-specific T cells in celiac disease. Eur J Histochem. 2002;46:13–22.

    CAS  PubMed  Google Scholar 

  14. Arato A, Savilahti E, Tainio VM, Verkasalo M, Klemola T. HLA-DR expression, natural killer cells and IgE containing cells in the jejunal mucosa of celiac children. Gut. 1987;28:988–994.

    Article  CAS  PubMed  Google Scholar 

  15. Halstensen TS, Farstad IN, Scott H, Fausa O, Brandtzaeg P. Intraepithelial TcR alpha/beta + lymphocytes express CD45RO more often than the TcR gamma/delta + counterparts in celiac disease. Immunology. 1990;71(4):460–466.

    CAS  PubMed  Google Scholar 

  16. Granzotto M, dal Bo S, Quaglia S, et al. Regulatory T-cell function is impaired in celiac disease. Dig Dis Sci. 2009;54:1513–1519.

    Article  CAS  PubMed  Google Scholar 

  17. Tiittanen M, Westerholm-Ormio M, Verkasalo M, Savilahti E, Vaarala O. Infiltration of forkhead box P3-expressing cells in small intestinal mucosa in celiac disease but not in type 1 diabetes. Clin Exp Immunol. 2008;152:498–507.

    Article  CAS  PubMed  Google Scholar 

  18. Vorobjova T, Uibo O, Heilman K, et al. Increased FOXP3 expression in small-bowel mucosa of children with celiac disease and type I diabetes mellitus. Scand J Gastroenterol. 2009;44:422–430.

    Article  CAS  PubMed  Google Scholar 

  19. MacDonald TT, Vossenkamper A, Di Sabatino A. Antigen presenting cells and T cell interactions in the gastrointestinal tract. Mol Nutr Food Res. 2009;53:947–951.

    Article  CAS  PubMed  Google Scholar 

  20. Bernardo D, van Hoogstraten IM, Verbeek WH, et al. Decreased circulating iNKT cell numbers in refractory celiac disease. Clin Immunol. 2008;126:172–179.

    Article  PubMed  Google Scholar 

  21. Grose RH, Thompson FM, Cummins AG. Deficiency of 6B11 + invariant NK T-cells in celiac disease. Dig Dis Sci. 2008;53:1846–1851.

    Article  CAS  PubMed  Google Scholar 

  22. van der Vliet HJ, von Blomberg BM, Nishi N, et al. Circulating V(alpha24 +) Vbeta11 + NKT cell numbers are decreased in a wide variety of diseases that are characterized by autoreactive tissue damage. Clin Immunol. 2001;100:144–148.

    Article  PubMed  Google Scholar 

  23. Ciccocioppo R, Ricci G, Rovati B, et al. Reduced number and function of peripheral dendritic cells in celiac disease. Clin Exp Immunol. 2007;149:487–496.

    Article  CAS  PubMed  Google Scholar 

  24. Vuckovic S, Withers G, Harris M, et al. Decreased blood dendritic cell counts in type 1 diabetic children. Clin Immunol. 2007;123:281–288.

    Article  CAS  PubMed  Google Scholar 

  25. Szebeni B, Veres G, Dezsofi A, et al. Increased mucosal expression of Toll-like receptor (TLR)2 and TLR4 in celiac disease. J Pediatr Gastroenterol Nutr. 2007;45:187–193.

    Article  CAS  PubMed  Google Scholar 

  26. Walker-Smith JA, Guandalini S, Schmitz J, et al. Revised criteria for diagnosis of celiac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch Dis Child. 1990;65:909–911.

    Article  Google Scholar 

  27. Marsh M. Gluten, major histocompability complex and small intestine. Gastroenterology. 1992;102:330–354.

    CAS  PubMed  Google Scholar 

  28. Mastrandrea F, Semeraro FP, Coradduzza G, et al. CD34 + hemopoietic precursor and stem cells traffic in peripheral blood of celiac patients is significantly increased but not directly related to epithelial damage severity. Eur Ann Allergy Clin Immunol. 2008;40(3):90–103.

    CAS  PubMed  Google Scholar 

  29. Lahat N, Shapiro S, Karban A, Gerstein R, Kinarty A, Lerner A. Cytokine profile in celiac disease. Scand J Immunol. 1999;49:441–446.

    Article  CAS  PubMed  Google Scholar 

  30. O’Donoghue DP, Lancaster-Smith M, Laviniere P, Kumar PJ. T cell depletion in untreated adult celiac disease. Gut. 1976;17:328–331.

    Article  PubMed  Google Scholar 

  31. Saurer L, Mueller C. T cell-mediated immunoregulation in the gastrointestinal tract. Allergy. 2009;64:505–519.

    Article  CAS  PubMed  Google Scholar 

  32. Kantele JM, Savilahti E, Westerholm-Ormio M, et al. Decreased numbers of circulating plasmablasts and differences in IgA1-plasmablast homing to skin in celiac disease and dermatitis herpetiformis. Clin Exp Immunol. 2009;156:535–541.

    Article  CAS  PubMed  Google Scholar 

  33. Agardh D, Lynch K, Brundin C, Ivarsson SA, Lernmark A, Cilio CM. 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. 2006;144:67–75.

    Article  CAS  PubMed  Google Scholar 

  34. Frisullo G, Nociti V, Iorio R, et al. Increased CD4 + CD25 + Foxp3 + T cells in peripheral blood of celiac disease patients: correlation with dietary treatment. Hum Immunol. 2009;70:430–435.

    Article  CAS  PubMed  Google Scholar 

  35. Kool M, Lambrecht BN. Dendritic cells in asthma and COPD: opportunities for drug development. Curr Opin Immunol. 2007;19:701–710.

    Article  CAS  PubMed  Google Scholar 

  36. Weiskopf D, Weinberger B, Grubeck-Loebenstein B. The aging of the immune system. Transpl Int. 2009;22:1041–1050.

    Article  CAS  PubMed  Google Scholar 

  37. Aspinall R. Age-related changes in the function of T cells. Microsc Res Tech. 2003;62:508–513.

    Article  CAS  PubMed  Google Scholar 

  38. Verkasalo MA, Arató A, Savilahti E, Tainio VM. Effect of diet and age on jejunal and circulating lymphocyte subsets in children with celiac disease: persistence of CD4-8-intraepithelial T cells through treatment. Gut. 1990;31:422–425.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants TÁMOP-4.2.2-08/1/KMR-2008-0004, OTKA-76316, OTKA-K81117 and ETT-028-02.

Author information

Authors and Affiliations

  1. Research Group for Pediatrics and Nephrology, Semmelweis University and Hungarian Academy of Sciences, First Department of Pediatrics, Bókay u. 53, 1083, Budapest, Hungary

    Áron Cseh, Barna Vásárhelyi, Balázs Szalay, Kriszta Molnár, Dorottya Nagy-Szakál, András Treszl & Ádám Vannay

  2. Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary

    Barna Vásárhelyi

  3. First Department of Pediatrics, Semmelweis University, Budapest, Hungary

    András Arató, Tivadar Tulassay & Gábor Veres

Authors
  1. Áron Cseh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barna Vásárhelyi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Balázs Szalay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kriszta Molnár
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dorottya Nagy-Szakál
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. András Treszl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ádám Vannay
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. András Arató
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tivadar Tulassay
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gábor Veres
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Áron Cseh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cseh, Á., Vásárhelyi, B., Szalay, B. et al. Immune Phenotype of Children with Newly Diagnosed and Gluten-Free Diet-Treated Celiac Disease. Dig Dis Sci 56, 792–798 (2011). https://doi.org/10.1007/s10620-010-1363-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-010-1363-6

Keywords

Search

Navigation