Skip to main content

Advertisement

Log in

Celiac disease: from etiological factors to evolving diagnostic approaches

  • Review
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Celiac disease has advanced from a medical rarity to a highly prevalent disorder. Patients with the disease show varying degrees of chronic inflammation within the small intestine due to an aberrant immune response to the digestion of gliadin found in wheat. As a result, cytokines and antibodies are produced in celiac patients that can be used as specific biomarkers for developing diagnostic tests. This review paper describes celiac disease in terms of its etiological cause, pathological effects, current diagnostic tests based on mucosal biopsy, and the genetic basis for the disease. In addition, it discusses the use of gliadin-induced cytokines, antibodies and autoantibodies as a diagnostic tool for celiac disease. Despite good initial results in terms of sensitivity and specificity, when these immunological tests were used on a large scale, even in combination with genetic testing, the results showed lower predictive value. This review addresses that issue and ends with an outlook on future work required to develop diagnostic tests with greater accuracy in predicting celiac disease in the general public, thus avoiding the need for endoscopy and mucosal biopsy.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

ELISA:

Enzyme-linked immunosorbent assay

NK:

Natural killer

HLA:

Human leukocyte antigen

TCR:

T-cell receptor

LMW:

Low molecular weight

CDR:

Complementarity-determining region

tTG:

Tissue transglutaminase

AGA:

Anti-gliadin antibodies

Anti-EMA:

Anti-endomysial antibodies

Anti-tTG:

Anti-transglutaminase antibodies

Anti-DGP:

Anti-deamidated gliadin peptide

IFA:

Indirect immunofluorescence

RIA:

Radioimmunoassay

GFD:

Gluten-free diet

SPR:

Surface plasmon resonance

DIG:

Diffusion in gel

IBD:

Inflammatory bowel disease

GIP:

Gluten immunogenic peptides

References

  1. Ludvigsson JF, Leffler DA, Bai JC, et al. The Oslo definitions for celiac disease and related terms. Gut. 2013;62:43–52.

    Article  PubMed  Google Scholar 

  2. Kang JY, Kang AHY, Green A, et al. Systematic review: worldwide variation in the frequency of celiac disease and changes over time. Aliment Pharmacol Ther. 2013;38:226–45.

    Article  CAS  PubMed  Google Scholar 

  3. Lionetti E, Gatti S, Pulvirenti A, et al. Celiac disease from a global perspective. Best Pract Res Clin Gastroenterol. 2015;29:365–79.

    Article  PubMed  Google Scholar 

  4. Hovell CJ, Collett JA, Vautier G, et al. High prevalence of celiac disease in a population-based study from Western Australia: a case for screening? Med J Aust. 2001;175:247–50.

    CAS  PubMed  Google Scholar 

  5. Rubio-Tapia A, Ludvigsson JF, Brantner TL, et al. The prevalence of celiac disease in the United States. Am J Gastroenetrol. 2012;107:1538–44.

    Article  Google Scholar 

  6. Woychik JH, Boundy JA, Dimler RJ. Starch gel-electrophoresis of wheat gluten proteins with concentrated urea. Arch Biochem Biophys. 1961;94:477–82.

    Article  CAS  PubMed  Google Scholar 

  7. Bushuk W, Zillman RR. Wheat cultivar identification by gliadin electrophoregrams: 1. Apparatus, method, and nomenclature. Can J Plant Sci. 1978;58:505–15.

    Article  Google Scholar 

  8. Metakovsky EV, Branlard G, Chernakov VM, et al. Recombinant mapping of some chromosome 1A-, 1B-, 1D-, and 6B-controlled gliadins and low molecular weight glutenin subunits in common wheat. Theor Appl Genet. 1997;94:788–95.

    Article  CAS  Google Scholar 

  9. Anderson OD, Dong L, Huo N, et al. A new class of wheat gliadin genes and proteins. PLoS ONE. 2012;7:12.

    Google Scholar 

  10. Kasarda DD, Okita TW, Bernardin JE, et al. Nucleic acid (cDNA) and amino acid sequences of α-type gliadins from wheat (Triticum aestivum). Proc Natl Acad Sci. 1984;81:4712–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Anderson OD, Greene FC. The α-gliadin gene family. DNA and protein sequence variation, subfamily structure, and origins of pseudogenes. Theor Appl Genet. 1997;95:59–65.

    Article  CAS  Google Scholar 

  12. Noma S, Kawaura K, Hayakawa K, et al. Comprehensive molecular characterization of the α/β gliadin multigene family in hexaploid wheat. Mol Genet Genom. 2016;291:65–77.

    Article  CAS  Google Scholar 

  13. Bronstein HD, Haeffner LJ, Kowlessar OD. Enzymatic digestion of gliadin: the effect of the resultant peptides in adult celiac disease. Clin Chim Acta. 1966;14:141–55.

    Article  CAS  PubMed  Google Scholar 

  14. Weiser H. Relation between gliadin structure and celiac toxicity. Acta Paediatr. 1996;412:3–9.

    Article  Google Scholar 

  15. Shan L, Molberg O, Parrot I, et al. Structural basis for gluten intolerance in celiac disease. Science. 2002;297:2275–9.

    Article  CAS  PubMed  Google Scholar 

  16. Qi PF, Chen Q, Oullet T, et al. The molecular diversity of α-gliadin genes in the tribe Triticea. Genetica. 2013;141:303–10.

    Article  CAS  PubMed  Google Scholar 

  17. Oberhuber G, Granditsch G, Vogelsang H. The histopathology of celiac disease: time for a standardised report scheme for pathologists. Eur J Gastroentrol. 1999;11:1185–94.

    Article  CAS  Google Scholar 

  18. Marsh MN, Vincenzo V, Srivastava A. Histology of gluten related disorders. Gastroenterol Hepatol Bed Bench. 2015;8:171–7.

    Google Scholar 

  19. Tonutti E, Bizzaro N. Diagnosis and classification of celiac disease and gluten sensitivity. Autoimmun Rev. 2014. doi:10.1016/j.autrev.2014.01.043.

    Google Scholar 

  20. Bao F, Green PH, Bhagat G. An update on celiac disease histopathology and the road ahead. Arch Pathol Lab Med. 2012;136:735–45.

    Article  PubMed  Google Scholar 

  21. Castillo NE, Theethira TG, Leffler DA. The present and the future in diagnosis and management of celiac disease. Gastroenterol Rep. 2015;3(1):3–11.

    Article  Google Scholar 

  22. Hardy MY, Tye-Din JA. Celiac disease: a unique model for investigating broken tolerance in autoimmunity. Clin Transl Immunol. 2016. doi:10.1038/cti.2016.58.

    Google Scholar 

  23. Greco L, Romino R, Coto I, et al. The first large population-based twin study of celiac disease. Gut. 2002;50:624–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Howell MD, Austin RK, Kelleher D, et al. An HLA-D region restriction length polymorphism associated with celiac disease. J Exp Med. 1986;169:345–50.

    Google Scholar 

  25. Olivares M, Neef A, Castillejo G, et al. The HLA-DQ2 genotype selects for early intestinal microbiota composition in infants at high risk of developing celiac disease. Gut. 2015;64:406–17.

    Article  CAS  PubMed  Google Scholar 

  26. Lundin KEA, Scott H, Hansen T, et al. Gliadin-specific, HLA-DQ (alpha1*0501, beta1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J Exp Med. 1993;178:187–96.

    Article  CAS  PubMed  Google Scholar 

  27. Costantini S, Rossi M, Colonna G, et al. Modelling of HLA-DQ2 and its interaction with gluten peptides to explain molecular recognition in celiac disease. J Mol Graph Model. 2005;23:419–31.

    Article  CAS  PubMed  Google Scholar 

  28. Henderson KN, Tye-Din JA, Reid H, et al. A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease. Immunity. 2007;27:23–34.

    Article  CAS  PubMed  Google Scholar 

  29. Broughton SE, Petersen J, Theodossis A, et al. Biased T cell receptor usage directed against human leukocyte antigen DQ8-restricted gliadin peptides is associated with celiac disease. Immunity. 2012;37:611–21.

    Article  CAS  PubMed  Google Scholar 

  30. Hadithi M, von Blomberg BM, Crusius JB, et al. Accuracy of serologic tests and HLA-DQ typing for diagnosing celiac disease. Ann Intern Med. 2007;147:294–302.

    Article  PubMed  Google Scholar 

  31. Husby S, Koletzko S, Korponay-Szabó IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of celiac disease. J Pediatr Gastroenterol Nutr. 2012;54:136–60.

    Article  CAS  PubMed  Google Scholar 

  32. Fukunaga M, Ishimura N, Fukuyama C, et al. Celiac disease in non-clinical populations of Japan. J Gastroenterol. 2017. doi:10.1007/s00535-017-1339-9.

    Google Scholar 

  33. Dubois PC, Trynka G, Franke L, et al. Multiple common variants for celiac disease influencing immune gene expression. Nat Genet. 2010;42(4):295–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Abraham G, Rohmer A, Tye-Din JA, et al. Genomic prediction of celiac disease targeting HLA-positive individuals. Genome Med. 2015;7:3–11.

    Article  CAS  Google Scholar 

  35. Kruppa K. Endomysial antibodies predict celiac disease irrespective of the titers or clinical presentation. World J Gastroenterol. 2012;18:2511–6.

    Article  CAS  Google Scholar 

  36. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011;91:151–75.

    Article  CAS  PubMed  Google Scholar 

  37. Lammers KM, Lu R, Brownley J, et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology. 2008;135:194–204.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Schumann M, Richter JF, Wedell I, et al. Mechanisms of epithelial translocation of the alpha(2)-gliadin-33 mer in celiac sprue. Gut. 2008;57:747–54.

    Article  CAS  PubMed  Google Scholar 

  39. Matysiak-Budnik T, Moura IC, Arcos-Fajardo M, et al. Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. J Exp Med. 2008;205:143–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Bodd M, Ráki M, Tollefsen S, et al. HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22. Mucosal Immunol. 2010;3:594–601.

    Article  CAS  PubMed  Google Scholar 

  41. Peluso I, Fantini MC, Fina D, et al. IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes. J Immunol. 2007;178:732–9.

    Article  CAS  PubMed  Google Scholar 

  42. Hüe S, Mention J-J, Monteiro RC, et al. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity. 2004;21:367–77.

    Article  PubMed  Google Scholar 

  43. Meresse B, Curran SA, Ciszewski C, et al. Reprogramming of CTLs into natural killer-like cells in celiac disease. J Exp Med. 2006;203:1343–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Sollid LM, Jabri B. Triggers and drivers of autoimmunity: lessons from celiac disease. Nat Rev Immunol. 2013;13:294–302.

    Article  CAS  PubMed  Google Scholar 

  45. Sabatino AD, Vanoli A, Giuffrida P, et al. The function of tissue transglutaminase in celiac disease. Autoimmun Rev. 2012;11:746–53.

    Article  PubMed  CAS  Google Scholar 

  46. Evans DF, Pye G, Bramley R, et al. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut. 1988;29:1035–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sollid LM. Molecular basis of celiac disease. Annu Rev Immunol. 2000;18:53–81.

    Article  CAS  PubMed  Google Scholar 

  48. Du Pre’ MF, Sollid LM. T-cell and B-cell immunity in celiac disease. Best Pract Res Clin Gastroenterol. 2015;29:413–23.

    Article  CAS  Google Scholar 

  49. Dieterich W, Laag E, Schopper H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology. 1998;115:1317–21.

    Article  CAS  PubMed  Google Scholar 

  50. O’Farrelly C, Kelly J, Hekkens W, et al. Alpha gliadin antibody levels: a serological test for celiac disease. Br Med J (Clin Res Ed). 1983;25:2007–10.

    Article  Google Scholar 

  51. Savilahti E, Viander M, Perkkio M, et al. IgA antigliadin antibodies: a marker of mucosal damage in childhood celiac disease. Lancet. 1983;1:320–2.

    Article  CAS  PubMed  Google Scholar 

  52. Tucker NT, Barghuthy FS, Prihoda TJ, et al. Antigliadin antibodies detected by enzyme-linked immunosorbent assay as a marker of childhood celiac disease. J Pediatr. 1988;113:286–9.

    Article  CAS  PubMed  Google Scholar 

  53. Bodé S, Weile B, Krasilnikoff PA, et al. The diagnostic value of the gliadin antibody test in celiac disease in children: a prospective study. J Pediatr Gastroenterol Nutr. 1993;17:260–4.

    Article  PubMed  Google Scholar 

  54. Lerner A, Kumar V, Iancu TC. Immunological diagnosis of childhood celiac disease: comparison between antigliadin, antireticulin and antiendomysial antibodies. Clin Exp Immunol. 1994;95:78–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chartrand LJ, Aglunik J, Vanounou T, et al. Effectiveness of anti-Gliadin antibodies as a screening test for celiac disease in children. Can Med Assoc J. 1997;1997(157):527–33.

    Google Scholar 

  56. Lagerqvist C, Ingrid D, Tony H, 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.

    Article  CAS  PubMed  Google Scholar 

  57. Pereira SV, Raba J, Messina GA. IgG anti-Gliadin determination with an immunological microfluidic system applied to the automated diagnostic of the celiac disease. Anal Bioanal Chem. 2010;396:2921–7.

    Article  CAS  PubMed  Google Scholar 

  58. Ladinser B, Rossipal E, Pittschieler K. Endomysium antibodies in celiac disease: an improved method. Gut. 1994;35:776–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Picarelli A. 31-43 amino acid sequence of the a-Gliadin induces anti-Endomysial antibody production during in vitro challenge. Scand J Gastroenterol. 1999;34:1099–102.

    Article  CAS  PubMed  Google Scholar 

  60. Rostami K, Jo Kerckhaert, Tiemessen R, et al. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice: sensitivity of IgA EMA and AGA in celiac disease. Am J Gastroenterol. 1994;94:888–94.

    Article  Google Scholar 

  61. Leffler DA, Schuppan D. Update on serologic testing in celiac disease. Am J Gastroenterol. 2010;105:2520–4.

    Article  PubMed  Google Scholar 

  62. Bruce SE, Bjarnason I, Peter I. Human jejunal transglutaminase: demonstration of activity, enzyme kinetics and substrate specificity with special relation to gliadin and celiac disease. Clin Sci. 1985;68:573–9.

    Article  CAS  PubMed  Google Scholar 

  63. Hill PG, Holmes GK. Celiac disease: a biopsy is not always necessary for diagnosis. Aliment Pharmacol Ther. 2008;27:572–7.

    Article  CAS  PubMed  Google Scholar 

  64. Vivas S, Ruiz de Morales JG, Riestra S, et al. Duodenal biopsy may be avoided when high transglutaminase antibody titres are present. World J Gastroenterol. 2009;15:4775–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tortara R, Imperatore N, Capone P, et al. The presence of anti-Endomysial antibodies and the level of anti-tissue transglutaminase can be used to diagnose adult celiac disease without duodenal biopsy. Aliment Pharmacol Ther. 2014;40:122–9.

    Google Scholar 

  66. Dahlbom I, Nyberg BI, Bernston L, et al. Simultaneous detection of IgA and IgG antibodies against tissue transglutaminase: the preferred pre-biopsy test in childhood celiac disease. Scand J Clin Lab Invest. 2016;76:208–16.

    Article  CAS  PubMed  Google Scholar 

  67. Sblattero D, Berti I, Trevisiol C, et al. Human recombinant tissue transglutaminase ELISA: an innovative diagnostic assay for celiac disease. Am J Gastroenterol. 2000;95:1253–7.

    Article  CAS  PubMed  Google Scholar 

  68. Lock RJ, Gilmour JEM, Unsworth DJ. Anti-tissue transglutaminase, anti-endomysium and anti-R1-reticulin autoantibodies: the antibody trinity of celiac disease. Clin Exp Immunol. 1999;116:258–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  70. Dahlbom I, Korponay-Szabo IR, Kovacs JB, et al. Prediction of clinical and mucosal severity of celiac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase. J Pediatr Gastroenterol Nutr. 2010;50:140–6.

    Article  CAS  PubMed  Google Scholar 

  71. Volta U, Granito A, Fiorini E, et al. Usefulness of antibodies to deamidated gliadin peptides in celiac disease diagnosis and follow-up. Dig Dis Sci. 2008;53:1582–8.

    Article  CAS  PubMed  Google Scholar 

  72. Dahle C, Hagman A, Ignatova S, et al. Antibodies against deamidated gliadin peptides identify adult celiac disease patients negative for antibodies against endomysium and tissue transglutaminase. Aliment Pharmacol Ther. 2010;32:254–60.

    Article  CAS  PubMed  Google Scholar 

  73. Barbato M, Maiellaa G, Camilloa CD, et al. The anti-deamidated gliadin peptide antibodies unmask celiac disease in small children with chronic diarrhoea. Dig Liver Dis. 2011;43:465–9.

    Article  CAS  PubMed  Google Scholar 

  74. Amarri S, Alvisi P, De Giorgio R, et al. Antibodies to deamidated gliadin peptides: an accurate predictor of celiac disease in infancy. J Clin Immunol. 2013;33:1027–30.

    Article  CAS  PubMed  Google Scholar 

  75. Schwertz E, Kahlberg F, Sack U, et al. Serologic assay based on gliadin-related nonapeptides as a highly sensitive and specific diagnostic aid in celiac disease. Clin Chem. 2004;50:2370–5.

    Article  CAS  PubMed  Google Scholar 

  76. Agardh A. Antibodies against synthetic deamidated gliadin peptides and tissue transglutaminase for the identification of childhood celiac disease. Clin Gastroenterol Hepatol. 2007;5:1276–81.

    Article  CAS  PubMed  Google Scholar 

  77. Ankelo M, Kleimola V, Simell S, et al. Antibody responses to deamidated gliadin peptide show high specificity and parallel antibodies to tissue transglutaminase in developing celiac disease. Clin Exp Immunol. 2007;150:285–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rashtak S, Ettore MW, Homburger HA, et al. Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease. Clin Gastroenetrol Hepatol. 2008;6:426–32.

    Article  CAS  Google Scholar 

  79. 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. 2008;55:150–7.

    Article  PubMed  CAS  Google Scholar 

  80. Sugai E, Moreno ML, Hwang HJ, et al. Celiac disease serology in patients with different pretest probabilities: is biopsy avoidable? World J Gastroenterol. 2010;16:3144–52.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Anderson RP, van Heel DA, Tye-Din JA, et al. T cells in peripheral blood after gluten challenge in celiac disease. Gut. 2005;54:1217–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Brottveit M, Ráki M, Bergseng E, et al. Assessing possible celiac disease by an HLA-DQ2-gliadin tetramer test. Am J Gastroenterol. 2011;106:1318–24.

    Article  CAS  PubMed  Google Scholar 

  83. Goletti D, Vincenti D, Carrara S, et al. Selected RD1 peptides for active tuberculosis diagnosis: comparison of a gamma interferon whole-blood enzyme-linked immunosorbent assay and an enzyme-linked immunospot assay. Clin Diagn Lab Immunol. 2005;12:1311–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Ruhwald M, Bjerregaard-Anderson M, Rabna P, et al. CXCL10/IP-10 release is induced by incubation of whole blood from tuberculosis patients with ESAT-6, CFP10 and TB7.7. Microbes Infect. 2007;9:806–12.

    Article  CAS  PubMed  Google Scholar 

  85. Lalvani A, Meroni PL, Millington KA, et al. Recent advances in diagnostic technology: applications in autoimmune and infectious diseases. Clin Exp Rheumatol. 2008;26:S62–6.

    CAS  PubMed  Google Scholar 

  86. Anderson RP, Degano P, Godkin AJ, et al. In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T cell epitope. Nat Med. 2000;6:337–42.

    Article  CAS  PubMed  Google Scholar 

  87. Tye-Din JA, Stewart JA, Dromey JA, et al. Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease. Sci Transl Med. 2010;2:41.

    Article  CAS  Google Scholar 

  88. Ontiveros N, Tye-Din JA, Hardy MY, et al. Ex-vivo whole blood secretion of interferon (IFN)-γ and IFN-γ-inducible protein-10 measured by enzyme-linked immunosorbent assay are as sensitive as IFN-γ enzyme-linked immunospot for the detection of gluten-reactive T cells in human leucocyte antigen (HLA)-DQ2.5+-associated celiac disease. Clin Exp Immunol. 2014;175:305–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Lehmann PV, Zhang W. Unique strengths of ELISPOT for T cell diagnostics. Methods Mol Biol. 2012;792:3–23.

    Article  CAS  PubMed  Google Scholar 

  90. Salazer C, Nagadia R, Pandit P, et al. A novel saliva-based micro-RNA biomarker panel to detect head and neck cancers. Cell Oncol. 2014;37:331–8.

    Article  CAS  Google Scholar 

  91. Baldini C, Giusti L, Ciregia F, et al. Proteomic analysis of saliva: a unique tool to distinguish primary Sjogren’s syndrome from secondary Sjogren’s syndrome and other sicca syndromes. Arthritis Res Ther. 2011;13(6):R194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Jacobs R, Maasdorp E, Malherbe S, et al. Diagnostic potential of novel salivary host biomarkers as candidates for the immunological diagnosis of tuberculosis disease and monitoring of tuberculosis treatment response. PLoS ONE. 2016;12:1311–6.

    Google Scholar 

  93. Sueki A, Matsuda K, Yamaguchi A, et al. Evaluation of saliva as a diagnostic materials for influenza virus infection by PCR-based assay. Clin Chim Acta. 2016;453:71–4.

    Article  CAS  PubMed  Google Scholar 

  94. Hakeem V, Fifield R, Al-Bayaty HF, et al. Salivary IgA antigliadin antibody as a marker for celiac disease. Arch Dis Child. 1992;67:724–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Lenander-Lumikari Ihalin R, Lahteenoja H. Changes in whole saliva in patients with celiac disease. Arch Oral Biol. 2000;45(5):347–54.

    Article  PubMed  Google Scholar 

  96. Bonamico M, Nenna R, Montuori M, et al. First salivary screening of celiac disease by detection of anti-transglutaminase autoantibody radioimmunoassay in 5000 Italian primary schoolchildren. J Pediatr Gastroenterol Nutr. 2011;52(1):17–20.

    Article  CAS  PubMed  Google Scholar 

  97. Adornetto G, Fabiani L, Volpe G, et al. An electrochemical immunoassay for the screening of celiac disease in saliva samples. Anal Bioanal Chem. 2015;407:7189–96.

    Article  CAS  PubMed  Google Scholar 

  98. Actis AB, Perovic NR, Defagó D, et al. Fatty acid profile of human saliva: a possible indicator of dietary fat intake. Arch Oral Biol. 2005;50:1–6.

    Article  CAS  PubMed  Google Scholar 

  99. Benkebil F, Combescure C, Anghel SI, et al. Diagnostic accuracy of a new point-of-care screening assay for celiac disease. World J Gastroenterol. 2013;19:5111–7.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Bienvenu F, Duvanel CB, Seignovert C, et al. Evaluation of a point-of-care test based on deamidated gliadin peptides for celiac disease screening in a large pediatric population. Eur J Gastroenterol Hepatol. 2012. doi:10.1097/meg.0b013e3283582d95.

    PubMed  Google Scholar 

  101. Watanabe C, Komoto S, Hokari R, et al. Prevalence of serum celiac antibody in patients with IBD in Japan. J Gastroenterol. 2014;49:825–34.

    Article  CAS  PubMed  Google Scholar 

  102. Wungjiranirun M, Kelly CP, Leffler DA. Current status of celiac disease drug development. Am J Gastroenterol. 2016;111:779–86.

    Article  CAS  PubMed  Google Scholar 

  103. Soler M, Estevez MC, Moreno Mde L, et al. Label-free SPR detection of gluten peptides in urine for non-invasive celiac disease follow-up. Biosens Bioelectron. 2016;79:158–64.

    Article  CAS  PubMed  Google Scholar 

  104. Comino I, Fernández-Bañares F, Esteve M, et al. Fecal gluten peptides reveal limitations of serological tests and food questionnaires for monitoring gluten-free diet in celiac disease patients. Am J Gastroenterol. 2016;111:1456–65.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Rohrman BA, Richards-Kortum RR. A paper and plastic device for performing recombinase polymerase amplification of HIV DNA. Lab Chip. 2012;12:3082–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Fu E, Liang T, Spicar-Mihalic P, et al. Two-dimensional paper network format that enables simple multistep assays for use in low-resource settings in the context of malaria antigen detection. Anal Chem. 2012;84:4574–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Veigas B, Jacob JM, Costa MN, et al. Gold on paper–paper platform for Au-nanoprobe TB detection. Lab Chip. 2012;12:4802–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Jason Tye-Din, MBBS, PhD, FRACP, Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia, for his critical review and feedback on the manuscript. This research is supported by an Australian Government Research Training Program Scholarship. O.S. acknowledges the Australian Research Council and National Health and Medical Research Council for financial support (APP1101258, IH150100028).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Olga Shimoni.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaur, A., Shimoni, O. & Wallach, M. Celiac disease: from etiological factors to evolving diagnostic approaches. J Gastroenterol 52, 1001–1012 (2017). https://doi.org/10.1007/s00535-017-1357-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-017-1357-7

Keywords

Navigation