Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Coeliac disease and autoimmune disease—genetic overlap and screening

Nature Reviews Gastroenterology & Hepatology volume 12, pages 507–515 (2015)Cite this article

Subjects

Key Points

  • Patients with coeliac disease demonstrate concurrent autoimmune diseases more frequently (∼5%) than healthy individuals, and patients with autoimmune diseases often have coeliac disease, particularly those with diabetes or thyroid disease

  • Screening for coeliac disease in patients with autoimmune disease should be done regularly by evaluating serum antibodies (serological testing), although negative serology results do not entirely exclude coeliac disease

  • HLA typing offers a good negative predictive value, but only a modest positive predictive value

  • Gastroduodenoscopy whilst on gluten-containing diet is required for final diagnosis in adults, whereas HLA typing is part of the recent diagnostic work-up in children (many can be diagnosed without endoscopy)

  • Extensive genetic overlap exists between coeliac disease and other autoimmune diseases and current genetic risk profiling does not enable a precise prediction of disease development

Abstract

Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening—and subsequent treatment if coeliac disease is detected—could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Organs involved in coeliac-disease-associated autoimmunity.
Figure 2: Interpretation of genetic findings in different autoimmune diseases.

Similar content being viewed by others

References

  1. Abadie, V., Sollid, L. M., Barreiro, L. B. & Jabri, B. Integration of genetic and immunological insights into a model of celiac disease pathogenesis. Annu. Rev. Immunol. 29, 493–525 (2011).

    CAS  PubMed  Google Scholar 

  2. Ludvigsson, J. F. et al. The Oslo definitions for coeliac disease and related terms. Gut 62, 43–52 (2013).

    PubMed  Google Scholar 

  3. Ludvigsson, J. F. et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 63, 1210–1228 (2014).

    PubMed  PubMed Central  Google Scholar 

  4. Rampertab, S. D., Pooran, N., Brar, P., Singh, P. & Green, P. H. Trends in the presentation of celiac disease. Am. J. Med. 119, 355 e9–e14 (2006).

    Google Scholar 

  5. Sollid, L. M. & Jabri, B. Triggers and drivers of autoimmunity: lessons from coeliac disease. Nat. Rev. Immunol. 13, 294–302 (2013).

    CAS  PubMed  Google Scholar 

  6. Sollid, L. M. et al. Evidence for a primary association of celiac disease to a particular HLA-DQ α/β heterodimer. J. Exp. Med. 169, 345–350 (1989).

    CAS  PubMed  Google Scholar 

  7. Anderson, R. P. et al. A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways. BMC Med. 11, 188 (2013).

    PubMed  PubMed Central  Google Scholar 

  8. Johnson, T. C. et al. Relationship of HLA-DQ8 and severity of celiac disease: comparison of New York and Parisian cohorts. Clin. Gastroenterol. Hepatol. 2, 888–894 (2004).

    CAS  PubMed  Google Scholar 

  9. Agardh, D. et al. Clinical features of celiac disease: a prospective birth cohort. Pediatrics 135, 627–634 (2015).

    PubMed  PubMed Central  Google Scholar 

  10. Thomas, H. J. et al. Contribution of histological, serological, and genetic factors to the clinical heterogeneity of adult-onset coeliac disease. Scand. J. Gastroenterol. 44, 1076–1083 (2009).

    PubMed  Google Scholar 

  11. de Haas, E. C., Kumar, V. & Wijmenga, C. in Celiac Disease (Clinical Gastroenterology) (eds Rampertab, S. D. & Mullin, G. E.) 53–66 (Springer Science+Business Media, 2014).

    Google Scholar 

  12. Parkes, M., Cortes, A., van Heel, D. A. & Brown, M. A. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat. Rev. Genet. 14, 661–673 (2013).

    CAS  PubMed  Google Scholar 

  13. Fasano, A. 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. 163, 286–292 (2003).

    PubMed  Google Scholar 

  14. Ludvigsson, J. F. et al. Screening for celiac disease in the general population and in high-risk groups. United European Gastroenterol. J. 3, 106–120 (2015).

    PubMed  PubMed Central  Google Scholar 

  15. Abdul Sultan, A. et al. Causes of death in people with coeliac disease in England compared with the general population: a competing risk analysis. Gut 64, 1220–1226 (2015).

    PubMed  Google Scholar 

  16. Junker, Y. et al. Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of Toll-like receptor 4. J. Exp. Med. 209, 2395–2408 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Lammers, K. M. et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. Gastroenterology 135, 194–204 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Palova-Jelinkova, L. et al. Pepsin digest of wheat gliadin fraction increases production of IL-1β via TLR4/MyD88/TRIF/MAPK/NF-kappaB signaling pathway and an NLRP3 inflammasome activation. PLoS ONE 8, e62426 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Barone, M. V., Troncone, R. & Auricchio, S. Gliadin peptides as triggers of the proliferative and stress/innate immune response of the celiac small intestinal mucosa. Int. J. Mol. Sci. 15, 20518–20537 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Sollid, L. M., Qiao, S. W., Anderson, R. P., Gianfrani, C. & Koning, F. Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics 64, 455–460 (2012).

    PubMed  PubMed Central  Google Scholar 

  21. Antvorskov, J. C., Josefsen, K., Engkilde, K., Funda, D. P. & Buschard, K. Dietary gluten and the development of type 1 diabetes. Diabetologia 57, 1770–1780 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Maurano, F. et al. Small intestinal enteropathy in non-obese diabetic mice fed a diet containing wheat. Diabetologia 48, 931–937 (2005).

    CAS  PubMed  Google Scholar 

  23. Sblattero, D. et al. Characterization of the anti-tissue transglutaminase antibody response in nonobese diabetic mice. J. Immunol. 174, 5830–5836 (2005).

    CAS  PubMed  Google Scholar 

  24. Marietta, E. V. et al. Low incidence of spontaneous type 1 diabetes in non-obese diabetic mice raised on gluten-free diets is associated with changes in the intestinal microbiome. PLoS ONE 8, e78687 (2013).

    PubMed  PubMed Central  Google Scholar 

  25. Ejsing-Duun, M., Josephsen, J., Aasted, B., Buschard, K. & Hansen, A. K. Dietary gluten reduces the number of intestinal regulatory T cells in mice. Scand. J. Immunol. 67, 553–559 (2008).

    CAS  PubMed  Google Scholar 

  26. Larsen, J. et al. Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion. Eur. J. Immunol. 44, 3056–3067 (2014).

    CAS  PubMed  Google Scholar 

  27. Adlercreutz, E. H. et al. A gluten-free diet lowers NKG2D and ligand expression in BALB/c and non-obese diabetic (NOD) mice. Clin. Exp. Immunol. 177, 391–403 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Schuppan, D., Pickert, G., Ashfaq-Khan, M. & Zevallos, V. Non-celiac wheat sensitivity: Differential diagnosis, triggers and implications. Best Pract. Res. Clin. Gastroenterol. 29, 469–476 (2015).

    CAS  PubMed  Google Scholar 

  29. Dieterich, W. et al. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat. Med. 3, 797–801 (1997).

    CAS  PubMed  Google Scholar 

  30. Sardy, M., Karpati, S., Merkl, B., Paulsson, M. & Smyth, N. Epidermal transglutaminase (TGase 3) is the autoantigen of dermatitis herpetiformis. J. Exp. Med. 195, 747–757 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Hadjivassiliou, M. et al. Transglutaminase 6 antibodies in the diagnosis of gluten ataxia. Neurology 80, 1740–1745 (2013).

    CAS  PubMed  Google Scholar 

  32. Sollid, L. M., Molberg, O., McAdam, S. & Lundin, K. E. Autoantibodies in coeliac disease: tissue transglutaminase—guilt by association? Gut 41, 851–852 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Sulkanen, S. et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 115, 1322–1328 (1998).

    CAS  PubMed  Google Scholar 

  34. Sjober, K. et al. Factor XIII and tissue transglutaminase antibodies in coeliac and inflammatory bowel disease. Autoimmunity 35, 357–364 (2002).

    PubMed  Google Scholar 

  35. Alaedini, A. & Green, P. H. Autoantibodies in celiac disease. Autoimmunity 41, 19–26 (2008).

    CAS  PubMed  Google Scholar 

  36. Stordal, K., Bakken, I. J., Suren, P. & Stene, L. C. Epidemiology of coeliac disease and comorbidity in Norwegian children. J. Pediatr. Gastroenterol. Nutr. 57, 467–471 (2013).

    PubMed  Google Scholar 

  37. Emilsson, L., Wijmenga, C., Murray, J. A. & Ludvigsson, J. F. Autoimmune disease in first-degree relatives and spouses of individuals with celiac disease. Clin. Gastroenterol. Hepatol 13, 1271–1277 (2015).

    PubMed  Google Scholar 

  38. Elfstrom, P., Sundstrom, J. & Ludvigsson, J. F. Systematic review with meta-analysis: associations between coeliac disease and type 1 diabetes. Aliment Pharmacol. Ther. 40, 1123–1132 (2014).

    CAS  PubMed  Google Scholar 

  39. Ludvigsson, J. F., Ludvigsson, J., Ekbom, A. & Montgomery, S. M. Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents. Diabetes Care 29, 2483–2488 (2006).

    PubMed  Google Scholar 

  40. Kahaly, G. J. & Schuppan, D. Celiac disease and endocrine autoimmunity. Dig. Dis. 33, 155–161 (2015).

    PubMed  Google Scholar 

  41. Borchers, A. T., Uibo, R. & Gershwin, M. E. The geoepidemiology of type 1 diabetes. Autoimmun. Rev. 9, A355–A365 (2010).

    PubMed  Google Scholar 

  42. Bjornstad, P., Snell-Bergeon, J. K., Nadeau, K. J. & Maahs, D. M. Insulin sensitivity and complications in type 1 diabetes: new insights. World J. Diabetes 6, 8–16 (2015).

    PubMed  PubMed Central  Google Scholar 

  43. Collin, P., Kaukinen, K., Valimaki, M. & Salmi, J. Endocrinological disorders and celiac disease. Endocr. Rev. 23, 464–483 (2002).

    CAS  PubMed  Google Scholar 

  44. Elfstrom, P., Montgomery, S. M., Kampe, O., Ekbom, A. & Ludvigsson, J. F. Risk of thyroid disease in individuals with celiac disease. J. Clin. Endocrinol. Metab. 93, 3915–3921 (2008).

    PubMed  Google Scholar 

  45. Ponto, K. A. et al. Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity. Clin. Exp. Immunol. 178, 57–64 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Iltanen, S. et al. Celiac disease and markers of celiac disease latency in patients with primary Sjogren's syndrome. Am. J. Gastroenterol. 94, 1042–1046 (1999).

    CAS  PubMed  Google Scholar 

  47. Collin, P. & Reunala, T. Recognition and management of the cutaneous manifestations of celiac disease: a guide for dermatologists. Am. J. Clin. Dermatol. 4, 13–20 (2003).

    PubMed  Google Scholar 

  48. Caproni, M., Antiga, E., Melani, L., Fabbri, P. & Italian Group for Cutaneous, I. Guidelines for the diagnosis and treatment of dermatitis herpetiformis. J. Eur. Acad. Dermatol. Venereol. 23, 633–638 (2009).

    CAS  PubMed  Google Scholar 

  49. West, J., Fleming, K. M., Tata, L. J., Card, T. R. & Crooks, C. J. Incidence and prevalence of celiac disease and dermatitis herpetiformis in the UK over two decades: population-based study. Am. J. Gastroenterol. 109, 757–768 (2014).

    PubMed  PubMed Central  Google Scholar 

  50. Salmi, T. T., Hervonen, K., Kautiainen, H., Collin, P. & Reunala, T. Prevalence and incidence of dermatitis herpetiformis: a 40-year prospective study from Finland. Br. J. Dermatol. 165, 354–359 (2011).

    CAS  PubMed  Google Scholar 

  51. Rubio-Tapia, A. & Murray, J. A. The liver in celiac disease. Hepatology 46, 1650–1658 (2007).

    CAS  PubMed  Google Scholar 

  52. Caprai, S. et al. Autoimmune liver disease associated with celiac disease in childhood: a multicenter study. Clin. Gastroenterol. Hepatol. 6, 803–806 (2008).

    PubMed  Google Scholar 

  53. Naess, S. et al. Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population. PLoS ONE 9, e114486 (2014).

    PubMed  PubMed Central  Google Scholar 

  54. Fosby, B. et al. Liver transplantation in the Nordic countries—An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982–2013. Scand. J. Gastroenterol. 50, 797–808 (2015).

    PubMed  PubMed Central  Google Scholar 

  55. Hadjivassiliou, M. et al. Neuropathy associated with gluten sensitivity. J. Neurol. Neurosurg. Psychiatry 77, 1262–1266 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Ong, M. S., Kohane, I. S., Cai, T., Gorman, M. P. & Mandl, K. D. Population-level evidence for an autoimmune etiology of epilepsy. JAMA Neurol. 71, 569–574 (2014).

    PubMed  PubMed Central  Google Scholar 

  57. Hadjivassiliou, M., Sanders, D. S., Woodroofe, N., Williamson, C. & Grunewald, R. A. Gluten ataxia. Cerebellum 7, 494–498 (2008).

    CAS  PubMed  Google Scholar 

  58. Ludvigsson, J. F., Osby, U., Ekbom, A. & Montgomery, S. M. Coeliac disease and risk of schizophrenia and other psychosis: a general population cohort study. Scand. J. Gastroenterol. 42, 179–185 (2007).

    PubMed  Google Scholar 

  59. van Heel, D. A. et al. A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21. Nat. Genet. 39, 827–829 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Dubois, P. C. et al. Multiple common variants for celiac disease influencing immune gene expression. Nat. Genet. 42, 295–302 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Monsuur, A. J. et al. Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms. PLoS ONE 3, e2270 (2008).

    PubMed  PubMed Central  Google Scholar 

  62. Gutierrez-Achury, J. et al. Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease. Nat. Genet. 46, 577–578 (2015).

    Google Scholar 

  63. Kumar, V., Wijmenga, C. & Xavier, R. J. Genetics of immune-mediated disorders: from genome-wide association to molecular mechanism. Curr. Opin. Immunol. 31, 51–57 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Kumar, V., Wijmenga, C. & Withoff, S. From genome-wide association studies to disease mechanisms: celiac disease as a model for autoimmune diseases. Semin. Immunopathol. 34, 567–580 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Wijmenga, C. & Gutierrez-Achury, J. Celiac disease genetics: past, present and future challenges. J. Pediatr. Gastroenterol. Nutr. 59 (Suppl. 1), S4–S7 (2014).

    CAS  PubMed  Google Scholar 

  66. Ricano-Ponce, I. & Wijmenga, C. Mapping of immune-mediated disease genes. Annu. Rev. Genomics Hum. Genet. 14, 325–353 (2013).

    CAS  PubMed  Google Scholar 

  67. Nikula, T. et al. A human ImmunoChip cDNA microarray provides a comprehensive tool to study immune responses. J. Immunol. Methods 303, 122–134 (2005).

    CAS  PubMed  Google Scholar 

  68. Cotsapas, C. et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genet. 7, e1002254 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Zhernakova, A., Withoff, S. & Wijmenga, C. Clinical implications of shared genetics and pathogenesis in autoimmune diseases. Nat. Rev. Endocrinol. 9, 646–659 (2013).

    CAS  PubMed  Google Scholar 

  70. Plenge, R. M., Scolnick, E. M. & Altshuler, D. Validating therapeutic targets through human genetics. Nat. Rev. Drug Discov. 12, 581–594 (2013).

    CAS  PubMed  Google Scholar 

  71. Baurecht, H. et al. Genome-wide comparative Analysis of atopic dermatitis and psoriasis gives insight into opposing genetic mechanisms. Am. J. Hum. Genet. 96, 104–120 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Eaton, W. W., Rose, N. R., Kalaydjian, A., Pedersen, M. G. & Mortensen, P. B. Epidemiology of autoimmune diseases in Denmark. J. Autoimmun. 29, 1–9 (2007).

    PubMed  PubMed Central  Google Scholar 

  73. Patsopoulos, N. A. et al. Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Ann. Neurol. 70, 897–912 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Zhernakova, A. et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet. 7, e1002004 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Webb, C. et al. Celiac disease can be predicted by high levels of anti-tissue transglutaminase antibodies in population-based screening. J. Pediatr. Gastroenterol. Nutr. 60, 787–791 (2015).

    CAS  PubMed  Google Scholar 

  76. Altobelli, E., Paduano, R., Petrocelli, R. & Di Orio, F. Burden of celiac disease in Europe: a review of its childhood and adulthood prevalence and incidence as of September 2014. Ann. Ig. 26, 485–498 (2014).

    CAS  PubMed  Google Scholar 

  77. Mustalahti, K. et al. The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann. Med. 42, 587–595 (2010).

    PubMed  Google Scholar 

  78. Ivarsson, A. et al. Prevalence of childhood celiac disease and changes in infant feeding. Pediatrics 131, e687–e694 (2013).

    PubMed  Google Scholar 

  79. Rubio-Tapia, A., Ludvigsson, J. F., Brantner, T. L., Murray, J. A. & Everhart, J. E. The prevalence of celiac disease in the United States. Am. J. Gastroenterol. 107, 1538–1544 (2012).

    PubMed  Google Scholar 

  80. Nenna, R. et al. The celiac iceberg: characterization of the disease in primary schoolchildren. J. Pediatr. Gastroenterol. Nutr. 56, 416–421 (2013).

    CAS  PubMed  Google Scholar 

  81. Mearin, M. L., Ivarsson, A. & Dickey, W. Coeliac disease: is it time for mass screening? Best Pract. Res. Clin. Gastroenterol. 19, 441–452 (2005).

    PubMed  Google Scholar 

  82. Godfrey, J. D. et al. Morbidity and mortality among older individuals with undiagnosed celiac disease. Gastroenterology 139, 763–769 (2010).

    PubMed  PubMed Central  Google Scholar 

  83. Catassi, C. & Fasano, A. Coeliac disease. The debate on coeliac disease screening—are we there yet? Nature Rev. Gastroenterol. Hepatol 11, 457–458 (2014).

    Google Scholar 

  84. Mooney, P. D., Hadjivassiliou, M. & Sanders, D. S. Coeliac disease. BMJ 348, g1561 (2014).

    PubMed  Google Scholar 

  85. Hill, I. D. Management of celiac disease in children. UpToDate[online], (2015).

  86. Leffler, D. A. & Schuppan, D. Update on serologic testing in celiac disease. Am. J. Gastroenterol. 105, 2520–2524 (2010).

    PubMed  Google Scholar 

  87. Biagi, F., Klersy, C., Balduzzi, D. & Corazza, G. R. Are we not over-estimating the prevalence of coeliac disease in the general population? Ann. Med. 42, 557–561 (2010).

    PubMed  Google Scholar 

  88. Castellaneta, S. et al. High rate of spontaneous normalization of celiac serology in a cohort of 446 children with type 1 diabetes: a prospective study. Diabetes Care 38, 760–766 (2015).

    CAS  PubMed  Google Scholar 

  89. Maki, M. et al. Prevalence of celiac disease among children in Finland. N. Engl. J. Med. 348, 2517–2524 (2003).

    PubMed  Google Scholar 

  90. Simell, S. et al. Natural history of transglutaminase autoantibodies and mucosal changes in children carrying HLA-conferred celiac disease susceptibility. Scand. J. Gastroenterol. 40, 1182–1191 (2005).

    CAS  PubMed  Google Scholar 

  91. Romanos, J. & Wijmenga, C. Predicting susceptibility to celiac disease by genetic testing profile. Ann. Gastroenterol. Hepatol. 1, 11–18 (2010).

    Google Scholar 

  92. Liu, E. et al. Risk of pediatric celiac disease according to HLA haplotype and country. N. Engl. J. Med. 371, 42–49 (2014).

    PubMed  PubMed Central  Google Scholar 

  93. Panetta, F. et al. Clinical accuracy of anti-tissue transglutaminase as screening test for celiac disease under 2 years. Acta Paediatr. 100, 728–731 (2011).

    CAS  PubMed  Google Scholar 

  94. Tortora, R. et al. The presence of anti-endomysial antibodies and the level of anti-tissue transglutaminases can be used to diagnose adult coeliac disease without duodenal biopsy. Aliment. Pharmacol. Ther. 40, 1223–1229 (2014).

    CAS  PubMed  Google Scholar 

  95. Vriezinga, S. L. et al. Randomized feeding intervention in infants at high risk for celiac disease. N. Engl. J. Med. 371, 1304–1315 (2014).

    CAS  PubMed  Google Scholar 

  96. Lionetti, E. et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. N. Engl. J. Med. 371, 1295–1303 (2014).

    PubMed  Google Scholar 

  97. Abraham, G. et al. Accurate and robust genomic prediction of celiac disease using statistical learning. PLoS Genet. 10, e1004137 (2014).

    PubMed  PubMed Central  Google Scholar 

  98. Romanos, J. et al. Improving coeliac disease risk prediction by testing non-HLA variants additional to HLA variants. Gut 63, 415–422 (2014).

    PubMed  Google Scholar 

  99. Christophersen, A. et al. Tetramer-visualized gluten-specific CD4+ T cells in blood as a potential diagnostic marker for coeliac disease without oral gluten challenge. United European Gastroenterol. J. 2, 268–278 (2014).

    PubMed  PubMed Central  Google Scholar 

  100. Ventura, A., Magazzu, 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 117, 297–303 (1999).

    CAS  PubMed  Google Scholar 

  101. Sategna Guidetti, C., Solerio, E., Scaglione, N., Aimo, G. & Mengozzi, G. Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders. Gut 49, 502–505 (2001).

    CAS  PubMed  Google Scholar 

  102. Viljamaa, M. et al. Coeliac disease, autoimmune diseases and gluten exposure. Scand. J. Gastroenterol. 40, 437–443 (2005).

    CAS  PubMed  Google Scholar 

  103. Cosnes, J. et al. Incidence of autoimmune diseases in celiac disease: protective effect of the gluten-free diet. Clin. Gastroenterol. Hepatol 6, 753–758 (2008).

    PubMed  Google Scholar 

  104. Schmid, S., Buuck, D., Knopff, A., Bonifacio, E. & Ziegler, A. G. BABYDIET, a feasibility study to prevent the appearance of islet autoantibodies in relatives of patients with Type 1 diabetes by delaying exposure to gluten. Diabetologia 47, 1130–1131 (2004).

    CAS  PubMed  Google Scholar 

  105. Hummel, S., Pfluger, M., Hummel, M., Bonifacio, E. & Ziegler, A. G. Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes: the BABYDIET study. Diabetes Care 34, 1301–1305 (2011).

    PubMed  PubMed Central  Google Scholar 

  106. Daifotis, A. G., Koenig, S., Chatenoud, L. & Herold, K. C. Anti-CD3 clinical trials in type 1 diabetes mellitus. Clin. Immunol. 149, 268–278 (2013).

    CAS  PubMed  Google Scholar 

  107. Mollazadegan, K. et al. Risk of renal disease in patients with both type 1 diabetes and coeliac disease. Diabetologia 57, 1339–1345 (2014).

    CAS  PubMed  Google Scholar 

  108. Mollazadegan, K. et al. A population-based study of the risk of diabetic retinopathy in patients with type 1 diabetes and celiac disease. Diabetes Care 36, 316–321 (2013).

    PubMed  PubMed Central  Google Scholar 

  109. Mollazadegan, K., Sanders, D. S., Ludvigsson, J. & Ludvigsson, J. F. Long-term coeliac disease influences risk of death in patients with type 1 diabetes. J. Intern. Med. 274, 273–280 (2013).

    CAS  PubMed  Google Scholar 

  110. Malalasekera, V., Cameron, F., Grixti, E. & Thomas, M. C. Potential reno-protective effects of a gluten-free diet in type 1 diabetes. Diabetologia 52, 798–800 (2009).

    CAS  PubMed  Google Scholar 

  111. Amin, R. et al. A longitudinal study of the effects of a gluten-free diet on glycemic control and weight gain in subjects with type 1 diabetes and celiac disease. Diabetes Care 25, 1117–1122 (2002).

    PubMed  Google Scholar 

  112. Kaukinen, K. et al. No effect of gluten-free diet on the metabolic control of type 1 diabetes in patients with diabetes and celiac disease. Retrospective and controlled prospective survey. Diabetes Care 22, 1747–1748 (1999).

    CAS  PubMed  Google Scholar 

  113. Sun, S. et al. The effect of biopsy-positive silent coeliac disease and treatment with a gluten-free diet on growth and glycaemic control in children with Type 1 diabetes. Diabet. Med. 26, 1250–1254 (2009).

    CAS  PubMed  Google Scholar 

  114. Scaramuzza, A. E., Mantegazza, C., Bosetti, A. & Zuccotti, G. V. Type 1 diabetes and celiac disease: The effects of gluten free diet on metabolic control. World J. Diabetes 4, 130–134 (2013).

    PubMed  PubMed Central  Google Scholar 

  115. Sanchez-Albisua, I. et al. Coeliac disease in children with Type 1 diabetes mellitus: the effect of the gluten-free diet. Diabet. Med. 22, 1079–1082 (2005).

    CAS  PubMed  Google Scholar 

  116. Hansen, D. et al. Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years' follow-up. Diabetes Care 29, 2452–2456 (2006).

    PubMed  Google Scholar 

  117. Taler, I. et al. Growth and metabolic control in patients with type 1 diabetes and celiac disease: a longitudinal observational case–control study. Pediatr. Diabetes 13, 597–606 (2012).

    PubMed  Google Scholar 

  118. Sategna-Guidetti, C. et al. Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study. Am. J. Gastroenterol. 96, 751–757 (2001).

    CAS  PubMed  Google Scholar 

  119. Metso, S. et al. Gluten-free diet and autoimmune thyroiditis in patients with celiac disease. A prospective controlled study. Scand. J. Gastroenterol. 47, 43–48 (2012).

    PubMed  Google Scholar 

  120. Ludvigsson, J. F., Elfstrom, P., Broome, U., Ekbom, A. & Montgomery, S. M. Celiac disease and risk of liver disease: a general population-based study. Clin. Gastroenterol. Hepatol. 5, 63–69 (2007).

    PubMed  Google Scholar 

  121. Rubio-Tapia, A. et al. Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation. Liver Int. 28, 467–476 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Kaukinen, K. et al. Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure. Gastroenterology 122, 881–888 (2002).

    PubMed  Google Scholar 

  123. Long, K. H. et al. The economics of coeliac disease: a population-based study. Aliment. Pharmacol. Ther. 32, 261–269 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Green, P. H. et al. Economic benefits of increased diagnosis of celiac disease in a national managed care population in the United States. J. Insur. Med. 40, 218–228 (2008).

    PubMed  Google Scholar 

  125. Celiac Support Association. Celiac Disease Facts. Celiac Support Association[online], (2015).

  126. Violato, M., Gray, A., Papanicolas, I. & Ouellet, M. Resource use and costs associated with coeliac disease before and after diagnosis in 3,646 cases: results of a UK primary care database analysis. PLoS ONE 7, e41308 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Bevan, S., Popat, S. & Houlston, R. S. Relative power of linkage and transmission disequilibrium test strategies to detect non-HLA linked coeliac disease susceptibility genes. Gut 45, 668–671 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Hunt, K. A. et al. Newly identified genetic risk variants for celiac disease related to the immune response. Nat. Genet. 40, 395–402 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Zhernakova, A., van Diemen, C. C. & Wijmenga, C. Detecting shared pathogenesis from the shared genetics of immune-related diseases. Nat. Rev. Genet. 10, 43–55 (2009).

    CAS  PubMed  Google Scholar 

  130. Trynka, G. et al. Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease. Nat. Genet. 43, 1193–1201 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Cortes, A. & Brown, M. A. Promise and pitfalls of the Immunochip. Arthritis Res. Ther. 13, 101 (2011).

    PubMed  PubMed Central  Google Scholar 

  132. Festen, E. A. et al. A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn's disease and celiac disease. PLoS Genet. 7, e1001283 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank J. Senior (University of Groningen, University Medical Centre, Department of Genetics, Groningen, Netherlands) and L. M. Sollid (Centre for Immune Regulation, University of Oslo, Oslo, Norway) for carefully reading the manuscript. The work in the Wijmenga laboratory on coeliac disease is funded by the European Research Council advanced grant (FP/2007–2013/ERC grant 2012-322698). K.E.A.L. is a senior faculty member at the Centre of Immune Regulation, which is funded by the Research Council of Norway through its Centres of Excellence funding scheme, project number 179573/V40, European Research Council advanced grant (FP/2007–2013/ERC grant 2010-268541 to L. M. Sollid), South-Eastern Norway Regional Health Authority and the Norwegian ExtraFoundation for Health and Rehabilitation through EXTRA funds.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, Oslo, 0378, Norway

    Knut E. A. Lundin

  2. Department of Genetics, University Medical Centre, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, Netherlands

    Cisca Wijmenga

Authors
  1. Knut E. A. Lundin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cisca Wijmenga
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed equally to this manuscript.

Corresponding author

Correspondence to Knut E. A. Lundin.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lundin, K., Wijmenga, C. Coeliac disease and autoimmune disease—genetic overlap and screening. Nat Rev Gastroenterol Hepatol 12, 507–515 (2015). https://doi.org/10.1038/nrgastro.2015.136

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2015.136

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing