Abstract

Wheat is one of the most consumed foods in the world. Although it is extremely nutrient rich for us humans, some of us have great difficulties in completely digesting its protein subunits. This review aims to understand the onset of Celiac Disease and its association with several other auto-immune diseases. The gliadin molecule, undigested in the small intestine, over time, ruptures the villi lining of the intestinal wall and enters the bloodstream which in turn activates the body's immune response. In some patients with the presence of HLA DQ2/DQ8 genes, this immune response results in Celiac Disease. Notably, researchers over the past several decades have found several links between Celiac Disease and multiple auto-immune diseases. Diabetes is one such auto-immune disease which has shown multiple associations with Celiac Disease. Similarly, in this review paper, we are critically analyzing the association of Celiac Disease with some of the most common autoimmune diseases namely Type-1 Diabetes, Multiple Sclerosis, Autism and Inflammatory Bowel Disease. In this paper, we have shown a clear correlation of celiac disease with several other auto-immune diseases. Further study is needed to understand the bidirectional association of Celiac Disease with different auto-immune diseases.

Keywords: Celiac disease, Type 1 diabetes, Multiple Sclerosis, Autism Spectrum Disorder, Inflammatory Bowel Disease

Downloads

Download data is not yet available.

References

  1. Akobeng A, Ramanan A, Basude D. EFFECT OF BREAST-FEEDING ON RISK OF COELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL STUDIES: PG1-18. Journal of Pediatric Gastroenterology and Nutrition. 2005;40:638-9.
  2. Awika JM. Major cereal grains production and use around the world. Advances in cereal science: implications to food processing and health promotion: ACS Publications; 2011;1-13.
  3. Bai D, Yip BHK, Windham GC, et al. Association of genetic and environmental factors with autism in a 5-country cohort. JAMA psychiatry. 2019;76:1035-43.
  4. Bao F, Yu L, Babu S, et al. One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies. Journal of autoimmunity. 1999;13:143-8.
  5. Barcia G, Posar A, Santucci M, et al. Autism and coeliac disease. Journal of autism and developmental disorders. 2008;38:407.
  6. Batur-Caglayan H, Irkec C, Yildirim-Capraz I, et al. A case of multiple sclerosis and celiac disease. Case reports in neurological medicine. 2013;2013.
  7. Bosi E, Molteni L, Radaelli M, et al. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabetologia. 2006;49:2824-7.
  8. Bruun SW, Josefsen K, Tanassi JT, et al. Large gliadin peptides detected in the pancreas of NOD and healthy mice following oral administration. Journal of diabetes research. 2016;2016.
  9. Bulger K, Griffin M, Dervan P, et al. Coeliac disease in association with inflammatory bowel disease. Postgraduate medical journal. 1988;64:336.
  10. Caio G, Volta U, Sapone A, et al. Celiac disease: a comprehensive current review. BMC medicine. 2019;17:1-20.
  11. Calderoni S, Santocchi E, Del Bianco T, et al. Serological screening for Celiac Disease in 382 pre-schoolers with Autism Spectrum Disorder. Italian journal of pediatrics. 2016;42:1-6.
  12. Camara-Lemarroy CR, Metz L, Meddings JB, et al. The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics. Brain. 2018;141:1900-16.
  13. Camarca ME, Mozzillo E, Nugnes R, et al. Celiac disease in type 1 diabetes mellitus. Italian journal of pediatrics. 2012;38:1-7.
  14. Camilleri á, Madsen K, Spiller R, et al. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterology & Motility. 2012;24:503-12.
  15. Caminero A, Meisel M, Jabri B, et al. Mechanisms by which gut microorganisms influence food sensitivities. Nature Reviews Gastroenterology & Hepatology. 2019;16:7-18.
  16. Casella G, D’Incà R, Oliva L, et al. Prevalence of celiac disease in inflammatory bowel diseases: An IG-IBD multicentre study. Digestive and liver disease. 2010;42:175-8.
  17. Cermak SA, Curtin C, Bandini LG. Food selectivity and sensory sensitivity in children with autism spectrum disorders. Journal of the American Dietetic Association. 2010;110:238-46.
  18. Chaidez V, Hansen RL, Hertz-Picciotto I. Gastrointestinal problems in children with autism, developmental delays or typical development. Journal of autism and developmental disorders. 2014;44:1117-27.
  19. Chirdo F, Rumbo M, Anon M, et al. Presence of high levels of non-degraded gliadin in breast milk from healthy mothers. Scandinavian journal of gastroenterology. 1998;33:1186-92.
  20. Cottone M, Marrone C, Casà A, et al. Familial occurrence of inflammatory bowel disease in celiac disease. Inflammatory bowel diseases. 2003;9:321-3.
  21. Dall M, Calloe K, Haupt-Jorgensen M, et al. Gliadin Fragments and a Specific Gliadin 33-mer Peptide Close K ATP Channels and Induce Insulin Secretion in INS-1E Cells and Rat Islets of Langerhans. PloS one. 2013;8:e66474.
  22. De Goffau MC, Luopajärvi K, Knip M, et al. Fecal microbiota composition differs between children with β-cell autoimmunity and those without. Diabetes. 2013;62:1238-44.
  23. De Re V, Caggiari L, Tabuso M, et al. The versatile role of gliadin peptides in celiac disease. Clinical biochemistry. 2013;46:552-60.
  24. Di Liberto D, D’Anneo A, Carlisi D, et al. Brain opioid activity and oxidative injury: Different molecular scenarios connecting celiac disease and autistic spectrum disorder. Brain Sciences. 2020;10:437.
  25. EL-ALAMEEY IR, AHMED HH, EID IM, et al. SERUM ANTIGLIADIN ANTIBODIES IN EGYPTIAN CHILDREN WITH AUTISM SPECTRUM DISORDER: RELATIONSHIP TO GASTROINTESTINAL SYMPTOMS, BEHAVIORAL AND SOCIAL COMMUNICATIONS. inflammation. 2018;3:4.
  26. Fallang L-E, Roh S, Holm A, et al. Complexes of two cohorts of CLIP peptides and HLA-DQ2 of the autoimmune DR3-DQ2 haplotype are poor substrates for HLA-DM. The Journal of Immunology. 2008;181:5451-61.
  27. Faras H, Al Ateeqi N, Tidmarsh L. Autism spectrum disorders. Annals of Saudi medicine. 2010;30:295-300.
  28. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiological reviews. 2011.
  29. Festen EA, Goyette P, Green T, 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. 2011;7:e1001283.
  30. Fiorentino M, Sapone A, Senger S, et al. Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Molecular autism. 2016;7:1-17.
  31. Fouda GG, Martinez DR, Swamy GK, et al. The Impact of IgG transplacental transfer on early life immunity. Immunohorizons. 2018;2:14-25.
  32. Funda DP, Kaas A, Bock T, et al. Gluten‐free diet prevents diabetes in NOD mice. Diabetes/metabolism research and reviews. 1999;15:323-7.
  33. Galli-Tsinopoulou A, Nousia-Arvanitakis S, Dracoulacos D, et al. Autoantibodies predicting diabetes mellitus type I in celiac disease. Hormone Research in Paediatrics. 1999;52:119-24.
  34. Garcia-Bennett AE, Ballell L. Non-absorbable mesoporous silica for the development of protein sequestration therapies. Biochemical and biophysical research communications. 2015;468:428-34.
  35. Gardner RM, Samuelsson I, Severance EG, et al. Maternal antibodies to gliadin and autism spectrum disorders in offspring-A population-based case-control study in Sweden. bioRxiv. 2020.
  36. Gillberg R, Dotevall G, Åhrén C. Chronic inflammatory bowel disease in patients with coeliac disease. Scandinavian journal of gastroenterology. 1982;17:491-6.
  37. Giongo A, Gano KA, Crabb DB, et al. Toward defining the autoimmune microbiome for type 1 diabetes. The ISME journal. 2011;5:82-91.
  38. Haider MN. Dynamic Cerebral Blood Flow Regulation in Adolescent Athletes with Sports-Related Concussion: State University of New York at Buffalo; 2021.
  39. Harris KG, Chang EB. The intestinal microbiota in the pathogenesis of inflammatory bowel diseases: new insights into complex disease. Clinical Science. 2018;132:2013-28.
  40. Hisamatsu T, Erben U, Kühl AA. The role of t-cell subsets in chronic inflammation in celiac disease and inflammatory bowel disease patients: More common mechanisms or more differences? Inflammatory intestinal diseases. 2016;1:52-62.
  41. Hmida NB, Ahmed MB, Moussa A, et al. Impaired control of effector T cells by regulatory T cells: a clue to loss of oral tolerance and autoimmunity in celiac disease? American Journal of Gastroenterology. 2012;107:604-11.
  42. Hollander D, Kaunitz JD. The “Leaky Gut”: tight junctions but loose associations? : Springer; 2020.
  43. Holmes G. Screening for coeliac disease in type 1 diabetes. Archives of Disease in Childhood. 2002;87:495-8.
  44. Jabri B, Abadie V. IL-15 functions as a danger signal to regulate tissue-resident T cells and tissue destruction. Nature Reviews Immunology. 2015;15:771-83.
  45. Jabri B, Sollid LM. T cells in celiac disease. The Journal of Immunology. 2017;198(8):3005-14.
  46. Jensen PE. Recent advances in antigen processing and presentation. Nature immunology. 2007;8:1041-8.
  47. Kamboj AK, Oxentenko AS. Clinical and histologic mimickers of celiac disease. Clinical and translational gastroenterology. 2017;8:e114.
  48. Kitis G, Holmes G, Cooper B, et al. Association of coeliac disease and inflammatory bowel disease. Gut. 1980;21:636-41.
  49. Knudsen KB, Hansen I. Gastrointestinal implications in pigs of wheat and oat fractions: 1. Digestibility and bulking properties of polysaccharides and other major constituents. British journal of nutrition. 1991;65:217-32.
  50. Kumar P, O'Donoghue D, Gibson J, et al. The existence of inflammatory bowel lesions in gluten-sensitive enteropathy. Postgraduate medical journal. 1979;55:753-6.
  51. Lahiri DK, Sokol DK, Erickson C, et al. Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway. Frontiers in cellular neuroscience. 2013;7:94.
  52. 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. e3.
  53. Lawlor G, Peppercorn MA. New genetic data support an association between celiac disease and inflammatory bowel disease. Inflammatory bowel diseases. 2011;17:E80-E1.
  54. Lebwohl B, Sanders DS, Green PH. Coeliac disease. The Lancet. 2018;391:70-81.
  55. Leeds JS, Höroldt BS, Sidhu R, et al. Is there an association between coeliac disease and inflammatory bowel diseases? A study of relative prevalence in comparison with population controls. Scandinavian journal of gastroenterology. 2007;42:1214-20.
  56. Lombardi F, Franzese A, Iafusco D, et al. Bone involvement in clusters of autoimmune diseases: just a complication? Bone. 2010;46:551-5.
  57. Ludvigsson JF, Reichenberg A, Hultman CM, et al. A nationwide study of the association between celiac disease and the risk of autistic spectrum disorders. JAMA psychiatry. 2013;70:1224-30.
  58. Lundin KE, Wijmenga C. Coeliac disease and autoimmune disease—genetic overlap and screening. Nature reviews Gastroenterology & hepatology. 2015;12:507.
  59. Malik TA. Inflammatory bowel disease: historical perspective, epidemiology, and risk factors. Surgical Clinics. 2015;95:1105-22.
  60. Marietta EV, Gomez AM, Yeoman C, 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. 2013;8:e78687.
  61. McElhanon BO, McCracken C, Karpen S, et al. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014;133:872-83.
  62. Mehanna M, Mneimneh A. Updated but not outdated “Gliadin”: A plant protein in advanced pharmaceutical nanotechnologies. International Journal of Pharmaceutics. 2020:119672.
  63. Meisel M, Mayassi T, Fehlner-Peach H, Koval JC, et al. Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis. The ISME journal. 2017;11:15-30.
  64. Mocan O, Dumitraşcu DL. The broad spectrum of celiac disease and gluten sensitive enteropathy. Clujul Medical. 2016;89:335.
  65. Mokarizadeh A, Esmaeili P, Soraya H, et al. Antibody against α-gliadin 33-mer peptide: Is the key initiating factor for development of multiple sclerosis during gluten sensitivity? Journal of Medical Hypotheses and Ideas. 2015;9:38-44.
  66. Murri M, Leiva I, Gomez-Zumaquero JM, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC medicine. 2013;11:1-12.
  67. Norris JM, Barriga K, Hoffenberg EJ, et al. Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease. Jama. 2005;293:2343-51.
  68. Norris JM, Barriga K, Klingensmith G, et al. Timing of initial cereal exposure in infancy and risk of islet autoimmunity. Jama. 2003;290:1713-20.
  69. Ordonez F, Lacaille F, Canioni D, et al. Pediatric ulcerative colitis associated with autoimmune diseases: a distinct form of inflammatory bowel disease? Inflammatory bowel diseases. 2012;18:1809-17.
  70. Oxford EC, Nguyen DD, Sauk J, et al. Impact of co-existent celiac disease on phenotype and natural history of inflammatory bowel diseases. The American journal of gastroenterology. 2013;108.
  71. Pascual V, Dieli-Crimi R, López-Palacios N, et al. Inflammatory bowel disease and celiac disease: overlaps and differences. World journal of gastroenterology: WJG. 2014;20:4846.
  72. Patel J, Agasti A, Rao S, et al. Celiac disease preceding Crohn’s disease? Tropical Gastroenterology. 2011;32:236-8.
  73. Pilli D, Zou A, Tea F, et al. Expanding role of T cells in human autoimmune diseases of the central nervous system. Frontiers in immunology. 2017;8:652.
  74. Pinto-Sanchez MI, Seiler CL, Santesso N, et al. Association between inflammatory bowel diseases and celiac disease: a systematic review and meta-analysis. Gastroenterology. 2020;159:884-903. e31.
  75. Pocecco M, Ventura A. Coeliac disease and insulin‐dependent diabetes mellitus: a causal association? Acta Paediatrica. 1995;84:1432-3.
  76. Pociot F, McDermott M. Genetics of type 1 diabetes mellitus. Genes & Immunity. 2002;3:235-49.
  77. Pos W, Sethi DK, Call MJ, et al. Crystal structure of the HLA-DM–HLA-DR1 complex defines mechanisms for rapid peptide selection. Cell. 2012;151:1557-68.
  78. Poulain C, Johanet C, Delcroix C, et al. Prevalence and clinical features of celiac disease in 950 children with type 1 diabetes in France. Diabetes & metabolism. 2007;33:453-8.
  79. Quan J, Panaccione N, King J, et al. A257 ASSOCIATION BETWEEN CELIAC DISEASE AND AUTISM SPECTRUM DISORDER: A SYSTEMATIC REVIEW. Journal of the Canadian Association of Gastroenterology. 2019;2:502-3.
  80. Rao M, Gershon MD. The bowel and beyond: the enteric nervous system in neurological disorders. Nature reviews Gastroenterology & hepatology. 2016;13:517.
  81. Reichelt KL, Jensen D. IgA antibodies against gliadin and gluten in multiple sclerosis. Acta neurologica scandinavica. 2004;110:239-41.
  82. Rodrigo L, Hernández-Lahoz C, Fuentes D, et al. Prevalence of celiac disease in multiple sclerosis. BMC neurology. 2011;11:1-7.
  83. Rubio-Tapia A, Hill ID, Kelly CP, et al. American College of Gastroenterology clinical guideline: diagnosis and management of celiac disease. The American journal of gastroenterology. 2013;108:656.
  84. Salem S, Truelove S, Richards W. Small-intestinal and gastric changes in ulcerative colitis: a biopsy study. British medical journal. 1964;1:394.
  85. Santiago JL, Martínez A, Núñez C, et al. Association of MYO9B haplotype with type 1 diabetes. Human immunology. 2008;69:112-5.
  86. Sapone A, De Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55:1443-9.
  87. Sblattero D, Maurano F, Mazzarella G, et al. Characterization of the anti-tissue transglutaminase antibody response in nonobese diabetic mice. The Journal of Immunology. 2005;174:5830-6.
  88. Schedel J, Rockmann F, Bongartz T, et al. Association of Crohn’s disease and latent celiac disease: a case report and review of the literature. International journal of colorectal disease. 2005;20:376-80.
  89. Schneeberger EE, Lynch RD. The tight junction: a multifunctional complex. American Journal of Physiology-Cell Physiology. 2004;286:C1213-C28.
  90. Schneider S, Wright CM, Heuckeroth RO. Unexpected roles for the second brain: enteric nervous system as master regulator of bowel function. Annual review of physiology. 2019;81:235-59.
  91. Scott FW, Marliss EB. Conference summary: diet as an environmental factor in development of insulin-dependent diabetes mellitus. Canadian journal of physiology and pharmacology. 1991;69:311-9.
  92. Shah A, Walker M, Burger D, et al. Link between celiac disease and inflammatory bowel disease. Journal of clinical gastroenterology. 2019;53:514-22.
  93. Shaygannejad V, Ghasemi M, Mirmohamadsadeghi M. Multiple sclerosis or neurological manifestations of Celiac disease. Advanced biomedical research. 2013;2.
  94. Shewry P. What is gluten—Why is it special? Frontiers in nutrition. 2019;6:101.
  95. Shewry PR, Halford NG, Belton PS, et al. The structure and properties of gluten: an elastic protein from wheat grain. Philosophical Transactions of the Royal Society of London Series B: Biological Sciences. 2002;357:133-42.
  96. Shimada S, Tanigawa T, Watanabe T, et al. Involvement of gliadin, a component of wheat gluten, in increased intestinal permeability leading to non-steroidal anti-inflammatory drug-induced small-intestinal damage. PloS one. 2019;14:e0211436.
  97. Slifka MK, Amanna IJ. Passive immunization. Plotkin's Vaccines. 2018:84.
  98. Soukou S, Brockmann L, Bedke T, et al. Role of IL-10 receptor signaling in the function of CD4+ T-regulatory type 1 cells: T-cell therapy in patients with inflammatory bowel disease. Critical reviews™ in immunology. 2018;38.
  99. Srinivasan B, Kolli AR, Esch MB, et al. TEER measurement techniques for in vitro barrier model systems. Journal of laboratory automation. 2015;20:107-26.
  100. Stene LC, Oikarinen S, Hyöty H, et al. Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the Diabetes and Autoimmunity Study in the Young (DAISY). Diabetes. 2010;59:3174-80.
  101. Stepniak D, Spaenij-Dekking L, Mitea C, et al. Highly efficient gluten degradation with a newly identified prolyl endoprotease: implications for celiac disease. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2006;291:G621-G9.
  102. Valerio G, Maiuri L, Troncone R, et al. Severe clinical onset of diabetes and increased prevalence of other autoimmune diseases in children with coeliac disease diagnosed before diabetes mellitus. Diabetologia. 2002;45:1719-22.
  103. Ventura A, Neri E, Ughi C, et al. Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. The Journal of pediatrics. 2000;137:263-5.
  104. Virtanen SM, Knip M. Nutritional risk predictors of β cell autoimmunity and type 1 diabetes at a young age. The American journal of clinical nutrition. 2003;78:1053-67.
  105. Vojdani A, O'Bryan T, Green J, et al. Immune response to dietary proteins, gliadin and cerebellar peptides in children with autism. Nutritional neuroscience. 2004;7:151-61.
  106. Vojdani A, Pangborn J, Vojdani E, et al. Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism. International journal of immunopathology and pharmacology. 2003;16:189-99.
  107. Vojdani A, Vojdani E. Gluten and non-gluten proteins of wheat as target antigens in autism, Crohn’s and celiac disease. Journal of Cereal Science. 2017;75:252-60.
  108. Volta U, Tovoli F, Caio G. Clinical and immunological features of celiac disease in patients with type 1 diabetes mellitus. Expert review of gastroenterology & hepatology. 2011;5:479-87.
  109. Watts T, Berti I, Sapone A, et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proceedings of the National Academy of Sciences. 2005;102:2916-21.
  110. Wrigley C, Békés F, Bushuk W. Gluten: A balance of gliadin and glutenin. Gliadin and glutenin: The unique balance of wheat quality. 2006:3-32.
  111. Yang A, Chen Y, Scherl E, et al. Inflammatory bowel disease in patients with celiac disease. Inflammatory bowel diseases. 2005;11:528-32.
  112. Yang J, Chow I-T, Sosinowski T, et al. Autoreactive T cells specific for insulin B: 11-23 recognize a low-affinity peptide register in human subjects with autoimmune diabetes. Proceedings of the National Academy of Sciences. 2014;111:14840-5.
  113. Yeung W-CG, Rawlinson WD, Craig ME. Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. Bmj. 2011;342.
  114. Zhang X-M, Liu C-Y, Shao Z-H. Advances in the role of helper T cells in autoimmune diseases. Chinese medical journal. 2020;133:968.
  115. Zhou Z, Reyes‐Vargas E, Escobar H, et al. Type 1 diabetes associated HLA‐DQ2 and DQ8 molecules are relatively resistant to HLA‐DM mediated release of invariant chain‐derived CLIP peptides. European journal of immunology. 2016;46:834-45.
  116. Ziegler A-G, Schmid S, Huber D, et al. Early infant feeding and risk of developing type 1 diabetes–associated autoantibodies. Jama. 2003;290:1721-8.
 How to Cite
Buchke, S., Bora, A., Mehta, B., Relekar, M., Varsha, P., Kumar, J., & Bhanu, P. (2021). Celiac Disease and Its Association with Organ-Specific Auto-Immune Diseases. International Journal of Innovative Research in Medical Science, 6(10), 687–697. https://doi.org/10.23958/ijirms/vol06-i10/1214

Copyrights & License