Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 Celiac Disease is an immune-mediated disease triggered by the ingestion of gluten from wheat and other cereals. The gluten intake induce alteration of gut barrier integrity, changes in intestinal microbiota composition and immune system stimulation. A li
Marianna Lauricella
 + 2472 word(s) 2472 2020-10-21 09:48:13 |
2 format change
Nicole Yin
 -1037 word(s) 1435 2020-10-29 03:09:32 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Di Liberto, D.; Carlisi, D.; D'anneo, A.; Emanuele, S.; Giuliano, M.; De Blasio, A.; Calvaruso, G.; Lauricella, M. Celiac Diseases. Encyclopedia. Available online: https://encyclopedia.pub/entry/2805 (accessed on 20 April 2024).
Di Liberto D, Carlisi D, D'anneo A, Emanuele S, Giuliano M, De Blasio A, et al. Celiac Diseases. Encyclopedia. Available at: https://encyclopedia.pub/entry/2805. Accessed April 20, 2024.
Di Liberto, Diana, Daniela Carlisi, Antonella D'anneo, Sonia Emanuele, Michela Giuliano, Anna De Blasio, Giuseppe Calvaruso, Marianna Lauricella. "Celiac Diseases" Encyclopedia, https://encyclopedia.pub/entry/2805 (accessed April 20, 2024).
Di Liberto, D., Carlisi, D., D'anneo, A., Emanuele, S., Giuliano, M., De Blasio, A., Calvaruso, G., & Lauricella, M. (2020, October 27). Celiac Diseases. In Encyclopedia. https://encyclopedia.pub/entry/2805
Di Liberto, Diana, et al. "Celiac Diseases." Encyclopedia. Web. 27 October, 2020.
Celiac Diseases
Edit
This entry is adapted from the peer-reviewed paper 10.3390/healthcare8040400

Celiac Disease (CD) is an immune-mediated disease triggered by the ingestion of gluten from wheat and other cereals, such as barley and rye. The gluten intake exerts toxic effects through several pathways involving gut barrier integrity, intestinal microbiota composition and immune system stimulation. Immunity against peptides generated by an incomplete gluten digestion is mediated by pro-inflammatory cytokines produced by both innate and adaptive system response in individuals unable to adequately digest them. A lifelong adherence to a gluten-free (GF) diet is currently the only treatment for CD. However, despite the great benefit of the GF diet for CD patients, the adherence to a GF diet determines nutritional deficiencies as well as the risk of an excessive intake of fats and carbohydrates. Therefore, it is necessary to integrate micronutrients and fibers, which are lacking in gluten free foods, as well as follow controlled dietary regimes. In this regard, it is very important to adjust and improve the formulations of GF products, in order to ensure the consumer a diet that is as balanced and tastier as possible.

Celiac disease autoimmune disease gluten gliadin glute-free diet

1. Introduction

Gluten is a complex molecule present in several grains, including wheat, rye an barley[1], consisting of glutenin polymers and gliadin monomers. Both glutenin and gliadin contain high percentage of prolines (20%) and glutamines (40%) protecting them from complete degradation in the gastrointestinal tract and resulting in their incomplete digestion[2].These undigested peptides have been demonstrated to play biological activities in gastrointestinal tracts, including increased gut permeability and cytotoxic and immunomodulatory effects[3].

Gluten ingestion is responsible for the development of Celiac Disease (CD), an autoimmune enteropathy activated in the lamina propria of the gut of genetically predisposed individuals[4] by gliadin peptides and resulting in the recruitment of infiltrating T lymphocytes producing Interferon-gamma (IFN-γ) and Interleukin-15 (IL-15). A typical feature observed in CD patients is malabsorption. This is a critical condition in CD pathogenesis resulting from the T-cell mediated damage of the intestinal mucosa and it is histologically represented by villous atrophy, crypt hyperplasia, and the infiltration of lymphoid cells both in the epithelium and in the lamina propria[5].The pathogenesis of CD is related to both genetic and environmental factors. Among genetic factors, major histocompatibility complex (MHC) class II, HLA DQ2 and DQ8, confer the greatest susceptibility to the disease, with a reported gene dosage effect according to which homozygous allotypes are associated to an increased risk[6][7]. In addition, among environmental factors, gastrointestinal dysbiosis seems to be associated to CD onset, consisting of an increased number of Proteobacteria and Bacteroidetes and a reduced number of Firmicutes, especially in the active phase of the disease[8].

The gluten intake exerts toxic effects through several pathways involving gut barrier integrity, intestinal microbiota composition and immune system stimulation. Experimental evidences showed that gliadin peptides are capable to trigger an adaptive immune response in CD patients, as demonstrated by the higher production of pro-inflammatory Th1/Th17 derived cytokines from intestinal biopsies of active CD patients when stimulated in vitro with gliadin[9]. In addition, peripheral blood mononuclear cells of CD patients produce Interleukin-1 β (IL-1β) and Interleukin-18 (IL-18) following their stimulation with gliadin[10]. Interleukin-15 (IL-15) is also up-regulated in the epithelium and the lamina propria of CD patients in the active phase[11]. To explain the toxic effect of gluten, it was hypothesized that, after gluten oral introduction, partially digested gliadin peptides, interacting with the small intestinal mucosa, may first activate an innate immune response. This is evidenced by the production of IL-8 by epithelial and lamina propria dendritic cells. IL-8, in turn, recruits neutrophils in situ amplifying the inflammatory process, whereas IL-15 induces enterocytes apoptosis[12]. Then, gliadin peptides, through the interaction with CXCR3 receptors present on the apical side of the epithelium, seem to trigger the release of zonulin, the regulator of the intestinal tight junctions, leading to an increase in intestinal permeability and consequent antigen trafficking that may cause autoimmune disorders[13][14]. As a consequence of the increased intestinal permeability, gliadin peptides may translocate into the lamina propria where they undergo to deamidation by transglutaminase 2[15]. This event has been shown to favor gliadin interaction with macrophages and dendritic cells of the submucosa[16], triggering an adaptive immune response with the production of increased pro-inflammatory cytokines such as IFN-γ, tumor necrosis factor-alpha (TNF-α) and IL-17[16], which damage the intestinal mucosa compromising its permeability[17].

2. Clinical Manifestations

Clinical manifestations of CD are mainly gastrointestinal symptoms, such as intermittent or chronic diarrhea, bloating and abdominal distension, colitis, flatulence, abdominal cramps, in association with malabsorption and consequent iron deficiency and weight loss. Extraintestinal symptoms are chronic fatigue, foggy mind, aphtous stomatitis, reduced bone density, growth retardation in children and short stature[18]. Beyond gastrointestinal symptoms, celiac patients can be affected by neurological and psychiatric disorders, including epilepsy, schizophrenia and Autistic Spectrum Disorder ASD [4]. Although the correlation between CD and ASD is supported by different clinical studies, the exact mechanism, on the basis of this correlation, remains unknown. Data presented in the literature correlating CD with ASD highlight how cereal-derived peptides produced in celiac patients cross the blood–brain barrier and bind to endogenous opioid receptors.  This effect could explain the defects in the brain maturation, attention, learning and public relations of autistic patients. Moreover, several clinical and in vitro studies supported the hypothesis that oxidative stress associated with gluten-related disorders can favor mitochondrial damage and neurological dysfunctions, which are involved in the pathogenesis of ASD[4].

3. Diagnosis

CD diagnosis is a multi-step process. First, patients are screened for serum IgA anti-tissue transglutaminase, if they have detectable IgA level[19], otherwise serum IgG anti-tissue transglutaminases are preferred. In addition, they can be screened for serum IgG anti-deamidated gliadin, an alternative test with an increased sensitivity and specificity[1], and anti-endomysium IgA, to confirm borderline results. Finally, a full-blown diagnosis requires small intestinal biopsy showing villous atrophy, an increased number of intraepithelial lymphocytes and elongated crypts[18].

4. Treatment

Currently, the only treatment of Celiac Disease is the complete elimination of gluten from diet, which leads to symptoms disappearance. The Gluten-free (GF) diet was introduced for the treatment for CD since 1941, as reported by the paediatrician Willem Karl Dicke[20]. However, despite the great benefit of GF diet for CD patients, its use has been debated. About 7–30% of CD patients do not fully improve after adopting a gluten-free (GF) diet. Therefore, alternative CD therapies are required, such as genetically modified gluten, inhibitors of zonulin and supplementary probiotics[5][21][22][23].

GF foods can be distinguished into those naturally GF, such as rice, corn, potatoes, some grains, seeds and legumes, and those that become GF after purification, a process that alters their macro-and micro-nutrient composition, as well as their nutritional values[24]. Gluten contained in wheat flours owns the unique ability to form aggregates, which are important for some products such as, bread, pasta and pretzels, whose production process requires a cohesive dough. Gluten is composed mostly of gliadin, the 70% ethanol-soluble protein fraction of wheat flour, and by glutenin and both contribute to the cohesiveness and to the elasticity of the dough[25]. Notably, wheat is not only a source of protein but also a food rich in micronutrients, including folate, iron, B vitamins (thiamine, riboflavin and niacin) and fibers. Therefore, a disadvantage in using a GF diet my result by the fact that often GF products have a lower amount of these components when compared to their gluten containing equivalents[26][27][28]. GF products have generally lower amounts of folate, iron, riboflavin, niacin and thiamine[29] and researchers in this field work to overcome these limits without altering their taste[30]. Furthermore, fibers are lost because they are mostly contained in the outer layer of grain which is eliminated during the refining process. Gluten replacing ingredients are starches, hydrocolloids, gluten-free flours of cereals/pseudocereals, proteins, enzymes and emulsifiers. These components are used in combination to improve rheological features of GF products, often leading to their substantial price increase[31]. Moreover, some GF products are foods richer in carbohydrates and lipids than their gluten containing equivalents[32], as for GF bread with a higher fat content and glycemic index and with a lower amount of proteins. The glycemic index of GF products changes according to the type and quality of contained ingredients and to the procedures used to obtain them[33].

Thus, the adherence to a GF diet is strictly necessary for celiac subjects. However, the use of a GF diet may imply disadvantages related to nutritional deficiencies and high carbohydrate and fat contents. Such a condition could be probably improved if manufacturers and health professional collaborated to continuously adjust and improve  the formulations and the processing techniques used in GF manufacturing, in order to ensure the consumer a diet that is as balanced and tastier as possible.

References

  1. Alessio Fasano; Carlo Catassi; Celiac Disease. New England Journal of Medicine 2012, 367, 2419-2426, 10.1056/nejmcp1113994.
  2. Hanne Skovbjerg; Claus Koch; Dorit Anthonsen; Hans Sjöström; Deamidation and cross-linking of gliadin peptides by transglutaminases and the relation to celiac disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2004, 1690, 220-230, 10.1016/j.bbadis.2004.06.009.
  3. Robert P. Anderson; Pilar Degano; Andrew J. Godkin; Derek P. Jewell; Adrian V.S. Hill; In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope. Nature Medicine 2000, 6, 337-342, 10.1038/73200.
  4. Diana Di Di Liberto; Antonella D’Anneo; Daniela Carlisi; Sonia Emanuele; Anna De Blasio; Giuseppe Calvaruso; Michela Giuliano; Marianna Lauricella; Brain Opioid Activity and Oxidative Injury: Different Molecular Scenarios Connecting Celiac Disease and Autistic Spectrum Disorder. Brain Sciences 2020, 10, 437, 10.3390/brainsci10070437.
  5. Luigi Maiuri; Carolina Ciacci; Ida Ricciardelli; Loredana Vacca; Valeria Raia; Antonio Rispo; Martin Griffin; Thomas Issekutz; Sonia Quaratino; Marco Londei; et al. Unexpected Role of Surface Transglutaminase Type II in Celiac Disease. Gastroenterology 2005, 129, 1400-1413, 10.1053/j.gastro.2005.07.054.
  6. Lionetti, E.; Castellaneta, S.; Francavilla, R.; Pulvirenti, A.; Tonutti, E.; Amarri, S.; Barbato, M.; Barbera, C.; Barera, G.; Bellantoni, A.; et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. Engl. J. Med. 2014, 371, 1295–1303, doi:10.1056/nejmoa1400697.
  7. Gutierrez-Achury, J.; Zhernakova, A.; Pulit, S.L.; Trynka, G.; Hunt, K.A.; Romanos, J.; Raychaudhuri, S.; Van Heel, D.A.; Wijmenga, C.; De Bakker, P. (Paul) Fine mapping in the MHC region accounts for 18% additional genetic risk for celiac disease. Genet. 2015, 47, 577–578, doi:10.1038/ng.3268.
  8. María Carmen Collado; Ester Donat; Carmen Ribes-Koninckx; Miguel Calabuig; Yolanda Sanz; Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease. Journal of Clinical Pathology 2008, 62, 264-269, 10.1136/jcp.2008.061366.
  9. Ainara Castellanos-Rubio; Izortze Santin; Inaki Irastorza; Luis Castaño; J. C. Vitoria; Jose Ramon Bilbao; TH17 (and TH1) signatures of intestinal biopsies of CD patients in response to gliadin. Autoimmunity 2009, 42, 69-73, 10.1080/08916930802350789.
  10. Lenka Palová-Jelínková; Klára Dáňová; Hana Drašarová; Miloš Dvořák; David P. Funda; Petra Fundová; Anna Kotrbová-Kozak; Marie Černá; Jana Kamanová; Stefan F. Martin; et al.Marina FreudenbergLudmila Tučková Pepsin Digest of Wheat Gliadin Fraction Increases Production of IL-1β via TLR4/MyD88/TRIF/MAPK/NF-κB Signaling Pathway and an NLRP3 Inflammasome Activation. PLOS ONE 2013, 8, e62426, 10.1371/journal.pone.0062426.
  11. Kristina M. Harris; Alessio Fasano; Dean L. Mann; Monocytes differentiated with IL-15 support Th17 and Th1 responses to wheat gliadin: Implications for celiac disease. Clinical Immunology 2010, 135, 430-439, 10.1016/j.clim.2010.01.003.
  12. Daniela De Nitto; Ivan Monteleone; Eleonora Franzè; Francesco Pallone; Giovanni Monteleone; Involvement of interleukin-15 and interleukin-21, two γ-chain-related cytokines, in celiac disease. World Journal of Gastroenterology 2009, 15, 4609-4614, 10.3748/wjg.15.4609.
  13. Lammers, K.M.; Lu, R.; Brownley, J.; Lu, B.; Gerard, C.; Thomas, K.; Rallabhandi, P.; Shea-Donohue, T.; Tamiz, A.; Alkan, S.; et al. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3. 2008, 135, 194–204.e3, doi:10.1053/j.gastro.2008.03.023.
  14. Fasano, A. Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity, and cancer. Rev. 2011, 91, 151–175, doi:10.1152/physrev.00003.2008.
  15. José Antonio Garrote; Emma Gómez-González; David Bernardo; Eduardo Arranz; Fernando Chirdo; Celiac Disease Pathogenesis: The Proinflammatory Cytokine Network. Journal of Pediatric Gastroenterology and Nutrition 2008, 47, S27-S32, 10.1097/mpg.0b013e3181818fb9.
  16. Karen E. Thomas; Anna Sapone; Alessio Fasano; Stefanie N. Vogel; Gliadin Stimulation of Murine Macrophage Inflammatory Gene Expression and Intestinal Permeability Are MyD88-Dependent: Role of the Innate Immune Response in Celiac Disease. The Journal of Immunology 2006, 176, 2512-2521, 10.4049/jimmunol.176.4.2512.
  17. Consuelo Ortega; Silvia Fernández; Orlando A. Estévez; Rocío Aguado; Ignacio J. Molina; Manuel Santamaria; IL-17 Producing T Cells in Celiac Disease: Angels or Devils?. International Reviews of Immunology 2013, 32, 534-543, 10.3109/08830185.2013.834898.
  18. Ciarán P. Kelly; Julio C. Bai; Edwin Liu; Daniel A. Leffler; Advances in Diagnosis and Management of Celiac Disease. Gastroenterology 2015, 148, 1175-1186, 10.1053/j.gastro.2015.01.044.
  19. Walburga Dieterich; Tobias Ehnis; Michael Bauer; Peter Donner; Umberto Volta; Ernst Otto Riecken; Detlef Schuppan; Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Medicine 1997, 3, 797-801, 10.1038/nm0797-797.
  20. G P Van Berge-Henegouwen; C J Mulder; Pioneer in the gluten free diet: Willem-Karel Dicke 1905-1962, over 50 years of gluten free diet.. Gut 1993, 34, 1473-1475, 10.1136/gut.34.11.1473.
  21. Fasano, A.; Not, T.; Wang, W.; Uzzau, S.; Berti, I.; Tommasini, A.; Goldblum, S.E. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 2000, 355, 1518–1519, doi:10.1016/s0140-6736(00)02169-3.
  22. Fasano, A. Surprises from celiac disease. Am. 2009, 301, 54–61, doi:10.1038/scientificamerican0809-54.
  23. Gianfrani, C.; Siciliano, R.A.; Facchiano, A.M.; Camarca, A.; Mazzeo, M.F.; Costantini, S.; Salvati, V.M.; Maurano, F.; Mazzarella, G.; Iaquinto, G.; et al. Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. Gastroenterology 2007, 133, 780–789, doi:10.1053/j.gastro.2007.06.023.
  24. 24. European Parliament Regulation (EU) No 609/2013 of the European Parliament and of the Council on food intended for infants and young children, food for special medical purposes, and total diet replacement for weight control. Off J Eur Union 2013, 2012, 35–56.
  25. Jan A. Delcour; Iris J. Joye; Bram Pareyt; Edith Wilderjans; Kristof Brijs; Bert Lagrain; Wheat Gluten Functionality as a Quality Determinant in Cereal-Based Food Products. Annual Review of Food Science and Technology 2012, 3, 469-492, 10.1146/annurev-food-022811-101303.
  26. Thompson, T. Thiamin, riboflavin, and niacin contents of the gluten-free diet: is there cause for concern? Am. Diet. Assoc. 1999, 99, 858–862, doi:10.1016/s0002-8223(99)00205-9.
  27. Thompson, T. Folate, iron, and dietary fiber contents of the gluten-free diet. Am. Diet. Assoc. 2000, 100, 1389–1396, doi:10.1016/s0002-8223(00)00386-2.
  28. Hallert, C.; Grant, C.; Grehn, S.; Granno, C.; Hulten, S.; Midhagen, G.; Strom, M.; Svensson, H.; Valdimarsson, T. Evidence of poor vitamin status in coeliac patients on a gluten-free diet for 10 years. Pharmacol. Ther. 2002, 16, 1333–1339, doi:10.1046/j.1365-2036.2002.01283.x.
  29. Francesco Valitutti; Donatella Iorfida; Caterina Anania; Chiara Maria Trovato; Monica Montuori; Salvatore Cucchiara; Carlo Catassi; Cereal Consumption among Subjects with Celiac Disease: A Snapshot for Nutritional Considerations. Nutrients 2017, 9, 396, 10.3390/nu9040396.
  30. D. Wild; G. G. Robins; V. J. Burley; P. D. Howdle; Evidence of high sugar intake, and low fibre and mineral intake, in the gluten-free diet. Alimentary Pharmacology & Therapeutics 2010, 32, 573-581, 10.1111/j.1365-2036.2010.04386.x.
  31. Núria Aguilar; Elena Albanell; Begoña Miñarro; Buenaventura Guamis; M. Capellas; Effect of tiger nut-derived products in gluten-free batter and bread. Food Science and Technology International 2014, 21, 323-331, 10.1177/1082013214535615.
  32. María Estela Matos Segura; Cristina M. Rosell; Chemical Composition and Starch Digestibility of Different Gluten-free Breads. Plant Foods for Human Nutrition 2011, 66, 224-230, 10.1007/s11130-011-0244-2.
  33. Natalia Manzatti Machado Alencar; Elisa Carvalho Morais; Caroline Joy Steel; Helena Maria André Bolini; Sensory characterisation of gluten-free bread with addition of quinoa, amaranth flour and sweeteners as an alternative for coeliac patients. International Journal of Food Science & Technology 2016, 52, 872-879, 10.1111/ijfs.13349.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Pathology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Diana Di Liberto
,
Daniela Carlisi
,
Antonella D'Anneo
,
Sonia Emanuele
,
Michela Giuliano
,
Anna De Blasio
,
Giuseppe Calvaruso
,
Marianna Lauricella
View Times: 467
Revisions: 2 times (View History)
Update Date: 29 Oct 2020
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback