1,333
Views
15
CrossRef citations to date
0
Altmetric
Review

The Gluten Gene: Unlocking the Understanding of Gluten Sensitivity and Intolerance

ORCID Icon, , & ORCID Icon
Pages 37-50 | Published online: 11 Feb 2021

References

  • Shiferaw B, Smale M, Braun H-J, et al. Crops that feed the world 10. Past successes and future challenges to the role played by wheat in global food security. Food Secur. 2013;5(3):291–317. doi:10.1007/s12571-013-0263-y
  • Utebayev M, Dashkevich S, Bome N, et al. Genetic diversity of gliadin-coding alleles in bread wheat (Triticum aestivum L.) from Northern Kazakhstan. PeerJ. 2019;7:e7082. doi:10.7717/peerj.7082
  • Bell G. The History of Wheat Cultivation. Wheat Breeding. Springer; 1987:31–49.
  • Wang D, Li F, Cao S, Zhang K. Genomic and functional genomics analyses of gluten proteins and prospect for simultaneous improvement of end-use and health-related traits in wheat. Theor Appl Genet. 2020;133(5):1521–1539. doi:10.1007/s00122-020-03557-5
  • Liaqat N, Liaqat A, Ali M, et al. Chapter 24 - Wheat genomics and genome editing. In: Ozturk M, Gul A, editors. Climate Change and Food Security with Emphasis on Wheat. Academic Press; 2020:331–346.
  • Rostami K, Malekzadeh R, Shahbazkhani B, et al. Coeliac disease in Middle Eastern countries: a challenge for the evolutionary history of this complex disorder? Dig Liver Dis. 2004;36(10):694–697. doi:10.1016/j.dld.2004.05.010
  • Huo N, Zhu T, Altenbach S, et al. Dynamic evolution of α-gliadin prolamin gene family in homeologous genomes of hexaploid wheat. Sci Rep. 2018;8(1):5181. doi:10.1038/s41598-018-23570-5
  • Metakovsky E, Melnik V, Rodriguez-Quijano M, et al. A catalog of gliadin alleles: polymorphism of 20th-century common wheat germplasm. Crop J. 2018;6(6):628–641. doi:10.1016/j.cj.2018.02.003
  • Altenbach SB, Kothari KM, Lieu D. Environmental conditions during wheat grain development alter temporal regulation of major gluten protein genes. Cereal Chem J. 2002;79(2):279–285. doi:10.1094/CCHEM.2002.79.2.279
  • Shewry PR, Hey SJ. The contribution of wheat to human diet and health. Food Energy Secur. 2015;4(3):178–202. doi:10.1002/fes3.64
  • Shewry P. What is gluten-why is it special? Front Nutr. 2019;6:101. doi:10.3389/fnut.2019.00101
  • Islam S, Yu Z, She M, et al. Wheat gluten protein and its impacts on wheat processing quality. Front Agric Sci Eng. 2019;6(3):279–287. doi:10.15302/J-FASE-2019267
  • Kumar P, Yadava R, Gollen B, et al. Nutritional contents and medicinal properties of wheat: a review. Life Sci Med Res. 2011;22:1–10.
  • Wieser H. Chemistry of gluten proteins. Food Microbiol. 2007;24:115–119. doi:10.1016/j.fm.2006.07.004
  • Jouanin A, Boyd L, Visser RGF, Smulders MJM. Development of wheat with hypoimmunogenic gluten obstructed by the gene editing policy in Europe. Front Plant Sci. 2018;9:1523. doi:10.3389/fpls.2018.01523
  • Freeman HJ. Celiac Disease☆. Reference Module in Biomedical Sciences. Elsevier; 2017.
  • Pasha I, Saeed F, Sultan MT, et al. Wheat allergy and intolerance; recent updates and perspectives. Crit Rev Food Sci Nutr. 2016;56(1):13–24. doi:10.1080/10408398.2012.659818
  • Barak S, Mudgil D, Khatkar BS. Influence of gliadin and glutenin fractions on rheological, pasting, and textural properties of dough. Int J Food Prop. 2014;17(7):1428–1438. doi:10.1080/10942912.2012.717154
  • Biesiekierski JR. What is gluten? J Gastroenterol Hepatol. 2017;32(S1):78–81. doi:10.1111/jgh.13703
  • Kajendran K, Chandrasekharan NV, Hettiarachchi CM, Sulochana Wijesundera WS. Molecular characterization and expression of α-gliadin genes from wheat cultivar Dacke in Bg 250 rice variety. GM Crops Food. 2019;10(2):102–114. doi:10.1080/21645698.2019.1622990
  • Tian N, Leffler DA, Kelly CP, et al. Despite sequence homologies to gluten, salivary proline-rich proteins do not elicit immune responses central to the pathogenesis of celiac disease. Am J Physiol Gastrointest Liver Physiol. 2015;309(11):G910–G917. doi:10.1152/ajpgi.00157.2015
  • Kumar J, Kumar M, Pandey R, Chauhan NS. Physiopathology and management of gluten-induced celiac disease. J Food Sci. 2017;82(2):270–277. doi:10.1111/1750-3841.13612
  • Phiarais BPN, Arendt EK. 15 - Malting and brewing with gluten-free cereals. In: Arendt EK, Dal Bello F, editors. Gluten-Free Cereal Products and Beverages. San Diego: Academic Press; 2008:347–372.
  • Sharma N, Bhatia S, Chunduri V, et al. Pathogenesis of celiac disease and other gluten related disorders in wheat and strategies for mitigating them. Front Nutr. 2020;7.
  • Cabanillas B. Gluten-related disorders: celiac disease, wheat allergy, and nonceliac gluten sensitivity. Crit Rev Food Sci Nutr. 2020;60(15):2606–2621. doi:10.1080/10408398.2019.1651689
  • Lammers KM, Herrera MG, Dodero VI. Translational chemistry meets gluten-related disorders. ChemistryOpen. 2018;7(3):217–232. doi:10.1002/open.201700197
  • Rostami Nejad M, Karkhane M, Marzban A, et al. Gluten related disorders. Gastroenterol Hepatol Bed Bench. 2012;5(Suppl 1):S1–S7.
  • Czerwińska K, Czerwiński G, Poniewierka E, et al. Spectrum of gluten-related disorders: celiac disease, wheat allergy, baker’s asthma and non-celiac gluten sensitivity. World Sci News. 2018;100:154–164.
  • Tanner G, Juhász A, Florides CG, et al. Preparation and characterization of avenin-enriched oat protein by chill precipitation for feeding trials in celiac disease. Front Nutr. 2019;6(162). doi:10.3389/fnut.2019.00162.
  • Spector Cohen I, Day AS, Shaoul R. To be oats or not to be? An update on the ongoing debate on oats for patients with celiac disease. Front Pediatr. 2019;7:384. doi:10.3389/fped.2019.00384
  • Hollén E, Holmgren Peterson K, Sundqvist T, et al. Coeliac children on a gluten-free diet with or without oats display equal anti-avenin antibody titres. Scand J Gastroenterol. 2006;41(1):42–47. doi:10.1080/00365520510023945
  • Haboubi NY, Taylor S, Jones S. Coeliac disease and oats: a systematic review. Postgrad Med J. 2006;82(972):672–678. doi:10.1136/pgmj.2006.045443
  • Hardy MY, Tye-Din JA, Stewart JA, et al. Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides. J Autoimmun. 2015;56:56–65.
  • Balakireva AV, Zamyatnin AA. Properties of gluten intolerance: gluten structure, evolution, pathogenicity and detoxification capabilities. Nutrients. 2016;8(10):644. doi:10.3390/nu8100644
  • Békés F, Gianibelli MC, Wrigley CW. The gluten proteins of the wheat grain in relation to flour quality. In: Wrigley C, Corke H, Seetharaman K, Faubion J, editors. Encyclopedia of Food Grains (Second Edition). Oxford: Academic Press; 2016:375–383.
  • Shewry PR, Halford NG, Lafiandra D. Genetics of wheat gluten proteins. In: Hall JC, Dunlap JC, Friedmann T, editors. Advances in Genetics. Vol. 49. Academic Press; 2003:111–184.
  • Zaefizadeh M, Jamaati-e-Somarin S, Ojaghi J, et al. Genetic diversity for gliadin patterns of durum wheat landraces in the Northwest of Iran and Azerbaijan. Pesquisa Agropecuária Brasileira. 2010;45(12):1425–1432. doi:10.1590/S0100-204X2010001200013
  • Wang D-W, Li D, Wang J, et al. Genome-wide analysis of complex wheat gliadins, the dominant carriers of celiac disease epitopes. Sci Rep. 2017;7(1):44609. doi:10.1038/srep44609
  • Žilić S. Wheat Gluten: Composition and Health Effects. Nova Science Publishers, lnc. 2013:71–86.
  • Dubois B, Bertin P, Mingeot D. Molecular diversity of α-gliadin expressed genes in genetically contrasted spelt (Triticum aestivum ssp. spelta) accessions and comparison with bread wheat (T. aestivum ssp. aestivum) and related diploid Triticum and Aegilops species. Mol Breed. 2016;36(11):152. doi:10.1007/s11032-016-0569-5
  • Gianibelli M, Larroque O, Macritchie F, Wrigley C. Biochemical, genetic, and molecular characterization of wheat endosperm proteins. Cereal Chem Rev. 2001;78(6):635–646. doi:10.1094/CCHEM.2001.78.6.635
  • Li Y, Xin R, Zhang D, Li S. Molecular characterization of α-gliadin genes from common wheat cultivar Zhengmai 004 and their role in quality and celiac disease. Crop J. 2014;2(1):10–21. doi:10.1016/j.cj.2013.11.003
  • Harberd N, Bartels D, Thompson R. Analysis of the gliadin multigene loci in bread wheat using nullisomic-tetrasomic lines. Mol Gen Genet. 1985;198(2):234–242. doi:10.1007/BF00383001
  • Anderson O, Litts J, Greene F. The α-gliadin gene family. I. Characterization of ten new wheat α-gliadin genomic clones, evidence for limited sequence conservation of flanking DNA, and southern analysis of the gene family. Theor Appl Genet. 1997;95(1–2):50–58. doi:10.1007/s001220050531
  • Okita T, Cheesbrough V, Reeves CD. Evolution and heterogeneity of the alpha-/beta-type and gamma-type gliadin DNA sequences. J Biol Chem. 1985;260(13):8203–8213. doi:10.1016/S0021-9258(17)39582-0
  • Ozuna CV, Iehisa JC, Giménez MJ, et al. Diversification of the celiac disease α-gliadin complex in wheat: a 33-mer peptide with six overlapping epitopes, evolved following polyploidization. Plant J. 2015;82(5):794–805. doi:10.1111/tpj.12851
  • 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):41ra51. doi:10.1126/scitranslmed.3001012
  • Rasheed F, Plivelic TS, Kuktaite R, et al. Unraveling the structural puzzle of the giant glutenin polymer-an interplay between protein polymerization, nanomorphology, and functional properties in bioplastic films. ACS Omega. 2018;3(5):5584–5592. doi:10.1021/acsomega.7b02081
  • Fu BX, Sapirstein HD. Procedure for isolating monomeric proteins and polymeric glutenin of wheat flour. Cereal Chem J. 1996;73(1):143–152.
  • Dangi P, Khatkar BS. Extraction and purification of low molecular weight glutenin subunits using size exclusion chromatography. J Food Sci Technol. 2019;56(2):951–956. doi:10.1007/s13197-018-03560-1
  • Wang Y, Zhen S, Luo N, et al. Low molecular weight glutenin subunit gene Glu-B3h confers superior dough strength and breadmaking quality in wheat (Triticum aestivum L.). Sci Rep. 2016;6(1):27182. doi:10.1038/srep27182
  • Liu L, Ikeda TM, Branlard G, et al. Comparison of low molecular weight glutenin subunits identified by SDS-PAGE, 2-DE, MALDI-TOF-MS and PCR in common wheat. BMC Plant Biol. 2010;10:124. doi:10.1186/1471-2229-10-124
  • Wang Z, Huang L, Wu B, et al. Characterization of an integrated active Glu-1Ay allele in common wheat from wild emmer and its potential role in flour improvement. Int J Mol Sci. 2018;19(4):923.
  • Anjum FM, Khan MR, Din A, et al. Wheat gluten: high molecular weight glutenin subunits—structure, genetics, and relation to dough elasticity. J Food Sci. 2007;72(3):R56–R63. doi:10.1111/j.1750-3841.2007.00292.x
  • Wang Z, Li Y, Yang Y, et al. New insight into the function of wheat glutenin proteins as investigated with two series of genetic mutants. Sci Rep. 2017;7(1):3428. doi:10.1038/s41598-017-03393-6
  • Wang D, Zhang K, Dong L, et al. Molecular genetic and genomic analysis of wheat milling and end-use traits in China: progress and perspectives. Crop J. 2018;6(1):68–81. doi:10.1016/j.cj.2017.10.001
  • Caminero A, McCarville JL, Galipeau HJ, et al. Duodenal bacterial proteolytic activity determines sensitivity to dietary antigen through protease-activated receptor-2. Nat Commun. 2019;10(1):1198. doi:10.1038/s41467-019-09037-9
  • Dubé C, Rostom A, Sy R, et al. The prevalence of celiac disease in average-risk and at-risk Western European populations: a systematic review. Gastroenterology. 2005;128(4 Suppl 1):S57–S67. doi:10.1053/j.gastro.2005.02.014
  • Taraghikhah N, Ashtari S, Asri N, et al. An updated overview of spectrum of gluten-related disorders: clinical and diagnostic aspects. BMC Gastroenterol. 2020;20(1):258. doi:10.1186/s12876-020-01390-0
  • Yoosuf S, Makharia GK. Evolving therapy for celiac disease. Front Pediatr. 2019;7:193. doi:10.3389/fped.2019.00193
  • Asri N, Rostami-Nejad M. The facts of celiac disease; a comprehensive review. Int J Celiac Dis. 2019;7(2):48–52.
  • Asri N, Rostami-Nejad M, Barzegar M, et al. Suppressive mechanisms induced by tregs in celiac disease. Iran Biomed J. 2020;24(3):140–147. doi:10.29252/ibj.24.3.140
  • Kårhus LL, Thuesen BH, Skaaby T, et al. The distribution of HLA DQ2 and DQ8 haplotypes and their association with health indicators in a general Danish population. United European Gastroenterol J. 2018;6(6):866–878. doi:10.1177/2050640618765506
  • Tye-Din JA, Daveson AJM, Goldstein KE, et al. Patient factors influencing acute gluten reactions and cytokine release in treated coeliac disease. BMC Med. 2020;18(1):362. doi:10.1186/s12916-020-01828-y
  • Sharma A, Liu X, Hadley D, et al. Identification of non-HLA genes associated with celiac disease and Country-specific differences in a large, international pediatric Cohort. PLoS One. 2016;11:e0152476. doi:10.1371/journal.pone.0152476
  • Sarno M, Discepolo V, Troncone R, Auricchio R. Risk factors for celiac disease. Ital J Pediatr. 2015;41:57. doi:10.1186/s13052-015-0166-y
  • Henderson KN, Tye-Din JA, Reid HH, et al. A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease. Immunity. 2007;27(1):23–34. doi:10.1016/j.immuni.2007.05.015
  • Sollid LM, Tye-Din JA, Qiao SW, et al. Update 2020: nomenclature and listing of celiac disease-relevant gluten epitopes recognized by CD4(+) T cells. Immunogenetics. 2020;72(1–2):85–88. doi:10.1007/s00251-019-01141-w
  • Shan L, Molberg Ø, Parrot I, et al. Structural basis for gluten intolerance in celiac sprue. Science (New York, NY). 2002;297(5590):2275–2279. doi:10.1126/science.1074129
  • Koning F. Adverse effects of wheat gluten. Ann Nutr Metab. 2015;67(Suppl. 2):7–14. doi:10.1159/000440989
  • Sollid LM, Qiao S-W, Anderson RP, et al. Nomenclature and listing of celiac disease relevant gluten T-cell epitopes restricted by HLA-DQ molecules. Immunogenetics. 2012;64(6):455–460. doi:10.1007/s00251-012-0599-z
  • Dahal-Koirala S, Risnes LF, Christophersen A, et al. TCR sequencing of single cells reactive to DQ2.5-glia-α2 and DQ2.5-glia-ω2 reveals clonal expansion and epitope-specific V-gene usage. Mucosal Immunol. 2016;9(3):587–596. doi:10.1038/mi.2015.147
  • Cebolla Á, Moreno M, Coto L, Sousa C. Gluten Immunogenic peptides as standard for the evaluation of potential harmful prolamin content in food and human specimen. Nutrients. 2018;10(12):1927. doi:10.3390/nu10121927
  • Li D, Jin H, Zhang K, et al. Analysis of the Gli-D2 locus identifies a genetic target for simultaneously improving the breadmaking and health-related traits of common wheat. Plant J. 2018;95(3):414–426. doi:10.1111/tpj.13956
  • Schalk K, Lang C, Wieser H, Koehler P, Scherf KA. Quantitation of the immunodominant 33-mer peptide from α-gliadin in wheat flours by liquid chromatography tandem mass spectrometry. Sci Rep. 2017;7(1):45092. doi:10.1038/srep45092
  • Zhou L, Kooy-Winkelaar YMC, Cordfunke RA, et al. Abrogation of immunogenic properties of gliadin peptides through transamidation by microbial transglutaminase Is Acyl-acceptor dependent. J Agric Food Chem. 2017;65(34):7542–7552. doi:10.1021/acs.jafc.7b02557
  • Bonciani D, Verdelli A, Bonciolini V, et al. Dermatitis herpetiformis: from the genetics to the development of skin lesions. Clin Dev Immunol. 2012;2012:239691. doi:10.1155/2012/239691
  • Skovbjerg H, Koch C, Anthonsen D, Sjöström H. Deamidation and cross-linking of gliadin peptides by transglutaminases and the relation to celiac disease. Biochim Biophys Acta Mol Basis Dis. 2004;1690(3):220–230. doi:10.1016/j.bbadis.2004.06.009
  • Quarsten H, Molberg O, Fugger L, McAdam SN, Sollid LM. HLA binding and T cell recognition of a tissue transglutaminase-modified gliadin epitope. Eur J Immunol. 1999;29(8):2506–2514. doi:10.1002/(SICI)1521-4141(199908)29:08<2506::AID-IMMU2506>3.0.CO;2-9
  • Anderson RP, Degano P, Godkin AJ, Jewell DP, Hill AV. 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(3):337–342. doi:10.1038/73200
  • Molberg O, McAdam SN, Körner R, et al. Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease. Nat Med. 1998;4(6):713–717. doi:10.1038/nm0698-713
  • Arentz-Hansen H, Körner R, Molberg O, et al. The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase. J Exp Med. 2000;191(4):603–612. doi:10.1084/jem.191.4.603
  • Goel G, Tye-Din JA, Qiao S-W, et al. Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Sci Adv. 2019;5(8):eaaw7756. doi:10.1126/sciadv.aaw7756
  • Kooy-Winkelaar YMC, Bouwer D, Janssen GMC, et al. CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes. Proc Natl Acad Sci. 2017;114(6):E980–E989. doi:10.1073/pnas.1620036114
  • Ciccocioppo R, Di Sabatino A, Corazza GR. The immune recognition of gluten in coeliac disease. Clin Exp Immunol. 2005;140(3):408–416. doi:10.1111/j.1365-2249.2005.02783.x
  • Gianfrani C, Auricchio S, Troncone R. Adaptive and innate immune responses in celiac disease. Immunol Lett. 2005;99(2):141–145. doi:10.1016/j.imlet.2005.02.017
  • van de Wal Y, Kooy YM, van Veelen P, et al. Glutenin is involved in the gluten-driven mucosal T cell response. Eur J Immunol. 1999;29(10):3133–3139. doi:10.1002/(SICI)1521-4141(199910)29:10<3133::AID-IMMU3133>3.0.CO;2-G
  • Barone MV, 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. 2014;15(11):20518–20537. doi:10.3390/ijms151120518
  • Abadie V, Jabri B. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev. 2014;260(1):221–234. doi:10.1111/imr.12191
  • Hardy MY, Tye-Din JA. Coeliac disease: a unique model for investigating broken tolerance in autoimmunity. Clin Transl Immunol. 2016;5(11):e112. doi:10.1038/cti.2016.58
  • Abadie V, Kim SM, Lejeune T, et al. IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease. Nature. 2020;578(7796):600–604. doi:10.1038/s41586-020-2003-8
  • Dickson BC, Streutker CJ, Chetty R. Coeliac disease: an update for pathologists. J Clin Pathol. 2006;59(10):1008–1016. doi:10.1136/jcp.2005.035345
  • Clarindo MV, Possebon AT, Soligo EM, et al. Dermatitis herpetiformis: pathophysiology, clinical presentation, diagnosis and treatment. An Bras Dermatol. 2014;89(6):865–877. doi:10.1590/abd1806-4841.20142966
  • Allardyce RA, Shearman DJ. Leukocyte reactivity to alpha-gliadin in dermatitis herpetiformis and adult coeliac disease. Int Arch Allergy Appl Immunol. 1975;48(3):395–400. doi:10.1159/000231324
  • Clark Huff J, Weston WL, Zirker DK. Wheat protein antibodies in dermatitis herpetiformis. J Invest Dermatol. 1979;73(6):570–574. doi:10.1111/1523-1747.ep12541611
  • Catassi C, Fasano A. 1 - Celiac disease. In: Arendt EK, Dal Bello F, editors. Gluten-Free Cereal Products and Beverages. San Diego: Academic Press; 2008:1.
  • Cianferoni A. Wheat allergy: diagnosis and management. J Asthma Allergy. 2016;9:13. doi:10.2147/JAA.S81550
  • Ricci G, Andreozzi L, Cipriani F, et al. Wheat allergy in children: a comprehensive update. Medicina. 2019;55(7):400. doi:10.3390/medicina55070400
  • Koehler P, Wieser H, Konitzer K. Chapter 1 - Celiac Disease—A Complex Disorder. In: Koehler P, Wieser H, Konitzer K, editors. Celiac Disease and Gluten. Boston: Academic Press; 2014:1–96.
  • Scherf K, Brockow K, Biedermann T, et al. Wheat-dependent exercise-induced anaphylaxis. Clin Exp Allergy. 2015;46.
  • De Santis MA, Giuliani MM, Giuzio L, et al. Differences in gluten protein composition between old and modern durum wheat genotypes in relation to 20th century breeding in Italy. Eur J Agron. 2017;87:19–29. doi:10.1016/j.eja.2017.04.003
  • Hofmann S, Fischer J, Eriksson C, et al. IgE detection to α/β/γ-gliadin and its clinical relevance in wheat-dependent exercise-induced anaphylaxis. Allergy. 2012;67:1457–1460. doi:10.1111/all.12020
  • Morita E, Matsuo H, Mihara S, et al. Fast ω-gliadin is a major allergen in wheat-dependent exercise-induced anaphylaxis. J Dermatol Sci. 2003;33(2):99–104. doi:10.1016/s0923-1811(03)00156-7
  • Palosuo K, Alenius H, Varjonen E, Kalkkinen N, Reunala T. Rye γ-70 and γ-35 secalins and barley γ-3 hordein cross-react with ω-5 gliadin, a major allergen in wheat-dependent, exercise-induced anaphylaxis. Clin Exp Allergy. 2001;31(3):466–473. doi:10.1046/j.1365-2222.2001.01023.x
  • Kennard L, Thomas I, Rutkowski K, et al. A multicenter evaluation of diagnosis and management of omega-5 gliadin allergy (Also known as wheat-dependent exercise-induced anaphylaxis) in 132 adults. J Allergy Clin Immunol Pract. 2018;6(6):1892–1897. doi:10.1016/j.jaip.2018.02.013
  • Sandiford CP, Tatham AS, Fido R, et al. Identification of the major water/salt insoluble wheat proteins involved in cereal hypersensitivity. Clin Exp Allergy. 1997;27(10):1120–1129. doi:10.1111/j.1365-2222.1997.tb01148.x
  • Baar A, Pahr S, Constantin C, et al. Molecular and immunological characterization of Tri a 36, a low molecular weight glutenin, as a novel major wheat food allergen. J Immunol. 2012;189:3018–3025. doi:10.4049/jimmunol.1200438
  • Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. 2012;18(5):693–704. doi:10.1038/nm.2755
  • Volta U, Caio G, Tovoli F, De Giorgio R. Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness. Cell Mol Immunol. 2013;10(5):383–392. doi:10.1038/cmi.2013.28
  • Rostami K, Hogg-Kollars S. A patient’s journey. non-coeliac gluten sensitivity. BMJ. 2012;345:e7982. doi:10.1136/bmj.e7982
  • Rostami-Nejad M, Lahmi F, Zali M. Non-celiac Gluten Sensitivity. J Army Univ Med Sci. 2013;11:243–251.
  • Catassi C, Alaedini A, Bojarski C, et al. The overlapping area of non-celiac gluten sensitivity (NCGS) and wheat-sensitive irritable bowel syndrome (IBS): an update. Nutrients. 2017;9(11):1268. doi:10.3390/nu9111268
  • Ierardi E, Losurdo G, Piscitelli D, et al. Biological markers for non-celiac gluten sensitivity: a question awaiting for a convincing answer. Gastroenterol Hepatol Bed Bench. 2018;11(3):203–208.
  • Losurdo G, Piscitelli D, Pezzuto F, et al. T helper lymphocyte and mast cell immunohistochemical pattern in nonceliac gluten sensitivity. Gastroenterol Res Pract. 2017;2017:5023680. doi:10.1155/2017/5023680
  • Sapone A, Lammers KM, Casolaro V, et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med. 2011;9(1):23. doi:10.1186/1741-7015-9-23
  • Barbaro MR, Cremon C, Stanghellini V, Barbara G. Recent advances in understanding non-celiac gluten sensitivity. F1000Res. 2018;7:F1000Faculty Rev–1631. doi:10.12688/f1000research.15849.1
  • Catassi C, Elli L, Bonaz B, et al. Diagnosis of non-celiac gluten sensitivity (NCGS): the Salerno experts’ criteria. Nutrients. 2015;7(6):4966–4977. doi:10.3390/nu7064966
  • Ortiz C, Valenzuela R, Lucero AY. [Celiac disease, non celiac gluten sensitivity and wheat allergy: comparison of 3 different diseases triggered by the same food]. [Spanish]. Rev Chil Pediatr. 2017;88(3):417–423. doi:10.4067/S0370-41062017000300017
  • Tye-Din JA, Skodje GI, Sarna VK, et al. Cytokine release after gluten ingestion differentiates coeliac disease from self-reported gluten sensitivity. United European Gastroenterol J. 2020;8(1):108–118. doi:10.1177/2050640619874173
  • Uhde M, Caio G, De Giorgio R, et al. Subclass profile of IgG antibody response to gluten differentiates nonceliac gluten sensitivity from celiac disease. Gastroenterology. 2020;159(5):1965–1967.e2. doi:10.1053/j.gastro.2020.07.032
  • Vojdani A, Perlmutter D. Differentiation between celiac disease, nonceliac gluten sensitivity, and their overlapping with Crohn’s disease: a case series. Case Rep Immunol. 2013;2013:248482. doi:10.1155/2013/248482
  • Skodje GI, Sarna VK, Minelle IH, et al. Fructan, rather than gluten, induces symptoms in patients with self-reported non-celiac gluten sensitivity. Gastroenterology. 2018;154(3):529–539.e522. doi:10.1053/j.gastro.2017.10.040
  • Daveson AJM, Tye-Din JA, Goel G, et al. Masked bolus gluten challenge low in FODMAPs implicates nausea and vomiting as key symptoms associated with immune activation in treated coeliac disease. Aliment Pharmacol Ther. 2020;51(2):244–252. doi:10.1111/apt.15551
  • El Khoury D, Balfour-Ducharme S, Joye IJ. A review on the gluten-free diet: technological and nutritional challenges. Nutrients. 2018;10(10):1410. doi:10.3390/nu10101410
  • Rostami K, Bold J, Parr A, Johnson MW. Gluten-free diet indications, safety, quality, labels, and challenges. Nutrients. 2017;9(8):846. doi:10.3390/nu9080846
  • Jouanin A, Gilissen LJWJ, Schaart JG, et al. CRISPR/Cas9 gene editing of gluten in wheat to reduce gluten content and exposure-reviewing methods to screen for coeliac safety. Front Nutr. 2020;7:51. doi:10.3389/fnut.2020.00051
  • Jouanin A, Schaart JG, Boyd LA, et al. Outlook for coeliac disease patients: towards bread wheat with hypoimmunogenic gluten by gene editing of α- and γ-gliadin gene families. BMC Plant Biol. 2019;19(1):333. doi:10.1186/s12870-019-1889-5
  • Borisjuk N, Kishchenko O, Eliby S, et al. Genetic modification for wheat improvement: from transgenesis to genome editing. Biomed Res Int. 2019;2019:6216304. doi:10.1155/2019/6216304
  • Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects. Signal Transduct Target Ther. 2020;5(1):1.
  • Wang K, Riaz B, Ye X. Wheat genome editing expedited by efficient transformation techniques: progress and perspectives. Crop J. 2018;6(1):22–31. doi:10.1016/j.cj.2017.09.009
  • Vasil V, Castillo AM, Fromm ME, Vasil IK. Herbicide resistant fertile transgenic wheat plants obtained by microprojectile bombardment of regenerable embryogenic callus. Bio/Technology. 1992;10(6):667–674.
  • Agrawal N, Dasaradhi PVN, Mohmmed A, et al. RNA interference: biology, mechanism, and applications. Microbiol Mol Biol Rev. 2003;67(4):657–685. doi:10.1128/MMBR.67.4.657-685.2003
  • Tenea G, Burlibasa L. RNAi Towards Functional Genomics Studies. InTech Publisher. 2012:67–94.
  • Ansari WA, Chandanshive SU, Bhatt V, et al. Genome editing in cereals: approaches, applications and challenges. Int J Mol Sci. 2020;21(11):4040. doi:10.3390/ijms21114040
  • Travella S, Klimm TE, Keller B. RNA interference-based gene Silencing as an efficient tool for functional genomics in hexaploid bread wheat. Plant Physiol. 2006;142(1):6–20. doi:10.1104/pp.106.084517
  • Gil-Humanes J, Pistón F, Altamirano-Fortoul R, et al. Reduced-gliadin wheat bread: an alternative to the gluten-free diet for consumers suffering gluten-related pathologies. PLoS One. 2014;9(3):e90898. doi:10.1371/journal.pone.0090898
  • Altenbach SB, Tanaka CK, Seabourn BW. Silencing of omega-5 gliadins in transgenic wheat eliminates a major source of environmental variability and improves dough mixing properties of flour. BMC Plant Biol. 2014;14(1):393. doi:10.1186/s12870-014-0393-1
  • Altenbach SB, Chang H-C, Rowe MH, et al. Reducing the immunogenic potential of wheat flour: silencing of alpha gliadin genes in a U.S. wheat cultivar. Front Plant Sci. 2020;11(20). doi:10.3389/fpls.2020.00020.
  • Barro F, Iehisa J, Gimenez M, et al. Targeting of prolamins by RNAi in bread wheat: effectiveness of seven silencing-fragment combinations for obtaining lines devoid of coeliac disease epitopes from highly immunogenic gliadins. Plant Biotechnol J. 2015;14. doi:10.1111/pbi.12455
  • Ervin E-H, Pook M, Teino I, et al. Targeted gene silencing in human embryonic stem cells using cell-penetrating peptide PepFect 14. Stem Cell Res Ther. 2019;10(1):43. doi:10.1186/s13287-019-1144-x
  • Gaj T, Gersbach CA, Barbas CF 3rd ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397–405. doi:10.1016/j.tibtech.2013.04.004
  • Deshpande K, Vyas A, Balakrishnan A, Vyas D. Clustered regularly interspaced short palindromic Repeats/Cas9 genetic engineering: robotic genetic surgery. Am J Robot Surg. 2015;2(1):49–52. doi:10.1166/ajrs.2015.1023
  • Campenhout CV, Cabochette P, Veillard A-C, et al. Guidelines for optimized gene knockout using CRISPR/Cas9. BioTechniques. 2019;66(6):295–302. doi:10.2144/btn-2018-0187
  • Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014;157(6):1262–1278. doi:10.1016/j.cell.2014.05.010
  • Shan Q, Wang Y, Li J, et al. Targeted genome modification of crop plants using a CRISPR-Cas system. Nat Biotechnol. 2013;31(8):686–688. doi:10.1038/nbt.2650
  • Sánchez-León S, Gil-Humanes J, Ozuna CV, et al. Low-gluten, nontransgenic wheat engineered with CRISPR/Cas9. Plant Biotechnol J. 2018;16(4):902–910. doi:10.1111/pbi.12837
  • Jouanin A, Borm T, Boyd LA, et al. Development of the GlutEnSeq capture system for sequencing gluten gene families in hexaploid bread wheat with deletions or mutations induced by γ-irradiation or CRISPR/Cas9. J Cereal Sci. 2019;88:157–166. doi:10.1016/j.jcs.2019.04.008
  • Purnhagen K, Wesseler J. EU regulation of new plant breeding technologies and their possible economic implications for the EU and beyond. Appl Econ Perspect Policy. 2020:1–17.