Editing Gluten (section)

===Pathophysiological research===

The gluten [[peptide]]s are responsible for triggering gluten-related disorders.<ref name=LammersHerrera2018 /> In people who have celiac disease, the peptides trigger an immune response that causes injury of the intestines, ranging from [[inflammation]] to partial or total destruction of the [[intestinal villus|intestinal villi]].<ref name=DicksonStreutker2006>{{cite journal| vauthors=Dickson BC, Streutker CJ, Chetty R| title=Coeliac disease: an update for pathologists | journal=J Clin Pathol | year= 2006 | volume= 59 | issue= 10 | pages= 1008–16 | pmid=17021129 | doi=10.1136/jcp.2005.035345 | pmc=1861744 | type=Review }}</ref><ref name=StovenMurray2013 /> To study mechanisms of this damage, laboratory experiments are done ''in vitro'' and ''in vivo''.<ref name=KupferJabri2012>{{cite journal| vauthors=Kupfer SS, Jabri B| title=Pathophysiology of celiac disease | journal=Gastrointest Endosc Clin N Am | year= 2012 | volume= 22 | issue= 4 | pages= 639–60 | pmid=23083984 | doi=10.1016/j.giec.2012.07.003 | pmc=3872820 |type=Review }}</ref><ref name=StovenMurray2013>{{cite journal| vauthors=Stoven S, Murray JA, Marietta EV| title=Latest in vitro and in vivo models of celiac disease | journal=Expert Opin Drug Discov | year= 2013 | volume= 8 | issue= 4 | pages= 445–57 | pmid=23293929 | doi=10.1517/17460441.2013.761203 | pmc=3605231 |type=Review }}</ref> Among the gluten peptides, [[gliadin]] has been studied extensively.<ref name=LammersHerrera2018 />

====''In vitro'' and ''in vivo'' studies====
In the context of celiac disease, [[Gliadin|gliadin peptides]] are classified in [[basic research|basic]] and [[clinical research]] as  [[Immunogenicity|immunogenic]], depending on their [[mechanism of action]]:<ref name=LammersHerrera2018>{{cite journal| vauthors=Lammers KM, Herrera MG, Dodero VI| title=Translational Chemistry Meets Gluten-Related Disorders | journal=ChemistryOpen | year= 2018 | volume= 7 | issue= 3 | pages= 217–232 | pmid=29531885 | doi=10.1002/open.201700197 | pmc=5838388 | type=Review }}</ref><ref name=SilanoVincentini2009>{{cite journal| vauthors=Silano M, Vincentini O, De Vincenzi M| title=Toxic, immunostimulatory and antagonist gluten peptides in celiac disease | journal=Curr Med Chem | year= 2009 | volume= 16 | issue= 12 | pages= 1489–98 | pmid=19355902 | type=Review | doi=10.2174/092986709787909613 }}</ref>

* The peptides are those capable of directly affecting cells and intestinal preparations ''in vitro'', producing cellular damage ''in vivo'' and eliciting the innate immune response.<ref name=LammersHerrera2018 /><ref name=SilanoVincentini2009 /> ''In vitro'', the peptides promote cell [[apoptosis]] (a form of [[programmed cell death]]) and inhibit the synthesis of [[nucleic acid]]s (DNA and RNA) and proteins, reducing the viability of cells.<ref name=ElliRoncoroni2015 /> Experiments ''in vivo'' with normal mice showed that they cause an increase in cell death and the production of [[interferon type I]] (an inflammatory mediator).<ref name=LammersHerrera2018 />  ''In vitro'', gluten alters cellular [[morphology (biology)|morphology]] and [[motility]], [[cytoskeleton]] organization, [[redox|oxidative balance]], and [[tight junction]]s.<ref name=Fasano2011>{{cite journal | author = Fasano A | date = Jan 2011 | title = Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer | journal = Physiol. Rev. | volume = 91 | issue = 1| pages = 151–75 | doi = 10.1152/physrev.00003.2008 | pmid = 21248165 | type = Review| citeseerx = 10.1.1.653.3967 | quote= There are at least 50 toxic epitopes in gluten peptides exerting cytotoxic, immunomodulatory, and gut-permeating activities. }}</ref><ref name=ElliRoncoroni2015>{{cite journal| vauthors=Elli L, Roncoroni L, Bardella MT| title=Non-celiac gluten sensitivity: Time for sifting the grain | journal=World J Gastroenterol | year= 2015 | volume= 21 | issue= 27 | pages= 8221–6 | pmid=26217073 | doi=10.3748/wjg.v21.i27.8221 | pmc=4507091 | type=Review | doi-access=free }}</ref><ref name=LeonardSapone2017 />
* The immunogenic peptides are those able to activate [[T cell]]s ''in vitro''.<ref name=LammersHerrera2018 />

At least 50 [[epitope]]s of gluten may produce cytotoxic, immunomodulatory, and [[intestinal permeability|gut-permeating]] activities.<ref name=Fasano2011 />

The effect of oat peptides (avenins) in celiac people depends on the oat [[cultivar]] consumed because of prolamin genes, protein amino acid sequences, and the immunotoxicity of prolamins which vary among oat varieties.<ref name=PenaginiDilillo>{{cite journal | vauthors = Penagini F, Dilillo D, Meneghin F, Mameli C, Fabiano V, Zuccotti GV| title = Gluten-free diet in children: an approach to a nutritionally adequate and balanced diet | journal = Nutrients | volume = 5| issue = 11| pages = 4553–65| date = Nov 18, 2013| pmid = 24253052|pmc= 3847748| doi = 10.3390/nu5114553| type=Review| doi-access = free }}</ref><ref name=DeSouzaDeschenes2016>{{cite journal| vauthors=de Souza MC, Deschênes ME, Laurencelle S, Godet P, Roy CC, Djilali-Saiah I| title=Pure Oats as Part of the Canadian Gluten-Free Diet in Celiac Disease: The Need to Revisit the Issue | journal=Can J Gastroenterol Hepatol | year= 2016 | volume= 2016 | pages= 1–8 | pmid=27446824 | doi=10.1155/2016/1576360 | pmc=4904650 | type= Review | doi-access=free }}</ref><ref name=CominoMoreno2015>{{cite journal | vauthors = Comino I, Moreno Mde L, Sousa C | title = Role of oats in celiac disease | journal = World J Gastroenterol | volume = 21 | issue = 41 | pages = 11825–31 | date = Nov 7, 2015 | pmid = 26557006 |pmc= 4631980 | doi = 10.3748/wjg.v21.i41.11825 |quote= It is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet. | doi-access = free }}</ref> In addition, oat products may be cross-contaminated with the other gluten-containing [[cereal]]s.<ref name="DeSouzaDeschenes2016"/>