Potential Celiac Patients A Model of Celiac Disease Pathogenesis 英文参考文献.docVIP

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Potential Celiac Patients A Model of Celiac Disease Pathogenesis 英文参考文献.doc

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Potential Celiac Patients A Model of Celiac Disease Pathogenesis 英文参考文献

PotentialCeliacPatients:AModelofCeliacDisease Pathogenesis MariaPiaSperandeo1,AntonellaTosco1,ValentinaIzzo1,FrancescaTucci1,RiccardoTroncone1 ,Renata Auricchio1,JihaneRomanos2,GosiaTrynka2,SalvatoreAuricchio1,BanaJabri3,LuigiGreco4* 1European Laboratory for Food Induced Disease, University of Naples Federico II, Naples, Italy, 2Department of Genetics, University Medical Centre of Groningen, UniversityofGroningen,Groningen,TheNetherlands,3DepartmentofMedicine,DepartmentofPathologyandDepartmentofPaediatrics,UniversityofChicago,Chicago, Illinois,UnitedStatesofAmerica,4DepartmentofPediatrics,UniversityofNaplesFedericoII,Naples,Italy Abstract BackgroundandAim:Potentialceliacshavethe‘celiactype’HLA,positiveanti-transglutaminaseantibodiesbutnodamage atsmallintestinalmucosa.Onlyaminorityofthemdevelopsmucosallesion.Morethan40geneswereassociatedtoCeliac Disease(CD)butwestilldonotknowhowthosepathwaystransformageneticallypredisposedindividualintoanaffected person.TheaimofthestudyistoexplorethegeneticfeaturesofPotentialCDindividuals. Methods:127‘potential’CDpatientsenteredthestudybecauseofpositiveanti-tissuetransglutaminaseandnomucosal lesions;about30%ofthosefollowedforfouryearsbecomefranklyceliac.Theyweregenotypedfor13polymorphismsof ‘candidategenes’andcomparedtocontrolsandceliacs.Moreover,60biopsyspecimenswereusedforexpressionstudies. Results:PotentialCDbearalighterHLA-relatedrisk,comparedtoceliac(x2=48.42;pvalue=161028).Theysharemostof thepolymorphismsoftheceliacs,butthefrequencyofc-REL*Gallelewassuggestiveforadifferencecomparedtoceliac (x2=5.42; p value=0.02). One marker of the KIAA1109/IL-2/IL-21 candidate region differentiated potentials from celiac (rs4374642:x2=7.17,pvalue=0.01).TheexpressionofIL-21wascompletelysuppressedinpotentialscomparedtoceliacs (pvalue=0.02)andtocontrols(pvalue=0.02),incontrastIL-2,KIAA1109andc-RELexpressionwereover-expressed. Conclusions: Potential CD show genetic features slightly different from celiacs. Genetic and expression markers help to