Development of coeliac disease in two populations with different environmental backgrounds

dc.contributor.advisorUibo, Raivo, juhendaja
dc.contributor.advisorUibo, Oivi, juhendaja
dc.contributor.advisorTillmann, Vallo, juhendaja
dc.contributor.authorSimre, Kärt
dc.contributor.otherTartu Ülikool. Meditsiiniteaduste valdkondet
dc.date.accessioned2023-06-29T07:30:27Z
dc.date.available2023-06-29T07:30:27Z
dc.date.issued2023-06-29
dc.descriptionVäitekirja elektrooniline versioon ei sisalda publikatsiooneet
dc.description.abstractTsöliaakia on immuunvahendatud haigus, mis tekib geneetilise eelsoodumusega isikutel gluteeni ja gluteeniga seotud prolamiinide toimel. Tsöliaakiat võivad vallandada nisuvalgu gluteeni laguprodukt gliadiin, rukkivalk sekaliin ja odravalk hordeiin. Viimastel aastakümnetel on tsöliaakia esinemissagedus suurenenud ülemaailmselt ning erinevate piirkondade vahel võib esineda suuri erinevusi. Kuna enamikel inimestel, kellel esineb geneetiline eelsoodumus tsöliaakia tekkeks ning on olnud kokkupuude gluteeniga, ei teki haigust, siis peavad haiguse tekkega olema seotud ka erinevad keskkondlikud tegurid. Doktoritöö peamine eesmärk oli uurida lapseea tsöliaakia teket kahes erineva sotsiaalmajandusliku tasutaga naaberriigis – Eestis ja Soomes ning uurida täpsemalt tsöliaakia erinevaid riskifaktoreid. Peamine huvi oli imikuea ja väikelapse toitumisel ja infektsioonidel. Lisaks rinnapiima mikrobioota määramine ning selle seos rinnapiima immunoloogiliste markeritega. Uuritavad ja uuringumaterjal pärinesid rahvusvahelisest DIABIMMUNE uuringust, mille eesmärgiks oli uurida 1. tüüpi diabeedi ja teiste immuunvahendatud haiguste teket. Uuring koosnes nn sünnikohordist, keda jälgiti sünnist 3. eluaastani ja nn lastekohordist, keda jälgiti 3. eluaastast 5. eluaastani. Eestis tekkis uuringuperioodi jooksul tsöliaakia kaheksal ja Soomes 21 lapsel, kes kõik kaasati käesolevasse uuringusse. Igale tsöliaakia diagnoosiga lapsele valiti kontrollgrupi laps samast DIABIMMUNE uuringust. Rinnapiima analüüsideks valiti nn sünnikohordist kuus last, keda oli jälgitud 3. eluaastani ning kelle kõigi emadelt oli kogutud rinnapiim lapse 3. elukuul ja lastel oli tekkinud tsöliaakia. 18 kontrolli valiti samast kohordist. Leidsime, et Eesti ja Soome laste vahel esines oluline erinevus tsöliaakia kumulatiivses haigestumises esimese viie eluaasta jooksul. Tsöliaakia kumulatiivne haigestumine on kõrgem Soomes (0,27% vs 0,77%) ning seal tekivad lastel varem ka tsöliaakia spetsiifilised autoantikehad. Tsöliaakiaga ning kontrollgrupi laste vahel ei olnud erinevust rinnapiimaga toitmise kestvuses ega teraviljade (nisu, rukkis, oder) menüüsse lisamise vanuses. Korduvad infektsioonid varajases eas võivad suurendada riski haigestuda tsöliaakiasse. Emadel, kelle lastel tekkis tsöliaakia, oli rinnapiima mikrobioomis erinevusi võrreldes emadega, kelle lastel tsöliaakiat ei tekkinud.et
dc.description.abstractCoeliac disease (CD) is a dietary gluten and gluten-related prolamines induced immune-mediated systemic disorder that occurs in genetically predisposed people. “Gluten” is a general term for alcohol-soluble proteins present in various cereals (wheat, barley and rye). In recent decades the prevalence of CD has increased worldwide and there can be marked differences between countries. It is known that most people with the genetic risk for CD and exposure to gluten do not develop CD, so different environmental factors must be involved. The general aim of the present thesis was to clarify the development of CD in two paediatric populations with different socio-economic backgrounds, Estonia and Finland, and to find out the role of different risk factors in this process. Paying special attention to early feeding and infections. In addition, to characterize the microbiota composition of the breast milk and its possible relationship with immunological markers. The study is based on the data and biomaterials collected during the international prospective observational DIABIMMUNE Study, which set out to assess the role of the hygiene hypothesis in the development of type 1 diabetes and other immune-mediated diseases. The study included two cohorts: a birth cohort (BC) observed from birth up to the age of 3 years and a cohort of young children (YCC) examined for the first time at the age of 3 years and followed up to the age of 5 years. During the study period 29 children developed CD: eight Estonian and 21 Finnish children. The control children were selected from the BC or YCC of the DIABIMMUNE Study. For breast milk sample analyses, six children of the BC were selected. 18 control children were selected from the BC. We found that there is a significant difference in the 5-year cumulative incidence of childhood CD between Estonia and Finland, which is higher in the latter country (0.27% vs 0.77%). The children from Finland tended to develop IgA-tTG antibodies earlier than the children from Estonia. No difference was seen in the age at cereal introduction or in the duration of breastfeeding between the children with CD and the control children. Sequential infections early in life may increase the risk for developing CD. The breast milk microbiota of the mothers of children who developed CD differed in terms of higher bacterial phylotype abundance and diversity, as well as in relation to bacterial composition when compared to the mothers of the unaffected children.en
dc.description.urihttps://www.ester.ee/record=b5561159et
dc.identifier.isbn978-9916-27-235-0
dc.identifier.isbn978-9916-27-236-7 (pdf)
dc.identifier.issn1024-395X
dc.identifier.issn2806-240X (pdf)
dc.identifier.urihttps://hdl.handle.net/10062/91138
dc.language.isoenget
dc.relation.ispartofseriesDissertationes medicinae Universitatis Tartuensis;347
dc.rightsopenAccesset
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectgluten-sensitive enteropathyen
dc.subjectpopulation geneticsen
dc.subjectchildrenen
dc.subjectbreast milken
dc.subjectantibodiesen
dc.subjectvirus diseasesen
dc.subjectEstoniaen
dc.subjectFinlanden
dc.subject.otherdissertatsioonidet
dc.subject.otherETDet
dc.subject.otherdissertationset
dc.subject.otherväitekirjadet
dc.subject.othertsöliaakiaet
dc.subject.otherpopulatsioonigeneetikaet
dc.subject.otherlapsedet
dc.subject.otherrinnapiimet
dc.subject.otherantikehadet
dc.subject.otherviirushaigusedet
dc.subject.otherEesti (riik)et
dc.subject.otherSoome (riik)et
dc.titleDevelopment of coeliac disease in two populations with different environmental backgroundset
dc.title.alternativeTsöliaakia teke kahes erineva keskkonna-taustaga naaberriigiset
dc.typeThesiset

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