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Antibodies to oat prolamines (avenins) in children with coeliac disease
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
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2003 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, Vol. 38, no 7, 742-746 p.Article in journal (Refereed) Published
Abstract [en]

Background: The use of oats in a gluten-free diet for children with coeliac disease is presently under investigation. In this study we measured the content of antibodies to oat prolamines (avenin) in sera from coeliac children and reference children.

Methods: Crude avenin was prepared by extraction with ethanol and salt-solution and used as antigen in a three-step ELISA. Sera from 81 children, including 34 children with verified coeliac disease, were analysed for both IgA and IgG antibodies to avenin and gliadin. Sera were also incubated with gliadin before exposure to avenin, and vice versa, to assess a possible cross-reaction between the species. Keyhole limpet hemocyanin (KLH) was used as a negative control.

Results: Children with coeliac disease on a normal diet had significantly higher levels of antibodies to avenin, both IgG and IgA, than reference children ( P < 0.001) and the levels correlated positively with gliadin antibodies, especially of IgA-type ( r = 0.798). Both anti-avenin and anti-gliadin antibodies were only absorbed by the corresponding protein.

Conclusions: Children with coeliac disease have antibodies to oat proteins at significantly higher levels than reference children. The absorption test did not indicate a cross-reactivity between the prolamines of wheat and oats. The method will be employed for repeated sampling of anti-avenin antibodies during a prospective interventional study with a gluten-free diet supplemented with oats.

Place, publisher, year, edition, pages
2003. Vol. 38, no 7, 742-746 p.
Keyword [en]
Anti-avenin Antibodies, Coeliac Disease, Oats
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14131DOI: 10.1080/00365520310003156OAI: oai:DiVA.org:liu-14131DiVA: diva2:22687
Available from: 2006-11-06 Created: 2006-11-06 Last updated: 2009-08-18
In thesis
1. Coeliac Disease in Childhood: On the Intestinal Mucosa and the Use of Oats
Open this publication in new window or tab >>Coeliac Disease in Childhood: On the Intestinal Mucosa and the Use of Oats
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [sv]

Celiaki, eller glutenintolerans, är en av våra vanligaste kroniska sjukdomar i barnaåren. Sjukdomen orsakar en kraftig inflammation i tunntarmens slemhinna efter intag av glutenhaltig föda hos personer med ärftlig benägenhet att utveckla celiaki. En frisk tarm är kraftigt veckad för att öka ytan för upptag av näringsämnen. Ytan består dessutom av åtskilliga fingerliknande utskott, s.k. villi, och mellan villi finns kryptorna där celldelning och celldifferentiering sker. Villi och kryptor kantas av epitelceller, enterocyter, vilkas uppgift är att ta upp näring från tarminnehållet samt att utgöra en selektiv barriär mellan den yttre och inre miljön i tarmen. Den typiska tarmskadan vid celiaki karakteriseras av avsaknad av villi och kraftigt förlängda kryptor, och både näringsupptaget och barriärfunktionen är dessutom störda. Den enda behandling som finns att tillgå vid celiaki är en livslång glutenfri diet. De skadliga proteinerna i vetegluten kallas gliadin, och det finns liknande proteiner i råg, korn, och havre. I havre kallas proteinet avenin. Möjligheten att använda havre vid celiaki har diskuterats flitigt, men numera anses det riskfritt för majoriteten av både barn och vuxna att använda havre i den glutenfria dieten.

Målet med den här avhandlingen var att undersöka hur barn med celiaki reagerar på havre i kosten. Detta studerades med avseende på antikroppar mot avenin samt med en metod som mäter halten av kväveoxid- (NO-) produkter i urinen. Ett andra mål var att studera tunntarmens struktur vid olika stadier av celiaki.

I den första studien undersökte vi om celiakibarn har antikroppar i serum mot avenin. Vi fann att så var fallet och att nivåerna var signifikant högre än hos friska kontrollbarn. När barnen sattes på glutenfri kost sjönk antikroppsnivåerna, för att öka igen när gluten återinfördes i kosten. Blodproverna till den här studien togs innan debatten om havre kom igång, vilket gör att vi tror att de olika dieterna även speglar ett sant intag av havre. Studien visade också att det inte var någon korsreaktion mellan antikroppar mot avenin och gliadin.

Vi använde sedan vår metod för att mäta antikroppar mot avenin i en randomiserad studie där havre gavs till barn med nydiagnostiserad celiaki. Barnen fick antingen en vanlig glutenfri diet eller en med tillsats av specialhavre. Antikroppsnivåerna sjönk markant redan efter tre månader i båda grupperna, och vid studietidens slut, efter ca ett år, hade alla utom ett par patienter återfått normala nivåer. Samma barn studerades även med avseende på NO-produkter i urinen. NO är en kortlivad molekyl som fungerar som budbärare i och mellan celler, och produktionen av den ökar markant vid en inflammation. Tidigare studier har visat att barn med obehandlad celiaki har extremt höga halter av NO-produkter i urinen. I vår studie sjönk även dessa värden signifikant efter tre månader, och det var ingen skillnad mellan grupperna. Efter ett år hade dock fyra barn i havregruppen och ett barn i den grupp som fick vanlig glutenfri kost, fortfarande extremt höga nivåer av NO-produkter.

Dessa båda studier styrker den kliniska uppfattningen att de flesta barn med celiaki kan tåla havre, men de visar också att man bör följa upp de celiakibarn som kompletterar sin glutenfria kost med havre eftersom vissa barn verkar ha kvarstående tecken på inflammation i tarmen.

I tarmbiopsier från barn med olika stadier av celiaki studerades förekomst och lokalisering av occludin och claudiner, proteiner som är viktiga för att upprätthålla barriärfunktionen i tarmen. Vi fann ett ökat uttryck av occludin vid obehandlad celiaki, vilket vi tror speglar den ökade celldelning och de förändrade barriäregenskaper som man ser vid aktiv celiaki. Resultaten tyder även på att uttrycket av claudin 1-5 inte tycks påverkas av kosten hos barn med celiaki.

Abstract [en]

Coeliac disease (CD) is one of our most common chronic diseases in childhood. The disease causes an intense inflammation in the small intestinal mucosa after ingestion of gluten-containing cereals in genetically predisposed individuals. The mucosal lesion in CD is characterised by villous atrophy and crypt hyperplasia, and both the absorptive and the barrier functions of the enterocytes are disturbed. The treatment of CD is a life-long adherence to a gluten-free diet (GFD). The toxic fraction of wheat gluten is gliadin, and there are similar proteins in rye, barley and oats. In oats this protein is called avenin, and it is proposed to be less toxic than the others. The use of oats in CD has been debated, but it is now considered safe for the majority of both children and adults with CD.

The aims of this thesis were to investigate the humoral and inflammatory reactions to oats in children with CD, and also to study the intestinal mucosa at different stages of the disease.

In a retrospective study we found that children with CD had antibodies to oats avenin, and that the levels were significantly higher than in controls. The levels attenuated during GFD, and we also showed that there was no crossreactivity between antibodies to oats and gliadin.

We then used our method for measuring antibodies to avenin in a randomised, double-blind trial of oats given to children with newly diagnosed CD. The children were given either a traditional GFD or a GFD supplemented with oats. There was a rapid decrease in antibody levels in both groups already after three months on diet, and at the end of the study period all but a few had normalised their levels. The same children were also studied using urinary nitric oxide (NO) products as markers for intestinal inflammation. Likewise, these values decreased significantly after three months. At the end of the study four children in the GFD-oats group and one in the standard GFD group still had extremely high concentrations of urinary NO metabolites. Taken together, these studies strengthen the clinical impression that oats can be tolerated by the majority of children with CD, but they also warrant a caution, since there seem to be children that do not tolerate oats in their diet.

The structure and distribution of occludin and claudins 1-5, tight junction proteins known to play a crucial role in maintaining the barrier function, was studied in biopsy specimens from children at different stages of CD. There was an increased expression of occludin in untreated CD, which reflects the characteristics of crypt cell hyperplasia and altered barrier properties seen in active CD. The findings also indicate that gluten intake does not significantly influence the expression and distribution of claudins 1-5 in coeliac children.

Place, publisher, year, edition, pages
Institutionen för molekylär och klinisk medicin, 2006
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 965
Keyword
celiaki, havre, avenin, anti-aveninantikroppar, NO, tight junctions, occludin, claudin
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-7690 (URN)91-85643-60-2 (ISBN)
Public defence
2006-11-23, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2006-11-06 Created: 2006-11-06 Last updated: 2009-02-26

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Hollén, ElisabetHögberg, LottaStenhammar, LarsFälth-Magnusson, KarinMagnusson, Karl-Eric

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