Viral infections during early infancy, pregnancy and type 1 diabetes risk

Populærvitenskapelig framstilling - English version Norway is one of the countries with the highest incidence of the type 1 diabetes, which is a common, chronic autoimmune disease that usually manifests in childhood. There is a broad consensus that type 1 diabetes has a genetic and environmental component with several known genetic risk factors. However, there are currently no known environmental risk factors for type 1 diabetes. This project is investigating the hypothesis that viral infections can act as triggers or accelerators of type 1 diabetes, using samples from the MIDIA study, which has followed children with regular samples and questionnaires from 3 months of age. Although we have chosen the most promising viral candidates as targets for study, it is also of great importance to test for currently unknown viruses as there is the possibility that any virus involved in the development of type 1 diabetes is currently undiscovered. Thus, viruses involved in the development of type 1 diabetes may be difficult to detect with traditional methods, and it must be noted that it has been technically (and practically) unfeasible to test for all possible viruses. This project has currently been working on testing the samples for several known candidate viruses, such as rotavirus and saffold virus. This project has tested if there is any association between the presence of Rotavirus, Saffold Virus and Astrovirus in stool samples and development of islet autoimmunity, which is the sub-clinical precursor t o type 1 diabetes. These results are being prepared for publication in international peer-reviewed scientific journals. In addition, blood samples are also being studied for viruses such as those mentioned above and other candidate viruses, such as human parechovirus. Recent advances in sequencing technology has also made it possible to screen for many, possibly all, viruses present in a sample and ascertain large part of their genomic sequence. Our close collaborator, Dr. Ondrej Cinek and his team, has s ucceeded in developing a sequencing protocol for testing the MIDIA samples and the project will hopefully soon be able to implement this new technology. Populærvitenskapelig framstilling - Norsk versjon Norge er et av landene med høyest forekomst av type 1 diabetes. Type 1 diabetes er en kronisk autoimmun sykdom som oppstår når kroppens immunforsvar angriper insulin-produserende beta-celler i bukspyttkjertelen. Det er kjente genetiske faktorer til sykdommen, men disse kan ikke alene forklare hvordan sykdommen utvikler seg. Det finnes per dags dato ingen kjente miljøfaktorer for type 1 diabetes, men virusinfeksjoner er en av kandidatene som har sterkest støtte. Dette prosjektet has om mål å undersøke om virusinfeksjoner i tidlig barndom og i mors liv kan være involvert i utviklingen av type 1 diabetes. Prosjektet er et underprosjekt i MIDIA-studien, som har fulgt barn fra 3 måneders alder med jevnlige prøver og spørreskjemaer. Etter utvikling av type 1 diabetes og/eller autoimmunitet mot øyceller, som er det første trinnet i sykdomsutviklingen, kan man gå tilbake og se hvilke infeksjoner som skjedde før sykdommen begynte å utvikle seg. Det må merkes at ukjente virus kan også være involvert, noe som gjør at nye teknikker må utvikles for å kunne måle di sse i prøver. Dette prosjektet har undersøkt om tilstedeværelsen av Rotavirus, Saffold Virus, Astrovirus og andre virus i avføringsprøver har en sammenheng med utviklingen av autoimmunitet mot øyceller, det første trinnet i utviklingen av type 1 diabetes. Disse resultatene skal snart publiseres i internasjonale vitenskapelige tidsskrift. Blodprøver blir også undersøkt, mot virusene nevnt over og andre virus som f.eks humant parechovirus. Prosjektet samarbeider tett sammen med forskere som har utviklet en metode som gjør det i teorien mulig å finne alle virusene tilstede i en prøve, og forhåpentligvis så blir denne nye teknikken for å undersøke prøver brukt i nærmeste framtid.

Type 1 diabetes (T1D) is a common autoimmune disease that mainly affects children and adolescents. Genetic factors contribute about 40% of the risk, but cannot explain the rising incidence or geographical differences of T1D, which must be attributed to un known environmental factors. The MIDIA project, which aims to discover these environmental factors, has recruited infants with high genetic risk for T1D and follows these with questionnaires, stool- and blood samples. Viruses are good candidates for envir onmental factors, as there are animal models of T1D that show both protection and higher risk by viral infections and certain viruses have been found to be more common in recent onset T1D patients. Also the lack of infections or maternal antibodies in ear ly infancy might be associated with development of autoimmunity. In this project we have already investigated in a nested case control 27 children who developed islet autoimmunity and 54 matched controls, and found a higher prevalence of human parechoviru s infections just before the onset of islet autoimmunity. The main goal of this project is to investigate the association between viral infections in early childhood or in pregnancy and T1D. The objectives are to test stool samples from children and blood samples from mothers for viruses and provide new data regarding what role they play in T1D. We want to investigate further our positive findings in a bigger material, and see if other viruses play a role in the development of autoimmunity. The main chall enges will be developing assays that are sensitive and specific enough for this purpose and the high amount of testing involved. The new knowledge may ultimately be used to devise prevention strategies, which will be of high value even if they prevent a f raction of the cases or delay the onset of T1D.