The Association Between Viral Infections, IgE Sensitization, and type 1 Diabetes

Abstract

Allergiset taudit ovat nopeasti yleistyneet kehittyneissä maissa. Samanaikaisesti myös useiden autoimmuunitautien, kuten tyypin 1 diabeteksen, esiintyvyys on lisääntynyt. Mahdollisen selityksen tarjoaa ”Hygienia hypoteesi”, jonka mukaan vähentynyt varhaislapsuuden aikainen mikrobialtistus ei riittävästi stimuloi kehittyvää immuunijärjestelmää, minkä seurauksena esiintyy lisääntyvässä määrin allergiaa ja autoimmuunitauteja. Tutkimuksen tavoitteena oli selvittää allergisen herkistymisen ja mikrobialtistusten välisiä yhteyksiä Suomessa ja Venäjän Karjalassa, sekä lisäksi tutkia allergisen herkistymisen ja tyypin 1 diabeteksen välisiä yhteyksiä.

Allerginen herkistyminen osoittautui Suomessa selvästi yleisemmäksi kuin Venäjän Karjalassa. Toisaalta vasta-aineet mikrobeja vastaan olivat Venäjän Karjalassa selvästi yleisempiä kuin Suomessa. Venäjän Karjalassa mikrobivasta-aineiden ja allergisen herkistymisen välillä oli lisäksi todettavissa käänteinen yhteys, joka oli voimakkain enteroviruksen kohdalla. Eri enterovirustyyppien välillä todettiin lisäksi eroavuuksia; erityisesti Echovirus 11 liittyi alhaiseen allergisen herkistymisen esiintymiseen. Allergisen herkistymisen todettiin lisääntyneen Suomessa vuosien 1983 ja 2001 välillä ja tämä ilmiö oli yhteydessä Helicobacter pylori -vasta-aineiden esiintyvyyteen. Tyypin 1 diabeteksen ja allergisen herkistymisen välillä todettiin yhteys Venäjän Karjalassa.

Tulokset viittaavat siihen, että ympäristötekijöillä on suuri merkitys allergisessa herkistymisessä. Mikrobeille altistuminen näyttää olevan yksi tärkeä ympäristötekijä.

During the past decades, the prevalence of allergic diseases has rapidly increased in developed countries. Simultaneously, the prevalence of autoimmune diseases such as type 1 diabetes has also increased.

Epidemiological data suggests that having older siblings or growing up in a farm environment is linked to a lower risk of allergic disorders. The reasons for these relationships remain unknown, but one possible explanation is 'the hygiene hypothesis'. Accordingly, the microbial stimulus to immune cells is hypothesised to guide the maturation of immune responses.

The hypothesis of this study was that diminished exposure to microbes in childhood can lead to impaired maturation of the regulatory elements of the immune system and impaired control of immune responses. This, in turn, leads to overwhelming inflammatory responses resulting in autoimmune and allergic diseases.

This study was carried out in two populations that lived close to each other – i.e. in Finland and Russian Karelia –and shared a similar genetic background, but were characterized by a conspicuous difference, for example, in their degree of affluence and their childhood microbial exposure. The prevalence of IgE mediated allergic sensitization and IgG antibodies against certain infective agents was studied in both populations. In addition, a possible association between type 1 diabetes and IgE sensitization was evaluated.

The prevalence of IgE mediated allergic sensitization as well as its association with infections were studied among 266 schoolchildren in the Oulu region of Finland and 266 schoolchildren in the Karelian Republic in Russia. In addition, 147 type 1 diabetic patients in Finland and 132 type 1 diabetic patients in Russian Karelia were included in the study. The association between type 1 diabetes and IgE mediated allergic sensitization was investigated among these diabetic children and healthy controls in both countries.

In addition, time trends in allergic sensitization and H. pylori infections were compared by analysing altogether 958 blood samples drawn from Finnish pregnant women in 1983, 1989, 1995 and 2001. The prevalence of IgE sensitization was significantly higher in Finland compared to Russian Karelia, whereas microbial antibodies were more frequent in Russian Karelia. Furthermore, infections were associated with a lower risk of allergic sensitization in Russian Karelia, enterovirus showing the strongest protective effect. Differences between enterovirus types were observed when associations of allergic sensitization and enteroviruses were analysed in more detail.

A clear birth cohort effect was found in the prevalence of IgE mediated allergic sensitization in Finland, IgE sensitization being more frequent in recent birth cohorts than earlier ones. The prevalence of H. pylori antibodies, in turn, followed the opposite trend. A positive association was observed between type 1 diabetes and IgE sensitization in Russian Karelia. Furthermore, the co-occurrence of type 1 diabetes and IgE sensitization in Russian Karelia was associated with a lack of antibodies against the hepatitis A virus. Taken together, results imply that environmental factors strongly contribute to the development of allergic diseases. Yet, the mechanisms affecting the development of IgE sensitization may differ in populations characterized by different standards of hygiene. Exposure to microbes seems to be important environmental factor, and it is possible that some microbe-specific effects are involved.