Relationship between the incidence of type 1 diabetes and maternal enterovirus antibodies: time trends and geographical variation

Abstract

Aims/hypothesis: We have previously observed an inverse correlation between the incidence of type 1 diabetes and enterovirus infections in the background population. The aim of this study was to analyse whether maternal enterovirus antibody status, which reflects both the frequency of enterovirus infections and the protection conferred by the mother on the offspring, also correlates with the incidence of type 1 diabetes. Methods: Maternal enterovirus antibodies were analysed from serum samples taken from pregnant women between 1983 and 2001 in Finland and Sweden using enzyme immunoassay and neutralisation assays. Comparable samples were also taken between 1999 and 2001 in countries with a lower incidence of diabetes (Estonia, Germany, Hungary, Israel, Lithuania, Russia). Results: A clear decrease was observed in maternal enterovirus antibody levels over the past 20 years (p<0.0001). The frequency of enterovirus antibodies was higher in countries with a low or intermediate incidence of type 1 diabetes compared with high-incidence countries (p<0.0001). Conclusions/interpretation: These findings are in line with our previous observations supporting the hypothesis that a low frequency of enterovirus infection in the background population increases the susceptibility of young children to the diabetogenic effect of enteroviruses.

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

“…First, as an indication of a declining 'herd immunity' to enteroviruses, maternal antibody levels have decreased in many European countries over the past 20 years [20]. Second, the frequency of maternal antibodies to different enteroviruses is higher in countries with a low or intermediate incidence of type 1 diabetes than in countries with a high incidence of the disease [20], suggesting a relationship between low herd immunity to enteroviruses and high risk for type 1 diabetes development. Finally, high levels of maternal enterovirus antibodies in serum and breast milk correlate with a reduced frequency of such infections in children [26].…”

“…Based upon the observations linking enterovirus infections to the development of type 1 diabetes [1][2][3][4][5], it would be expected that such infections are more common in countries with a high disease incidence compared with those with an intermediate or low incidence. In contrast to this assumption, epidemiological studies conducted in different geographical regions of Europe have demonstrated that the frequency of enterovirus infections in the background population shows an inverse correlation to the incidence of type 1 diabetes [18][19][20].…”

Enterovirus infections in young infants: Are children still protected by maternal antibodies?

“…11,12,22 In the present study we evaluated polio hypothesis by analyzing how frequently infants can experience enterovirus infections in the absence of maternal antibodies. Even though maternal antibodies were quite frequent in general, the results suggest that antibodies against certain serotypes can be relatively rare, especially in high titers (such as CBV5 and E9).…”

“…11,12 The development of IgA antibodies is regarded as a major advantage of orally administered live poliovirus vaccine vs. parenterally administered inactive virus vaccine. 2 According to our study 88% of children had IgA class poliovirus 1 antibodies by ©2 0 1 1 L a n d e s B i o s c i e n c e .…”

“…[8][9][10] Our previous epidemiological investigations clearly speak about the existence of inverse association between the prevalence of enterovirus infections and frequency of type 1 diabetes in background population. 11,12 Based on these findings we have launched "polio hypothesis" according to which the increase in type 1 diabetes incidence in some countries is due to a change in the epidemiology of enterovirus infections. This phenomenon could also be augmented by concomitant decrease in the levels of maternal antibodies in the population.…”