Introduction
Atopy is defined as a tendency to produce IgE antibodies in response to ordinary harmless exposures to allergens. The prevalence of atopic IgE sensitization in developed countries is extremely high, rising from around 12% at the age of 1 year to around 30% at the age of 6 years1 and staying at around 20-50% throughout adulthood 2. The rapid increase in the prevalence during the last half a century 3 suggests involvement of environmental factors.
According to the hygiene/biodiversity hypothesis 4,5the increase in atopy and allergic diseases is caused by reduction in microbial exposures in childhood and thus, skewing of the immune responses towards allergy prone Th2-based reactions. Viruses guide the immune system towards Th1-direction 6. One could thus hypothesize that virus infections reduce the risk of atopy and allergy. Accordingly, low-grade inflammation, induced for example by microbial exposure during infancy, has been shown to decrease allergen specific IgE (s-IgE) sensitization7. Multiple viruses have been linked to reduction of allergic diseases and/or IgE sensitization8–13 but there are also reports contradicting the role of viruses 3,9,14,15.
Enterovirus infections (EVs) are among the most common human virus infections worldwide. The classic human EVs can be classified into four species (EV-A, -B, -C and -D) comprising more than 100 serotypes. The pathophysiology of different serotypes differs depending on their tropisms to different tissues and cells. Enterovirus infections are mostly asymptomatic or mild such as common cold or hand, foot and mouth disease, but also serious diseases such as meningitis, myocarditis, and paralysis may occur 16. In in vitro models EVs have been shown to bias the immune reactions towards the mature Th1-like pathway 17,18. They have also been linked with reduced risk of allergic diseases/atopy 11,12,19, but the results are contradictory 20,21.
We contribute new insight into the association between EVs and atopy with respect to the individual EV serotypes. This study is the most comprehensive of its kind, containing 41 different human EV serotypes analyzed in a large case-control setting.