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.