PURPOSE OF THE STUDY.
The goal of this study was to assess the relationship between enterovirus infections in the first 2 years of life and atopic diseases. It also studied the importance of different enterovirus serotypes in atopic diseases.
The study population was derived from the Finnish DIPP (Diabetes Prediction and Prevention) Study. Newborn infants with HLA-DQB1 risk alleles had clinic visits every 3 to 6 months for the first 2 years of life and at subsequent intervals of 6 to 12 months. At each visit, children had a comprehensive history and physical examination performed and a venous blood sample obtained. For the present study, 71 subjects were identified as case children if they had the following: a diagnosis of asthma, atopic dermatitis, or allergic rhinitis; who had stored serum obtained at 1, 2, and 5 years available; and had serum-specific immunoglobulin E antibodies against a mixture of aeroallergens (birch, timothy, mugwort, cat, dog, horse, mite, and Cladosporium). There were 142 control subjects matched for HLA-DQB1 genotype, age, and gender.
This study had a nested case-control design. Serum samples obtained at 1 year were analyzed for the presence of neutralizing antibodies against 5 echovirus serotypes. Serum samples obtained at 2 years were analyzed for the presence of neutralizing antibodies against 12 enterovirus serotypes. Conditional logistic regression analysis was used to determine the association between enterovirus infections and atopic diseases. Categorized variables were used for confounding factors of pets at home, maternal education, paternal education, maternal tobacco use during pregnancy, older siblings, and day care attendance.
Cumulative exposure to different enterovirus serotypes by measured neutralizing antibodies was inversely associated with atopy (odds ratio: 0.73 [95% confidence interval: 0.56–0.96]; P = .025). The most pronounced protection was seen when echoviruses were analyzed as a separate group from coxsackieviruses (odds ratio: 0.63 [95% confidence interval: 0.46–0.88]; P = .006). The number of neutralizing antibodies against different coxsackievirus serotypes did not differ between case and control children.
An inverse association was found between cumulative exposure to echoviruses and atopic diseases with immunoglobulin E sensitization. Exposure to a high number of different echoviruses during the first years of life may protect from atopic diseases.
The prospective nature and use of serologic assays to detect viral infections in this study are unique. Measurement of virus neutralizing antibodies at 2 time points yields reliable information about accumulation of antibodies over time. Viruses induce a strong T helper 1 response, which may suppress the excessive T helper 2 response typically seen in atopic disease. The present study supports the previously reported theory that atopic diseases develop less frequently in children with early microbial contacts. The gut is an important organ in the development of immunologic tolerance. The study of enteroviruses is particularly interesting because they are transmitted orofecally and replicate primarily in the gut. As acknowledged by the authors, further studies are needed to determine whether enteroviruses are surrogate markers for environmental factors or total infection burden.
- Copyright © 2014 by the American Academy of Pediatrics