Assessment of Enterovirus Antibodies during Early Childhood Using a Multiplex Immunoassay

Enteroviruses are a group of positive single-stranded viruses that belong to the Picornaviridae family. They regularly infect humans and cause symptoms ranging from the common cold and hand-foot-and-mouth disease to life-threatening conditions, such as dilated cardiomyopathy and poliomyelitis. Enteroviruses have also been associated with chronic immune-mediated diseases, such as type 1 diabetes, celiac disease, and asthma. Studying these disease-pathogen connections is challenging due to the high prevalence of enterovirus infections in the population and the transient appearance of the virus during the acute infection phase, which limit the identification of the causative agent via methods based on the virus genome. Serological assays can detect the antibodies induced by acute and past infections, which is useful when direct virus detection is not possible. We describe in this immuno-epidemiological study how the antibody levels against VP1 proteins from eight different enterovirus types, representing all seven of the human infecting enterovirus species, vary over time. VP1 responses first significantly (P < 0.001) decline until 6 months of age, reflecting maternal antibodies, and they then start to increase as the infections accumulate and the immune system develops. All 58 children in this study were selected from the DiabImmnune cohort for having PCR-confirmed enterovirus infections. Additionally, we show that there is great, although not complete, cross-reactivity of VP1 proteins from different enteroviruses and that the response against 3C-pro could reasonably well reflect the recent Enterovirus infection history (ρ = 0.94, P = 0.017). The serological analysis of enterovirus antibodies in sera from children paves the way for the development of tools for monitoring the Enterovirus epidemics and associated diseases. IMPORTANCE Enteroviruses cause a wide variety of symptoms ranging from a mild rash and the common cold to paralyzing poliomyelitis. While enteroviruses are among the most common human pathogens, there is a need for new, affordable serological assays with which to study pathogen-disease connections in large cohorts, as enteroviruses have been linked to several chronic illnesses, such as type 1 diabetes mellitus and asthma exacerbations. However, proving causality remains an issue. In this study, we describe the use of an easily customizable multiplexed assay that is based on structural and nonstructural enterovirus proteins to study antibody responses in a cohort of 58 children from birth to 3 years of age. We demonstrate how declining maternal antibody levels can obscure the serological detection of enteroviruses before the age of six months and how antibody responses to nonstructural enterovirus proteins could be interesting targets for serodiagnosis.Peer reviewe

Test of the Kolmogorov-Johnson-Mehl-Avrami picture of metastable decay in a model with microscopic dynamics

The Kolmogorov-Johnson-Mehl-Avrami (KJMA) theory for the time evolution of the order parameter in systems undergoing first-order phase transformations has been extended by Sekimoto to the level of two-point correlation functions. Here, this extended KJMA theory is applied to a kinetic Ising lattice-gas model, in which the elementary kinetic processes act on microscopic length and time scales. The theoretical framework is used to analyze data from extensive Monte Carlo simulations. The theory is inherently a mesoscopic continuum picture, and in principle it requires a large separation between the microscopic scales and the mesoscopic scales characteristic of the evolving two-phase structure. Nevertheless, we find excellent quantitative agreement with the simulations in a large parameter regime, extending remarkably far towards strong fields (large supersaturations) and correspondingly small nucleation barriers. The original KJMA theory permits direct measurement of the order parameter in the metastable phase, and using the extension to correlation functions one can also perform separate measurements of the nucleation rate and the average velocity of the convoluted interface between the metastable and stable phase regions. The values obtained for all three quantities are verified by other theoretical and computational methods. As these quantities are often difficult to measure directly during a process of phase transformation, data analysis using the extended KJMA theory may provide a useful experimental alternative.Comment: RevTex, 21 pages including 14 ps figures. Submitted to Phys. Rev. B. One misprint corrected in Eq.(C1