Association of different enteroviruses with atopy and allergic diseases in early childhood

Background Enterovirus (EV) infections, being among the most prevalent viruses worldwide, have been associated with reduced risk of allergic diseases. We sought to determine the association between EVs and allergic sensitization and disease in early childhood. Methods The study was carried out in a nested case-control setting within a prospective birth cohort in Finland. We included 138 case children who had specific IgE (s-IgE) sensitization at the age of 5 years and 138 control children without s-IgE sensitization. Allergic disease was recorded at study visits and identified with the ISAAC questionnaire. We screened for the presence of serotype-specific antibodies against 41 EVs at 1-5 years of age and assessed their association with allergic sensitization and disease. Results The overall number of EV infections did not differ between s-IgE-sensitized children and non-sensitized control children. However, there was a tendency of case children with an allergic disease having less EV infections than their controls. This observation was statistically significant for species A EVs in case children with atopic dermatitis vs. control children: OR 0.6 (95% CI 0.36-0.99), p = .048. Conclusion This study supports the evidence that EV exposure and development of allergic disease are inversely associated. Interestingly, the inverse association was not observed for bare atopic IgE sensitization, but for IgE sensitization coupled with clinical atopic disease. This suggests that environmental factors influencing IgE sensitization may differ from those influencing progression to clinical allergic disease.Peer reviewe

Association of different enteroviruses with atopy and allergic diseases in early childhood

Background: Enterovirus (EV) infections, being among the most prevalent viruses worldwide, have been associated with reduced risk of allergic diseases. We sought to determine the association between EVs and allergic sensitization and disease in early childhood. Methods: The study was carried out in a nested case-control setting within a prospective birth cohort in Finland. We included 138 case children who had specific IgE (s-IgE) sensitization at the age of 5 years and 138 control children without s-IgE sensitization. Allergic disease was recorded at study visits and identified with the ISAAC questionnaire. We screened for the presence of serotype-specific antibodies against 41 EVs at 1-5 years of age and assessed their association with allergic sensitization and disease. Results: The overall number of EV infections did not differ between s-IgE-sensitized children and non-sensitized control children. However, there was a tendency of case children with an allergic disease having less EV infections than their controls. This observation was statistically significant for species A EVs in case children with atopic dermatitis vs. control children: OR 0.6 (95% CI 0.36-0.99), p = .048. Conclusion: This study supports the evidence that EV exposure and development of allergic disease are inversely associated. Interestingly, the inverse association was not observed for bare atopic IgE sensitization, but for IgE sensitization coupled with clinical atopic disease. This suggests that environmental factors influencing IgE sensitization may differ from those influencing progression to clinical allergic disease.</p

Land Cover of Early Life Environment Modulates the Risk of Type 1 Diabetes

Objective: Environmental microbial exposures have been implicated to protect against immune-mediated diseases such as type 1 diabetes. Our objective was to study the association of land cover around the early-life dwelling with the development of islet autoimmunity and type 1 diabetes to evaluate the role of environmental microbial biodiversity in the pathogenesis. Research design and methods: Association between land cover types and the future risk of type 1 diabetes was studied by analyzing land cover types classified according to Coordination of Information on the Environment (CORINE) 2012 and 2000 data around the dwelling during the first year of life for 10,681 children genotyped for disease associated HLA-DQ alleles and monitored from birth in the Type 1 Diabetes Prediction and Prevention (DIPP) study. Land cover was compared between children who developed type 1 diabetes (n = 271) or multiple diabetes-associated islet autoantibodies (n = 384) and children without diabetes who are negative for diabetes autoantibodies. Results: Agricultural land cover around the home was inversely associated with diabetes risk (odds ratio 0.37, 95% CI 0.16-0.87, P = 0.02 within a distance of 1,500 m). The association was observed among children with the high-risk HLA-genotype and among those living in the southernmost study region. Snow cover on the ground seemed to block the transfer of the microbial community indoors, leading to reduced bacterial richness and diversity indoors, which might explain the regional difference in the association. In survival models, an agricultural environment was associated with a decreased risk of multiple islet autoantibodies (hazard ratio [HR] 1.60, P = 0.008) and a decreased risk of progression from single to multiple autoantibody positivity (HR 2.07, P = 0.001) compared with an urban environment known to have lower environmental microbial diversity. Conclusions: The study suggests that exposure to an agricultural environment (comprising nonirrigated arable land, fruit trees and berry plantations, pastures, natural pastures, land principally occupied by agriculture with significant areas of natural vegetation, and agroforestry areas) early in life is inversely associated with the risk of type 1 diabetes. This association may be mediated by early exposure to environmental microbial diversity.acceptedVersionPeer reviewe

Enterovirus infection during pregnancy is inversely associated with atopic disease in the offspring

Background: Prenatal environment has been shown to influence child's risk of atopic diseases. Laboratory-confirmed data about the role of maternal infections during pregnancy is scarce. Objective: The aim of this study was to determine the associations between serologically confirmed maternal infections during pregnancy and atopic disease in the offspring. Methods: This was a nested case-control study within a prospective birth cohort study. Altogether 202 atopic case children and 333 matched non-atopic control children were included. Atopic outcome was defined as having an atopic disease and IgE sensitization by the age of 5 years. We analysed serologically acute enterovirus (EV), influenza virus A (IAV) and Mycoplasma pneumoniae (M. pneumoniae) infections during pregnancy, and mother's seropositivity against human cytomegalovirus (CMV) and Helicobacter pylori. Results: Maternal EV infection during pregnancy was inversely associated with atopic outcome in the offspring (odds ratio 0.43; 95% confidence interval: 0.23-0.80, P = 0.008). Acute IAV or M. pneumoniae infections or seropositivity against CMV or Helicobacter pylori were not associated with the atopic outcome. Conclusions and Clinical Relevance: Our results suggest that maternal EV infections during pregnancy are inversely associated with atopic disease in the offspring. Our finding provides further support to the previous studies suggesting an important role of the in utero environment in the development of atopic diseases.Peer reviewe

Rhinoviruses in infancy and risk of immunoglobulin E sensitization

Previous data about the role of viruses in the development of allergic immunoglobulin E (IgE) sensitization are contradictory. The aim of this study was to determine the possible associations between exposure to different viruses (rhinovirus, enterovirus, norovirus, and parechovirus) during the first year of life and IgE sensitization. Viruses were analyzed from stool samples collected monthly from infants participating in a prospective birth cohort study. From that study, 244 IgE sensitized case children and 244 nonsensitized control children were identified based on their allergen-specific IgE antibody levels at the age of 6, 18, and 36 months. Stool samples (n = 4576) from the case and control children were screened for the presence of rhinovirus, enterovirus, norovirus, and parechovirus RNA by reverse transcription quantitative polymerase chain reaction. The study showed that rhinovirus was the most prevalent virus detected, present in 921 (20%) samples. None of the viruses were associated with IgE sensitization in the full cohort but after stratifying by sex, the number of rhinovirus positive samples was inversely associated with IgE sensitization in boys (odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.69-0.94; P = 0.006). There was also a temporal relation between rhinoviruses and IgE sensitization, as rhinovirus exposure during the first 6 months of life was associated with a reduced risk of subsequent IgE sensitization in boys (OR: 0.76; 95% CI: 0.6-0.94; P = 0.016). In conclusion, early exposure to rhinoviruses was inversely associated with IgE sensitization but this protective association was restricted to boys.Peer reviewe

Enterovirus infections in the pathogenesis of type 1 diabetes

Enterovirusinfektioiden on todettu altistavan nuoruustyypin diabetekselle. Tutkimuksessa py-rittiin selvittämään niiden riskivaikutusta suomalaisissa lapsissa. Enterovirusinfektioiden esiintyvyyttä tutkittiin laajoissa seuranta-aineistoissa, mm. Lasten Diabetes Suomessa (DiMe) tutkimuksessa ja Diabeteksen Ennustaminen ja Ehkäisy (DIPP) tutkimuksessa, analysoimalla seurannan aikana diabetekseen sairastuneiden ja terveiden verrokkilasten seeruminäytteitä enterovirusvasta-ainetesteillä ja enteroviruksen perimäaineksen monistamiseen perustuvalla RT-PCR -testillä. Enterovirusten 2C -proteiinin ja haiman saarekesolujen välisen immunologi-sen ristireaktion mahdollisuutta selvitettiin tutkimalla ristireagoivien vasta-aineiden esiinty-vyyttä diabetekseen sairastuneilla ja terveillä lapsilla. Enterovirusinfektioiden esiintyvyyden ja nuoruustyypin diabeteksen ilmaantuvuuden välistä yhteyttä arvioitiin väestötasolla analysoi-malla terveiden suomalaisten ja liettualaisten koululaisten seeruminäytteitä. Lisäksi kehitettiin uusi entistä herkempi RT-PCR-monistustuotteet tunnistava hybridisaatiomenetelmä. Seu-rantatutkimuksissa havaittiin, että enterovirusinfektioihin liittyi lisääntynyt riski sairastua dia-betekseen. Lisääntynyt riski liittyi jopa vuosia ennen diabeteksen diagnosoimista sairastettui-hin enterovirusinfektioihin. Enterovirusinfektioiden yhteys diabetekseen ei näyttänyt välittyvän enterovirusten 2C -proteiinin ja haiman saarekesolujen välisen vasta-aineiden ristireagoivuu-den kautta, sillä ko. ristireagoivia vasta-aineita todettiin yhtä paljon diabetekseen sairastu-neilla kuin terveillä lapsilla. Väestötasolla todettiin käänteinen suhde enterovirusinfektioiden esiintyvyyden ja nuoruustyypin diabeteksen ilmaantuvuuden kesken. Tästä pääteltiin, että si-kiöaikana ja varhaislapsuudessa sairastetut enterovirusinfektiot saattavat olla merkittäviä nuoruustyypin diabeteksen riskitekijöitä erityisesti Suomessa ja muissa korkean elintason maissa, joissa äidin sikiölle ja imeväiselle antama vasta-ainevälitteinen suoja enterovirusin-fektioita vastaan on heikko. Tutkimus vahvisti aiemmat havainnot enterovirusinfektioiden dia-betesriskiä lisäävästä vaikutuksesta. Edelleen on kuitenkin epäselvää, miten enterovirusin-fektion riskivaikutus välittyy. Tulevaisuudessa tullaan arvioimaan, voitaisiinko nuoruustyypin diabetesta ehkäistä suojaamalla lapset enterovirusinfektioita vastaan rokotteella

Antibody cross-reactivity induced by homologous regions in glutamic acid decarboxylase (GAD65) and 2c protein of coxsackievirus B4

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Antibody cross-reactivity induced by homologous regions in glutamic acid decarboxylase (GAD65) and 2c protein of coxsackievirus B4

Syventävä työ ei kirjastoss