Does early EBV infection protect against IgE sensitization?

Nilsson, Caroline; Linde, Annika; Montgomery, Scott; Gustafsson, Liselotte; Näsman, Per; Blomberg, Marita Troye; Lilja, G.

doi:10.1016/j.jaci.2005.04.027

Cited by 72 publications

(121 citation statements)

References 32 publications

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“…However, EBV infection in childhood is presumed to follow a mild or asymptomatic course and therefore goes unnoticed in most cases. This type of silent EBV acquisition early on in life has in fact been connected to positive effects regarding allergy development (3,4), indicating that EBV may have beneficial immunomodulatory effects, at least when acquired during infancy.…”

Section: E Pstein-barr Virus Infection Is Commonly Contracted Inmentioning

confidence: 99%

“…PBMC were obtained from 2-or 5-y-old children who were selected from an earlier described family cohort (3,4) on the basis of EBV seronegativity and CMV serostatus. The presence of serum IgG against EBV capsid Ag was determined according to previously published immunofluorescence assays (31) where a specific fluorescence at a dilution of 1:20 was regarded as a sign of seropositivity.…”

Section: Characterization and Serostatus Of Childrenmentioning

confidence: 99%

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Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

Sohlberg

Saghafian–Hedengren

Rasul

et al. 2013

The Journal of Immunology

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EBV, a human herpesvirus, is commonly acquired during childhood and persists latently in B cells. EBV seropositivity has been connected to immunomodulatory effects such as altered T and NK cell functional responses as well as protection against early IgE sensitization; however, owing to the asymptomatic presentation during childhood little is known regarding the infection process in children of different ages. In this study, we used mononuclear cells from cord blood and from 2- and 5-y-old EBV-naive children for in vitro EBV infection. We show that the degree of EBV-induced B cell activation and expansion differs between age groups and in particular in relationship to IFN-γ production capacity. EBV infection induced redistribution between B cell subsets with enrichment of IgD+CD27+ cells (commonly referred to as non–switched memory) in infected cord blood cell cultures, and of IgD−CD27+ cells (switched memory) in cell cultures from older children. We also related results to serostatus to CMV, a persistent herpesvirus that can affect differentiation status of T and NK cells. As compared with CMV− children, the EBV-induced enrichment of IgD−CD27+ B cells was significantly reduced in infected cell cultures from CMV+ children. This effect was associated with high levels of IFN-γ and frequencies of highly mature CD8+CD57+ T cells in CMV+ children. Our results demonstrate that both a child’s age and serostatus to CMV will have an impact on EBV-induced B cell activation and expansion, and they point to the ability of viruses with immunomodulatory functions, such as CMV, to affect immune responses within the host system.

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Section: E Pstein-barr Virus Infection Is Commonly Contracted Inmentioning

confidence: 99%

Section: Characterization and Serostatus Of Childrenmentioning

confidence: 99%

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

Sohlberg

Saghafian–Hedengren

Rasul

et al. 2013

The Journal of Immunology

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“…In connection with this, our group has previously reported an inverse association between EBV seropositivity and IgE sensitization in 2-year-old children (25). Recent observations from our laboratory did not provide support for a Th1-biased cytokine profile in EBV SP children (26), which could have explained the protection against the allergic phenotype (32, 33).…”

Section: Discussionmentioning

confidence: 79%

“…Our group has previously reported an inverse association between EBV seropositivity and IgE sensitization in 2-year-old children, which seems to be augmented by the presence of CMV coinfection (25). When investigating plausible mechanisms behind this protection in the T cell compartment, an overall increased cytokine production in PHA-stimulated PBMCs in EBV-seropositive (SP) 2-year-old subjects was observed, whereas CMV infection was associated with a bias toward a Th1-type cytokine profile (26).…”

mentioning

confidence: 73%

“…A total of 51 IgE-nonsensitized 2-year-old children (Table I) were selected from an earlier described family cohort (25). The presence of serum IgG against EBV capsid Ag was determined according to previously published immunofluorescence assays (30) where a specific fluorescence at a dilution of 1/20 was regarded as a sign of seropositivity.…”

Section: Characterization and Serostatus Of Subjectsmentioning

confidence: 99%

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Herpesvirus Seropositivity in Childhood Associates with Decreased Monocyte-Induced NK Cell IFN-γ Production

Saghafian–Hedengren

Sundström

Sohlberg

et al. 2009

The Journal of Immunology

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EBV infection is inversely associated with IgE sensitization in children, and this association is further enhanced by CMV coinfection. In mice, herpesvirus latency causes systemic innate activation and protection from bacterial coinfection, implying the importance of herpesviruses in skewing immune responses during latent infection. Early control of viral infections depends on IFN-γ release by NK cells, which generally requires the presence of accessory cells. We investigated IFN-γ production by NK cells in PBMCs from children seropositive (SP) for EBV alone, for both EBV and CMV, or seronegative for both viruses. The ability of classical (CD14++CD16−) and proinflammatory (CD14+CD16+) monocytes to induce autologous NK cell IFN-γ was studied by coculture experiments with enriched CD3−CD56+ cells. Transwell experiments were used to evaluate how monocytes interact with NK cells to induce IFN-γ synthesis. SP children had a significantly reduced proportion of IFN-γ+ NK cells and cognate intracellular IFN-γ levels, which was more pronounced in CMV-coinfected subjects. Also, resting PBMCs of SP children displayed lower proportions of proinflammatory monocytes. IFN-γ production by NK cells was dependent on interactions with monocytes, with the proinflammatory subset inducing the highest IFN-γ. Finally, SP children had markedly lower levels of plasma IFN-γ, concurrent with in vitro findings. Herpesvirus infections could be one contributing factor for maturation toward balanced Th1-Th2 responses. Our data indicate that early infection by herpesviruses may affect NK cell and monocyte interactions and thereby also influence the development of allergies.

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The allergic phenotype during the first 10 years of life in a prospective cohort

Björkander

Hallberg

Persson

et al. 2019

Immunity Inflam & Disease

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Background Heredity and environmental parameters jointly affect allergy development. Here, we used a Swedish prospective cohort to study the influence of heredity and factors usually associated with allergic disease and the development of allergic manifestations in combination with immunoglobulin E (IgE) sensitization at four different time points until 10 years of age. Methods Parents‐to‐be were characterized concerning allergy and their children (n = 281) were divided based on allergic heredity and followed from birth and clinically examined for IgE‐associated allergic symptoms until 10 years of age. The relation between allergy and early‐life parameters was analyzed by logistic regression. Group‐wise comparisons were made by nonparametrical tests. Results Early life eczema and/or asthma in combination with IgE sensitization, was a strong indicator of allergy at a later time point. Further, the early occurrence of multiple allergic symptoms among IgE‐sensitized children predisposed for a more complex allergic phenotype at later ages, independently of allergic heredity. At 10 years of age, allergic children had higher fractional exhaled nitrogen oxide (FeNO) levels, regardless of asthma, and FeNO levels were also influenced by heredity. Birth season was strongly associated with allergy development, but only in children with two allergic parents. Conclusion Allergic eczema/asthma in early life, being born during the autumn/winter, having multiple allergic symptoms and two allergic parents were all strong predictors for having allergic diseases at 5 and 10 years of age. However, the allergic march seems to be independent of heredity, as IgE‐mediated allergies follow the same trajectories in children with and without allergic heredity.

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Does early EBV infection protect against IgE sensitization?

Abstract: Our results indicate that acquisition of EBV infection during the first 2 years of life is associated with a reduced risk of IgE sensitization, and this effect is enhanced by CMV coinfection.

Cited by 72 publications

References 32 publications

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

Herpesvirus Seropositivity in Childhood Associates with Decreased Monocyte-Induced NK Cell IFN-γ Production

The allergic phenotype during the first 10 years of life in a prospective cohort

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