Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort

Rowe, Julie; Kusel, Merci; Holt, Barbara J.; Suriyaarachchi, Devinda; Serralha, Michael; Hollams, Elysia M.; Yerkovich, Stephanie T.; Subrata, Lily S.; Ladyman, Claire; Sadowska, Agata; Gillett, Jamie; Fisher, Elizabeth; Loh, Richard; Söderström, Lars; Ahlstedt, S.; Sly, Peter D.; Holt, Patrick G.

doi:10.1016/j.jaci.2007.02.016

Cited by 109 publications

(82 citation statements)

References 43 publications

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“…However, the clinical relevance of cord blood IgE has been called into question as it does not seem to consistently correlate with or predict the development of disease (32). Others have shown that cord blood allergen-specific IgE is not of fetal origin but rather due to maternal contamination likely at the time of delivery (33), although one recent study claims to have controlled for maternal contamination (34).…”

Section: The Maternal/fetal Interface and In Utero Primingmentioning

confidence: 99%

The Role of Microbes in Developmental Immunologic Programming

2011

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ABSTRACT:The role of microorganisms in the gastrointestinal tract has undergone significant modification in the past few decades with new observations from clinical, epidemiologic, and basic science research. We now know that the perception of these gut microbes as pathogens or even as commensals is somewhat outdated. It is becoming increasingly clear that the gut microbiome plays an important role in a host of activities including digestion, protection from potentially pathogenic organisms, and the regulation and development of the host immune system. The complex interactions between microbes and host combined with recent clinical observations and epidemiologic trends may point to the convergence of two well-supported (though imperfect) hypotheses: the "hygiene hypothesis" and the "fetal programming hypothesis." We are beginning to understand that exposure to microbes before conception, during gestation, and in the neonatal period have profound effects on the developing immune system. Recent observations from a variety of fields help support the expansion of the "fetal programming hypothesis" to a host-microbe corollary that microbe-host interactions at critical windows influence the future immune phenotype, the maintenance of immune health, and the development of immune-mediated disease. (Pediatr Res 69: 465-472, 2011)

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Section: The Maternal/fetal Interface and In Utero Primingmentioning

confidence: 99%

The Role of Microbes in Developmental Immunologic Programming

2011

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“…During pregnancy, the maternal immunologic status influences the fetal immune system and may thereby have an impact on future clinical outcomes in the child (7). The debate about prenatal vs postnatal sensitization is intense (8,9). Still, it is reasonable to believe that the fetal immune system is primed during the prenatal period and studies exploring the effect of environmental factors on the development of allergic disease in childhood need to be performed in pregnant women.…”

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confidence: 99%

The Effects of Omega-3 Fatty Acid Supplementation in Pregnancy on Maternal Eicosanoid, Cytokine, and Chemokine Secretion

et al. 2009

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ABSTRACT:The incidence of allergic diseases has increased, and a relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcomes in the child. The aim of this study was to determine the effects of omega ()-3 long-chain polyunsaturated fatty acids (LCPUFA) supplementation during pregnancy on the plasma fatty acid composition in relation to the maternal immune function. Pregnant women with allergic disease in their immediate family were supplemented daily with 2.7 g -3 LCPUFA (n ϭ 70) or 2.8 g soybean oil as placebo (n ϭ 75) from the 25th gestational week. The proportions of eicosapentaenoic acid and docosahexaenoic acid in plasma/serum phospholipids increased in the -3-supplemented group, whereas arachidonic acid decreased during intervention. Lipopolysaccharide-induced prostaglandin E 2 secretion from whole blood culture supernatants (n ϭ 59) decreased in a majority of the -3-supplemented mothers (18 of 28, p ϭ 0.002). The decreased prostaglandin E 2 production was more pronounced among nonatopic than atopic mothers. The lipopolysaccharideinduced cytokine and chemokine secretion was not affected.

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“…Briefly, PBMC were cultured for 48 h in AIM‐V medium containing 2‐mercaptoethanol (50 μ m ) alone (medium control), with phytoheamagglutinin (PHA, 1 μg/ml, positive control), or with HDM ( Dermatophagoides pteronyssinus ) extract (10 μg/ml) which was prepared in‐house, with a single batch used for the whole study (endotoxin level was not quantified). This stimulation time (48 h) was validated in our previous studies 5, 20, 23, 24, 25. IL‐5, IL‐10, IL‐13 and interferon (IFN)‐γ protein in supernatants were assayed using time‐resolved fluorescence as previously described 20.…”

Section: Methodsmentioning

confidence: 99%

“…Coefficients of variation for both cohorts are shown in Table S3. We used identical protocols for in vitro studies in both cohorts; the methods are described in detail in our previous studies 5, 20, 23, 24. Briefly, PBMC were cultured for 48 h in AIM‐V medium containing 2‐mercaptoethanol (50 μ m ) alone (medium control), with phytoheamagglutinin (PHA, 1 μg/ml, positive control), or with HDM ( Dermatophagoides pteronyssinus ) extract (10 μg/ml) which was prepared in‐house, with a single batch used for the whole study (endotoxin level was not quantified).…”

Section: Methodsmentioning

confidence: 99%

Relationship between cytokine expression patterns and clinical outcomes: two population‐based birth cohorts

Prosperi

Simpson

et al. 2015

Clin Experimental Allergy

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SummaryBackgroundModels that incorporate patterns of multiple cytokine responses to allergens, rather than individual cytokine production, may better predict sensitization and asthma.ObjectiveTo characterize the patterns of peripheral blood mononuclear cells’ (PBMCs) cytokine responses to house dust mite (HDM) allergens among children from two population‐based birth cohorts using machine learning techniques.Methods PBMCs collected at 8 years of age from the UK Manchester Asthma and Allergy Study (n = 268) and at 14 years of age from the Australian Raine Study (n = 1374) were cultured with HDM extract (10 μg/ml). Cytokine expression (IL‐13, IL‐5, IFN‐γ, and IL10) was measured in the supernatant. Cytokine patterns were identified using a Gaussian mixture model clustering, and classification stability was assessed by bootstrapping.ResultsA six‐class model indicated complex latent structure of cytokine expression. Based on the characteristics of each class, we designated them as follows: ‘Nonresponders’ (n = 905, 55%); ‘IL‐10 responders’ (n = 49, 3%); ‘IFN‐γ and IL‐13 medium responders’ (n = 56, 3.4%); ‘IL‐13 medium responders’ (n = 351, 21.4%); ‘IL‐5 and IL‐13 medium responders’ (n = 77, 4.7%); and ‘IL‐13 and IL‐5 high responders’ (n = 204, 12.4%). ‘IL‐13 and IL‐5 high responders’ were at much higher risk of HDM sensitization and asthma compared to all other classes, with 88% of children assigned to this class being sensitized and 28.5% having asthma.ConclusionUsing model‐based clustering, we identified several distinct patterns of cytokine response to HDM and observed interplay between cytokine expression level, cytokine patterns (especially IL‐13 and IL‐5), and clinical outcomes. ‘IL‐13 and IL‐5 high responders’ class was strongly associated with HDM sensitization. However, among HDM‐sensitized children, one‐third showed no PBMC response to HDM, and the majority of HDM‐sensitized children did not have asthma or wheeze. Our findings suggest that positive HDM ‘allergy tests’ and asthma are associated with a broad range of immunophenotypes, which may have important implications for the use of cytokine‐targeted treatment approaches.

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Prenatal versus postnatal sensitization to environmental allergens in a high-risk birth cohort

Cited by 109 publications

References 43 publications

The Role of Microbes in Developmental Immunologic Programming

The Role of Microbes in Developmental Immunologic Programming

The Effects of Omega-3 Fatty Acid Supplementation in Pregnancy on Maternal Eicosanoid, Cytokine, and Chemokine Secretion

Relationship between cytokine expression patterns and clinical outcomes: two population‐based birth cohorts

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