Background
Vitamin D levels are known to be associated with atopic disease development; however, existing data are controversial. The aim of this study was to investigate whether corresponding ...maternal and cord blood vitamin D levels are associated with atopic outcomes in early infancy.
Methods
Within the LINA cohort study (Lifestyle and environmental factors and their Influence on Newborns Allergy risk), 25(OH)D was measured in blood samples of 378 mother–child pairs during pregnancy and at birth. Information about children's atopic manifestations during the first 2 years of life was obtained from questionnaires filled out by the parents during pregnancy and annually thereafter. Cord blood regulatory T cells (Treg) were detected by methylation‐specific PCR using a Treg‐specific demethylated region in the FOXP3 gene.
Results
The median maternal 25(OH)D3 level was 22.19 ng/ml (IQR 14.40–31.19 ng/ml); the median cord blood 25(OH)D3 10.95 ng/ml (6.99–17.39 ng/ml). A high correlation was seen between maternal and cord blood 25(OH)D3 levels, both showing a seasonal distribution. Maternal and cord blood 25(OH)D3 was positively associated with children's risk for food allergy within the first 2 years. Further, higher maternal 25(OH)D3 resulted in a higher risk for sensitization against food allergens at the age of two. Cord blood 25(OH)D3 levels were negatively correlated with regulatory T cell numbers.
Conclusion
Our study demonstrates that high vitamin D levels in pregnancy and at birth may contribute to a higher risk for food allergy and therefore argues against vitamin D supplement to protect against allergy.
Sara was a 65‐year‐old Caucasian woman who requested art therapy after the death of her partner. She had experienced incest by her father and verbal abuse by her mother until she left home at 21. Her ...life was characterized by broken relationships due to alienating anger outbursts and an interrupted work history; she met three criteria for narcissistic personality disorder. Sara initially was socially isolated and intellectualizing. She desired recognition but was fearful of exposure. The Expressive Therapies Continuum (ETC) theoretical framework, which consisted of a gradual progression from cognitively‐dominated sessions to more emotionally focused processing, guided the therapeutic work. The ETC theory encourages transparency and collaboration between therapist and client regarding therapeutic tasks and goals, and provides a framework for addressing and repairing ruptures in the therapeutic alliance. Art therapy began with the cognitive tasks which Sara completed relatively comfortably, then encouraged integration of emotion via expressive writing, diagrams, and body mapping. Through careful attention to repair of ruptures by directly discussing and adapting the direction and tasks of therapy, Sara slowly was able to experience emotions other than anger. She integrated cognitive and emotional insights about her life and developed empathy for her childhood self. At termination Sara had cultivated two friendships and met only one criterion of NPD. Limitations of this case study include a lack of research evidence for ETC‐guided art therapy with NPD clients and by the retrospective approach. Future research efforts could provide this support by encouraging clinicians to conduct prospective case study research.
Background:
Regulatory T cells (Tregs) with stable FOXP3 expression are characterized by a specific demethylated region in the FOXP3 gene (Treg‐specific demethylated region, TSDR). The aim of this ...study was to analyse the influence of prenatal factors on cord blood Treg numbers, as detected by changes in the TSDR demethylation, and the subsequent risk for allergic diseases.
Methods:
Analyses were performed within the LINA study in blood samples from pregnant women (34th gestational week) and in cord blood (n = 346 mother–child pairs). Treg numbers were detected via DNA demethylation in the FOXP3 TSDR. At age 1, total and specific IgE was measured in children's blood. In addition, maternal cytokine production (Th1/Th2/Th17) was analysed. Exposure and disease outcomes were assessed by questionnaires.
Results:
Boys had lower Treg numbers compared with girls (P < 0.001). Parental atopy history, particularly maternal hay fever and paternal asthma were related to lower Treg numbers in cord blood (adj. MR = 0.81, 95% CI = 0.68–0.97; adj. MR = 0.60, 95% CI = 0.45–0.81). Maternal cytokines (IL‐13, IL‐17E and IFN‐γ) and maternal smoking/exposure to tobacco smoke during pregnancy were also associated with decreased cord blood Treg numbers (adj. MR = 0.89, 95% CI = 0.97–1.00). Children with lower Treg numbers at birth had a higher risk to develop atopic dermatitis (adj. OR = 1.55, 95% CI = 1.00–2.41) and sensitization to food allergens (adj. OR = 1.55, 95% CI = 1.06–2.25) during the first year of life.
Conclusions:
These results indicate that both genetic and environmental factors presumably influence the development of foetal Tregs. Low cord blood Treg numbers may predict early atopic dermatitis.
Summary
Background
Allergens from house dust mites (HDM) are a common cause of asthma. Der p and Der f from Dermatophagoides sp. are strong immunogens in humans. Allergen extracts are used to study T ...helper (Th2) cell responses to HDM, which are implicated in the development and regulation of allergic disease.
Objective
To define an epitope mixture that recapitulates, and might substitute for, HDM extract in terms of detecting and characterizing Th2 cell responses.
Methods
Peripheral blood mononuclear cells (PBMC) from 52 HDM allergic and 10 non‐allergic individuals were stimulated with HDM extracts and assayed with a set of 178 peptides spanning mite allergens group Der p 1, 2, 23 and Der f group 1 and 2 allergens. A pool of the most dominant T cell epitopes identified in the present study and from published literature was assembled and tested for ex vivo T cell responses. Correlation with HDM‐specific IgE titres was examined.
Results
Patterns of T cell reactivity to Der p and Der f – derived peptides revealed a large number of epitopes. Clear patterns of immunodominance were apparent, with HDM allergen group 1 and 2 dominant over group 23. Furthermore, within a given antigen, 6–11 epitopes accounted for the vast majority of responses. Based on these results and published data, a comprehensive dust mite pool (DMP) of epitopes was designed and found to allow detection of ex vivo T cell responses. DMP ex vivo reactivity correlated with HDM‐specific IgE titres and was similar to that detected with commonly used HDM extracts. Ex vivo DMP stimulation was associated with a predominant Th2 response in allergic donors, and minor reactivity of T cells producing IFNγ, IL17 and IL10.
Conclusions & Clinical Relevance
A detailed map of Der p and Der f antigens defined a pool of epitopes that can be used to detect ex vivo HDM responses.
•Women with overweight/obesity show alterations in the hedonic and homeostatic systems that regulate normal eating.•Hedonic responses are more strongly associated with high ad libitum consumption ...levels in women with obesity.•Neural responses to food rewards are less sensitive to satiety in women with higher BMI.
Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Obesity rates are on the rise worldwide with women more frequently affected than men. Hedonic responses to food seem to play a key role in obesity, but the exact mechanisms and relationships are still poorly understood. In this study, we investigate the perceived pleasantness of food rewards in relation to satiety and calories consumed during an ad libitum meal in women. Using functional magnetic resonance imaging (fMRI) and a milkshake consumption task, we studied how experienced food values are encoded in women with healthy weight, overweight or obesity. Participants rated the pleasantness and intensity of high and low caloric milkshakes in the fMRI scanner during both the fasted and fed states. We found differences in the neural responses and experienced pleasantness of high and low caloric milkshakes depending on satiety and Body Mass Index (BMI). Women with both high ad libitum consumption levels and high BMI reported greater experienced pleasantness for milkshakes. In contrast, among women with low ad libitum consumption levels, greater BMI was associated with less experienced pleasantness. At the neural level, satiety affected women with obesity to a lesser degree than women with healthy weight. Thus, having obesity was associated with altered relationships between food consumption and the hedonic responses to food rewards as well as reduced satiety effects in women.
Summary
Background
Ragweed is a major cause of seasonal allergy, affecting millions of people worldwide. Several allergens have been defined based on IgE reactivity, but their relative immunogenicity ...in terms of T cell responses has not been studied.
Objective
We comprehensively characterized T cell responses from atopic, ragweed‐allergic subjects to Amb a 1, Amb a 3, Amb a 4, Amb a 5, Amb a 6, Amb a 8, Amb a 9, Amb a 10, Amb a 11, and Amb p 5 and examined their correlation with serological reactivity and sequence conservation in other allergens.
Methods
Peripheral blood mononuclear cells (PBMCs) from donors positive for IgE towards ragweed extracts after in vitro expansion for secretion of IL‐5 (a representative Th2 cytokine) and IFN‐γ (Th1) in response to a panel of overlapping peptides spanning the above‐listed allergens were assessed.
Results
Three previously identified dominant T cell epitopes (Amb a 1 176–191, 200–215, and 344–359) were confirmed, and three novel dominant epitopes (Amb a 1 280–295, 304–319, and 320–335) were identified. Amb a 1, the dominant IgE allergen, was also the dominant T cell allergen, but dominance patterns for T cell and IgE responses for the other ragweed allergens did not correlate. Dominance for T cell responses correlated with conservation of ragweed epitopes with sequences of other well‐known allergens.
Conclusions and Clinical Relevance
These results provide the first assessment of the hierarchy of T cell reactivity in ragweed allergens, which is distinct from that observed for IgE reactivity and influenced by T cell epitope sequence conservation. The results suggest that ragweed allergens associated with lesser IgE reactivity and significant T cell reactivity may be targeted for T cell immunotherapy, and further support the development of immunotherapies against epitopes conserved across species to generate broad reactivity against many common allergens.
To cite this article: Herberth G, Hinz D, Röder S, Schlink U, Sack U, Diez U, Borte M, Lehmann I. Maternal immune status in pregnancy is related to offspring’s immune responses and atopy risk. ...Allergy 2011; 66: 1065–1074.
Background: The influence of maternal immune responses in pregnancy on children’s immune competence and the development of atopic diseases later in life are poorly understood. To determine potential maternal effects on the maturation of children’s immune system and resulting disease risks, we analysed immune responses in mother–child pairs in a prospective birth cohort study.
Methods: Within the Lifestyle and Environmental factors and their Influence on Newborns Allergy risk (LINA) study, concentrations of Th1/Th2/Th17 and inflammatory cytokines/chemokines as well as IgE were measured in phytohemagglutinin and lipopolysaccharide stimulated maternal blood in the 34th week of gestation and in corresponding children’s blood at birth and 1 year after (n = 353 mother–child pairs). Information on atopic outcomes during the first year of life was obtained from questionnaires.
Results: Concentrations of inflammatory markers, excepting TNF‐α, were manifold higher in cord blood samples compared with maternal blood. Th1/Th2 cytokines were lower in children’s blood with a Th2 bias at birth. Maternal inflammatory parameters (MCP‐1, IL‐10, TNF‐α) in pregnancy showed an association with corresponding cytokines blood levels in children at the age of one. High maternal IgE concentrations in pregnancy were associated with increased children’s IgE at birth and at the age of one, whereas children’s atopic dermatitis (AD) was determined by maternal AD.
Conclusions: Maternal inflammatory cytokines during pregnancy correlate with children’s corresponding cytokines at the age of one but are not related to IgE or AD. While maternal IgE predicts children’s IgE, AD in children is only associated with maternal disease.
Summary
Background
Timothy grass (TG) pollen is a common seasonal airborne allergen associated with symptoms ranging from mild rhinitis to severe asthma.
Objective
The aim of this study was to ...characterize changes in TG‐specific T cell responses as a function of seasonality.
Methods
Peripheral blood mononuclear cells (PBMCs) obtained from allergic individuals and non‐allergic controls, either during the pollen season or out of season, were stimulated with either TG extract or a pool of previously identified immunodominant antigenic regions.
Results
PBMCs from allergic subjects exhibit higher IL‐5 and IL‐10 responses in season than when collected out of season. In the case of non‐allergic subjects, as expected we observed lower IL‐5 responses and robust production of IFN‐γ compared to allergic individuals. Strikingly, non‐allergic donors exhibited an opposing pattern, with decreased immune reactivity in season. The broad down‐regulation in non‐allergic donors indicates that healthy individuals are not oblivious to allergen exposure, but rather react with an active modulation of responses following the antigenic stimulus provided during the pollen season. Transcriptomic analysis of allergen‐specific T cells defined genes modulated in concomitance with the allergen exposure and inhibition of responses in non‐allergic donors.
Conclusion and Clinical Relevance
Magnitude and functionality of T helper cell responses differ substantially in season vs. out of season in allergic and non‐allergic subjects. The results indicate the specific and opposing modulation of immune responses following the antigenic stimulation during the pollen season. This seasonal modulation reflects the enactment of specific molecular programmes associated with health and allergic disease.
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