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EARLY DIETARY EXPOSURE IS ASSOCIATED WITH ALLERGY DEVELOPMENT IN THE FARMFLORA BIRTH COHORT

http://publications.lib.chalmers.se/records/fulltext/242689/242689.pdf

KARIN JONSSON

Department. of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden

ABSTRACT

The prevalence of allergy is markedly low in children who grow up on farms. Contact with livestock and consumption of unpasteurized milk have been associated with allergy protection, although other elements in the environment may contribute. The FARMFLORA birth cohort was established to identify factors that may be part of the allergy protection of the farming environment. In this thesis, early dietary exposures of farm and control children were evaluated in relation to allergy at three years of age, including: 1) maternal diet during pregnancy and lactation; 2) fatty acid composition of infant sera at birth and in sera and breast milk four months postpartum; 3) introduction practices of complementary foods; and 4) diet at one year of age. Twenty-eight children from dairy farms in southwestern Sweden and 37 non-farm control children from the same rural area were included in the cohort. The children were examined clinically by paediatricians to diagnose food allergy, eczema, asthma and rhinitis.

Farming mothers consumed more full-fat dairy and saturated fats during pregnancy and lactation than control mothers, who instead consumed more margarines and oils. The same pattern was found in the children’s diet at one year of age. The higher intake of saturated fats among the farming mothers was reflected in their breast milk as higher proportions of saturated fatty acids and lower proportions of the polyunsaturated fatty acids linoleic and alpha-linolenic acid. However, the only difference found in the infants’ sera was higher proportions of arachidonic acid at birth and lower proportions of the monounsaturated omega-7 fatty acid 18:1 four months postpartum in farmers’ children. Neither did the timing of the introduction of complementary foods differ between farm and control children, except for an earlier introduction of nuts in farm children.

One farm child (4%) and ten control children (25%) were allergic by the age of three years. The intake of margarines and oils both by the mothers during pregnancy and lactation and by the children at one year of age was weakly associated with allergy development at three years of age. Higher intake of pork was also found in subsequently allergic as compared to healthy children when farmers were excluded from the analysis. The most pronounced difference between healthy and subsequently allergic children was higher proportions of the long-chain omega-3 polyunsaturated fatty acid eicosapentaenoic acid in serum, both at birth and four months postpartum, reflecting maternal fish intake during pregnancy and lactation. Concordantly, a pattern of earlier introduction of fish in the healthy children was observed, together with higher intake of seafood at one year of age. There was also a tendency among healthy children that flour and eggs were introduced earlier. Exclusive breastfeeding was associated with less allergy, although the protective effect was only observed for breastfeeding up to three months of age.

In conclusion, a low margarine consumption by the mother and child was weakly associated with less allergy as well as with growing up on a farm. Consumption of fish by mothers during pregnancy and lactation as well as in the early diet of children was associated with a decreased risk of allergy development, although unrelated to farm residence. Tendencies of late introduction of complementary foods were related to an increased risk of allergy development.

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Age-Related Cataract Is Associated with Elevated Serum Immunoglobulin E Levels in the South Korean Population: A Cross-Sectional Study

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0166331

PLOS, published: November 18, 2016

Tae Keun Yoo, Sun Woong Kim , Kyoung Yul Seo

Abstract

Background

Previous research has suggested that immunoglobulin E (IgE)-mediated events lead to several chronic diseases. We investigated the association between allergic conditions and age-related cataracts in the South Korean adult population.

Methods

A cross-sectional study was performed using data obtained from 1,170 participants aged 40 years or older who were enrolled in the Korean National Health and Nutrition Examination Survey 2010. Multivariable logistic regression was used to examine the relationship between age-related cataracts and allergic conditions, including total serum IgE and allergen-specific serum IgE levels, after adjustment for potential confounders (age, sex, alcohol consumption, smoking, sun exposure, blood pressure, plasma glucose and cholesterol levels, as well as histories of asthma, atopic dermatitis, and rheumatoid arthritis).

Results

After adjusting for potential confounders, the odds ratio (OR) for age-related cataract was greater in participants with higher total serum IgE levels (OR = 1.37; P = 0.044). In particular, increased IgE levels were significantly associated with nuclear cataract (OR = 1.42; P = 0.032). However, allergen-specific serum IgE levels did not differ significantly between groups. In the trend analysis, no significant relationship was observed between serum IgE and any type of age-related cataract.

Conclusion

Increased total serum IgE level is independently associated with age-related cataracts after adjustment for confounding factors.

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From IgE to Omalizumab

http://www.jimmunol.org/content/197/11/4187.abstract

The Journal of Immunology December 1, 2016 vol. 197 no. 11 4187-4192

Toshiaki Kawakami and Ulrich Blank

Abstract

IgE is the least abundant Ig isotype, yet it plays a critical role in allergic reactions and host protection from helminth infection. Although IgE was discovered 50 years ago, the ultimate evidence for its role in human allergic diseases was obtained by the efficacy of anti-IgE therapy in many clinical trials on asthma and other allergic diseases. Beginning from the discovery of IgE 50 y ago, followed by studies of IgE receptors and activation mechanisms, this review provides a historic perspective of allergy research that has led to the development of anti-IgE therapy and other strategies targeting IgE and its receptors. Current IgE studies toward future precision medicine are also reviewed.

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Positive CD63 Basophil Activation Tests Are Common in Children with Chronic Spontaneous Urticaria and Linked to High Disease Activity

http://www.karger.com/Article/Abstract/451084

Int Arch Allergy Immunol 2016;171:81-88

Netchiporouk E.· Moreau L. · Rahme E. · Maurer M. · Lejtenyi D. · Ben-Shoshan M. (Division of Dermatology, Division of Clinical Epidemiology, Department of Medicine, and Division of Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada; Department of Dermatology and Allergy, Charité – Universitätsmedizin, Berlin, Germany)

Abstract

Background: The basophil activation test (BAT) using CD63 expression is a sensitive and specific tool for the diagnostic workup of autoimmune chronic spontaneous urticaria (CSU). The definition of a positive BAT is directly dependent on the reference range and the cutoff values established in control populations. As of now, the pediatric reference range and cutoff values of the CD63 BAT remain to be established. Methods: In this study, we analyzed CD63 expression in 80 children (1-17 years old) without chronic urticaria (i.e., controls) and compared the values to those of a pediatric cohort of 105 CSU patients and 23 physical urticaria (PU) patients. Results: Based on the log-normal distribution of CD63 values in control subjects, the reference range and the cutoff for positive CD63 BAT values was established to be 1.2-1.8% (95% CI) and 1.8%, respectively. Children with CSU showed significantly elevated and significantly increased BAT values compared to healthy controls (Wilcoxon rank test p value <0.001). In contrast, no difference was found between BAT results in controls and PU patients. In pediatric CSU patients, a higher disease activity was associated with higher BAT values. Conclusions: Our study provides, for the first time, reference and cutoff values for the CD63 BAT in children. Our findings show that positive CD63 BAT are common in children with CSU and linked to a high disease activity.

© 2016 S. Karger AG, Basel

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Regulation of mast cell function and survival in health and disease

https://openarchive.ki.se/xmlui/handle/10616/45211

Karolinska Instutet

Author: Lyberg, Katarina

Department: Inst för medicin, Solna / Dept of Medicine, Solna

Abstract

Mast cells are sentinels of danger but they are also the major effector cells in allergic disease causing the well-known allergic symptoms caused by their mediators such as histamine and prostaglandin D2 that are released upon activation. Mastocytosis is a disease characterized by the clonal expansion of mast cells in the skin and/or other organs where the patients suffer from mediator-related symptoms and/or organ failure due to mast cell infiltration. The aim of the work presented in this thesis was to investigate mast cell function in health and disease, particularly systemic mastocytosis.

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GPR91 deletion enhances mast cell activation while preventing arthritic disease

http://oak.novartis.com/27765/

Allergy, DO – (DO – ). pp. 1-9. ISSN 1398-9995

Rubic-Schneider, Tina and Carballido-Perrig, Nicole and Regairaz Kalenga Kapiamba, Camille and Raad, Layla and Jost, Sandra and Christen, Brigitte and Wieczorek, Grazyna and Kreutzer, Robert and Dawson King, Janet and Lametschwandner, Guenther and Littlewood-Evans, Amanda and Carballido, Jose (2016)

Abstract

While searching for a role of succinate on skin inflammation we discovered that its specific receptor, GPR91/SUCNR1 is also expressed by mast cells. Sucnr1-/- mast cells displayed enhanced reactivity to allergen-IgE crosslinking. However, such responses were acute in nature and did not contribute to the enhancement of asthma or arthritis and, we therefore suggest, they are due to alterations during mast cell differentiation. The fact that sucnr1-/- mice were protected from arthritis development, using two different in vivo models, indicates that GPR91 antagonists may have great therapeutic potential in autoimmune disease.

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Pyruvate dehydrogenase has a major role in mast cell function and its activity is regulated by mitochondrial MITF

http://www.sciencedirect.com/science/article/pii/S0091674916313446

Journal of Allergy and Clinical Immunology – Available online 18 November 2016

Israa Sharkia, MSc, Tal Hadad Erlich, PhD, Nadine Landolina, PhD, Miri Assayag, PhD, Alex Motzik, MSc, Inbal Rachmin, PhD, Gillian Kay, PhD, Ziv Porat, PhD, Sagi Tshori, MD, PhD, Neville Berkman, MD, PhD, Francesca Levi-Schaffer, PharmD, PhD, Ehud Razin, PhD

Summary

Background

We have recently observed that OXPHOS mediated ATP production is essential for mast cell function. Pyruvate dehydrogenase (PDH) is the main regulator of the Krebs cycle and is located upstream to the electron transport chain. However, the role of PDH in mast cell function has not been described. Microphthalmia transcription factor (MITF) regulates the development, number and function of mast cells. The localization of MITF to the mitochondria and its interaction with mitochondrial proteins has not been explored.

Objective

To explore the role played by PDH in mast cell exocytosis and to determine whether MITF is localized in the mitochondria and is involved in the regulation of PDH activity.

Methods

Experiments were performed in vitro using human and mouse mast cells as well as RBL cells, and in vivo in mice. The effect of PDH inhibition on mast cell function was examined. PDH interaction with MITF was measured before and after immunological activation. Furthermore, mitochondrial localization of MITF and its effect on PDH activity were determined.

Results

PDH is essential for immunologically mediated degranulation of mast cells. Following activation PDH is serine dephosphorylated. In addition, we show for the first time that MITF is partially located in the mitochondria and interacts with PDH. This interaction is dependent on the phosphorylation state of PDH. Furthermore, mitochondrial MITF regulates PDH activity.

Conclusion

The association of mitochondrial MITF with PDH emerges as an important regulator of mast cell function. Our findings indicate that PDH could arise as a new target for the manipulation of allergic diseases.

Key words

Allergy; Mast cells; Degranulation; Cytokines; PDH; MITF; Asthma; Mitochondria

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