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Dysregulated Th1 and Th2 responses in food-allergic children: Does elimination diet contribute to the dysregulation?
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
2010 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 21, no 4, 649-655 p.Article in journal (Refereed) Published
Abstract [en]

Infants with eczema and sensitization to foods are recommended skin care and, if food allergy is proven, an elimination diet. Although most of these children tolerate foods before 3 yr of age, some children experience prolonged food allergy. To our knowledge, no prospective study has investigated the cytokine profile in food-sensitized eczematous children with prolonged food intolerance. The aim of the study was to prospectively investigate the development of cytokine production induced by food allergen in food-sensitized eczematous children who, at 41/2 yr of age, were allergic or tolerant to egg or milk. Twenty-one eczematous infants, [age 5 (3-10) months; median and range], sensitized to egg and/or milk were included, put on elimination diet and followed prospectively. At 41/2 yr of age, the children were defined as tolerant or allergic to egg and/or milk based on open or double-blind placebo-controlled food challenges. Peripheral blood mononuclear cells (PBMC) were isolated from the children on inclusion, after 6 wk of elimination diet, and at 3 and 41/2 yr of age. Ovalbumin, beta-lactoglobulin and tetanus toxoid-induced IL-4, -5, -10, -13 and IFN-gamma production from PBMC were analyzed with enzyme-linked immunosorbent assay. The IFN-gamma and IL-5 secretion induced by food allergen at 41/2 yr was higher in cell cultures from children who were allergic to egg or milk than in tolerant children. In food-allergic children, the levels of IFN-gamma and IL-5 were higher at 41/2 yr compared with inclusion levels, but this increase was generally not observed in the tolerant children who consumed milk and egg. In conclusion, immune cells from food-allergic children on an elimination diet respond with up-regulated T helper 1 and T helper 2 cytokine secretion induced by food allergen. We hypothesize that allergen elimination may influence the regulatory mechanisms maintaining balanced immune responses to innocuous food antigens.

Place, publisher, year, edition, pages
Blackwell Publishing Ltd , 2010. Vol. 21, no 4, 649-655 p.
Keyword [en]
children; cytokines; elimination diet; food allergy; tolerance
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-13207DOI: 10.1111/j.1399-3038.2009.00937.xISI: 000278526100011OAI: diva2:18033
Available from: 2008-04-17 Created: 2008-04-17 Last updated: 2010-08-13
In thesis
1. Environmental and immunological factors associated with allergic disease in children
Open this publication in new window or tab >>Environmental and immunological factors associated with allergic disease in children
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Allergic diseases are characterised by dysregulated immune responses. The first manifestation of the atopic phenotype is often food allergy, with symptoms like eczema. Food allergy in children is generally outgrown before 3 years of age, but a temporary food elimination diet is often advocated. The prevalence of allergic diseases has increased in affluent countries during the last decades, possibly as a consequence of a changed lifestyle leading to decreased microbial load.

Aim: To investigate humoral, mucosal and cell-mediated immunity in association to allergy and allergy development in young children and relate this to environmental factors.

Subjects: Two cohorts of children were investigated; 1) Children from countries with high (Sweden) and low (Estonia) prevalence of allergy that were followed prospectively from birth to 5 years of age. 2) Infants with eczema and suspected food allergy that were followed prospectively to 4 ½ years of age.

Methods: Endotoxin levels were analysed in house dust samples. Antibodies were measured in serum and saliva samples with ELISA. Food allergen induced cytokine responses were analysed in mononuclear cells.

Results: The microbial load, delineated as endotoxin levels, was higher in house dust from Estonia than Sweden and was, in Swedish children, inversely associated with sensitisation and clinical symptoms of allergy. The decreased microbial load in Sweden may have an impact on mucosal immune responses as different IgA antibody patterns were observed in Sweden and Estonian children with much lower secretory (S)IgA antibody levels and high proportion of non-SIgA, i.e. IgA antibodies lacking the secretory component, in the Swedish children. Moreover, low levels of SIgA were associated with clinical symptoms in sensitised children.

High IgG4 antibody levels to food allergens during infancy were associated with faster tolerance development in food allergic children. Cytokine responses by mononuclear cells after allergen stimulation was upregulated with age in children with prolonged food allergy, but not in children who develop tolerance before 4 ½ years of age, possibly because of the prolonged elimination diet in the former group.

Summary: Reduced microbial exposure in affluent countries may affect the mucosal immune responses during infancy, possibly resulting in an increased risk of developing allergic disease. High levels of IgG4 antibodies during infancy are associated with faster achievement of tolerance in food allergic children. Allergen elimination during infancy may result in a dysfunctional cytokine response.

Place, publisher, year, edition, pages
Linköping University Electronic Press, 2008
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1061
Allergic diseases, dysregulated immune responses, IgG4
National Category
Immunology in the medical area
urn:nbn:se:liu:diva-11615 (URN)978-91-7393-913-3 (ISBN)
Public defence
2008-05-15, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Available from: 2008-04-17 Created: 2008-04-17 Last updated: 2015-11-19

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