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Slow salivary secretory IgA maturation may relate to low microbial pressure and allergic symptoms in sensitized children
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
Children's Clinic of Tartu University Clinics, Tartu, Estonia.
Institute of Environmental Health, Karolinska Institutet, Stockholm, Sweden.
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2011 (Engelska)Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 70, nr 6, s. 572-577Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

It is unknown why allergic symptoms do not develop in all sensitized children. We analyzed prospectively the postnatal secretory IgA (SIgA) development and whether high SIgA levels would protect sensitized infants from developing allergic symptoms. Salivary total IgA and SIgA levels were determined by ELISA, and allergy development was investigated at 3, 6, and 12 mo and at 2 and 5 y in two birth cohorts in Estonia (n = 110) and Sweden (n = 91), two geographically adjacent countries with different living conditions and allergy incidence. Total and SIgA levels increased with age, reaching adult levels at the age of 5. Virtually, all salivary IgA in Estonian children was in the secretory form, while a major part of IgA in Swedish saliva lacked the secretory component up to 2 y of age. In Sweden, high levels of salivary IgA without secretory component correlated inversely with house dust endotoxin levels. High SIgA levels were associated with less development of allergic symptoms in sensitized Swedish children. In conclusion, postnatal maturation of the salivary SIgA system proceeds markedly slower in Swedish than Estonian children, possibly as a consequence of low microbial pressure. SIgA may limit allergy-mediated tissue damage at mucosal surfaces in sensitized individuals.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2011. Vol. 70, nr 6, s. 572-577
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-73314DOI: 10.1203/PDR.0b013e318232169eISI: 297433900005PubMedID: 21857384OAI: oai:DiVA.org:liu-73314DiVA, id: diva2:472077
Anmärkning

When submitted this article was titled "Slower maturation of the secretory IgA system in Swedish than Estonian children: possibly caused by low microbial pressure and related to expression of allergy in sensitised individuals".

Tillgänglig från: 2012-01-03 Skapad: 2012-01-02 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
Ingår i avhandling
1. Environmental and immunological factors associated with allergic disease in children
Öppna denna publikation i ny flik eller fönster >>Environmental and immunological factors associated with allergic disease in children
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Linköping University Electronic Press, 2008
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1061
Nyckelord
Allergic diseases, dysregulated immune responses, IgG4
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
urn:nbn:se:liu:diva-11615 (URN)978-91-7393-913-3 (ISBN)
Disputation
2008-05-15, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2008-04-17 Skapad: 2008-04-17 Senast uppdaterad: 2018-01-13

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Fagerås Böttcher, MalinTomicic, SaraJenmalm, Maria

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