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    Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease

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    Authors
    D'Vaz, N.
    Ma, Y.
    Dunstan, J.
    Lee-Pullen, T.
    Hii, C.
    Meldrum, S.
    Zhang, Guicheng
    Metcalfe, J.
    Ferrante, A.
    Prescott, S.
    Date
    2012
    Type
    Journal Article
    
    Metadata
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    Citation
    D'Vaz, N. and Ma, Y. and Dunstan, J. and Lee-Pullen, T. and Hii, C. and Meldrum, S. and Zhang, G. et al. 2012. Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease. Allergy: European Journal of Allergy and Clinical Immunology. 67 (12): pp. 1511-1518.
    Source Title
    Allergy: European Journal of Allergy and Clinical Immunology
    DOI
    10.1111/all.12027
    ISSN
    0105-4538
    School
    School of Public Health
    URI
    http://hdl.handle.net/20.500.11937/8092
    Collection
    • Curtin Research Publications
    Abstract

    Background - Previous studies have demonstrated that reduced T-cell protein kinase C zeta (PKCζ) expression is associated with allergy development in infants born to atopic mothers. This study examined whether this relationship extends to a general population and addressed the basis for the association. Methods - A flow cytometry assay was developed for the measurement of T-cell PKCζ levels in PBMC, cord blood mononuclear cell and whole blood. Cord blood T-cell PKCζ levels were measured in 135 neonates, and allergic disease was evaluated by skin prick test and clinical examination at 12 months of age. Results - Allergic children (particularly those with eczema) had significantly lower neonatal T-cell PKCζ expression than nonallergic children (P < 0.001). PKCζ levels predicted allergic disease with optimal specificity of 86% and sensitivity of 54%. The sensitivity was increased in the children of allergic mothers, who had significantly lower PKC levels than the children of nonallergic mothers. Cord blood PKCζ levels did not affect T-cell maturation in culture as assessed by CD45RA/RO expression, but low PKCζ expression was associated with reduced capacity for IFNγ production by matured T cells. Low cord blood PKC expression was further associated with increased IL-13 responses at 6 months. Conclusions - The findings suggest a potential role for the use of PKCζ levels in cord blood T cells as a presymptomatic test to predict allergy risk in children, particularly offspring of allergic mothers, and that the basis of this relationship is related to cytokine patterns in mature T cells.

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