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

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 associat...

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Main Authors: D'Vaz, N., Ma, Y., Dunstan, J., Lee-Pullen, T., Hii, C., Meldrum, S., Zhang, Guicheng, Metcalfe, J., Ferrante, A., Prescott, S.
Format: Journal Article
Published: 2012
Online Access:http://hdl.handle.net/20.500.11937/8092
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author D'Vaz, N.
Ma, Y.
Dunstan, J.
Lee-Pullen, T.
Hii, C.
Meldrum, S.
Zhang, Guicheng
Metcalfe, J.
Ferrante, A.
Prescott, S.
author_facet D'Vaz, N.
Ma, Y.
Dunstan, J.
Lee-Pullen, T.
Hii, C.
Meldrum, S.
Zhang, Guicheng
Metcalfe, J.
Ferrante, A.
Prescott, S.
author_sort D'Vaz, N.
building Curtin Institutional Repository
collection Online Access
description 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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spelling curtin-20.500.11937-80922017-09-13T14:38:33Z Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease D'Vaz, N. Ma, Y. Dunstan, J. Lee-Pullen, T. Hii, C. Meldrum, S. Zhang, Guicheng Metcalfe, J. Ferrante, A. Prescott, S. 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/8092 10.1111/all.12027 restricted
spellingShingle D'Vaz, N.
Ma, Y.
Dunstan, J.
Lee-Pullen, T.
Hii, C.
Meldrum, S.
Zhang, Guicheng
Metcalfe, J.
Ferrante, A.
Prescott, S.
Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease
title Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease
title_full Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease
title_fullStr Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease
title_full_unstemmed Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease
title_short Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease
title_sort neonatal protein kinase c zeta expression determines the neonatal t-cell cytokine phenotype and predicts the development and severity of infant allergic disease
url http://hdl.handle.net/20.500.11937/8092