Premium
Neonatal protein kinase C zeta expression determines the neonatal T ‐ C ell cytokine phenotype and predicts the development and severity of infant allergic disease
Author(s) -
D'Vaz N.,
Ma Y.,
Dunstan J. A.,
LeePullen T. F.,
Hii C.,
Meldrum S.,
Zhang G.,
Metcalfe J.,
Ferrante A.,
Prescott S. L.
Publication year - 2012
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12027
Subject(s) - cord blood , medicine , immunology , peripheral blood mononuclear cell , allergy , umbilical cord , cytokine , population , t cell , immunophenotyping , flow cytometry , immune system , in vitro , biology , biochemistry , environmental health
Background Previous studies have demonstrated that reduced T ‐cell protein kinase C zeta ( PKC ζ) 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 PKC ζ levels in PBMC , cord blood mononuclear cell and whole blood. Cord blood T‐cell PKC ζ 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 PKC ζ expression than nonallergic children ( P < 0.001). PKC ζ 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 PKC ζ levels did not affect T‐cell maturation in culture as assessed by CD 45 RA / RO expression, but low PKC ζ expression was associated with reduced capacity for IFN γ 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 PKC ζ 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.