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

Allergy. 2012 Dec;67(12):1511-8. doi: 10.1111/all.12027. Epub 2012 Sep 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytokines / immunology
  • Cytokines / metabolism*
  • Female
  • Flow Cytometry
  • Humans
  • Hypersensitivity / diagnosis
  • Hypersensitivity / enzymology*
  • Hypersensitivity / immunology*
  • Immunophenotyping
  • Infant
  • Infant, Newborn
  • Male
  • Phenotype*
  • Prognosis
  • Protein Kinase C / metabolism*
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*

Substances

  • Cytokines
  • protein kinase C zeta
  • Protein Kinase C