title: Neonatal protein kinase C zeta expression determines the neonatal T-Cell cytokine phenotype and predicts the development and severity of infant allergic disease.
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.
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
authors.forename: N
authors.initials: N
authors.lastname: D'Vaz
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: J A
authors.initials: JA
authors.lastname: Dunstan
authors.forename: T F
authors.initials: TF
authors.lastname: Lee-Pullen
authors.forename: C
authors.initials: C
authors.lastname: Hii
authors.forename: S
authors.initials: S
authors.lastname: Meldrum
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Metcalfe
authors.forename: A
authors.initials: A
authors.lastname: Ferrante
authors.forename: S L
authors.initials: SL
authors.lastname: Prescott
mesh_terms: D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000201:enzymology* / Q000276:immunology*; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D011379:Prognosis; D011493:Protein Kinase C / Q000378:metabolism*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000201:enzymology* / Q000276:immunology*; D000099221:Protein Kinase C zeta
chemical_list: D016207:Cytokines; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta