Protein kinase Cζ: A novel protective neonatal T-cell marker that can be upregulated by allergy prevention strategies

Background

Variations in neonatal T-cell function have been associated with allergic disease.

Objectives

To examine the relationship between neonatal T-cell protein kinase (PKC) expression and subsequent allergic disease.

Methods

T cells were purified from cord blood samples (n = 74) obtained from a cohort of mothers who received either 4 g/d fish oil or a placebo from 20 weeks of gestation. PKC expression was examined in relationship to supplementation, fatty acid levels, cytokine production, and allergic outcomes at 1 year and 2.5 years of age.

Results

Neonatal T-cell PKCζ expression was lower in children who had evidence of allergic disease at 1 year (P = .001) and 2.5 years (P = .052) of age. It was also lower in children with sensitization (positive skin prick test) at each age (P = .02 and P = .072, respectively). PKCζ expression was inversely correlated to PKCα (r = −0.28; P = .025), which was strongly related to IL-5 responses to allergens (ovalbumin, r = 0.59; P = .003; dust mite, r = 0.52; P = .011) at 1 year of age. Fish oil supplementation was associated with significantly higher PKCζ expression (P = .014), whereas most other isozymes were reduced by fish oil supplementation.

Conclusion

This is the first study to show that allergic disease is associated with altered expression of T-cell PKC isozymes in the neonatal period. It has also demonstrated that fish oil can modulate expression of PKC isozymes in a potentially favorable direction.

Clinical implications

Protein kinase Cζ should be explored further as an early marker and potential target for disease prevention.

Key words: Protein kinase C, neonate, cytokines, fish oil, polyunsaturated fatty acids, atopic dermatitis, sensitization, allergy prevention, predictive markers, cord blood, allergy

Abbreviations used: DHA, Docosahexaenoic acid, EPA, Eicosapentaenoic acid, MC, Mononuclear cell, ω-3 LCPUFA, ω-3 Long chain polyunsaturated fatty acid, OR, Odds ratio, PKC, Protein kinase C, SEB, Staphylococcus aureus enterotoxin B, SPT, Skin prick test