CoA-mediated Th2 adjuvant activity in mothers’ milk linked to infant AD
MedWire News: Infants exposed to breast milk with a high T helper cell (Th2) adjuvant activity are more likely to develop atopic dermatitis (AD) than those exposed to normal breast milk, suggest study findings.
The results also suggest that coenzyme A (CoA) may be responsible for the observed elevated Th2 adjuvant activity.
Sho Matsushita (Saitama Medical University, Moroyama, Japan) and team analyzed questionnaires from 110 mothers with or without AD detailing parental allergic disease and exposures, focusing on symptoms related to eczema lasting for at least 2 months when their child was 6 months of age. In addition, frozen stock of the mothers' milk was subjected to Th2 adjuvant activity assay.
The authors found that some AD-associated milk samples showed increased cyclic adenosine 3',5'-monophosphate (cAMP) formation in THP-1 cells. However, none of the mothers' milk fed to healthy infants showed such an activity.
Mass spectrometry analysis using AD+ infants' milk showed signals that originated from factors with a molecular weight corresponding with that of CoA. Furthermore, CoA was shown to increase cAMP levels in phorbol 12-myristate 13-acetate-derived THP-1 cells and induced Th2 polarization in a mixed lymphocyte reaction system and ovalbumin-specific immune response.
Importantly, the team found CoA levels of 18.8 µg ml on average in samples from five mothers with AD, which were sufficient to induce Th2 polarization. This was found to contrast with the average concentration of 6.0 µg ml in milk from mothers without AD.
Furthermore, inhibition of CoA activity by oxidation of mothers' milk was shown to markedly decrease Th2 adjuvant activity. "The current results suggest a direct effect of mothers' milk with the development of AD," say the authors.
The team then confirmed the findings by showing that CoA demonstrated Th2 adjuvant activity in mice by oral administration. CoA-treated mice also showed modulated epidermal differentiation, which was mediated by CoA.
The researchers are performing additional studies to investigate why CoA concentration in milk varies among women and whether intervention can have a preventive effect on development of AD.
By Ingrid Grasmo