2146 Gestational Secondhand Smoke Exposure Could Affect Maternal n-Glycosylation and Cause Filaggrin Loss in Children with Atopic Dermatitis

Thursday, 15 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Galina Kuznecova , Allergy and Dermatology, Preventive Medicine Institute, Riga, Latvia

Ivans Sergejs Kuznecovs, MD , Allergy and Immunology, Preventive Medicine Institute, Riga, Latvia

Background: Atopic dermatitis (AD) affects approximately 10% of  children with rising tendency. The exact cause of AD is not known, but more than 50% of pregnant women are still exposed to secondhand smoke in Latvia and smoke exposure during pregnancy might increase the risk of AD in children. The aim of the present study is to investigate the mechanism of AD development in children, born of pregnancies affected with secondhand smoke. The objectives  are in favour of the idea that N-glycosylation in keratinocytes cells is limited by Dolichyl Phosphate Cycle (DPC) intermediates, regulated by DPAGT1 (Dolichyl-phosphate (UDP-N-acetylglucosamine) N-acetylglucosaminephosphotransferase 1 (GlcNAc-1-P transferase). Dysregulation of DPAGT1 causes disturbances in filaggrin expression. In epithelial cells loss of filaggrin correlates with atopic dermatitis (AD) presence and activity.
Methods: Two groups of mothers and children were compared. The samples were obtained from 154 women with self-reported secondhand smoke during pregnancy and their 156 children (group 1) and 180 women who did not have contact with tobacco smoke during pregnancy (group 2). Cotinine (Cot) and  dolichol (Dol) were measured in blood and urine during pregnancy. Filaggrin expression was measured in skin biopsies in newborns with follow up for 2 years.  Immunohistochemical and Western blotting methods were used to detect the changes in the expression levels of filaggrin and DPAGT1. Intermediates of DPC fractions were analysed by HPLC method.
Results: In group 1 during the period of observation 117 (75%) of children were diagnosed with AD. Mothers of these children (92%) have had Cot in blood and elevated urinal Dol excretion in pregnancy. In group 2 during the period of observation 9 (5%) of children were diagnosed with AD and 16 mothers have had elevated urinal Dol excretion.  Overexpression of DPAGT1 was 5-fold higher in AD skin biopsies than in normal skin biopsies and  differ from normal one in filaggrin content lost by 3-4 times. Suspected urinary Dol level in pregnancy with positive Cot for AD risk in newborns is calculated as 18.0 mkg/mmol.
Conclusion: Secondhand smoke during pregnancy could cause DPAGT overexpression and dysregulation of N-glycosylation in keratinocytes which leads to AD fenotype affecting the stability of tight assembly and adherence junctions in skin of newborns.  There is a reason to suggest that elevated Dol correlated with detected Cot in  urine  in pregnancy   may evidence of secondhand smoke related disorder of N-glycosylation. Dol appeared in urinary excretion in pregnancy affected by secondhand smoke is one of the first manifestation of AD risk for newborns . Dol detection in urine during gestational secondhand smoke exposure opens up possibilities for environmental control and for additional motivation to prevent AD in children.