Cord Blood Decoy Receptor 3 as a New Biomarker in Predicting Neonates at Risk of Atopic Disease

Autor: I-Jan Hu, 胡逸然
Rok vydání: 2009
Druh dokumentu: 學位論文 ; thesis
Popis: 97
Introduction: The incidence of atopic diseases has increased in Taiwan during recent decade. Early identification of infants at risk may help in prevention of atopic symptoms, including atopic dermatitis (AD), allergic rhinitis (AR), or asthma. Previous researches revealed that cord blood immunoglobulin E (IgE) could be used to predict infants at risk of atopy for many years but the predictive ability was questionable due to low sensitivity and specificity reported in recent studies. Identifying high-risk infants at an early age remains major task for pediatricians and immunologists. The development of atopic disease is associated with overwhelmed T-helper 2 cell (Th2) - dependent immune response. Decoy receptor 3 (DcR3) is a soluble receptor that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 was found to be able to modulate human immune system via suppressing CD4+ T cell proliferation. DcR3-treated dendritic cells up-regulate IL-4 secretion of T cells suggests that DcR3 may act as an effector molecule to skew T cell response to the Th2 phenotype. Serum DcR3 level had been found to be elevated among atopic children and adolescences in clinical study. The application of cord blood DcR3 level at birth in predicting infants at risk has not been explored. We hypothesized that cord blood DcR3 concentrations were higher in infants with early onset atopic diseases and cord blood DcR3 could serve as a new biomarker in predicting neonates at risk of atopic disease. The role of DcR3 in modulating immune system responsiveness can be explored in animal models of atopic disease according to the finding of this study. Further prevention or treatment strategy for the management of high risk infants may be developed based on the pathogenesis of DcR3. Materials and methods: This is a prospective study in the Taiwan birth panel cohort study (TBPS). 430 paired maternal serum and cord blood from full-term healthy neonates born in northern Taiwan from April 2004 to January 2006 were collected after informed consent was obtained from the parents. 231 mothers and newborns pairs were recruited for DcR3 and IgE levels measurement. Maternal health status, pregnancy conditions, and neonates’ birth conditions, feeding conditions, parental atopic history, environmental tobacco smoke exposure, and family income per year were recorded. The enrolled infants received regular follow up during their health check-up clinics until 2 year of age. The diagnosis of atopic disease was based on doctor diagnosis and physical examinations, International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and objective measurement. Results: 174 Mother – infant pairs completed two years follow-up were enrolled for analysis. 48 (27.6%) infants developed atopic diseases during the study period. The cumulative incidence for AD, AR, and recurrent wheezing/asthma of 2-year olds was 18.4%, 10.3%, and 7.5% in the study cohort. The DcR3 levels of the maternal, cord blood, and 2-year serum samples were 0.49 ng/mL, 0.64 ng/mL, and 0.56 ng/mL (mean). The maternal, cord blood, and 2-year serum IgE levels were 76.31 kU/L, 0.64 kU/L, and 47.83 kU/L (mean), respectively. The cord blood and 2-year serum DcR3 levels were significant higher in infants with atopic disease than in non-atopic group (p< 0.05). The risks of atopic disease for infants with elevated cord DcR3 and for infants with parental atopy history were 2.44 and 2.75 compared to those without these risk factors (p=0.002, p= 0.038, respectively). The maternal DcR3 level, maternal, cord blood, and 2-year serum IgE levels were not statistically different between two groups. Cord blood DcR3 level was a potential biomarker in predicting early onset atopic diseases in the study population. The highest positive predictive value of 66.9% was achieved for cord DcR3 with a cut-off point of 0.66 ng/mL, sensitivity of 48%, and a specificity of 75%. Discussions: The overall cumulative incidence of 2-year olds atopic diseases in the study population was 27.6% and was similar with previous studies. Our report showed that serum DcR3 was measurable among healthy pregnant women and paired term newborns at birth and at 2-year-old. We observed that serum DcR3 level was significantly higher in neonates and in young children than in mothers, especially of infants with early onset atopic diseases. This study showed that both parental atopic disease history and elevated cord blood DcR3 were predictors for early childhood atopic diseases. The strength of this prospective cohort study included less recall bias and better temporal analysis. The limitations of the study included, first, 75.3% subjects completed follow-up and 24.7% did not. We performed data analysis and found no significant differences of demographic characteristics between those completed study and those who dropped out, therefore the representative of study population was acceptable. Second, the diagnosis for atopic diseases is difficult in young infants. We used ISAAC questionnaires, physical examination at check-up clinics, and parental reports of doctor diagnosis or medical records of atopic diseases to assist in subject identification. The method we applied to identified atopic infants had been used in previous studies and was applicable in our study cohort. Our results found that cord blood DcR3 concentration was higher in infants with early onset atopiic disease and that cord DcR3may serve as a substitute biomarker for the IgE in predicting the occurrence of early childhood atopic diseases. Conclusion: In conclusion, our study results suggest that cord blood DcR3 concentration may serve as a potential alternative biomarker in predicting high risk infants of atopic disease.
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