Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/38837
Title: Soluble mediator profiles of cord blood mononuclear cells in early onset childhood allergic disorders
Authors: QUAH PHAIK LING
Keywords: Cord blood mononuclear cells, early life risk factors, eczema , wheeze, rhinitis
Issue Date: 21-Jan-2013
Source: QUAH PHAIK LING (2013-01-21). Soluble mediator profiles of cord blood mononuclear cells in early onset childhood allergic disorders. ScholarBank@NUS Repository.
Abstract: SUMMARY Background Neonates with a family history of atopy are at higher risk for developing allergic disorders in early life. The inherent immunological responses at birth are emerging as an important participant in allergic disorders. Objectives This dissertation aims to: i) study the early life demographic and clinical risk factors and the progression of allergic phenotypes in a 5 year follow-up from a birth cohort of high risk ( first degree relative with allergic disorder and allergen sensitization) for atopy infants. ii) evaluate the influence of intrinsic immunologic responses in cord blood mononuclear cells on eczema and wheezing disorders and allergen sensitization at 2 years and 5 years of age. Methods This study is centered in a cohort of 253 newborn infants who participated in a double-blind, placebo-controlled randomized clinical trial with a family history of allergic disease from the antenatal clinics at the National University Hospital, Singapore. Cord blood samples were collected from 195 eligible subjects. Soluble mediators from lipopolysaccharide (LPS) and phytohaemagglutinin (PHA) stimulated mononuclear cells were analyzed using the fluorescent activated cell sorting (FACS)-array and Bio-Plex 200 instrument. These profiles were assessed in relation to the clinical outcomes of wheezing, eczema or allergen sensitization and healthy control at 2 years and 5 years of age. Results I) Clinical outcomes In this cohort, 63% of the wheeze and 85% of the eczema subjects developed symptoms in the first 2 years of life. Early onset is defined as clinical phenotype outcomes in the first 2 years of life. Early onset of eczema alone (adjusted OR, 5.00; 95% CI 1.33-18.8) or early onset eczema and concomitant allergen sensitization (adjusted OR, 13.5; 95% CI 3.97-45.5) was associated to subsequent eczema at 5 years. Early onset wheeze (OR, 4.34; 95%CI, 1.26-14.9) or early onset wheeze with concomitant early onset allergen sensitization (OR, 7.17; 95%CI, 1.51-34.2) or eczema, wheeze and allergen sensitization co-existing together (OR, 9.24; 95%CI, 1.76-48.5) were associated with subsequent of wheeze at 5 years. II) Cord blood cytokine responses Using factor analysis, wheeze in the first 2 years was significantly associated with enhanced combined LPS stimulated IL-1?, IL-6 and IL-12/IL-23p40 compared to healthy controls (OR=2.45; 95% CI=1.50?3.93, p=0.001). Wheeze had hyper-responsive cytokine profiles with increased production of T-cell cytokines IL-2, IL-5, and IL-13. IL-5 was the strongest risk factor associated to the outcome of wheeze at 2 years (adjusted OR, 35; 95% CI, and 5.0 ? 246.7). Eczema was associated to hypo-responsive LPS and PHA stimulated IL-8 (LPS: Adjusted OR, 0.7; 95% CI, 0.5 ? 0.7) and (PHA: Adjusted OR, 0.6; 95% CI, 0.4 ? 0.8) respectively.Reduced productions of chemokines were associated to the development of eczema and wheeze. In contrast, asymptomatic subject?s sensitized to allergens was associated to elevated chemokine levels. Conclusions This study emphasizes the importance of early allergic clinical phenotypes as predictors of subsequent allergic disorders. The inherent aberrant immunological responses involving soluble mediators from cord blood mononuclear cells influence the development of early onset phenotypes. Future work is needed to provide a roadmap to gain more insights on the pathogenesis and identify novel signature biomarkers for prognosis or early diagnosis of allergic disorders in early childhood.
URI: http://scholarbank.nus.edu.sg/handle/10635/38837
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