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Biomedical subjects

B M Colwell

Publications and source records attributed to B M Colwell.

6 recordsLinked to original sources
PubMed1997

Prenatal origins of asthma and allergy.

The prevalence of asthma and related allergic disorders has increased considerably over the last 25 years. Genetic stock has not changed, so environmental factors must have influenced the phenotype. Infants who develop allergy already have an altered immune response at birth. We have investigated the development of immune responses during gestation and the effect of maternal allergen exposure during pregnancy and infant exposure in the first month of life on the development of allergy and disease. There was higher specific peripheral blood mononuclear cell proliferation to house dust mite (P = 0.01) and birch pollen (P = 0.004) in the third trimester compared with the second trimester, with the first positive responses seen at 22 weeks gestation. Maternal exposure to birch pollen after 22 weeks resulted in higher (P = 0.005) infant peripheral blood mononuclear cell responses to birch pollen at birth. Infants born at term, with at least one atopic, asthmatic parent, who developed allergic symptoms and positive skin prick test by one year of age had raised proliferative responses to house dust mites at birth compared to those with no symptoms (P = 0.01). In genetically predisposed individuals, antenatal factors, including maternal and thereby fetal exposure to allergens and maternoplacental-fetal immunological interactions, are active in determining whether an allergic predisposition is manifested as disease.

Allergens↗
PubMed1996

Fetal peripheral blood mononuclear cell proliferative responses to mitogenic and allergenic stimuli during gestation.

Blood samples were obtained from fetuses and premature babies (n = 51) (15-34 weeks gestation) to determine at what stage the fetal immune system was able to produce a positive proliferative response to common allergens. Peripheral blood mononuclear cells (PBMC) were stimulated with the mitogen, phytohaemagglutinin (PHA), and the allergens, house dust mite, cat fur, birch tree pollen, beta-lactoglobulin, ovalbumin and bee venom (mellitin). Results were expressed as ratios of stimulated to unstimulated 3H thymidine incorporation, and as percent positive responders. There was an increase in proliferation ratio which correlated with increasing gestational age for PHA (p < 0.0001), cat fur (p = 0.042), birch pollen (p = 0.022) and beta-lactoglobulin (p = 0.006). The point in gestation when cells from some individuals began responding to the allergens with a ratio of 2.0 was at approximately 22 weeks. PBMC proliferative response ratios were higher from samples from babies > 22 weeks gestation compared to < 22 weeks for the mitogen and all allergens, except mellitin. There was also a greater proportion of positive responders from samples > 22 weeks compared to < 22 weeks for the mitogen and all allergens, except mellitin. Maternal exposure to birch pollen, which has a discrete season, was assessed to determine whether exposure had occurred at 22 weeks gestation or beyond. Results showed a higher proliferative response in infant cells stimulated with birch pollen (p = 0.005) and higher proportion of positive responders (p = 0.01) in the group of babies whose mothers had been exposed to birch pollen beyond 22 weeks, compared to those whose mothers had not been so exposed. These results suggest that in utero fetal exposure to an allergen from around 22 weeks gestation may result in primary sensitisation to that allergen, leading to positive proliferative responses, at birth.

Adult↗
PubMed1996

Peripheral blood mononuclear cell proliferative responses in the first year of life in babies born to allergic parents.

BACKGROUND: Raised peripheral blood mononuclear cells (PBMCs) proliferative responses to food allergens have been demonstrated in children with established atopic dermatitis. OBJECTIVE: In this report we investigate the PBMC proliferative responses to inhalant and food allergens from babies at birth, 6 months and 1 year of age, born to atopic and non-atopic parents. METHODS: PBMCs, separated by density gradient centrifugation, were cultured for 6 days with autologous plasma and a range of allergens (house dust mite [HDM], cat, grass pollen, tree pollen, betalactoglobulin and ovalbumin). Proliferative responses were measured by the uptake of [3H] thymidine added for the final 18 h of culture. RESULTS: At birth, infants born to atopic parents who developed allergic disease by 1 year of age had significantly more positive responses (stimulation index > or = 2 with a value of > or = 1000 cpm above background) to HDM (P = 0.0097), betalactoglobulin (P = 0.0166) and ovalbumin (P = 0.0035) than newborns who did not develop allergy. Infants who developed allergy also had significantly more positive responses to HDM (P = 0.03) and ovalbumin (P = 0.0057) than babies, born to non-atopic parents, who did not develop allergies. At 6 months of age a significant fall in response to HDM (P = 0.003) and cat fur extract (P = 0.006) was seen in infants who developed allergic disease by 1 year of age. A similar pattern was seen for proliferative responses to betalactoglobulin and ovalbumin (P = 0.0006, P = 0.004). Conversely, proliferations to grass and tree pollen extracts increased at 6 months (P = 0.04, P = NS) and 1 year (P = NS, P = 0.01) compared with birth which was significant for infants who did not develop allergic disease. CONCLUSION: Proliferative responses to seasonal allergens increased over the first year of life whilst those to perennial allergens, both inhalant and food, fell. This suggests either the induction of a systemic immune tolerance by perennial exposure to antigens or movement of sensitized cells to target organs where allergen exposure occurs. This process may be independent of the development allergic disease.

Aging↗
PubMed1994

Is deficiency of interferon gamma production by allergen triggered cord blood cells a predictor of atopic eczema?

Peripheral blood mononuclear cell proliferative responses and interferon-gamma production to anti-CD3, cat fur extract, betalactoglobulin and ovalbumin were determined at birth in a group of 34 babies born to families where at least one parent was atopic. The development of atopic eczema with positive allergy skin-prick tests to cows' milk and egg at 1 year of age, where the symptoms improved on an egg and milk-free diet, was significantly associated with raised proliferative responses and defective IFN-gamma production to stimulation with betalactoglobulin with a trend for similar responses to ovalbumin. This was not observed in those who did not develop atopic eczema or those with atopic eczema not associated with foods. Responses to cat fur extract were not significantly different between those with and without atopic eczema. This has important implications for the prediction at birth, not only of the probability of being allergic, but also of the specific allergens which will cause problems. The implementation of specific targeted allergen avoidance during the critical period in infancy, therefore, should be more easily applied and should facilitate attempts to prevent disease.

Allergens↗
PubMed1994

Altered T lymphocyte phenotype at birth in babies born to atopic parents.

Flow cytometry was used to analyse the cord blood T cells of 33 babies at high risk 'HR' for developing allergy (born to at least one atopic, asthmatic parent), and 10 low risk 'LR' babies (born to non-atopic parents), following normal term deliveries. Significantly lower numbers of CD25+, (activated) T cells (p < 0.005) were seen in the cord blood of the HR babies who had developed both allergic symptoms and positive skin prick tests by one year of age when compared with the LR group. CD45RO+ (memory) T cells were detected in both HR and LR babies with a trend for lower numbers of memory cells to be detected in HR infants who later developed allergic symptoms and/or positive skin prick tests. Significantly lower numbers of CD4+/CD45RO+ were seen in the cord blood of HR babies who developed allergic symptoms compared to HR babies who showed no sign of allergy by one year and to the LR babies (p < 0.05 and p < 0.005). The presence of activated and memory T cells at birth implies intra-uterine priming. The significantly lower numbers of memory T cells in the HR babies suggests a suppression of T cell activation or lack of antigenic priming in this group. This prenatal influence on babies born to atopic parents may have important implications with regard to the mechanisms underlying atopic sensitisation.

Antigens, CD↗