Differences in both prevalence and titre of specific immunoglobulin E among children with asthma in affluent and poor communities within a large town in Ghana.

Background Reports from several African countries have noted an increasing prevalence of asthma in areas of extensive urbanization. Objective To investigate the relevance of allergen-specific sensitization and body mass index (BMI) to asthma/wheezing and exercise-induced bronchospasm (EIB) among children from affluent and poorer communities within a large town in Ghana. Methods Children with physician-diagnosed asthma and/or current wheezing aged 9-16 years (n=99; cases) from three schools with differing socio-economic backgrounds [urban affluent (UA), urban poor (UP) or suburban/rural (SR)] were recruited from a cross-sectional study (n=1848) in Kumasi, Ghana, and matched according to age, sex and area of residence with non-asthmatic/non-wheezy controls. We assayed sera for IgE antibodies to mite, cat, dog, cockroach, Ascaris and galactose-α-1,3-galactose. Results Children from the UA school had the lowest total serum IgE. However, cases from the UA school had a higher prevalence and mean titre of sIgE to mite (71.4%, 21.2IU/mL) when compared with controls (14.3%, 0.8IU/mL) or cases from UP (30%, 0.8IU/mL) and SR community (47.8%, 1.6IU/mL). While similar findings were observed with EIB in the whole population, among cases there was no difference in IgE antibody prevalence or titre between children with or without EIB. BMI was higher among UA children with and without asthma; in UP and SR communities, children with EIB (n=14) had a significantly higher BMI compared with children with asthma/wheezing without EIB (n=38) (18.2 vs. 16.4, respectively, P<0.01). Conclusions and Clinical Relevance In the relatively affluent school, asthma/wheezing and EIB were associated with high titre IgE antibodies to mite, decreased total IgE, and increased BMI. This contrasted with children in the urban poor school and suggests that changes relevant to a Western model of childhood asthma can occur within a short geographical distance within a large city in Africa. © 2011 Blackwell Publishing Ltd

Prediction of Peptide Binding to Major Histocompatibility II Receptors with Molecular Mechanics and Semi-Empirical Quantum Mechanics Methods

Methods for prediction of the binding of peptides to major histocompatibility complex (MHC) II receptors are examined, using literature values of IC50 as a benchmark. Two sets of IC50 data for closely structurally related peptides based on hen egg lysozyme (HEL) and myelin basic protein (MBP) are reported first. This shows that methods based on both molecular mechanics and semi-empirical quantum mechanics can predict binding with good-to-reasonable accuracy, as long as a suitable method for estimation of solvation effects is included. A more diverse set of 22 peptides bound to HLA-DR1 provides a tougher test of such methods, especially since no crystal structure is available for these peptide-MHC complexes. We therefore use sequence based methods such as SYFPEITHI and SVMHC to generate possible binding poses, using a consensus approach to determine the most likely anchor residues, which are then mapped onto the crystal structure of an unrelated peptide bound to the same receptor. This analysis shows that the MM/GBVI method performs particularly well, as does the AMBER94 forcefield with Born solvation model. Indeed, MM/GBVI can be used as an alternative to sequence based methods in generating binding poses, leading to still better accuracy

Giardia: a pathogen or commensal for children in high-prevalence settings?

Giardia is a common intestinal parasite worldwide, and infection can be associated with clear and sometimes persistent symptomatology. However, in children in high prevalence settings, it is not associated with or is perhaps even protective against acute diarrhea, and the association with long-term outcomes has been difficult to discern

Asthma Severity and Prevalence: An Ongoing Interaction between Exposure, Hygiene, and Lifestyle

Why are the prevalence and severity of asthma increasing? Platts-Mills looks at the key studies that can help to anwer this important questio

The use of machine learning to understand the relationship between IgE to specific allergens and asthma

In a study recently published in PLOS Medicine, Custovic and colleagues report an elegant analysis of the results of specific Immunoglobulin E (IgE) assays on sera from a birth cohort that they have studied in detail over the last 15 years. The IgE assays used a microchip with >100 purified allergens, and their machine learning approach used a hypothesis-free statistical approach to group children with similar allergen sensitization profiles. The primary objective was to evaluate the relationship of the results to the diagnosis of current asthma. The goal of employing a “machine learning” approach is both as a form of data reduction to avoid spuriously identified associations resulting from multiple comparisons and to identify biologically relevant groupings that may not be recognized with conventional approaches. The use of “hypothesis free” clustering methods with individual allergen components in itself is not novel. However, the authors have employed a new network analysis method, which is improved over previous methods because it can capture nonlinear relationships and does not rely on assumption of a parametric probability. As the authors show, this approach can lead to improved sensitivity and specificity. With this model, they were able to show that pairings of allergens (e.g., the cat allergen Fel d 1 and the peanut allergen Ara h 1) were more predictive of the child having asthma than individual components, although we must be cautious in the generalizability of the specific patterns identified, in this single cohort in the United Kingdom, because the pairing may represent host susceptibility to making an IgE response or common co-exposures, which could be allergens or adjuvants. Still, the concept of complicated connections between individual allergenic proteins and allergic disease are likely to apply more broadly and are important to consider in future studies