Dysfunctional Gut Microbiome Networks in Childhood IgE-Mediated Food Allergy.

The development of food allergy has been reported to be related with the changes in the gut microbiome, however the specific microbe associated with the pathogenesis of food allergy remains elusive. This study aimed to comprehensively characterize the gut microbiome and identify individual or group gut microbes relating to food-allergy using 16S rRNA gene sequencing with network analysis. Faecal samples were collected from children with IgE-mediated food allergies ( = 33) and without food allergy ( = 27).

Linking the westernised oropharyngeal microbiome to the immune response in Chinese immigrants.

Background: Human microbiota plays a fundamental role in modulating the immune response. Western environment and lifestyle are envisaged to alter the human microbiota with a new microbiome profile established in Chinese immigrants, which fails to prime the immune system. Here, we investigated how differences in composition of oropharyngeal microbiome may contribute to patterns of interaction between the microbiome and immune system in Chinese immigrants living in Australia.

Differential Gene Expression of Lymphocytes Stimulated with Rhinovirus A and C in Children with Asthma.

Individuals with asthma have heightened antibody responses to rhinoviruses (RVs), although those specific for RV-C are lower than responses specific for RV-A, suggesting poor immunity to this species. To ascertain and compare T-cell memory responses induced by RV-A and RV-C in children with and without asthma. Peripheral blood mononuclear cells from 17 children with asthma and 19 control subjects without asthma were stimulated with peptide formulations to induce representative species-specific responses to RV-A and RV-C.

Effects of Ser47-Point Mutation on Conformation Structure and Allergenicity of the Allergen of Der p 2, a Major House Dust Mite Allergen.

Purpose: Hypoallergenic recombinant Der p 2 has been produced by various genetic manipulations, but mutation of a naturally polymorphic amino acid residue known to affect IgE binding has not been studied. This study aimed to determine the effect of a point mutation (S47W) of residue 47 of Der p 2 on its structure and immunoglobulin (Ig) E binding. Its ability to induce pro-inflammatory responses and to induce blocking IgG antibody was also determined.

Clinical significance of circulating microRNAs as markers in detecting and predicting congenital heart defects in children.

Background: Circulating microRNAs (miRNAs) are emerging as novel biomarkers for detecting cardiovascular diseases. In this study, we aimed to investigate the usefulness of miRNAs as biomarkers in diagnosing and predicting children with congenital heart defects (CHD), particularly in the context of multiple subtypes of CHD.

Methods: We recruited 26 families, each having a child with CHD and parents who do not have any cardiovascular disorder.

T-cell responses against rhinovirus species A and C in asthmatic and healthy children.

Background: Infections by rhinovirus (RV) species A and C are the most common causes of exacerbations of asthma and a major cause of exacerbations of other acute and chronic respiratory diseases. Infections by both species are prevalent in pre-school and school-aged children and, particularly for RV-C, can cause severe symptoms and a need for hospitalization. While associations between RV infection and asthma are well established, the adaptive immune-mechanisms by which RV infections influence asthma exacerbations are yet to be defined.

A longitudinal study of natural antibody development to pneumococcal surface protein A families 1 and 2 in Papua New Guinean Highland children: a cohort study.

Background: Pneumococcal surface protein A (PspA), a conserved virulence factor essential for attachment to upper respiratory tract (URT) epithelia, is a potential vaccine candidate for preventing colonisation.

Methods: This cohort study was conducted in the Asaro Valley in the Eastern Highlands Province of Papua New Guinea, of which Goroka town is the provincial capital. The children included in the analysis were participants in a neonatal pneumococcal conjugate vaccine trial (ClinicalTrials.

Immunodominant T-Cell Epitopes in the VP1 Capsid Protein of Rhinovirus Species A and C.

Unlabelled: Rhinovirus (RV) species A and C are the most frequent cause of respiratory viral illness worldwide, and RV-C has been linked to more severe exacerbations of asthma in young children. Little is known about the immune responses to the different RV species, although studies comparing IgG1 antibody titers found impaired antibody responses to RV-C. Therefore, the aim of this study was to assess whether T-cell immunity to RV-C is similarly impaired.

Western environment/lifestyle is associated with increased genome methylation and decreased gene expression in Chinese immigrants living in Australia.

Introduction: Several human diseases and conditions are disproportionally distributed in the world with a significant "Western-developed" vs. "Eastern-developing" gradient.

Methods: We compared genome-wide DNA methylation of peripheral blood mononuclear cells in 25 newly arrived Chinese immigrants living in a Western environment for less than 6 months ("Newly arrived") with 23 Chinese immigrants living in the Western environment for more than two years ("Long-term") with a mean of 8.

Effect of Amino Acid Polymorphisms of House Dust Mite Der p 2 Variants on Allergic Sensitization.

Purpose: The sequence variations of the Der p 2 allergen of Dermatophagoides pteronyssinus diverge along 2 pathways with particular amino acid substitutions at positions 40,47,111, and 114. The environmental prevalence and IgE binding to Der p 2 variants differ among regions. To compare IgE binding to Der p 2 variants between sera from Bangkok, Thailand and Perth, Western Australia with different variants and to determine the variant-specificity of antibodies induced by vaccination with recombinant variants.

Distinguishing benign from pathologic TH2 immunity in atopic children.

Background: Although most children with asthma and rhinitis are sensitized to aeroallergens, only a minority of sensitized children are symptomatic, implying the underlying operation of efficient anti-inflammatory control mechanisms.

Objective: We sought to identify endogenous control mechanisms that attenuate expression of IgE-associated responsiveness to aeroallergens in sensitized children.

Methods: In 3 independent population samples we analyzed relationships between aeroallergen-specific IgE and corresponding allergen-specific IgG (sIgG) and associated immunophenotypes in atopic children and susceptibility to asthma and rhinitis, focusing on responses to house dust mite and grass.

Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization.

Background: In human subjects, allergen tolerance has been observed after high-dose allergen exposure or after completed allergen immunotherapy, which is related to the accumulation of anti-inflammatory IgG4. However, the specific T-cell response that leads to IgG4 induction during chronic allergen exposure remains poorly understood.

Objective: We sought to evaluate the relationship between cat allergen-specific T-cell frequency, cat allergen-specific IgE and IgG4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG4 is produced.

The infant nasopharyngeal microbiome impacts severity of lower respiratory infection and risk of asthma development.

The nasopharynx (NP) is a reservoir for microbes associated with acute respiratory infections (ARIs). Lung inflammation resulting from ARIs during infancy is linked to asthma development. We examined the NP microbiome during the critical first year of life in a prospective cohort of 234 children, capturing both the viral and bacterial communities and documenting all incidents of ARIs.

Improving immunity to Haemophilus influenzae in children with chronic suppurative lung disease.

Background: Endobronchial infections related to non-typeable Haemophilus influenzae (NTHi) are common in children and adults with suppurative airway disease such as bronchiectasis and COPD. Impaired cell mediated immune responses to NTHi have been described in these patients. Currently there are no interventions known to correct the deficiency in cell mediated immune responses to NTHi.

Children with chronic suppurative lung disease have a reduced capacity to synthesize interferon-gamma in vitro in response to non-typeable Haemophilus influenzae.

Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children.

Comparison of rhinovirus antibody titers in children with asthma exacerbations and species-specific rhinovirus infection.

Background: Asthma exacerbations are associated with human rhinovirus (HRV) infections, and more severe exacerbations are associated with HRV-C. We have previously shown that the HRV-C-specific antibody response is low in healthy adult sera and that most of the antibody to HRV-C is cross-reactive with HRV-A.

Objectives: To compare the antibody response to each HRV species in asthmatic and nonasthmatic children in whom the type of HRV infection was known.

IgE and IgG binding patterns and T-cell recognition of Fel d 1 and non-Fel d 1 cat allergens.

Background: Cat allergy affects approximately 15% of the population and is a major risk factor for asthma. The relative importance of cat allergens other than Fel d 1 is not known.

Objective: To compare IgE and IgG antibody binding and T-cell recognition of the major cat allergen Fel d 1 with other cat proteins with known IgE binding properties.

Defective respiratory tract immune surveillance in asthma: a primary causal factor in disease onset and progression.

The relative importance of respiratory viral infections vs inhalant allergy in asthma pathogenesis is the subject of ongoing debate. Emerging data from long-term prospective birth cohorts are bringing increasing clarity to this issue, in particular through the demonstration that while both of these factors can contribute independently to asthma initiation and progression, their effects are strongest when they act in synergy to drive cycles of episodic airways inflammation. An important question is whether susceptibility to infection and allergic sensitization in children with asthma arises from common or shared defect(s).

Species-specific and cross-reactive IgG1 antibody binding to viral capsid protein 1 (VP1) antigens of human rhinovirus species A, B and C.

Background: Human rhinoviruses (HRV) are associated with upper and lower respiratory illnesses, including severe infections causing hospitalization in both children and adults. Although the clinical significance of HRV infections is now well established, no detailed investigation of the immune response against HRV has been performed. The purpose of this study was to assess the IgG1 antibody response to the three known HRV species, HRV-A, -B and -C in healthy subjects.

Quantitation of IgE binding to the chitinase and chitinase-like house dust mite allergens Der p 15 and Der p 18 compared to the major and mid-range allergens.

Background: The prevalence of IgE binding to the group 15 and 18 house dust mite (HDM) allergens of the Dermatophagoides species is reported to be >50% and they are the major allergens of HDM-sensitised dogs. The objective was to quantitate the IgE titres to Der p 15 and Der p 18 and evaluate their importance in human HDM sensitisation compared to the known major and mid-tier allergens.

Methods: Der p 15 and Der p 18 were produced in Pichia pastoris, and their structure validated by circular dichroism.

Reduced rhinovirus-specific antibodies are associated with acute exacerbations of chronic obstructive pulmonary disease requiring hospitalisation.

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are often linked to respiratory infections. However, it is unknown if COPD patients who experience frequent exacerbations have impaired humoral immunity. The aim of this study was to determine if antibodies specific for common respiratory pathogens are associated with AECOPD.

Effect of early carriage of Streptococcus pneumoniae on the development of pneumococcal protein-specific cellular immune responses in infancy.

Background: The aim of this study was to examine the relationship between nasopharyngeal pneumococcal colonization in early life and the subsequent development of pneumococcal-specific T cell responses.

Methods: Pernasal swabs were collected from Papua New Guinean infants at the ages of 1 and 2 weeks (n = 279). At 9 months, in vitro cellular immune responses to choline-binding protein A (n = 132), pneumococcal surface protein A (n = 132), pneumolysin (n = 99), and the pneumococcal conjugate vaccine carrier CRM197 were determined.