Professor Pat Holt

Multi-centre, multi-disciplinary study using a systems biology approach to investigate immunomodulation in children with acute wheeze

Towards a diagnostic test for rheumatic fever

Using Systems Biology to understand asthma exacerbations and develop better treatments

An immunometabolomic approach to unmask developmental regulation of innate immunity and asthma risk

Acute viral bronchiolitis in infants and young children

Towards the establishment of the PREVAIL Centre, a Centre for PREcision in VAccine ImpLmentation at The Kids Research Institute Australia

PIFA - Pertussis and Food allergy, a case-cohort study of the association between pertussis vaccination in infancy and the risk of IgE-mediated food allergy

OPTIMUM: OPTimising IMmunisation Using Mixed schedules

Asthma: Acute asthma flare-up in school-age children

The aim of this study is to identify differences in immune cells that are involved in the disease.

Acute viral bronchiolitis in infants and young children

This project aims to plug this knowledge gap, and to open up new opportunities for development of better treatments targeted specifically at infants.

Mapping changes in immune cell populations in gestational tissues over the course of pregnancy

This is a strategic “pilot” project in which we are seeking basic information on the immune cell content of gestational tissues.

Long-term derangement of antigen presenting cell populations in the respiratory tract following Influenza A infection

This project investigates how different populations of cells within the respiratory tract immune system are altered during a viral infection.

Finding the cellular explanation for recurrent asthma exacerbations

This study is designed to identify the specific unique immune cell response that occurs in these children with recurrent disease.

Targeting the mucosal immune system in a pregnant mouse model to prevent experimental allergic airways disease in the offspring

Studies in Europe show exposure of pregnant women to high levels of microbial products stimulate immune function maturation in their offspring

The cellular effects of estrogen on allergic asthma

The study aims to identify the mechanism for this so that this knowledge can be used to better treat asthma and allergies in both males and females.

Mechanisms of IgE sensitization

This project investigates how cells of the immune system respond to substances to cause allergies to help develop new treatments.

Targeting the mucosal immune system in a mouse model to prevent pregnancy complications following maternal bacterial infection

This work is the first step to develop safe treatments for pregnant mums to protect against preterm delivery and low birth weight caused by maternal infections.

Prediction of asthma in childhood from wheezing phenotypes up to age 3 years: findings from community cohorts in Western Australian and the United Kingdom

In this project we are examining how well different wheezing phenotypes in the first 3 years of life predict current asthma in adolescents and young adults.

Examining relationships between vitamin D over the first decade of life and development of asthma and allergy

This study shows for the first time the importance of considering vitamin D levels over a prolonged period during childhood, rather than at just one or two ages

Developmental-associated dysregulation of innate anti-microbial immunity in early life as a determinant of susceptibility to atopic asthma

One of the strongest risk factors for asthma is having chest infections during infancy that are so severe that they trigger symptoms of fever & wheeze

The role of bacterial infections during infancy in asthma development

In this project we are studying how interactions between bacteria and viruses in children's airways promote the development of allergy and asthma.

Studies on the immunological mechanisms underlying progression versus resolution of asthma between adolescence and adulthood

This project seeks new information on asthma disease mechanisms, to help propel development of new and better anti-asthma drugs.

Epigenetic changes underpinning allergen sensitization: a twin-based study

We are studying immune cells from identical twins of which one suffers and one does not suffer from allergic disease to identify specific mechanisms that may pl

Characterization of “bystander” effects of the diphtheria-pertussis-tetanus (DTP) vaccine on the IgE system

We are seeking more detailed information on how the immune system of infants responds to the vaccine, with the aim of identifying which aspects of the immune r

Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial

In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule.

Mapping Lung Hematopoietic Progenitors: Developmental Kinetics and Response to Influenza A Infection

The bone marrow is a specialised niche responsible for the maintenance of hematopoietic stem and progenitor cells during homeostasis and inflammation. Recent studies however have extended this essential role to the extramedullary and extravascular lung microenvironment. Here, we provide further evidence for a reservoir of hematopoietic stem and progenitor cells within the lung from embryonic day 18.5 until adulthood.

Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze

Impaired interferon response and allergic sensitization may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells play a key role in antiviral immunity as critical producers of type I interferons. 

Single cell transcriptomics reveals cell type specific features of developmentally regulated responses to lipopolysaccharide between birth and 5 years

Human perinatal life is characterized by a period of extraordinary change during which newborns encounter abundant environmental stimuli and exposure to potential pathogens. To meet such challenges, the neonatal immune system is equipped with unique functional characteristics that adapt to changing conditions as development progresses across the early years of life, but the molecular characteristics of such adaptations remain poorly understood.

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Atopic dermatitis is a common inflammatory skin condition and prior genome-wide association studies have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date combining previously reported cohorts with additional available data.

Rhinoviruses A and C elicit long-lasting antibody responses with limited cross-neutralization

Rhinoviruses (RVs) can cause severe wheezing illnesses in young children and patients with asthma. Vaccine development has been hampered by the multitude of RV types with little information about cross-neutralization. We previously showed that neutralizing antibody (nAb) responses to RV-C are detected twofold to threefold more often than those to RV-A throughout childhood. Based on those findings, we hypothesized that RV-C infections are more likely to induce either cross-neutralizing or longer-lasting antibody responses compared with RV-A infections.

LPS binding protein and activation signatures are upregulated during asthma exacerbations in children

Asthma exacerbations in children are associated with respiratory viral infection and atopy, resulting in systemic immune activation and infiltration of immune cells into the airways. The gene networks driving the immune activation and subsequent migration of immune cells into the airways remains incompletely understood. Cellular and molecular profiling of PBMC was employed on paired samples obtained from atopic asthmatic children during acute virus-associated exacerbations and later during convalescence.

Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell recruitment and perturbation of regulatory T cell expansion in the lungs.

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group.

Protection against severe infant lower respiratory tract infections by immune training: Mechanistic studies

Results from recent clinical studies suggest potential efficacy of immune training (IT)-based approaches for protection against severe lower respiratory tract infections in infants, but underlying mechanisms are unclear.

Asthma and allergies in a cohort of adolescents conceived with ART

Research question: Are asthma and allergies more common in adolescents conceived with assisted reproductive technologies (ART) compared with adolescents conceived without?

Remission of peanut allergy is associated with rewiring of allergen-driven T helper 2-related gene networks

The immunological changes underpinning acquisition of remission (also called sustained unresponsiveness) following food immunotherapy remain poorly defined. Limited access to effective therapies and biosamples from treatment responders has prevented progress. Probiotic peanut oral immunotherapy is highly effective at inducing remission, providing an opportunity to investigate immune changes.

Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4

Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels.

Whole-cell pertussis vaccine in early infancy for the prevention of allergy in children

Atopic diseases are the most common chronic conditions of childhood. The apparent rise in food anaphylaxis in young children over the past three decades is of particular concern, owing to the lack of proven prevention strategies other than the timely introduction of peanut and egg.

Cord-blood respiratory syncytial virus antibodies and respiratory health in first 5 years of life

To determine the potential longer-term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord-blood RSV-neutralizing antibodies (RSV-NA) and RSV infections in the first 2 years of life, RSV-NA at 3 years, and respiratory health to age 5 years.

Whole‐cell pertussis vaccine in early infancy for the prevention of allergy in children

Atopic diseases are the most common chronic conditions of childhood. The apparent rise in food anaphylaxis in young children over the past three decades is of particular concern, owing to the lack of proven prevention strategies other than the timely introduction of peanut and egg.

Innate Immune Training for Prevention of Recurrent Wheeze in Early Childhood

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high versus low susceptibility to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype.

Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85

Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways.

Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85

Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways.

Enhanced Neutralizing Antibody Responses to Rhinovirus C and Age-Dependent Patterns of Infection

Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. The aim was to identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay.

The intersect of genetics, environment, and microbiota in asthma-perspectives and challenges

In asthma, a significant portion of the interaction between genetics and environment occurs through microbiota. The proposed mechanisms behind this interaction are complex and at times contradictory. This review covers recent developments in our understanding of this interaction: the "microbial hypothesis" and the "farm effect"; the role of endotoxin and genetic variation in pattern recognition systems; the interaction with allergen exposure; the additional involvement of host gut and airway microbiota; the role of viral respiratory infections in interaction with the 17q21 and CDHR3 genetic loci; and the importance of in utero and early-life timing of exposures.

Time spent outdoors through childhood and adolescence - assessed by 25-hydroxyvitamin D concentration - and risk of myopia at 20 years

To investigate the relationship between time spent outdoors, at particular ages in childhood and adolescence, and myopia status in young adulthood using serum 25-hydroxyvitamin D [25(OH)D] concentration as a biomarker of time spent outdoors. Participants of the Raine Study Generation 2 cohort had 25(OH)D concentrations measured at the 6-, 14-, 17- and 20-year follow-ups. Participants underwent cycloplegic autorefraction at age 20 years, and myopia was defined as a mean spherical equivalent -0.50 dioptres or more myopic. Logistic regression was used to analyse the association between risk of myopia at age 20 years and age-specific 25(OH)D concentrations. Linear mixed-effects models were used to analyse trajectory of 25(OH)D concentrations from 6 to 20 years.

OPTIMUM study protocol: an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine schedule

Combination vaccines containing whole-cell pertussis antigens were phased out from the Australian national immunisation programme between 1997 and 1999 and replaced by the less reactogenic acellular pertussis (aP) antigens. In a large case-control study of Australian children born during the transition period, those with allergist diagnosed IgE-mediated food allergy were less likely to have received whole-cell vaccine in early infancy than matched population controls (OR: 0.77 (95% CI, 0.62 to 0.95)). We hypothesise that a single dose of whole-cell vaccine in early infancy is protective against IgE-mediated food allergy.

Transplacental Innate Immune Training via Maternal Microbial Exposure: Role of XBP1-ERN1 Axis in Dendritic Cell Precursor Programming

We recently reported that offspring of mice treated during pregnancy with the microbial-derived immunomodulator OM-85 manifest striking resistance to allergic airways inflammation, and localized the potential treatment target to fetal conventional dendritic cell (cDC) progenitors. Here, we profile maternal OM-85 treatment-associated transcriptomic signatures in fetal bone marrow, and identify a series of immunometabolic pathways which provide essential metabolites for accelerated myelopoiesis.

Whole-cell pertussis vaccine in early infancy for the prevention of allergy

This is a protocol for a Cochrane Review (intervention). The objectives were to assess the efficacy and safety of whole‐cell pertussis (wP) vaccinations in comparison to acellular pertussis (aP) vaccinations in early infancy for the prevention of atopic diseases in children.

Whole-Cell Pertussis Vaccination and Decreased Risk of IgE-Mediated Food Allergy: A Nested Case-Control Study

Australian infants who received whole-cell pertussis vaccines were less likely to be diagnosed with food allergy in childhood

Interaction between filaggrin mutations and neonatal cat exposure in atopic dermatitis

Recent birth cohort studies showed a significant interaction between cat ownership at birth and mutations in FLG on the development of early‐onset atopic dermatitis

Immune function during early adolescence positively predicts adult facial sexual dimorphism in both men and women

Our results support a fundamental assumption that facial sexual dimorphism is an indicator of immune function during the development of facial sexual dimorphism

Oestrogen amplifies pre-existing atopy-associated Th2 bias in an experimental asthma model

The role of oestrogen in experimental atopic asthma, and guide future research on sex-related variations in atopic asthma susceptibility/intensity

A method for the generation of large numbers of dendritic cells from CD34+ hematopoietic stem cells from cord blood

Neonatal dendritic cells generated form CD34+ cord blood progenitors have a higher inflammatory potential when exposed to viral than bacterial related stimuli

Systems biology and big data in asthma and allergy: recent discoveries and emerging challenges

We describe recent "omic"-level findings, and examine how these findings have been systematically integrated to generate further insight

Immunoinflammatory responses to febrile lower respiratory infections in infants display uniquely complex/intense transcriptomic profiles

the association between infant LRTI and risk for persistent wheeze/asthma in this cohort is generally stronger for fLRTIs than for other infection categories

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children

The expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children

Primary prevention of severe lower respiratory illnesses in at-risk infants using the immunomodulator OM-85

The effects of OM-85 were strongest in the first winter season, with a trend for fewer children in the OM-85 group to have sLRIs and URIs

Risk factors and prognosis of recurrent wheezing in Chinese young children: A prospective cohort study

We aimed to investigate the risk factors for different wheezing phenotypes in Chinese young children and to explore the prognosis of recurrent wheezing

Personalized transcriptomics reveals heterogeneous immunophenotypes in children with viral bronchiolitis

Dysregulated expression of IFN-dependent pathways after respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants

Pregnancy Induces a Steady-State Shift in Alveolar Macrophage M1/M2 Phenotype That Is Associated With a Heightened Severity of Influenza Virus Infection

Pregnancy is associated with an alternatively activated phenotype of alveolar macrophage before infection

Quantification of Serum Ovalbumin-specific Immunoglobulin E Titre via in vivo Passive Cutaneous Anaphylaxis Assay

We describe herein a highly reproducible in vivo passive cutaneous anaphylaxis assay using Sprague Dawley rats for the quantification of ovalbumin-specific IgE

Early Life Ovalbumin Sensitization and Aerosol Challenge for the Induction of Allergic Airway Inflammation in a BALB/c Murine Model

This protocol adapted an experimental animal model of disease for sensitization to ovalbumin during the immediate post-weaning period beginning at 21 days of age

Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development

Type 1 and 3 interferon response capacity appears strongly developmentally constrained at birth

Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation

These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention

Basophil counts in PBMC populations during childhood acute wheeze/asthma are associated with future exacerbations

Our findings suggest that the proportion of degranulated basophils can also be associated with recurrent exacerbations

Trajectories of childhood immune development and respiratory health relevant to asthma and allergy

Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis

A marked shift in innate and adaptive immune response in chinese immigrants living in a western environment

There is a marked shift in innate and adaptive immune responses in Chinese immigrants after living in a Western environment for several years

Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease

To complement early allergic sensitization, monitoring NPM composition may enable early detection and intervention in high-risk children

Atopy-dependent and independent immune responses in the heightened severity of atopics to respiratory viral infections: Rat model studies

The co-exposure responses in the Th2high BN incorporated type I interferon/Th1, alternative macrophage activation/Th2 and Th17 signatures

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

GWAS analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis suggested shared genetic mechanisms across rhinitis-related traits

Functional differences in airway dendritic cells determine susceptibility to IgE-sensitization

Respiratory IgE-sensitization to innocuous antigens increases the risk for developing diseases such as allergic asthma.

Streptococcus pneumoniae colonization of the nasopharynx is associated with increased severity during respiratory syncytial virus infection in young children.

The present study aimed to clarify the effect of viral and bacterial co-detections on disease severity during paediatric ARI.

After asthma: Redefining airways diseases

Identify entrenched areas of asthma management and treatment in which progress has stalled and to challenge current principles

Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks

We identified new asthma loci, found new associations at loci implicated in the comorbidity of asthma plus hay fever and confirmed nine known loci.

Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics

Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatic with natural aeroallergen exposure

Asthma is responsible for considerable global morbidity and health-care costs. Substantial progress was made against key outcomes such as hospital admissions with asthma and mortality in the 1990s and early 2000s, but little improvement has been observed

We aim to provide our view of where we are and where we need to go as a community of clinicians and researchers who tackle the public health problem of asthma.

Streptococcus pneumoniae colonization of the nasopharynx is associated with increased severity during respiratory syncytial virus infection in young children

The present study aimed to clarify the effect of viral and bacterial co-detections on disease severity during paediatric acute respiratory infection (ARI).

An exposome perspective: Early-life events and immune development in a changing world

Here we review the historical origins of exposome research and define a new concept, the metaexposome

Tracking of Vitamin D status from childhood to early adulthood and its association with peak bone mass

There are moderate associations between vitamin D status measured in prepuberty, adolescence, and early adulthood

CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis

CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease

Protection against maternal infection-associated fetal growth restriction: Proof-of-concept with a microbial-derived immunomodulator

This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress represents an achievable therapeutic goal

Mannitol challenge testing for asthma in a community cohort of young adults

We aimed to quantify the diagnostic utility of mannitol challenge testing for asthma in a community cohort and a symptomatic wheezing subset of this cohort.

Identification and characterization of a dendritic cell precursor in parenchymal lung tissue

This is the first study to describe a pulmonary precursor cell for dendritic cells in lung tissue

Cord blood Streptococcus pneumoniae-specific cellular immune responses predict early pneumococcal carriage in high-risk infants in Papua New Guinea

We aimed to explore whether newborns in high-risk areas have pre-existing pneumococcal-specific cellular immune responses that effects early acquisition.

Vitamin D over the first decade and susceptibility to childhood allergy and asthma

We aimed to research relationships between 25(OH)D levels from birth to 10 y/o and susceptibility to allergic sensitization, respiratory issues and asthma.

Severe winter asthma exacerbations can be prevented by omalizumab, but there is no carryover effect.

Recurrent severe asthma exacerbations are associated with decreased lung growth or accelerated loss of long function and add substantially to cost and morbidity

Childhood atopy and mental health: a prospective, longitudinal investigation

Findings are the first linking atopy (measured by both parent report and objective verification) with increased vulnerability to affective and anxiety problems

Transiently increased IgE responses in infants and pre-schoolers receiving only (DTaP) vaccines compared to those initially receiving at least one dose of DTwP vaccine

Confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants

Serum 25-hydroxyvitamin D concentrations and cardiometabolic risk factors in adolescents and young adults

Associations between serum 25(OH)D concentrations and cardiometabolic risk factors from adolescence to young adulthood in the Raine Study

Timing of routine infant vaccinations and risk of food allergy and eczema at one year of age

There was no overall association between delayed DTaP and food allergy; however, children with delayed DTaP had less eczema and less use of eczema medication

Prevention of Allergy/Asthma - New Strategies

This review focuses on the scientific rationale for early intervention aimed at asthma prophylaxis and discusses therapeutic approaches

Distinguishing benign from pathologic TH2 immunity in atopic children

In addition to its role in blocking TH2 effector activation in the late-phase allergic response, IL-10 is a known IgG1 switch factor

Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses

Differential network analysis of allergen-induced CD4 T cell responses can unmask covert disease-associated genes and pin point novel therapeutic targets

Environmental microbial exposure and protection against asthma

This article looks at the clinical implications of the research into microbial exposure & protection against asthma.

The Infant Nasopharyngeal Microbiome Impacts Severity of Lower Respiratory Infection and Risk of Asthma Development

Lung inflammation resulting from ARIs during infancy is linked to asthma development.

The mechanism or mechanisms driving atopic asthma initiation: The infant respiratory microbiome moves to center stage

Although debate surrounding the mechanism or mechanisms governing this causal pathway remains intense, demonstration of the capacity of pretreatment...

Relationship between cytokine expression patterns and clinical outcomes: two population-based birth cohorts

Our findings suggest that positive HDM 'allergy tests' and asthma are associated with a broad range of immunophenotypes, which may have important...

Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages

Human peripheral blood monocytes were differentiated into uncommitted macrophages (M0) and then polarized to M1 and M2 phenotypes using LPS/IFN-gamma...

Environmental Factors in Children's Asthma and Respiratory Effects

Asthma is more common in childhood than in adulthood and is more correctly thought of as a syndrome than as a discrete condition.

Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem.

Meta-analysis identifies seven susceptibility loci involved in the atopic march

Eczema often precedes the development of asthma in a disease course called the 'atopic march'.

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma...

Persistent and compartmentalised disruption of dendritic cell subpopulations in the lung following influenza A virus infection

Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets in lung...

Anti-infective proteins in breast milk and asthma-associated phenotypes during early childhood

The impact of breast milk feeding on susceptibility to asthma in childhood is highly controversial, due in part to failure of the majority of studies in the...

Genome-wide association study of vitamin D levels in children: replication in the Western Australian Pregnancy Cohort (Raine) study

This genome-wide association study (GWAS) utilises data from the Western Australian Pregnancy Cohort (Raine) Study for 25-hydroxyvitamin D (25(OH)D) levels...

Elucidation of pathways driving asthma pathogenesis: Development of a systems-level analytic strategy

Whereas asthma was rare in the late 1800s and early 1900s, the marked increase in its incidence and prevalence since the 1960s points to substantial gene ×...

Vitamin D status and predictors of serum 25-hydroxyvitamin D concentrations in Western Australian adolescents

Using prospective data from the Western Australian Pregnancy Cohort (Raine) Study, we investigated vitamin D status and predictors of serum 25-hydroxyvitamin...

Global allergy forum and second davos declaration 2013 allergy: Barriers to cure - Challenges and actions to be taken

The epidemic increase in the prevalence of allergic disease, which first started in the industrialized countries in the 1960s, may have reached a peak in the...

Prenatal adverse life events increase the risk for atopic diseases in children, which is enhanced in the absence of a maternal atopic predisposition

There is evidence to suggest an association between prenatal maternal stress and the development of asthma or other atopic diseases in offspring.

Low serum 25-hydroxyvitamin D concentrations associate with non-alcoholic fatty liver disease in adolescents independent of adiposity

This paper examined the link between low serum Vitamin D levels and development of non-alcoholic fatty liver disease (NAFLD) in adolescents between 14 and 17...

Vitamin D deficiency at 16 to 20 weeks' gestation is associated with impaired lung function and asthma at 6 years of age

This paper examines whether a Vitamin D deficiency during pregnancy affects the child's lung function predisposition towards lung disease such as asthma.

Antibody and cell-mediated immunity to pertussis 4 years after monovalent acellular pertussis vaccine at birth

In the longest reported follow-up of infants who received aP vaccine at birth, we found a trend to lower PT IgG antibodies post booster compared with receipt...

Birth cohorts in asthma and allergic diseases: Report of a NIAID/NHLBI/MeDALL joint workshop

Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases.

Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms

Pregnancy is a time of vulnerability for vitamin D insufficiency, and there is an emerging literature associating low levels of 25(OH)-vitamin D with...

Prevention - what is the most promising approach?

This paper is an editorial comment by Professor Patrick Holt on the potential for developing early intervention strategies in children with allergies and asthma

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.

Genetic polymorphism of KIR2DL4 (CD158d), a putative NK cell receptor for HLA-G, does not influence susceptibility to asthma

No reproducible associations with KIR2DL4 genotype were identified, leading us to conclude that the KIR2DL4 9A/10A polymorphism has no influence...

Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease.

Size-Dependent Uptake of Particles by Pulmonary Antigen-Presenting Cell Populations

The respiratory tract is an attractive target organ for novel diagnostic and therapeutic applications with nano-sized carriers, but their immune effects and...

Prophylactic use of sublingual allergen immunotherapy in high-risk children: A pilot study

These findings suggest that this modified version of SLIT should be considered for retesting of mucosal-based immunotherapy for atopic asthma prevention.

Persistent Effects of Maternal Smoking during Pregnancy on Lung Function and Asthma in Adolescents

The extent to which maternal smoking in pregnancy (MSP) has persisting effects on respiratory health remains uncertain and the mechanisms involved are not...

Maternal Vitamin D Levels and the Autism Phenotype Among Offspring

We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype.

Safety and Immunogenicity of Neonatal Pneumococcal Conjugate Vaccination in Papua New Guinean Children: A Randomised Controlled Trial

We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in...

Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis

Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic...

Neonatal antigen-presenting cells are functionally more quiescent in children born under traditional compared with modern environmental conditions

One explanation for the high burden of allergic and autoimmune diseases in industrialized countries is inappropriate immune development under modern...

Ontogeny of toll-like and NOD-like receptor-mediated innate immune responses in Papua New Guinean infants

Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in...

Viral infections and atopy in asthma pathogenesis: New rationales for asthma prevention and treatment

Prospective birth cohort studies tracking asthma initiation and consolidation in community cohorts have identified viral infections occurring against a...

Hospitalisation for bronchiolitis in infants is more common after elective caesarean delivery

The authors previously reported an increased risk of hospitalisation for acute lower respiratory infection up to age 2 years in children delivered by...

Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk

A hallmark of atopic asthma is development of chronic airways hyper-responsiveness (AHR) that persists in the face of ongoing exposure to perennial...

Virus infection and allergy in the development of asthma: What is the connection?

Information is accumulating which implicates airway inflammation resulting from respiratory viral infections, acting against a background of atopy.

Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children

We aimed to measure the antibody development to 2 bacteria in a birth cohort at high risk of allergic disease, and to assess which responses are asthma-linked.

Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze

The aim of this study was to explore associations between severe respiratory infections and atopy in early childhood with persisting wheeze and asthma.

A novel role for interleukin-1 receptor signaling in the developmental regulation of immune responses to endotoxin

Suggests that IL-1R1 expression provides an additional level of Myd88-dependent signaling during this period of heighted susceptibility to infection.

Comparison of neonatal T regulatory cell function in Papua New Guinean and Australian newborns

We compared neonatal T reg from children born in western conditions (Australia) with those of neonates born in high microbial conditions (Papua New Guinea)...

Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development

The objective was to determine the association between maternal serum 25(OH)-vitamin D concentrations and behavioural, emotional and language outcomes...

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

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

A genomics-based approach to assessment of vaccine safety and immunogenicity in children

This methodology has significant potential to identify covert interactions between inflammatory pathways triggered by vaccination, and as such may be a...

Maternal Serum Vitamin D Levels During Pregnancy and Offspring Neurocognitive Development

New research links poor language to lack of Vitamin D in womb.

T-cell activation genes differentially expressed at birth in CD4+ T-cells from children who develop IgE food allergy

To show underlying mechanisms, we examined differences in T-cell gene expression in samples at birth and at 1 year in children with and without IgE allergy.

Sensitizing and Th2 Adjuvant Activity of Cysteine Protease Allergens

Here, we report on a model that does not use Th2-skewing adjuvants and yet achieves sensitization solely via the nasal mucosa.

Airway Epithelial Cells Condition Dendritic Cells to Express Multiple Immune Surveillance Genes

AEC-conditioned DC showed selective upregulation of chemokines that recruit Th1 cells, but minimal change in chemokines linked to Th2 cell recruitment.

Hospitalisation for bronchiolitis in infants is more common after elective caesarean delivery

The authors previously reported an increased risk of hospitalisation for acute lower respiratory infection up to age 2 years in children delivered by...

T regulatory cells in childhood asthma

Asthma is a chronic disease of the airways, most commonly driven by immuno-inflammatory responses to ubiquitous airborne antigens.

Restricted aeroallergen access to airway mucosal dendritic cells in vivo limits allergen-specific

Chronic innocuous aeroallergen exposure attenuates CD4+ T cell-mediated airways hyperresponsiveness in mice; however, the mechanism(s) remain unclear

Risk factors for bronchial hyperresponsiveness in teenagers differ with sex and atopic status

Sex-related differences in bronchial hyperresponsiveness (BHR) have been reported in adolescents, but the mechanisms remain obscure.

Pneumococcal conjugate vaccination at birth in a high-risk setting: No evidence for neonatal T-cell tolerance

Concerns about the risk of inducing immune deviation-associated "neonatal tolerance" as described in mice have restricted the widespread adoption...

Gene-vitamin D interactions on food sensitization: A prospective birth cohort study

It has been hypothesized that vitamin D deficiency (VDD) contributes to the development of food sensitization (FS) and then food allergy.

Gene polymorphisms, breast-feeding, and development of food sensitization in early childhood

The effect of breast-feeding on the development of allergic disease is uncertain

Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study

Vitamin D has been linked in some studies with atopy- and asthma-associated phenotypes in children with established disease,but its role in disease inception...

Interaction between adaptive and innate immune pathways in the pathogenesis of atopic asthma: Operation of a lung/bone marrow axis

Atopic asthma is the most common form of asthma, particularly during childhood, and in many cases it persists into adult life.

Regulatory role of IL10 genetic variations in determining allergen-induced TH2 cytokine responses in children

Interleukin-10 is a key immunomodulatory cytokine the principal function of which is to limit the magnitude of immune response.

Infection and the development of allergic disease

An improved understanding of the roles of protein kinases in intracellular signalling and disease progression has driven significant advances in protein...

Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control

The hallmark of atopic asthma is transient airways hyperresponsiveness (AHR) preceded by aeroallergen-induced Th-cell activation.

Environmental Factors in Children's Asthma and Respiratory Effects

Childhood asthma is a condition characterized by airflow obstruction that varies in time spontaneously, in response to various environmental stimuli...

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease.

Epithelial-dendritic cell interactions in allergic disorders

Airway epithelial cells act through multiple mechanisms to function as an important component of the pulmonary defence strategy that is crucial...

Does genetic regulation of IgE begin in utero?

Elucidation of early life factors is critical to understand the development of allergic diseases, especially those manifesting in early life such as food allerg

The hygiene hypothesis revisited: role of materno-fetal interactions

For 20 years, the hygiene hypothesis has dominated attempts to explain the increasing prevalence of allergic disease. A causal link between maternal innate immu

Th2-associated immunity to bacteria in asthma in teenagers and susceptibility to asthma

Bacterial colonisation of the airways is associated with increased risk of childhood asthma

Lung homing T-cell generation is dependent on strength and timing of antigen delivery to lymph nodes

Inhaled allergens are known for their immediate and ongoing effects in the respiratory tract (RT).

Do early-life viral infections cause asthma?

Epidemiologic associations between viral lower respiratory infections (LRIs) and asthma in later childhood are well known

Interactions between innate and adaptive immunity in asthma pathogenesis: new perspectives from studies on acute exacerbations

Atopic asthma, which is at its highest prevalence during childhood/young adulthood, represents the main focus of this review.

Dahlem Conference

There is increasing evidence that the functional state of the immune system at birth is predictive of the kinetics of immune maturation in early infancy.

Toward improved prediction of risk for atopy and asthma among preschoolers: A prospective cohort study

Atopy and asthma are commonly initiated during early life, and there is increasing interest in the development of preventive treatments for at-risk children.

Th2-polarisation of cellular immune memory to neonatal pertussis vaccination

Current infant vaccination against pertussis in North America and Australia requires three doses of vaccines including diphtheria, tetanus and acellular...

Early aberrant antibody responses of aeroallergen sensitised people to subclinical bacterial infection

Early aberrant antibody responses, aeroallergen sensitised people, subclinical bacterial infection

The developing immune system and allergy

The developing immune system and allergy

Early immunological influences on asthma development: opportunities for early intervention

Early immunological influences on asthma development: opportunities for early intervention

Toll-like receptor 7 function is reduced in adolescents with asthma

Anti-viral innate immune responses may be impaired in asthma, although the mechanisms are not well understood.

Identification and Isolation of Rodent Respiratory Tract Dendritic Cells

This chapter describes the preparation of respiratory tract tissue from both mice and rats for the isolation of respiratory tract dendritic cells (RTDC).

Assessment of the potency and potential immunomodulatory effects of the Measles Mumps Rubella-Varicella vaccine in infants

This study compared the potency and immunomodulatory effects of measles mumps rubella (MMR) vaccine given to infants alone or in combination with varicella...