Tag: Sensitization

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Allergic Sensitization at School Age is a Systemic Low-grade Inflammatory Disorder.

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Allergic Sensitization at School Age is a Systemic Low-grade Inflammatory Disorder.

Allergy. 2016 Dec 19;:

Authors: Chawes BL, Stokholm J, Schoos AM, Rahman N, Brix S, Bisgaard H

Abstract
BACKGROUND: Systemic low-grade inflammation has been demonstrated in a range of the frequent noncommunicable diseases (NCDs) proposing a shared mechanism, but is largely unexplored in relation to allergic sensitization. We therefore aimed to investigate the possible association with childhood allergic sensitization.
METHODS: High sensitivity C-reactive protein (hs-CRP), interleukin-1? (IL-1?), IL-6, tumor necrosis factor-? (TNF-?) and chemokine (C-X-C motif) ligand 8 (CXCL8) were measured in plasma at age 6mo (N=214) and 7yrs (N=277) in children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000 ) birth cohort. Allergic sensitization against common inhalant and food allergens was determined longitudinally at age ½, 1½, 4 and 6yrs by specific-IgE assessments and skin prick tests. Associations between inflammatory biomarkers and sensitization phenotypes were tested with logistic regression and principle component analyses (PCA).
RESULTS: Adjusted for gender, recent infections and a CRP genetic risk-score, hs-CRP at 7yrs was associated with concurrent elevated specific-IgE against any allergen (adjusted OR (aOR) =1.40; 95% CI, 1.14-1.72; p=0.001), aeroallergens (aOR, 1.43; 1.15-1.77; p=0.001), food allergens (aOR, 1.31; 95% CI, 1.02-1.67; p=0.04), sensitization without any clinical allergy symptoms (aOR=1.40; 1.06-1.85; p=0.02), and with similar findings for skin prick tests. The other inflammatory markers were not univariantly associated with sensitization, but multi-parametric PCA suggested a specific inflammatory response among sensitized children. Inflammatory markers at age 6mo were not associated with subsequent development of sensitization phenotypes.
CONCLUSIONS: Elevated hs-CRP is associated with allergic sensitization in school-aged children suggesting systemic low-grade inflammation as a phenotypic characteristic of this early onset NCD. This article is protected by copyright. All rights reserved.

PMID: 27992959 [PubMed – as supplied by publisher]

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Genetics of allergy and allergic sensitization: common variants, rare mutations.

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Genetics of allergy and allergic sensitization: common variants, rare mutations.

Curr Opin Immunol. 2015 Sep 16;36:115-126

Authors: Bønnelykke K, Sparks R, Waage J, Milner JD

Abstract
Our understanding of the specific genetic lesions in allergy has improved in recent years due to identification of common risk variants from genome-wide association studies (GWAS) and studies of rare, monogenic diseases. Large-scale GWAS have identified novel susceptibility loci and provided information about shared genetics between allergy, related phenotypes and autoimmunity. Studies of monogenic diseases have elucidated critical cellular pathways and protein functions responsible for allergy. These complementary approaches imply genetic mechanisms involved in Th2 immunity, T-cell differentiation, TGF? signaling, regulatory T-cell function and skin/mucosal function as well as yet unknown mechanisms associated with newly identified genes. Future studies, in combination with data on gene expression and epigenetics, are expected to increase our understanding of the pathogenesis of allergy.

PMID: 26386198 [PubMed – as supplied by publisher]

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Endotoxin Exposure during Sensitization to Blomia tropicalis Allergens Shifts TH2 Immunity Towards a TH17-Mediated Airway Neutrophilic Inflammation: Role of TLR4 and TLR2.

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Endotoxin Exposure during Sensitization to Blomia tropicalis Allergens Shifts TH2 Immunity Towards a TH17-Mediated Airway Neutrophilic Inflammation: Role of TLR4 and TLR2.

PLoS One. 2013;8(6):e67115

Authors: Barboza R, Câmara NO, Gomes E, Sá-Nunes A, Florsheim E, Mirotti L, Labrada A, Alcântara-Neves NM, Russo M

Abstract
Experimental evidence and epidemiological studies indicate that exposure to endotoxin lipopolysaccharide (eLPS) or other TLR agonists prevent asthma. We have previously shown in the OVA-model of asthma that eLPS administration during alum-based allergen sensitization blocked the development of lung TH2 immune responses via MyD88 pathway and IL-12/IFN-? axis. In the present work we determined the effect of eLPS exposure during sensitization to a natural airborne allergen extract derived from the house dust mite Blomia tropicalis (Bt). Mice were subcutaneously sensitized with Bt allergens co-adsorbed onto alum with or without eLPS and challenged twice intranasally with Bt. Cellular and molecular parameters of allergic lung inflammation were evaluated 24 h after the last Bt challenge. Exposure to eLPS but not to ultrapure LPS (upLPS) preparation during sensitization to Bt allergens decreased the influx of eosinophils and increased the influx of neutrophils to the airways. Inhibition of airway eosinophilia was not observed in IFN-?deficient mice while airway neutrophilia was not observed in IL-17RA-deficient mice as well in mice lacking MyD88, CD14, TLR4 and, surprisingly, TLR2 molecules. Notably, exposure to a synthetic TLR2 agonist (PamCSK4) also induced airway neutrophilia that was dependent on TLR2 and TLR4 molecules. In the OVA model, exposure to eLPS or PamCSK4 suppressed OVA-induced airway inflammation. Our results suggest that B. tropicalis allergens engage TLR4 that potentiates TLR2 signaling. This dual TLR activation during sensitization results in airway neutrophilic inflammation associated with increased frequency of lung TH17 cells. Our work highlight the complex interplay between bacterial products, house dust mite allergens and TLR signaling in the induction of different phenotypes of airway inflammation.

PMID: 23805294 [PubMed – as supplied by publisher]

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Proteome changes in auricular lymph nodes and serum after dermal sensitization to toluene diisocyanate in mice.

Proteome changes in auricular lymph nodes and serum after dermal sensitization to toluene diisocyanate in mice.

Proteomics. 2012 Oct 4;

Authors: Haenen S, Clynen E, De Vooght V, Schoofs L, Nemery B, Hoet PH, Vanoirbeek JA

Abstract
Some reactive chemicals, such as diisocyanates, are capable of initiating an allergic response, which can lead to occupational asthma after a latency period. Clinical symptoms such as cough, wheezing and dyspnea occur only late, making it difficult to intervene at an early stage. So far, most studies using proteomics in lung research have focused on comparisons of healthy vs. diseased subjects. Here, using two-dimensional difference gel electrophoresis (2D-DIGE), we explored proteome changes in the local draining lymph nodes and serum of mice dermally sensitized once or twice with TDI before asthma is induced. In the lymph nodes, we found 38 and 58 differentially expressed proteins after one and two treatments, respectively, between toluene diisocyanate-treated and vehicle-treated mice. In serum, 7 and 16 differentially expressed proteins were detected after one and two treatments, respectively. We identified 80-85% of the differentially expressed proteins by mass spectrometry. Among them, lymphocyte specific protein-1, coronin 1a and hemopexin were verified by Western blotting or ELISA in an independent group of mice. This study revealed alterations in the proteomes early during sensitization in a mouse model before the onset of chemical-induced asthma. If validated in humans, these changes could lead to earlier diagnosis of TDI-exposed workers.

PMID: 23038679 [PubMed – as supplied by publisher]

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