Tag: AllergenSpecific

Posted on

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

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

BMC Med Genomics. 2016;9(1):9

Authors: Troy NM, Hollams EM, Holt PG, Bosco A

Abstract
BACKGROUND: Asthma is strongly associated with allergic sensitization, but the mechanisms that determine why only a subset of atopics develop asthma are not well understood. The aim of this study was to test the hypothesis that variations in allergen-driven CD4 T cell responses are associated with susceptibility to expression of asthma symptoms.
METHODS: The study population consisted of house dust mite (HDM) sensitized atopics with current asthma (n?=?22), HDM-sensitized atopics without current asthma (n?=?26), and HDM-nonsensitized controls (n?=?24). Peripheral blood mononuclear cells from these groups were cultured in the presence or absence of HDM extract for 24 h. CD4 T cells were then isolated by immunomagnetic separation, and gene expression patterns were profiled on microarrays.
RESULTS: Differential network analysis of HDM-induced CD4 T cell responses in sensitized atopics with or without asthma unveiled a cohort of asthma-associated genes that escaped detection by more conventional data analysis techniques. These asthma-associated genes were enriched for targets of STAT6 signaling, and they were nested within a larger coexpression module comprising 406 genes. Upstream regulator analysis suggested that this module was driven primarily by IL-2, IL-4, and TNF signaling; reconstruction of the wiring diagram of the module revealed a series of hub genes involved in inflammation (IL-1B, NFkB, STAT1, STAT3), apoptosis (BCL2, MYC), and regulatory T cells (IL-2Ra, FoxP3). Finally, we identified several negative regulators of asthmatic CD4 T cell responses to allergens (e.g. IL-10, type I interferons, microRNAs, drugs, metabolites), and these represent logical candidates for therapeutic intervention.
CONCLUSION: Differential network analysis of allergen-induced CD4 T cell responses can unmask covert disease-associated genes and pin point novel therapeutic targets.

PMID: 26922672 [PubMed – as supplied by publisher]

View full post on pubmed: asthma

Posted on

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma.

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma.

J Immunol. 2014 Dec 19;

Authors: Böhm L, Maxeiner J, Meyer-Martin H, Reuter S, Finotto S, Klein M, Schild H, Schmitt E, Bopp T, Taube C

Abstract
Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3(+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3(+), and IL-10-producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3(+) Treg cells, thymic Foxp3(+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.

PMID: 25527785 [PubMed – as supplied by publisher]

View full post on pubmed: asthma

Posted on

Allergy Testing in Childhood: Using Allergen-Specific IgE Tests.

Allergy Testing in Childhood: Using Allergen-Specific IgE Tests.

Pediatrics. 2011 Dec 26;

Authors: Sicherer SH, Wood RA,

Abstract
A variety of triggers can induce common pediatric allergic diseases which include asthma, allergic rhinitis, atopic dermatitis, food allergy, and anaphylaxis. Allergy testing serves to confirm an allergic trigger suspected on the basis of history. Tests for allergen-specific immunoglobulin E (IgE) are performed by in vitro assays or skin tests. The tests are excellent for identifying a sensitized state in which allergen-specific IgE is present, and may identify triggers to be eliminated and help guide immunotherapy treatment. However, a positive test result does not always equate with clinical allergy. Newer enzymatic assays based on anti-IgE antibodies have supplanted the radioallergosorbent test (RAST). This clinical report focuses on allergen-specific IgE testing, emphasizing that the medical history and knowledge of disease characteristics are crucial for rational test selection and interpretation.

PMID: 22201146 [PubMed – as supplied by publisher]

View full post on pubmed: asthma