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Sample records for allergen challenge induces

  1. Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

    Science.gov (United States)

    Bossi, R; Banfi, P; Filipazzi, V; Castelli, C; Braga, P C

    1994-04-01

    The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

  2. Histamine and tryptase in nasal lavage fluid after allergen challenge

    DEFF Research Database (Denmark)

    Jacobi, H H; Skov, P S; Poulsen, L K

    1999-01-01

    BACKGROUND: Antihistamines (H1-receptor antagonists) act by competitive antagonism of histamine at H1-receptors. In addition, high concentrations of some antihistamines inhibit allergen-induced histamine release from mast cells in vitro. OBJECTIVE: The purpose of this study was to determine......, nasal allergen challenges were performed, and the number of sneezes were counted. In addition, nasal lavage fluid was collected, and the levels of mast-cell mediators (histamine and tryptase) were measured. RESULTS: The allergen challenge of patients allergic to pollen produced sneezing...... and a significant increase in the levels of histamine and tryptase. The challenge of subjects not allergic to pollen produced no such response. Azelastine and cetirizine significantly reduced allergen-induced sneezing and the associated increase in histamine and tryptase levels. No significant differences were...

  3. Allergen challenge induces Ifng dependent GTPases in the lungs as part of a Th1 transcriptome response in a murine model of allergic asthma.

    Directory of Open Access Journals (Sweden)

    Nilesh Dharajiya

    Full Text Available According to the current paradigm, allergic airway inflammation is mediated by Th2 cytokines and pro-inflammatory chemokines. Since allergic inflammation is self-limited, we hypothesized that allergen challenge simultaneously induces anti-inflammatory genes to counter-balance the effects of Th2 cytokines and chemokines. To identify these putative anti-inflammatory genes, we compared the gene expression profile in the lungs of ragweed-sensitized mice four hours after challenge with either PBS or ragweed extract (RWE using a micro-array platform. Consistent with our hypothesis, RWE challenge concurrently upregulated Th1-associated early target genes of the Il12/Stat4 pathway, such as p47 and p65 GTPases (Iigp, Tgtp and Gbp1, Socs1, Cxcl9, Cxcl10 and Gadd45g with the Th2 genes Il4, Il5, Ccl2 and Ccl7. These Th1-associated genes remain upregulated longer than the Th2 genes. Augmentation of the local Th1 milieu by administration of Il12 or CpG prior to RWE challenge further upregulated these Th1 genes. Abolition of the Th1 response by disrupting the Ifng gene increased allergic airway inflammation and abrogated RWE challenge-induced upregulation of GTPases, Cxcl9, Cxcl10 and Socs1, but not Gadd45g. Our data demonstrate that allergen challenge induces two sets of Th1-associated genes in the lungs: 1 Ifng-dependent genes such as p47 and p65 GTPases, Socs1, Cxcl9 and Cxcl10 and 2 Ifng-independent Th1-inducing genes like Gadd45g. We propose that allergen-induced airway inflammation is regulated by simultaneous upregulation of Th1 and Th2 genes, and that persistent unopposed upregulation of Th1 genes resolves allergic inflammation.

  4. Allergen-induced changes in airway responsiveness are related to baseline airway responsiveness

    NARCIS (Netherlands)

    deBruinWeller, MS; Weller, FR; RijssenbeekNouwens, LHM; Jansen, HM; deMonchy, JGR

    1996-01-01

    In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in

  5. Animal models of protein allergenicity: potential benefits, pitfalls and challenges.

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    Dearman, R J; Kimber, I

    2009-04-01

    Food allergy is an important health issue. With an increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches suitable for the characterization of the allergenic potential of proteins. There are methods available currently (such as homology searches and serological testing) that are very effective at identifying proteins that are likely to cross-react with known allergens. However, animal models may play a role in the identification of truly novel proteins, such as bacterial or fungal proteins, that have not been experienced previously in the diet. We consider here the potential benefits, pitfalls and challenges of the selection of various animal models, including the mouse, the rat, the dog and the neonatal swine. The advantages and disadvantages of various experimental end-points are discussed, including the measurement of specific IgE by ELISA, Western blotting or functional tests such as the passive cutaneous anaphylaxis assay, and the assessment of challenge-induced clinical symptoms in previously sensitized animals. The experimental variables of route of exposure to test proteins and the incorporation of adjuvant to increase the sensitivity of the responses are considered also. It is important to emphasize that currently none of these approaches has been validated for the purposes of hazard identification in the context of a safety assessment. However, the available evidence suggests that the judicious use of an accurate and robust animal model could provide important additional data that would contribute significantly to the assessment of the potential allergenicity of novel proteins.

  6. Therapeutic Effects of DNA Vaccine on Allergen-Induced Allergic Airway Inflammation in Mouse Model

    Institute of Scientific and Technical Information of China (English)

    Guoping Li; Zhigang Liu; Nanshan Zhong; Bin Liao1; Ying Xiong

    2006-01-01

    Vaccination with DNA encoding Dermatophagoides pteronyssinus group 2 (Der p 2) allergen previously showed its effects of immunologic protection on Der p 2 allergen-induced allergic airway inflammation in mice. In present study, we investigated whether DNA vaccine encoding Der p 2 could exert therapeutic role on allergen-induced allergic airway inflammation in mouse model and explored the mechanism of DNA vaccination in asthma specific-allergen immunotherapy. After sensitized and challenged by Der p 2, the BALB/c mice were immunized with DNA vaccine. The degrees of cellular infiltration were scored. IgE levels in serum and IL-4/lL-13 levels in BALF were determined by ELISA. The lung tissues were assessed by histological examinations. Expressions of STAT6 and NF-κB in lung were determined by immunohistochemistry staining. Vaccination of mice with DNA vaccine inhibited the development of airway inflammation and the production of mucin induced by allergen, and reduced the level of Der p 2-specific IgE level. Significant reductions of eosinophii infiltration and levels of IL-4and IL-13 in BALF were observed after vaccination. Further more, DNA vaccination inhibited STAT6 and NF-κBexpression in lung tissue in Der p 2-immunized mice. These results indicated that DNA vaccine encoding Der p 2allergen could be used for therapy of allergen-induced allergic airway inflammation in our mouse model.

  7. Peripheral erythrocytes decrease upon specific respiratory challenge with grass pollen allergen in sensitized mice and in human subjects.

    Directory of Open Access Journals (Sweden)

    Galateja Jordakieva

    Full Text Available BACKGROUND AND AIMS: Specific hyper-responsiveness towards an allergen and non-specific airway hyperreactivity both impair quality of life in patients with respiratory allergic diseases. We aimed to investigate cellular responses following specific and non-specific airway challenges locally and systemically in i sensitized BALB/c mice challenged with grass pollen allergen Phl p 5, and in ii grass pollen sensitized allergic rhinitis subjects undergoing specific airway challenge in the Vienna Challenge Chamber (VCC. METHODS AND RESULTS: BALB/c mice (n = 20 were intraperitoneally immunized with grass pollen allergen Phl p 5 and afterwards aerosol challenged with either the specific allergen Phl p 5 (n = 10 or the non-specific antigen ovalbumin (OVA (n = 10. A protocol for inducing allergic asthma as well as allergic rhinitis, according to the united airway concept, was used. Both groups of exposed mice showed significantly reduced physical activity after airway challenge. Specific airway challenge further resulted in goblet cell hyperplasia, enhanced mucous secretion, intrapulmonary leukocyte infiltration and lymphoid follicle formation, associated with significant expression of IL-4, IL-5 and IL-13 in splenocytes and also partially in lung tissue. Concerning circulating blood cell dynamics, we observed a significant drop of erythrocyte counts, hemoglobin and hematocrit levels in both mouse groups, challenged with allergen or OVA. A significant decrease in circulating erythrocytes and hematocrit levels after airway challenges with grass pollen allergen was also found in grass pollen sensitized human rhinitis subjects (n = 42 at the VCC. The effects on peripheral leukocyte counts in mice and humans however were opposed, possibly due to the different primary inflammation sites. CONCLUSION: Our data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens

  8. Banishing Asthma-Inducing Mice Allergens on The Cheap

    Science.gov (United States)

    ... gov/news/fullstory_163963.html Banishing Asthma-Inducing Mice Allergens on the Cheap Do-it-yourself approach ... in kids with a mouse allergy, researchers say. Mice are a common cause of asthma flare-ups ...

  9. Immunological aspects of the immune response induced by mosquito allergens.

    Science.gov (United States)

    Cantillo, José Fernando; Fernández-Caldas, Enrique; Puerta, Leonardo

    2014-01-01

    Allergies caused by mosquito bites may produce local or systemic reactions. The inhalation of mosquito allergens may also cause asthma and/or allergic rhinoconjunctivitis in sensitized individuals. The mechanisms implicated in the development of these immune responses involve IgE antibodies, different subtypes of IgG and proinflammatory cytokines as well as basophils, eosinophils and mast cells. Several allergenic components have been identified in the saliva and bodies of mosquitoes and some of these are present in different mosquito species. The most common species implicated in allergic reactions belong to the genera Aedes, Culex and Anopheles. Several Aedes aegypti allergens have been cloned and sequenced. The recombinant molecules show IgE reactivity similar to that of the native allergens, making them good candidates for the diagnosis of mosquito allergies. Allergen-specific immunotherapy with mosquito extracts induces a protective response characterized by a decreased production of IgE antibodies, increased IgG levels, a reduction in the severity of cutaneous and respiratory symptoms and the need for medication. The aims of this review are to summarize the progress made in the characterization of mosquito allergens and discuss the types of immune responses induced by mosquito bites and the inhalation of mosquito allergens in atopic individuals.

  10. Differential effects of allergen challenge on large and small airway reactivity in mice.

    Directory of Open Access Journals (Sweden)

    Chantal Donovan

    Full Text Available The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways disease to induce inflammation and remodelling and determine whether in vivo hyperresponsiveness to methacholine is consistent with in vitro reactivity of trachea and small airways. Balb/C mice were sensitised (days 0, 14 and challenged (3 times/week, 6 weeks with ovalbumin. Airway reactivity was compared with saline-challenged controls in vivo assessing whole lung resistance, and in vitro measuring the force of tracheal contraction and the magnitude/rate of small airway narrowing within lung slices. Increased airway inflammation, epithelial remodelling and fibrosis were evident following allergen challenge. In vivo hyperresponsiveness to methacholine was maintained in isolated trachea. In contrast, methacholine induced slower narrowing, with reduced potency in small airways compared to controls. In vitro incubation with IL-1/TNFα did not alter reactivity. The hyporesponsiveness to methacholine in small airways within lung slices following chronic ovalbumin challenge was unexpected, given hyperresponsiveness to the same agonist both in vivo and in vitro in tracheal preparations. This finding may reflect the altered interactions of small airways with surrounding parenchymal tissue after allergen challenge to oppose airway narrowing and closure.

  11. DNA vaccine encoding Der p 2 allergen generates immunologic protection in recombinant Der p 2 allergen-induced allergic airway inflammation mice model

    Institute of Scientific and Technical Information of China (English)

    LI Guo-ping; LIU Zhi-gang; QIU Jing; RAN Pi-xin; ZHONG Nan-shan

    2005-01-01

    Background DNA immunization is a promising novel type of immunotherapy against allergy. An estimated 79.2% patients with asthma, wheezing and/or rhinitis suffer from Dermatophagoides pteronyssinus group 2 (Der p 2) allegen. The aim of the present study was to determine whether DNA vaccine encoding Der p 2 could generate immunologic protection in recombinant Der p 2 (rDer p 2) allergen-induced allergic airway inflammation mice model and to understand the role of DNA vaccination in specific-allergen immunotherapy for asthma. Methods After DNA vaccination, BALB/c mice were sensitized by intraperitoneal injection (i.p) and challenged by intranasal instillation of rDer p 2. The lung tissues were assessed using hematoxylin and eosin. Mucus-producing goblet cells were identifed using periodic acid-Schiff(PAS)/alcian blue. The total cell number and composition of bronchoalveolar lavage samples were determined. The levels of the cytokines IL-4 and IFN-γ, as well as IgE and IgG2a in the serum were determined by enzyme-linked immunosorbent assay. Allergen-specific IL-4 and IFN-γ production by spleen cells were also measured by enzyme-linked immunosorbent assay. Expression of signal transducer and activator of transcription 6 (STAT6) in splenocytes were determined by Western blot. Results DNA vaccine encoding Der p 2 allergen inhibited extensive infiltration of inflammatory cells and production of mucin induced by allergen. The influx of eosinophils into the lung interstitium was significantly reduced after administration of DNA vaccine. Significant reductions of IL-4 and increase in levels of IFN-γ in bronchoalveolar lavage fluid were observed. The allergen-specific IgE was markedly decreased in mice receiving DNA vaccination. Allergen could induce higher IFN-γ, weaker IL-4 in cultured spleen cells from mice receiving DNA vaccine. DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. Conclusion These results indicated that DNA vaccine encoding

  12. Understanding allergic asthma from allergen inhalation tests

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    Cockcroft, Donald W; Hargreave, Fredrick E; O’Byrne, Paul M; Boulet, Louis-Philippe

    2007-01-01

    The allergen challenge has evolved, in less than 150 years, from a crude tool used to document the etiology of allergen-induced disease to a well-controlled tool used today to investigate the pathophysiology and pharmacotherapy of asthma. Highlights of the authors’ involvement with the allergen challenge include confirmation of the immunoglobulin E-dependence of the late asthmatic response, importance of (nonallergic) airway hyper-responsiveness as a determinant of the airway response to allergen, identification of allergen-induced increase in airway hyper-responsiveness, documentation of beta2-agonist-induced increase in airway response to allergen (including eosinophilic inflammation), advances in understanding the pathophysiology and kinetics of allergen-induced airway responses, and development of a muticentre clinical trial group devoted to using the allergen challenge for investigating promising new therapeutic strategies for asthma. PMID:17948142

  13. Inhaled allergen bronchoprovocation tests

    NARCIS (Netherlands)

    Diamant, Zuzana; Gauvreau, Gail M.; Cockcroft, Don W.; Boulet, Louis-Philippe; Sterk, Peter J.; Jongh, de Frans H.C.; Dahlen, Barbo; O'Byrne, Paul M.

    2013-01-01

    The allergen bronchoprovocation test is a long-standing exacerbation model of allergic asthma that can induce several clinical and pathophysiologic features of asthma in sensitized subjects. Standardized allergen challenge is primarily a research tool, and when properly conducted by qualified and ex

  14. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; van Bilsen, Jolanda; Głogowski, Robert

    2016-01-01

    validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant...... produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential...... of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally...

  15. Workshop proceedings: challenges and opportunities in evaluating protein allergenicity across biotechnology industries.

    Science.gov (United States)

    Stagg, Nicola J; Ghantous, Hanan N; Ladics, Gregory S; House, Robert V; Gendel, Steven M; Hastings, Kenneth L

    2013-01-01

    A workshop entitled "Challenges and Opportunities in Evaluating Protein Allergenicity across Biotechnology Industries" was held at the 51st Annual Meeting of the Society of Toxicology (SOT) in San Francisco, California. The workshop was sponsored by the Biotechnology Specialty Section of SOT and was designed to present the science-based approaches used in biotechnology industries to evaluate and regulate protein allergenicity. A panel of experts from industry and government highlighted the allergenicity testing requirements and research in the agricultural, pharmaceutical/biopharma, and vaccine biotechnology industries and addressed challenges and opportunities for advancing the science of protein allergenicity. The main learning from the workshop was that immunoglobulin E-mediated allergenicity of biotechnology-derived products is difficult to assess without human data. The approaches currently being used to evaluate potential for allergenicity across biotechnology industries are very different and range from bioinformatics, in vitro serology, in vivo animal testing, in vitro and in vivo functional assays, and "biosimilar" assessments (ie, biotherapeutic equivalents to innovator products). The challenge remains with regard to the different or lack of regulatory requirements for allergenicity testing across industries, but the novel approaches being used with bioinformatics and biosimilars may lead to opportunities in the future to collaborate across biotechnology industries.

  16. Long-term allergen exposure induces adipose tissue inflammation and circulatory system injury.

    Science.gov (United States)

    Jung, Chien-Cheng; Su, Huey-Jen

    2016-05-01

    The purpose of this study was to study whether allergen exposure can induce inflammation and lower the anti-inflammation levels in serum and in adipose tissues, and further develop cardiovascular injury. Our data showed that heart rate was significantly higher in the OVA-challenged mice compared to control mice. Moreover, there were higher expressions of pro-inflammation genes in the OVA-challenged mice in adipose tissues, and the expressions of anti-inflammation genes were lower. The levels of inflammation mediators were associated in serum and adipose tissues. The level of circulatory injury lactate dehydrogenase was significantly associated with the levels of E-selectin, resistin and adiponectin in the serum. The hematoxylin and eosin and immunohistochemistry stains indicated the OVA-challenged mice had higher levels of inflammation. In summary, the current study demonstrated allergen exposure can cause cardiovascular injury, and inflammatory mediators in adipose tissues play an important role in the pathogenesis of cardiovascular injury.

  17. Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results

    DEFF Research Database (Denmark)

    Pastorello, Elide A; Vieths, Stefan; Pravettoni, Valerio

    2002-01-01

    The hazelnut major allergens identified to date are an 18-kd protein homologous to Bet v 1 and a 14-kd allergen homologous to Bet v 2. No studies have reported hazelnut allergens recognized in patients with positive double-blind, placebo-controlled food challenge (DBPCFC) results or in patients...... allergic to hazelnut but not to birch....

  18. AGR2 is induced in asthma and promotes allergen-induced mucin overproduction.

    Science.gov (United States)

    Schroeder, Bradley W; Verhaeghe, Catherine; Park, Sung-Woo; Nguyenvu, Louis T; Huang, Xiaozhu; Zhen, Guohua; Erle, David J

    2012-08-01

    Mucins are gel-forming proteins that are responsible for the characteristic viscoelastic properties of mucus. Mucin overproduction is a hallmark of asthma, but the cellular requirements for airway mucin production are poorly understood. The endoplasmic reticulum (ER) protein anterior gradient homolog 2 (AGR2) is required for production of the intestinal mucin MUC2, but its role in the production of the airway mucins MUC5AC and MUC5B is not established. Microarray data were analyzed to examine the relationship between AGR2 and MUC5AC expression in asthma. Immunofluorescence was used to localize AGR2 in airway cells. Coimmunoprecipitation was used to identify AGR2-immature MUC5AC complexes. Agr2(-/-) mice were used to determine the role of AGR2 in allergic airway disease. AGR2 localized to the ER of MUC5AC- and MUC5B-producing airway cells and formed a complex with immature MUC5AC. AGR2 expression increased together with MUC5AC expression in airway epithelium from "Th2-high" asthmatics. Allergen-challenged Agr2(-/-) mice had greater than 50% reductions in MUC5AC and MUC5B proteins compared with allergen-challenged wild-type mice. Impaired mucin production in Agr2(-/-) mice was accompanied by an increase in the proportion of mucins contained within the ER and by evidence of ER stress in airway epithelium. This study shows that AGR2 increases with mucin overproduction in individuals with asthma and in mouse models of allergic airway disease. AGR2 interacts with immature mucin in the ER and loss of AGR2 impairs allergen-induced MUC5AC and MUC5B overproduction.

  19. Setting Occupational Exposure Limits for Chemical Allergens--Understanding the Challenges.

    Science.gov (United States)

    Dotson, G S; Maier, A; Siegel, P D; Anderson, S E; Green, B J; Stefaniak, A B; Codispoti, C D; Kimber, I

    2015-01-01

    Chemical allergens represent a significant health burden in the workplace. Exposures to such chemicals can cause the onset of a diverse group of adverse health effects triggered by immune-mediated responses. Common responses associated with workplace exposures to low molecular weight (LMW) chemical allergens range from allergic contact dermatitis to life-threatening cases of asthma. Establishing occupational exposure limits (OELs) for chemical allergens presents numerous difficulties for occupational hygiene professionals. Few OELs have been developed for LMW allergens because of the unique biological mechanisms that govern the immune-mediated responses. The purpose of this article is to explore the primary challenges confronting the establishment of OELs for LMW allergens. Specific topics include: (1) understanding the biology of LMW chemical allergies as it applies to setting OELs; (2) selecting the appropriate immune-mediated response (i.e., sensitization versus elicitation); (3) characterizing the dose (concentration)-response relationship of immune-mediated responses; (4) determining the impact of temporal exposure patterns (i.e., cumulative versus acute exposures); and (5) understanding the role of individual susceptibility and exposure route. Additional information is presented on the importance of using alternative exposure recommendations and risk management practices, including medical surveillance, to aid in protecting workers from exposures to LMW allergens when OELs cannot be established.

  20. Allergen-induced cytokine production, atopic disease, IgE, and wheeze in children

    NARCIS (Netherlands)

    Contreras, JP; Ly, NR; Gold, DR; He, HZ; Wand, M; Weiss, ST; Perkins, DL; Platts-Mills, TAE; Finn, PW

    2003-01-01

    Background: The early childhood allergen-induced immune responses associated with atopic disease and IgE production in early life are not well understood. Objective: We assessed the relationship of allergen-induced cytokine production by PBMCs to both atopic disease and to IgE increase in a cohort o

  1. Effects of oral cetirizine, a selective H1 antagonist, on allergen- and exercise-induced bronchoconstriction in subjects with asthma.

    LENUS (Irish Health Repository)

    Gong, H

    1990-03-01

    The protective efficacy of oral cetirizine, a selective and potent H1-receptor antagonist, against the immediate bronchoconstrictive response to allergen inhalation and exercise challenge was evaluated in 16 subjects with stable, predominantly mild asthma. The subjects underwent double-blind, crossover pretreatments in randomized order in two separate protocols with (1) three daily oral doses of 20 mg of cetirizine and placebo, followed by allergen inhalation, and (2) single oral doses of cetirizine (5, 10, and 20 mg), albuterol (4 mg), and placebo, followed by exercise with cold-air inhalation. Cetirizine failed to decrease bronchial sensitivity to inhaled allergen in eight of 10 subjects. Neither cetirizine nor albuterol uniformly inhibited exercise-induced bronchoconstriction. Serum concentrations of cetirizine were consistent with systemic H1-blocking activity. Modest bronchodilation occurred after administration of cetirizine and albuterol before exercise but not after the third dose of cetirizine in the allergen protocol. One subject developed moderate drowsiness during multiple dosing with cetirizine. Thus, cetirizine, in the doses studied, is not uniformly effective in preventing allergen- or exercise-induced bronchoconstriction. Histamine is one of many mediators participating in immediate asthmatic responses, and selective H1 antagonists do not completely block these airway events. However, cetirizine may still clinically benefit some patients with asthma, such as patients with allergic rhinitis or urticaria.

  2. Effect of allergen-specific immunotherapy on recombinant human interleukin 3-mediated amplification of allergen-induced basophil histamine release.

    Science.gov (United States)

    Kowal, Krzysztof; Nolte, Hendrik; Skov, Per Stahl; DuBuske, Lawrence M

    2005-01-01

    Decreased allergen-induced histamine release from peripheral blood basophils in allergic rhinitis patients treated with specific immunotherapy (SIT) correlates with clinical outcomes of SIT. The aim of this study was to investigate if decreased histamine release is a permanent effect of SIT. Fifty-one patients (mean age, 35.3 years) with allergic rhinitis, diagnosed based on clinical history and positive skin-prick test results to common aeroallergens, were studied. Twenty-three patients had never received SIT (group A), and 28 patients had been treated with inhalant allergen extracts (group B). Eleven patients from group A participated in a prospective part of this study. Basophil histamine release in these patients was evaluated before (TO) and after-1 year (TI) of SIT. Histamine release from peripheral blood with and without interleukin (IL)-3 pretreatment was performed using the glass-fiber-based histamine release test. Brief pretreatment of whole blood basophils with one of the four concentrations (0.01, 0.1, 1, or 10 ng/mL) of recombinant human IL(rhIL)-3, rhIL-5, or rh-granulocyte-macrophage colony-stimulating factor resulted in a significant amplification of allergen-induced basophil histamine release. The amplification using cytokines at the optimal concentrations was the greatest with rhIL-3 and the lowest with rhIL-5; therefore, for further studies rhIL-3 was used. Prospective analysis showed no significant difference in allergen-induced basophil histamine release on rhIL-3 pretreatment after 1 year of SIT (192.7 +/- 75.3 ng and 176.1 +/- 76.4 ng for T0 and T1, respectively; p = 0.18). Short-term SIT does not decrease rhIL-3-mediated amplification of allergen-induced histamine release from peripheral blood basophils.

  3. ALLERGEN-INDUCED CHANGES IN ADENOSINE 5'-MONOPHOSPHATE BRONCHIAL RESPONSIVENESS - EFFECT OF NEDOCROMIL SODIUM

    NARCIS (Netherlands)

    AALBERS, R; KAUFMAN, HF; GROEN, H; KOETER, GH; DEMONCHY, JGR

    1992-01-01

    Bronchial hyperresponsiveness to adenosine 5'-monophosphate (AMP) was studied after allergen challenge in allergic asthmatic patients. Measurements were made with and without nedocromil sodium pretreatment. Nedocromil sodium inhibited both the early and late asthmatic reactions (P <.01). After aller

  4. Assessing mucus and airway morphology in response to a segmental allergen challenge using OCT (Conference Presentation)

    Science.gov (United States)

    Adams, David C.; Miller, Alyssa J.; Holz, Jasmin A.; Szabari, Margit V.; Hariri, Lida P.; Harris, R. Scott; Cho, Jocelyn L.; Hamilos, Daniel L.; Luster, Andrew D.; Medoff, Benjamin D.; Suter, Melissa J.

    2016-03-01

    Asthma affects hundreds of millions of people worldwide, and the prevalence of the disease appears to be increasing. One of the most important aspects of asthma is the excessive bronchoconstriction that results in many of the symptoms experienced by asthma sufferers, but the relationship between bronchoconstriction and airway morphology is not clearly established. We present the imaging results of a study involving a segmental allergen challenge given to both allergic asthmatic (n = 12) and allergic non-asthmatic (n = 19) human volunteers. Using OCT, we have imaged and assessed baseline morphology in a right upper lobe (RUL) airway, serving as the control, and a right middle lobe (RML) airway, in which the allergen was to be administered. After a period of 24 hours had elapsed following the administration of the allergen, both airways were again imaged and the response morphology assessed. A number of airway parameters were measured and compared, including epithelial thickness, mucosal thickness and buckling, lumen area, and mucus content. We found that at baseline epithelial thickness, mucosal thickness, and mucosal buckling were greater in AAs than ANAs. We also observed statistically significant increases in these values 24 hours after the allergen had been administered for both the ANA and AA sets. In comparison, the control airway which received a diluent showed no statistically significant change.

  5. Carcinogenicity, allergenicity, and lupus-inducibility of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2016-01-01

    Arylamines are widely used in food, drugs, and cosmetics as well as other industries. These chemicals are present ubiquitously in cigarette smoke, smoke emitted from cooking fume hoods as well as are generated by diverse industries. Arylamines can be generated by cleavage of azo dyes by intestinal and skin microbiota. Some arylamines are used as drugs while others are constituents of human metabolism. Many of the arylamines are mutagenic and carcinogenic. They are generally recognized as the major cause of human bladder cancer, but arylamines can induce cancers of other organs in humans and animals. Some arylamines are allergenic, causing lupus like syndrome, or other maladies. In view of their unbiquitious nature and the diseases they cause, arylamines are probably the most important chemicals causing health problems.

  6. Influence of sensitization and allergen provocation procedures on the development of allergen-induced bronchial hyperreactivity in conscious, unrestrained guinea-pigs

    Directory of Open Access Journals (Sweden)

    R. E. Santing

    1995-01-01

    Full Text Available The effects of different sensitization and allergen provocation regimens on the development of allergen-induced bronchial hyperreactivity (BHR to histamine were investigated in conscious, unrestrained guinea-pigs. Similar early and late phase asthmatic reactions, BHR for inhaled histamine after the early (6 h as well as after the late reaction (24 h, and airway inflammation were observed after a single allergen provocation in animals sensitized to produce mainly IgG or IgE antibodies, respectively. Repeating the allergen provocation in the IgE-sensitized animals after 7 days, using identical provocation conditions, resulted in a similar development of BHR to histamine inhalation. Repetition of the allergen provocation during 4 subsequent days resulted in a decreased development of BHR after each provocation, despite a significant increase in the allergen provocation dose necessary to obtain similar airway obstruction. The number of inflammatory cells in the bronchoalveolar lavage was not significantly changed after repeated provocation, when compared with a single allergen provocation. Finally, we investigated allergen-induced bronchial hyperreactivity by repetition of the sensitization procedure at day 7 and 14 (booster, followed by repeated allergen provocation twice a week for 5 weeks. Surprisingly, no BHR to histamine could be observed after either provocation, while the number of inflammatory cells in the bronchoalveolar lavage fluid after 5 weeks was enhanced compared with controls. These data indicate that both IgE and IgG sensitized guinea-pigs may develop bronchial hyperreactivity after a single allergen provocation. Repeated allergen exposure of IgE sensitized animals causes a gradual fading of the induced hyperreactivity despite the on-going presence of inflammatory cells in the airways, indicating a mechanism of reduced cellular activation.

  7. Chronic Mild Prenatal Stress Exacerbates the Allergen-Induced Airway Inflammation in Rats

    Directory of Open Access Journals (Sweden)

    Paulo J. Nogueira

    1999-01-01

    Full Text Available The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0 and intratracheally challenged (day 14 with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the nonstressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.

  8. Alternaria alternata allergens: Markers of exposure, phylogeny and risk of fungi-induced respiratory allergy.

    Science.gov (United States)

    Gabriel, Marta F; Postigo, Idoia; Tomaz, Cândida T; Martínez, Jorge

    2016-01-01

    Alternaria alternata spores are considered a well-known biological contaminant and a very common potent aeroallergen source that is found in environmental samples. The most intense exposure to A. alternata allergens is likely to occur outdoors; however, Alternaria and other allergenic fungi can colonize in indoor environments and thereby increase the fungal aeroallergen exposure levels. A consequence of human exposure to fungal aeroallergens, sensitization to A. alternata, has been unequivocally associated with increased asthma severity. Among allergenic proteins described in this fungal specie, the major allergen, Alt a 1, has been reported as the main elicitor of airborne allergies in patients affected by a mold allergy and considered a marker of primary sensitization to A. alternata. Moreover, A. alternata sensitization seems to be a triggering factor in the development of poly-sensitization, most likely because of the capability of A. alternata to produce, in addition to Alt a 1, a broad and complex array of cross-reactive allergens that present homologs in several other allergenic sources. The study and understanding of A. alternata allergen information may be the key to explaining why sensitization to A. alternata is a risk factor for asthma and also why the severity of asthma is associated to this mold. Compared to other common environmental allergenic sources, such as pollens and dust mites, fungi are reported to be neglected and underestimated. The rise of the A. alternata allergy has enabled more research into the role of this fungal specie and its allergenic components in the induction of IgE-mediated respiratory diseases. Indeed, recent research on the identification and characterization of A. alternata allergens has allowed for the consideration of new perspectives in the categorization of allergenic molds, assessment of exposure and diagnosis of fungi-induced allergies.

  9. Protective Effects of Fluticasone on Allergen-Induced Airway Responses and Sputum Inflammatory Markers

    Directory of Open Access Journals (Sweden)

    Krishnan Parameswaran

    2000-01-01

    Full Text Available BACKGROUND: A direct comparison of the protective effects of single and regular doses of inhaled glucocorticoid on allergen-induced asthmatic responses and inflammation has not been made.

  10. Effects of Flavin7 on allergen induced hyperreactivity of airways

    Directory of Open Access Journals (Sweden)

    Franova S

    2009-12-01

    Full Text Available Abstract Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4, and interleukin 5 (IL-5 in bronchoalveolar lavage fluid (BALF. Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.

  11. DNA vaccine encoding Der p2 allergen down-regulates STAT6 expression in mouse model of allergen-induced allergic airway inflammation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Activation of signal transducer and activator of transcription 6 (STAT6 ) plays a critical role in the late phase of Th2-dependent allergy induction. STAT6 is essential to Th2 cell differentiation, recruitment, and effector function. Our previous study confirmed that DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. In the present study, we determined whether DNA vaccine encoding Dermatophagoides pteronyssinus group 2 (Der p2 ) could down-regulate the expression and activation of STAT6 in lung tissue from asthmatic mice.Methods After DNA vaccine immunization, BALB/c mice were sensitized by intraperitoneal injection and challenged by intranasal instillation of rDer p2. The levels of the cytokines IL-4 and IL-13 in BAL fluid were measured by enzyme-linked immunosorbent assay. The lung tissue was assessed by immunohistochemical staining with anti-STAT6. The protein expression of STAT6 was determined by Western blot. The activation of STAT6 binding ability was analyzed with electrophoretic mobility shift assay.Results DNA vaccine encoding Der p2 allergen effectively decreased the levels of IL-4 and IL-13 in the asthmatic mice. Histological evidence and Western blot showed that the expression of STAT6 in the DNA treated mice was markedly attenuated. STAT6 binding to specific DNA motif in lung tissue from the gene vaccinated mice was inhibited.Conclusion DNA vaccine encoding Der p2 prevents allergic pulmonary inflammation probably by inhibiting the STAT6 signaling pathway in mice with Der p2 allergen-induced allergic airway inflammation.

  12. Screening and identification of putative allergens in berry fruits of the Rosaceae family: technical challenges.

    Science.gov (United States)

    Marzban, Gorji; Maghuly, Fatemeh; Herndl, Anita; Katinger, Hermann; Laimer, Margit

    2008-01-01

    Cross-reactive proteins in small fruits of the Rosaceae family like strawberry, raspberry and blackberry revealed an unexpected complex IgE-reactivity pattern. Several copies of PR-10 and PR-14 proteins were detected by Southern blots in strawberry, raspberry and blackberry. In raspberry, the highest similarity at the DNA level for PR-10 and PR-14 (Rub i 1 and Rub i 3) was detected to strawberry sequences of Fra a 1 and Fra a 3. At the protein level, Rub i 1 and Rub i 3 showed more than 70% identity with homologous proteins of rosaceous fruits. Furthermore, raspberries contained additional putative allergens, e.g. class III acidic chitinases and cyclophilins. Blackberries were shown to share at least two well-known major fruit allergens with other rosaceous fruits, namely PR-10s and PR-14s homologous proteins. However the IgE-reactive proteins of small fruits are still not extensively investigated. The main challenges in studying small fruit allergens are the complexity of the fruit matrix, the diversity of physico-chemical properties of fruit proteins, the lack of appropriate protein extraction procedures and the missing information about the influence of processing treatments on food components.

  13. Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses

    Directory of Open Access Journals (Sweden)

    Koga Hikari

    2013-01-01

    Full Text Available Abstract Background Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR in previously sensitized and challenged mice. Methods BALB/c mice were sensitized and challenged (primary with ovalbumin (OVA. Six weeks later, a single OVA aerosol (secondary challenge was delivered and airway inflammation and airway responses were monitored 6 and 48 hrs later. An inhibitor of neutrophil elastase was administered prior to secondary challenge. Results Mice developed a two-phase airway inflammatory response after secondary allergen challenge, one neutrophilic at 6 hr and the other eosinophilic, at 48 hr. PAR-2 expression in the lung tissues was enhanced following secondary challenge, and that PAR-2 intracellular expression on peribronchial lymph node (PBLN T cells was also increased following allergen challenge of sensitized mice. Inhibition of neutrophil elastase significantly attenuated AHR, goblet cell metaplasia, and inflammatory cell accumulation in the airways following secondary OVA challenge. Levels of IL-4, IL-5 and IL-13, and eotaxin in BAL fluid 6 hr after secondary allergen challenge were significantly suppressed by the treatment. At 48 hr, treatment with the neutrophil elastase inhibitor significantly reduced the levels of IL-13 and TGF-β1 in the BAL fluid. In parallel, in vitro IL-13 production was significantly inhibited in spleen cells from sensitized mice. Conclusion These data indicate that neutrophil elastase plays an important role in the development of allergic airway inflammation and hyperresponsiveness, and would suggest that the

  14. Does allergen-specific immunotherapy induce contact allergy to aluminium?

    Science.gov (United States)

    Netterlid, Eva; Hindsén, Monica; Siemund, Ingrid; Björk, Jonas; Werner, Sonja; Jacobsson, Helene; Güner, Nuray; Bruze, Magnus

    2013-01-01

    Persistent, itching nodules have been reported to appear at the injection site after allergen-specific immuno-therapy with aluminium-precipitated antigen extract, occasionally in conjunction with contact allergy to aluminium. This study aimed to quantify the development of contact allergy to aluminium during allergen-specific immunotherapy. A randomized, controlled, single-blind multicentre study of children and adults entering allergen-specific immunotherapy was performed using questionnaires and patch-testing. A total of 205 individuals completed the study. In the 3 study groups all subjects tested negative to aluminium before allergen-specific immunotherapy and 4 tested positive after therapy. In the control group 4 participants tested positive to aluminium. Six out of 8 who tested positive also had atopic dermatitis. Positive test results were found in 5/78 children and 3/127 adults. Allergen-specific immunotherapy was not shown to be a risk factor for contact allergy to aluminium. Among those who did develop aluminium allergy, children and those with atopic dermatitis were more highly represented.

  15. Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice

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    Rothenberg Marc E

    2009-06-01

    Full Text Available Abstract Background Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice. Results In order to test the hypothesis that arginase has a role in allergic airway inflammation we generated arginase I-deficient bone marrow (BM chimeric mice. Following transfer of arginase I-deficient BM into irradiated recipient mice, arginase I expression was not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreased allergen-induced lung arginase by 85.8 ± 5.6%. In contrast, arginase II-deficient mice had increased lung arginase activity following allergen challenge to a similar level to wild type mice. BM-derived arginase I was not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Furthermore, allergen-induced airway hyperresponsiveness and collagen deposition were similar in arginase-deficient and wild type mice. Additionally, arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition. Conclusion Bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition.

  16. Immune modulatory effects of IL-22 on allergen-induced pulmonary inflammation.

    Directory of Open Access Journals (Sweden)

    Ping Fang

    Full Text Available IL-22 is a Th17/Th22 cytokine that is increased in asthma. However, recent animal studies showed controversial findings in the effects of IL-22 in allergic asthma. To determine the role of IL-22 in ovalbumin-induced allergic inflammation we generated inducible lung-specific IL-22 transgenic mice. Transgenic IL-22 expression and signaling activity in the lung were determined. Ovalbumin (OVA-induced pulmonary inflammation, immune responses, and airway hyperresponsiveness (AHR were examined and compared between IL-22 transgenic mice and wild type controls. Following doxycycline (Dox induction, IL-22 protein was readily detected in the large (CC10 promoter and small (SPC promoter airway epithelial cells. IL-22 signaling was evidenced by phosphorylated STAT3. After OVA sensitization and challenge, compared to wild type littermates, IL-22 transgenic mice showed decreased eosinophils in the bronchoalveolar lavage (BAL, and in lung tissue, decreased mucus metaplasia in the airways, and reduced AHR. Among the cytokines and chemokines examined, IL-13 levels were reduced in the BAL fluid as well as in lymphocytes from local draining lymph nodes of IL-22 transgenic mice. No effect was seen on the levels of serum total or OVA-specific IgE or IgG. These findings indicate that IL-22 has immune modulatory effects on pulmonary inflammatory responses in allergen-induced asthma.

  17. Development of asthmatic inflammation in mice following early-life exposure to ambient environmental particulates and chronic allergen challenge

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    Cristan Herbert

    2013-03-01

    Childhood exposure to environmental particulates increases the risk of development of asthma. The underlying mechanisms might include oxidant injury to airway epithelial cells (AEC. We investigated the ability of ambient environmental particulates to contribute to sensitization via the airways, and thus to the pathogenesis of childhood asthma. To do so, we devised a novel model in which weanling BALB/c mice were exposed to both ambient particulate pollutants and ovalbumin for sensitization via the respiratory tract, followed by chronic inhalational challenge with a low mass concentration of the antigen. We also examined whether these particulates caused oxidant injury and activation of AEC in vitro. Furthermore, we assessed the potential benefit of minimizing oxidative stress to AEC through the period of sensitization and challenge by dietary intervention. We found that characteristic features of asthmatic inflammation developed only in animals that received particulates at the same time as respiratory sensitization, and were then chronically challenged with allergen. However, these animals did not develop airway hyper-responsiveness. Ambient particulates induced epithelial injury in vitro, with evidence of oxidative stress and production of both pro-inflammatory cytokines and Th2-promoting cytokines such as IL-33. Treatment of AEC with an antioxidant in vitro inhibited the pro-inflammatory cytokine response to these particulates. Ambient particulates also induced pro-inflammatory cytokine expression following administration to weanling mice. However, early-life dietary supplementation with antioxidants did not prevent the development of an asthmatic inflammatory response in animals that were exposed to particulates, sensitized and challenged. We conclude that injury to airway epithelium by ambient environmental particulates in early life is capable of promoting the development of an asthmatic inflammatory response in sensitized and antigen-challenged mice. These

  18. Challenges in testing genetically modified crops for potential increases in endogenous allergen expression for safety.

    Science.gov (United States)

    Panda, R; Ariyarathna, H; Amnuaycheewa, P; Tetteh, A; Pramod, S N; Taylor, S L; Ballmer-Weber, B K; Goodman, R E

    2013-02-01

    Premarket, genetically modified (GM) plants are assessed for potential risks of food allergy. The major risk would be transfer of a gene encoding an allergen or protein nearly identical to an allergen into a different food source, which can be assessed by specific serum testing. The potential that a newly expressed protein might become an allergen is evaluated based on resistance to digestion in pepsin and abundance in food fractions. If the modified plant is a common allergenic source (e.g. soybean), regulatory guidelines suggest testing for increases in the expression of endogenous allergens. Some regulators request evaluating endogenous allergens for rarely allergenic plants (e.g. maize and rice). Since allergic individuals must avoid foods containing their allergen (e.g. peanut, soybean, maize, or rice), the relevance of the tests is unclear. Furthermore, no acceptance criteria are established and little is known about the natural variation in allergen concentrations in these crops. Our results demonstrate a 15-fold difference in the major maize allergen, lipid transfer protein between nine varieties, and complex variation in IgE binding to various soybean varieties. We question the value of evaluating endogenous allergens in GM plants unless the intent of the modification was production of a hypoallergenic crop.

  19. Allergen-induced increase of eosinophil cationic protein in nasal lavage fluid

    DEFF Research Database (Denmark)

    Bisgaard, H; Grønborg, H; Mygind, N;

    1990-01-01

    It was our aim to study the effect of nasal allergen provocation on the concentration of eosinophil cationic protein (ECP) in nasal lavage fluid, with and without glucocorticoid pretreatment. Twenty grass-pollen sensitive volunteers were provoked outside the pollen season on 2 consecutive days...... untreated, prechallenge noses was 400 micrograms/L. (3) The ECP level did not increase during the early phase response. (4) There was a late occurring increase in the ECP concentration (6 to 24 hours). (5) This increase was completely inhibited by budesonide pretreatment. (6) The glucocorticoid therapy also...... reduced the prechallenge ECP concentration. In conclusion, allergen provocation in the nose results in a late occurring increase of ECP in nasal lavage fluid, and one of the therapeutic effects of topical glucocorticoid therapy may be an inhibition of the allergen-induced increase of this cytotoxic...

  20. Identification and quantification of basophils in the airways of asthmatics following segmental allergen challenge.

    Science.gov (United States)

    Dijkstra, Dorothea; Hennig, Christian; Hansen, Gesine; Biller, Heike; Krug, Norbert; Hohlfeld, Jens M

    2014-07-01

    During asthma attacks, allergens activate sensitized basophils in the lung, thereby aggravating symptoms. Due to the paucity of basophils in bronchial lavage fluid and the lack of specific basophil detection and quantification methods, basophil-directed research in these samples was hampered in the past. This study aimed to establish and validate a flow cytometry-based basophil detection and quantification method for human basophils from bronchoalveolar lavage (BAL) and blood as a prerequisite for a better understanding of their pathogenic contribution and subtyping of asthma phenotypes. BAL and blood leukocytes from seasonal asthmatics were analyzed by flow cytometry. Chipcytometry, a highly sensitive single-cell analysis method, was used to validate the staining panel for basophils. Cell differentials of May-Grünwald-Giemsa-stained cytospins were used to compare basophil percentages. BAL basophils are identifiable as CD123(+) HLA-DR(-) CD3(-) CD14(-) CD19(-) CD20(-) CD56(-) cells in flow cytometrical analysis. Their identity was validated by Chipcytometry. CD203c was highly expressed by BAL basophils, whereas it was expressed at variable levels on blood basophils. The two quantification methods correlated, although more basophils were detected by flow cytometry. Furthermore, the increase in basophil percentages in the lung correlated with the decrease in the basophil percentages in the blood after allergen challenge. We here validated a reliable basophil quantification method, which is independent of the cell's activation and degranulation state. The results obtained with this method indicate that basophils are directly recruited from the blood circulation to the airway lumen.

  1. Comparing the effects of two inhaled glucocorticoids on allergen-induced bronchoconstriction and markers of systemic effects, a randomised cross-over double-blind study

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    Lötvall Jan

    2011-10-01

    Full Text Available Abstract Background Inhaled glucocorticoids are efficient in protecting against asthma exacerbations, but methods to compare their efficacy vs systemic effects have only been attempted in larger multi-centre studies. The aim of the current study was therefore to directly compare the effects of two separate inhaled glucocorticoids, mometasone and budesonide, to compare the effects on the early and late asthmatic responses to inhaled allergen in patients with mild allergic asthma, and sputum eosinophils, and to relate the clinical positive effects to any systemic effects observed. Methods Twelve patients with documented early and late asthmatic responses (EAR and LAR to inhaled allergen at a screening visit were randomized in a double-blind fashion to treatment with mometasone (200 μg × 2 or 400 μg × 2, budesonide (400 μg × 2 or placebo in a double-blind crossover fashion for a period of seven days. Challenge with the total allergen dose causing both an EAR and LAR was given on the last day of treatment taken in the morning. Lung function was assessed using FEV1, and systemic glucocorticoid activity was quantified using 24 h urinary cortisol. Results Mometasone and budesonide attenuate both EAR and LAR to allergen to a similar degree. No significant dose-related effects on the lung function parameters were observed. Both treatments reduced the relative amount of sputum eosinophils (% after allergen. At the dose of 800 μg daily, mometasone reduced 24 h urinary cortisol by approximately 35%. Both drugs were well tolerated. Conclusions Mometasone and budesonide are equieffective in reducing early and late asthmatic responses induced by inhaled allergen challenge. Mometasone 800 μg given for seven days partially affects the HPA axis.

  2. Subtoxic concentrations of allergenic haptens induce LC migration and maturation in a human organotypic skin explant culture model: A novel method for identifying potential contact allergens

    NARCIS (Netherlands)

    Lehé, C.L.; Jacobs, J.J.L.; Hua, C.M.; Courtellemont, P.; Elliott, G.R.; Das, P.K.

    2006-01-01

    The accelerated migration of Langerhans cells (LCs) out of the epidermis and up-regulation of maturation markers, upon treatment with subtoxic concentrations of chemicals, were used as the criteria to determine the potential of allergenic chemicals capable of inducing a hapten-specific delayed-type

  3. Involvement of fibrocytes in allergen-induced T cell responses and rhinovirus infections in asthma.

    Science.gov (United States)

    Isgrò, Mirko; Bianchetti, Lorenza; Marini, Maurizio A; Mattoli, Sabrina

    2013-08-02

    Allergen exposure and rhinovirus infections that propagate from the upper to the lower airways are the most frequent causes of asthma exacerbation. In patients at increased risk of disease exacerbations, chronic airway inflammation is associated with the airway recruitment of circulating fibrocytes, bone marrow-derived CD34(+)CD45RO(+)CD11b(+)CD13(+)HLA-DR(+) progenitors that have antigen-presenting function and fibroblast-like properties. This study demonstrates that allergen-pulsed circulating fibrocytes from patients with allergic asthma are potent inducer of the predominant release of the T helper type (Th)2 cytokines IL-4 and IL-5 from autologous naïve and memory CD4(+) T cells. This study also provides evidence that circulating fibrocytes from allergic asthmatics are susceptible to rhinovirus infection. Infected cells release high amounts of pro-inflammatory cytokines with minimal production of IFN-α/β. Moreover, allergen-pulsed fibrocytes support prolonged rhinovirus replication and release larger quantities of pro-inflammatory cytokines upon rhinovirus infection than unpulsed fibrocytes. Thus, fibrocytes may amplify allergen-induced, Th2 cell-driven inflammatory responses and promote further inflammation by functioning as a reservoir for rhinovirus replication in asthmatic airways. Through these mechanisms, fibrocytes may play an important role in the provocation of disease exacerbations.

  4. Food allergen digestibility: The influence on allergenicity

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Madsen, Charlotte Bernhard

    Food allergy is a major health problem in the Western countries, affecting 3-8% of the population. What makes a dietary protein a food allergen has not yet been established, though several characteristics have been proposed to be shared by the food allergens. One of the features believed...... to be a general characteristic is resistance to digestion. This is based on studies showing that allergenic dietary proteins in general were more resistant to digestion than dietary proteins with no proven allergenicity, leading to the conclusion, that a correlation between stability to digestion and allergenic...... potential exist. Resistance to digestion is therefore a test parameter included in the safety assessment of the allergenic potential of novel proteins in genetically modified foods. In recent years, the association between resistance to digestion and allergenic potential has been challenged. When reviewing...

  5. Assessment of the allergenic potential of transgenic wheat (Triticum aestivum) with reduced levels of omega-5 gliadins, the major sensitizing allergen in wheat-dependent exercise-induced anaphylaxis

    Science.gov (United States)

    The omega-5 gliadins are the major sensitizing allergens in wheat-dependent exercise-induced anaphylaxis (WDEIA). In this study, two-dimensional immunoblot analysis was used to assess the allergenic potential of two transgenic wheat lines in which omega-5 gliadin genes were silenced by RNA interfe...

  6. Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8(+) T cells

    DEFF Research Database (Denmark)

    Schmidt, Jonas D; Ahlström, Malin G; Johansen, Jeanne D;

    2016-01-01

    BACKGROUND: Skin-resident memory T (TRM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore......, the mechanisms whereby TRM cells induce rapid recall responses need further investigation. OBJECTIVES: To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. METHODS: To address these questions, we analysed responses......, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8(+) TRM cells....

  7. Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory study

    Directory of Open Access Journals (Sweden)

    Natarajan Sudha

    2010-11-01

    Full Text Available Abstract Background Antigen desensitization through oral tolerance is becoming an increasingly attractive treatment option for allergic diseases. However, the mechanism(s by which tolerization is achieved remain poorly defined. In this study we endeavored to induce oral tolerance to cockroach allergen (CRA: a complex mixture of insect components in order to ameliorate asthma-like, allergic pulmonary inflammation. Methods We compared the pulmonary inflammation of mice which had received four CRA feedings prior to intratracheal allergen sensitization and challenge to mice fed PBS on the same time course. Respiratory parameters were assessed by whole body unrestrained plethysmography and mechanical ventilation with forced oscillation. Bronchoalveolar lavage fluid (BAL and lung homogenate (LH were assessed for cytokines and chemokines by ELISA. BAL inflammatory cells were also collected and examined by light microscopy. Results CRA feeding prior to allergen sensitization and challenge led to a significant improvement in respiratory health. Airways hyperreactivity measured indirectly via enhanced pause (Penh was meaningfully reduced in the CRA-fed mice compared to the PBS fed mice (2.3 ± 0.4 vs 3.9 ± 0.6; p = 0.03. Directly measured airways resistance confirmed this trend when comparing the CRA-fed to the PBS-fed animals (2.97 ± 0.98 vs 4.95 ± 1.41. This effect was not due to reduced traditional inflammatory cell chemotactic factors, Th2 or other cytokines and chemokines. The mechanism of improved respiratory health in the tolerized mice was due to significantly reduced eosinophil numbers in the bronchoalveolar lavage fluid (43300 ± 11445 vs 158786 ± 38908; p = 0.007 and eosinophil specific peroxidase activity in the lung homogenate (0.59 ± 0.13 vs 1.19 ± 0.19; p = 0.017. The decreased eosinophilia was likely the result of increased IL-10 in the lung homogenate of the tolerized mice (6320 ± 354 ng/mL vs 5190 ± 404 ng/mL, p = 0

  8. Roasted hazelnuts--allergenic activity evaluated by double-blind, placebo-controlled food challenge

    DEFF Research Database (Denmark)

    Hansen, K Skamstrup; Ballmer-Weber, B K; Lüttkopf, D

    2003-01-01

    Allergy to hazelnuts is a common example of birch pollen related food allergy. Symptoms upon ingestion are often confined to the mouth and throat, but severe systemic reactions have been described in some patients. The aim of the study was to evaluate the reduction in allergenicity by roasting...

  9. Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5-lipoxygenase pathways

    Directory of Open Access Journals (Sweden)

    Cui Zhi-Hua

    2012-03-01

    Full Text Available Abstract Background Allergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs and thromboxane A2 (TXA2. The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge. Methods A trimellitic anhydride (TMA sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2 after allergen challenge. Results Repeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high-dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187 induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5-lipoxygenase and cyclooxygenase pathways. Conclusions The inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.

  10. Pacific oyster-derived polysaccharides attenuate allergen-induced intestinal inflammation in a murine model of food allergy

    Directory of Open Access Journals (Sweden)

    Chiung-Hsiang Cheng

    2016-01-01

    Full Text Available Oyster-derived polysaccharides (OPS have been shown to modulate the T helper (Th1/Th2 immunobalance toward the Th1-dominant direction in antigen-primed splenocytes. In the present study, we hypothesized that OPS might attenuate intestinal inflammation associated with food allergy, a Th2-dominant immune disorder. BALB/c mice were sensitized twice with ovalbumin (OVA absorbed to alum and then repeatedly challenged with intragastric OVA to induce intestinal allergic responses. The mice were administered by gavage with OPS and/or vehicle (distilled water once/d during the two sensitization phases, and once every other day during the challenge phase. Administration with OPS attenuated OVA challenge-elicited diarrhea, and the infiltration of mast cells in the intestine. OPS demonstrated a protective effect on the reduced ratio of villus length over crypt depth of the intestine in allergic mice. Furthermore, OPS administration markedly attenuated the intestinal expression of the Th2 signature cytokine interleukin-4 (IL-4. Collectively, these results demonstrated the in vivo antiallergic activity of OPS, which is associated with the suppression of allergen-induced intestinal Th2 responses and mast cell activation.

  11. Anti-inflammatory effect of amurensin H on asthma-like reaction induced by allergen in sensitized mice

    Institute of Scientific and Technical Information of China (English)

    Yi-tang LI; Chun-suo YAO; Jin-ye BAI; Mao LIN; Gui-fang CHENG

    2006-01-01

    Aim: To explore the anti-inflammatory effects of amurensin H on asthma-like reaction induced by allergen in sensitized mice. Methods: BALB/c mice were sensitized by ovalbumin (OVA, ip) on d 0 and d 14 and challenged with 1 % OVA on d 18 to 22. Mice developed airway eosinophilia, mucus hypersecretion, and elevation in cytokine levels. Mice were administered amurensin H orally at the doses of 49, 70, or 100 mg/kg once every day from d 15 to the last day. Bronchoalveolar lavage fluid (BALE) were collected at 24 h and 48 h after the last OVA challenge. Levels of tumor necrosis factor-a (TNF-α), interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13) in BALF were measured using ELISA method. Differential cell counts of macrophages, lymphocytes, neutrophils and eosinophils were performed in 200 cells per slide (one slide per animal). Lung tissue sections of 6-um thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration, mucus production, and tissue damage. Results: Oral administration of amurensin H significantly inhibited OVA-induced increases in total cell counts, eosinophil counts, and TNF-α, IL-4, IL-5 and IL-13 levels in BALF. In addition, amuresin H dramatically decreased OVA-induced lung tissue damage and mucus production. Conclusion: Amurensin H may have therapeutic potential for the treatment of allergic airway inflammation.

  12. Why are some proteins allergenic? Implications for biotechnology.

    Science.gov (United States)

    Lehrer, S B; Horner, W E; Reese, G

    1996-07-01

    In recent years, a number of agricultural crops have been developed with recombinant DNA technology. Because the transferred genes code for proteins that are ordinarily not present in these particular foods, there is concern about the potential allergenicity of these new crop varieties. Foods contain many proteins; however, only a small fraction are allergens. Although the structural properties of proteins that cause allergic reactions have not been characterized completely, known food allergens in general have molecular weights between 10 and 70 kDa, stimulate the immune response (induce the production of allergen-specific IgE), and are stable molecules that are resistant to processing, cooking, and digestion. Although any type of food is potentially allergenic, the majority of food allergies are caused by a small group of foods (cows' milk, nuts, legumes, eggs, seafood). Cross-reactivities occur within a given food group and between foods and seemingly unrelated proteins. Even though most transgenic foods are considered safe, biotechnological manipulation can affect crop allergenicity. The safety evaluation of transgenic foods is relatively easy when the allergenicity of the gene sources are known. The recombinant food can be assayed using traditional in vitro inhibition assays. Recently, reduced allergen content of biotechnologically altered rice was shown. In contrast, increased allergenicity was demonstrated in transgenic soybeans after a methionine- and cystine-rich protein from Brazil nuts, identified as a major Brazil nut allergen, was expressed in soybean to increase its content of sulfur-rich amino acids. The most difficult issue regarding transgenic food allergenicity is the effect of transfer of proteins of unknown allergenicity. The challenge is to determine whether these proteins are allergenic as there is no generally accepted, established, definitive procedure to define or predict a protein's allergenicity. Comparing the structures of the

  13. Early and late nasal symptom response to allergen challenge. The effect of pretreatment with a glucocorticosteroid spray

    DEFF Research Database (Denmark)

    Grønborg, H; Bisgaard, H; Rømeling, Frans

    1993-01-01

    with the glucocorticosteroid budesonide (200 micrograms twice daily) for 14 d and with placebo in a double-blind, cross-over trial. The early response, consisting of sneezing, discharge, and blockage, was followed by a weak late response, consisting of a few sneezes and nose-blowings, and of a sustained nasal blockage......We challenged 30 pollen-sensitive volunteers with allergen, recorded symptoms and signs over a 10-h period, and rechallenged them after 24 h, in order to characterize the early and late allergic symptom response in the nose. The challenge was performed after topical pretreatment....... These symptoms did not have a well-defined peak in time, and a biphasic symptom curve could not be identified. The rechallenge response showed increased nasal responsiveness. The degree of budesonide effect on the early response varied, depending on the symptom; there was a marked effect on sneezing (72...

  14. Plant food allergens--structural and functional aspects of allergenicity.

    Science.gov (United States)

    Breiteneder, Heimo; Clare Mills, E N

    2005-09-01

    The three dominating plant food allergen groups belong to the prolamin and cupin superfamilies and to the family 10 of pathogenesis-related proteins. The prolamin superfamily comprises allergenic 2S albumins, nonspecific lipid transfer proteins and cereal alpha-amylase/trypsin inhibitors. These allergens have related structures and are stable to thermal processing and proteolysis. The cupin superfamily comprises the allergenic 7S and 11S globulin storage proteins from peanuts, soybean and tree nuts which are heat stable and can form immunogenicity enhancing aggregates. The Bet v 1 family of allergens includes tree pollinosis-associated food allergens with low stability which induce the symptoms of the oral allergy syndrome.

  15. THE EFFECT OF NEDOCROMIL SODIUM ON THE EARLY AND LATE REACTION AND ALLERGEN-INDUCED BRONCHIAL HYPERRESPONSIVENESS

    NARCIS (Netherlands)

    AALBERS, R; KAUFFMAN, HF; GROEN, H; KOETER, GH; DEMONCHY, JGR

    1991-01-01

    Bronchial hyperresponsiveness (BHR) to methacholine was studied in 14 patients with asthma and five healthy control subjects, with and without pretreatment with nedocromil sodium, 3 and 24 hours after allergen challenge. Eleven patients demonstrated a dual asthmatic response. A significant decrease

  16. Fungal allergens.

    OpenAIRE

    1995-01-01

    Airborne fungal spores occur widely and often in far greater concentrations than pollen grains. Immunoglobulin E-specific antigens (allergens) on airborne fungal spores induce type I hypersensitivity (allergic) respiratory reactions in sensitized atopic subjects, causing rhinitis and/or asthma. The prevalence of respiratory allergy to fungi is imprecisely known but is estimated at 20 to 30% of atopic (allergy-predisposed) individuals or up to 6% of the general population. Diagnosis and immuno...

  17. Specific allergen immunotherapy attenuates allergic airway inflammation in a rat model of Alstonia scholaris pollen induced airway allergy.

    Science.gov (United States)

    Datta, Ankur; Moitra, Saibal; Hazra, Iman; Mondal, Somnath; Das, Prasanta Kumar; Singh, Manoj Kumar; Chaudhuri, Suhnrita; Bhattacharya, Debanjan; Tripathi, Santanu Kumar; Chaudhuri, Swapna

    2016-01-01

    Pollen grains are well established to be an important cause of respiratory allergy. Current pharmacologic therapies for allergic asthma do not cure the disease. Allergen specific immunotherapy is the only treatment method which re-directs the immune system away from allergic response leading to a long lasting effect. The mechanism by which immunotherapy achieves this goal is an area of active research world-wide. The present experimental study was designed to develop an experimental model of allergic lung inflammation based on a relevant human allergen, Alstonia scholaris pollen, and to establish the immunological and cellular features of specific allergen immunotherapy using this same pollen extract. Our results revealed that Alstonia scholaris pollen sensitization and challenge causes eosinophilic airway inflammation with mucin hypersecretion. This is associated with increased total IgE, increased expression of FcɛRI on lung mast cells and increased levels of IL-4, IL-5 & IL-13 as confirmed by ELISA, in-situ immunofluorescence and FACS assay. Allergen specific immunotherapy reduced airway inflammation and also decreased total IgE level, FcɛRI expression, IL-4, IL-5 & IL-13 levels. It was further noted that the reduction of these levels was more by intra-nasal route than by intra-peritoneal route. Thus we present a novel animal model of Alstonia scholaris pollen allergic disease and specific allergen immunotherapy which will pave the way towards the development of better treatment modalities.

  18. Food processing and allergenicity.

    Science.gov (United States)

    Verhoeckx, Kitty C M; Vissers, Yvonne M; Baumert, Joseph L; Faludi, Roland; Feys, Marcel; Flanagan, Simon; Herouet-Guicheney, Corinne; Holzhauser, Thomas; Shimojo, Ryo; van der Bolt, Nieke; Wichers, Harry; Kimber, Ian

    2015-06-01

    Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat treatment) on the allergenic potential of proteins, and on the antigenic (IgG-binding) and allergenic (IgE-binding) properties of proteins has been considered. A variety of allergenic foods (peanuts, tree nuts, cows' milk, hens' eggs, soy, wheat and mustard) have been reviewed. The overall conclusion drawn is that processing does not completely abolish the allergenic potential of allergens. Currently, only fermentation and hydrolysis may have potential to reduce allergenicity to such an extent that symptoms will not be elicited, while other methods might be promising but need more data. Literature on the effect of processing on allergenic potential and the ability to induce sensitisation is scarce. This is an important issue since processing may impact on the ability of proteins to cause the acquisition of allergic sensitisation, and the subject should be a focus of future research. Also, there remains a need to develop robust and integrated methods for the risk assessment of food allergenicity.

  19. Allergens of mites

    Directory of Open Access Journals (Sweden)

    Emilia Siwak

    2014-04-01

    Full Text Available Mite allergens belong to the group of inhalant allergens and represent antigenic substances which are particutlarly important in the pathogenesis of respiratory system diseases and skin diseases. The most common diseases associated with chronic exposure to these aeroallergens include: allergic rhinitis, bronchial asthma and atopic dermatitis. Mite allergens are simple proteins or glycoproteins with different molecular structures and various biochemical functions. The sensitizing capacity of these proteins is connected from their physicochemical properties. Individual allergens perform, among others, the functions of structural proteins, act as enzymes, transport lipids, bind metal ions, and are capable of glycosylation. In addition, mite allergenic proteases degrade proteins of the skin epithelium-resulting in a weakening of its natural protective barrier-and induce the immune response. The proteases also induce the release of pro-inflammatory cytokines: interleukin-4 (IL-4, interleukin 6 (IL-6, interleukin 8 (IL-8, eotaxin, and granulocyte-macrophage colony-stimulating factor-GM-CSF. The article presents the tertiary structure of major and mid-range mite allergens and their classification. Based on literature reports concerning the chemical structure of allergenic proteins, it was emphasized that the structural differences between homologous proteins with allergenic pozoproperties relate to the distribution of amino acid residues on the surface of the molecule. IgE binding affinity and the similarities and differences in the amino acid sequence of the allergens were also the basis for determining cross-reactivity of allergenic proteins. The paper shows an example of this phenomenon, describing the existence of common allergens for various mite species.

  20. Airway inflammation and IgE production induced by dust mite allergen-specific memory/effector Th2 cell line can be effectively attenuated by IL-35.

    Science.gov (United States)

    Huang, Chiung-Hui; Loo, Evelyn Xiu-Ling; Kuo, I-Chun; Soh, Gim Hooi; Goh, Denise Li-Meng; Lee, Bee Wah; Chua, Kaw Yan

    2011-07-01

    CD4(+) memory/effector T cells play a central role in orchestrating the rapid and robust immune responses upon re-encounter with specific Ags. However, the immunologic mechanism(s) underlying these responses are still not fully understood. To investigate this, we generated an allergen (major house dust mite allergen, Blo t 5)-specific murine Th2 cell line that secreted IL-4, IL-5, IL-10, and IL-13, but not IL-9 or TNF-α, upon activation by the cognate Ag. These cells also exhibited CD44(high)CD62L(-) and CD127(+) (IL-7Rα(+)) phenotypes, which are characteristics of memory/effector T cells. Experiments involving adoptive transfer of this Th2 cell line in mice, followed by three intranasal challenges with Blo t 5, induced a dexamethasone-sensitive eosinophilic airway inflammation. This was accompanied by elevation of Th2 cytokines and CC- and CXC-motif chemokines, as well as recruitment of lymphocytes and polymorphic mononuclear cells into the lungs. Moreover, Blo t 5-specific IgE was detected 4 d after the last intranasal challenge, whereas elevation of Blo t 5-specific IgG1 was found at week two. Finally, pulmonary delivery of the pVAX-IL-35 DNA construct effectively downregulated Blo t 5-specific allergic airway inflammation, and i.m. injection of pVAX-IL-35 led to long-lasting suppression of circulating Blo t 5-specific and total IgE. This model provides a robust research tool to elucidate the immunopathogenic role of memory/effector Th2 cells in allergic airway inflammation. Our results suggested that IL-35 could be a potential therapeutic target for allergic asthma through its attenuating effects on allergen-specific CD4(+) memory/effector Th2 cell-mediated airway inflammation.

  1. The influence of digestibility on the allergenicity of food allergens

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Madsen, Charlotte Bernhard

    2012-01-01

    Food allergy is a major health problem in the Western countries, affecting 3-8% of the population. What makes a dietary protein a food allergen has not yet been established, though several characteristics have been proposed to be shared by the food allergens. One of the features believed...... to be a general characteristic is resistance to digestion. This is based on studies showing that allergenic dietary proteins in general were more resistant to digestion than dietary proteins with no proven allergenicity, leading to the conclusion, that a correlation between stability to digestion and allergenic...... potential exist. Resistance to digestion is therefore a test parameter included in the safety assessment of the allergenic potential of novel proteins in genetically modified foods. In recent years, the association between resistance to digestion and allergenic potential has been challenged. When reviewing...

  2. Inhibition of NF-κB Expression and Allergen-induced Airway Inflammation in a Mouse Allergic Asthma Model by Andrographolide

    Institute of Scientific and Technical Information of China (English)

    Jing Li; Li Luo; Xiaoyun Wang; Bin Liao; Guoping Li

    2009-01-01

    Andrographolide from traditional Chinese herbal medicines previously showed it possesses a strong anti-inflammatory activity. In present study, we investigated whether Andrographolide could inhibit allergen-induced airway inflammation and airways hyper-responsiveness and explored the mechanism of Andrographolide on allergen-induced airway inflammation and airways hyper-responsiveness. After sensitized and challenged by ovalbumin, the BALB/c mice were administered intraperitoneally with Andrographolide. Hyper-responsiveness was recorded. The lung tissues were assessed by histological examinations. NF-κB in lung was determined by immunofluorescence staining and Western blotting. Treatment of mice with Androqrapholide displayed lower Penh in response to asthma group mice. After treatment with Andrographolide, the extent of inflammation and cellular infltrafion in the airway were reduced. Andrographolide interrupted NF-κB to express in cell nucleus. The level of NF-κB expression was inhibited by Andrographolide. The data indicate that Andrographolide from traditional Chinese herbal medicines could inhibit extensive infiltration of inflammatory cells in lung and decrease airway hyperreactivity. Andrographolide could inhibit NF-κB expression in lung and suppress NF-κB expressed in the nucleus of airway epithelial cells. Cellular & Molecular Immunology. 2009;6(5):381-385.

  3. Effects of nebulized ketamine on allergen-induced airway hyperresponsiveness and inflammation in actively sensitized Brown-Norway rats

    Directory of Open Access Journals (Sweden)

    Qian Yan

    2007-05-01

    Full Text Available Abstract Since airway hyperresponsiveness (AHR and allergic inflammatory changes are regarded as the primary manifestations of asthma, the main goals of asthma treatment are to decrease inflammation and maximize bronchodilation. These goals can be achieved with aerosol therapy. Intravenous administration of the anesthetic, ketamine, has been shown to trigger bronchial smooth muscle relaxation. Furthermore, increasing evidence suggests that the anti-inflammatory properties of ketamine may protect against lung injury. However, ketamine inhalation might yield the same or better results at higher airway and lower ketamine plasma concentrations for the treatment of asthma. Here, we studied the effect of ketamine inhalation on bronchial hyperresponsiveness and airway inflammation in a Brown-Norway rat model of ovalbumin(OVA-induced allergic asthma. Animals were actively sensitized by subcutaneous injection of OVA and challenged by repeated intermittent (thrice weekly exposure to aerosolized OVA for two weeks. Before challenge, the sensitizened rats received inhalation of aerosol of phosphate-buffered saline (PBS or aerosol of ketamine or injection of ketamine respectivity. Airway reactivity to acetylcholine (Ach was measured in vivo, and various inflammatory markers, including Th2 cytokines in bronchoalveolar lavage fluid (BALF, as well as induciable nitric oxide synthase (iNOS and nitric oxide (NO in lungs were examined. Our results revealed that delivery of aerosolized ketamine using an ultrasonic nebulizer markedly suppressed allergen-mediated airway hyperreactivity, airway inflammation and airway inflammatory cell infiltration into the BALF, and significantly decreased the levels of interleukin-4 (IL-4 in the BALF and expression of iNOS and the concentration of NO in the inflamed airways from OVA-treated rats. These findings collectively indicate that nebulized ketamine attenuated many of the central components of inflammatory changes and AHR in

  4. Large particulate allergens can elicit mast cell-mediated anaphylaxis without exit from blood vessels as efficiently as do small soluble allergens.

    Science.gov (United States)

    LiHua, Li; Yoshikawa, Soichiro; Ohta, Takuya; Horiguchi, Kayo; Kawano, Yohei; Ohtsu, Hiroshi; Yamanishi, Yoshinori; Karasuyama, Hajime

    2015-11-06

    Anaphylaxis is a rapid-onset, life-threatening allergic reaction in that IgE, mast cells and histamine are commonly involved. It can be experimentally induced in IgE-sensitized animals by intravenous injection of corresponding allergens, and the sign of anaphylactic reaction can be detected within minutes after allergen challenge. However, it remains puzzling why the anaphylactic reaction can be initiated in vivo so quickly, considering that allergens are delivered into the blood circulation while mast cells reside within peripheral tissues but not in the blood circulation. To address this issue, we compared two different forms of the same allergen, small soluble and large particulate ones, in their ability to induce anaphylaxis in IgE-sensitized mice. In contrast to our expectation, particulate allergens could induce anaphylaxis as quickly and efficiently as did soluble allergens, even though they remained inside of blood vessels. In vivo imaging analysis suggested the direct interaction of intravascular particulate allergens and perivascular mast cells across the capillary wall. Taken together with previous report that perivascular mast cells can capture IgE in the blood circulation by extending cell processes across the vessel wall, our findings imply that blood-circulating allergens, regardless of their size, can stimulate mast cells without exit from blood vessels, by means of cross-linking IgE on mast cell processes inserted into the vessel lumen, and hence initiate anaphylactic reaction so quickly.

  5. Circulating histamine and neutrophil chemotactic activity during allergen-induced asthma: the effect of inhaled antihistamines and anti-allergic compounds.

    Science.gov (United States)

    Morgan, D J; Moodley, I; Cundell, D R; Sheinman, B D; Smart, W; Davies, R J

    1985-07-01

    Plasma histamine and serum neutrophil chemotactic activity (S-NCA) were measured in ten atopic asthmatic patients on four separate occasions after allergen bronchial provocation testing (BPT). Single doses of inhaled sodium cromoglycate (SCG; 20 mg), clemastine (0.5 mg), ketotifen (0.5 mg) and isotonic saline (0.9% NaCl) placebo were administered 30 min before bronchial provocation testing in random order and double-blind. The airflow obstruction after BPT was monitored by measurement of forced expiratory volume in 1 s (FEV1). Plasma histamine was measured by the double-isotope radioenzymatic assay and S-NCA by a modified Boyden chamber technique. A highly significant decrease in FEV1 after BPT occurred on the placebo pre-treatment visit (P less than 0.001). Prior administration of inhaled SCG, clemastine and ketotifen significantly reduced the decrease in airflow obstruction seen after BPT when compared with placebo treatment (P less than 0.01, P less than 0.02, P less than 0.05 respectively). No significant alteration in plasma histamine was detected during allergen-induced airflow obstruction. Levels of S-NCA were significantly higher 5, 10 and 15 min after BPT when compared with the pre-challenge level (P less than 0.01, P less than 0.01, P less than 0.001 respectively). These levels were not significantly decreased when airflow obstruction was inhibited by the prior inhalation of SCG, clemastine or ketotifen.

  6. Inbred and outbred mice have equivalent variability in a cockroach allergen-induced model of asthma.

    Science.gov (United States)

    Vaickus, Louis J; Bouchard, Jacqueline; Kim, Jiyoun; Natarajan, Sudha; Remick, Daniel G

    2010-12-01

    Outbred mice traditionally are considered to display high variability, thereby limiting their use in some studies. Researchers frequently are encouraged to use inbred strains of mice because of the greater homogeneity of these experimental animals. We compared the pulmonary inflammatory response of inbred BALB/cJ mice to that of outbred HSD-ICR mice by measuring multiple variables, including cytokines, chemokines, number of pulmonary inflammatory cells, and respiratory parameters. Cockroach allergens induced significant pulmonary inflammation in both BALB and ICR mice. Our comparisons of the coefficients of variance for 148 discrete data sets for each strain or stock indicated that BALB and ICR mice have roughly equivalent intrastrain or -stock variability in our model of asthma-like pulmonary inflammation. The average coefficient of variance, calculated as the ratio of the SD to the mean of a data set, was 0.35 ± 0.34 for BALB mice compared with 0.31 ± 0.32 for ICR mice. In conclusion, inbred BALB and outbred ICR mice have roughly equivalent intrastrain or -stock variability in a murine model of asthma-like pulmonary inflammation.

  7. Several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge

    DEFF Research Database (Denmark)

    Christensen, Lars Harder; Holm, Jens-Christian; Lund, Gitte;

    2008-01-01

    BACKGROUND: On cross-linking of receptor-bound IgE antibodies by allergens, effector cells (basophils and mast cells) involved in type I allergic reactions degranulate and release the potent chemical mediators stored inside their granules. Total and allergen-specific IgE concentrations, Ig......E affinity for allergen, and IgE clonality are all distinct properties of allergic patients' IgE repertoires. However, the inability to isolate individual IgE antibodies from allergic patients' sera presents a major barrier to understanding the importance of patient-specific IgE repertoires...... for the manifestation and severity of allergic symptoms. OBJECTIVE: We sought to investigate how individual properties of an IgE repertoire affect effector cell degranulation. METHODS: A panel of recombinant IgE (rIgE) antibodies specific for the major house dust mite allergen Der p 2 was developed and characterized...

  8. Aryl Hydrocarbon Receptor (AhR Modulates Cockroach Allergen-Induced Immune Responses through Active TGFβ1 Release

    Directory of Open Access Journals (Sweden)

    Yufeng Zhou

    2014-01-01

    Full Text Available Background. Aryl hydrocarbon receptor (AhR, a multifunctional regulator that senses and responds to environmental stimuli, plays a role in normal cell development and immune regulation. Recent evidence supports a significant link between environmental exposure and AhR in the development of allergic diseases. We sought to investigate whether AhR plays a role in mediating cockroach allergen-induced allergic immune responses. Methods. AhR expression in human lung fibroblasts from asthmatic and healthy individuals and in cockroach extract (CRE treated human lung fibroblasts (WI-38 was examined. The role of AhR in modulating CRE induced TGFβ1 production was investigated by using AhR agonist, TCDD, antagonist CH122319, and knockdown of AhR. The role of latent TGFβ1 binding protein-1 (LTBP1 in mediating TCDD induced active TGFβ1 release was also examined. Results. AhR expression was higher in airway fibroblasts from asthmatic subjects as compared to healthy controls. AhR in fibroblasts was activated by TCDD with an increased expression of cyp1a1 and cyp1b1. Increased AhR expression was observed in CRE-treated fibroblasts. Importantly, CRE induced TGFβ1 production in fibroblasts was significantly enhanced by TCDD but inhibited by CH122319. Reduced TGFβ1 production was further confirmed in fibroblasts with AhR knockdown. Moreover, AhR knockdown inhibited CRE induced fibroblast differentiation. Furthermore, TCDD induced active TGFβ1 release was significantly inhibited by LTBP1 knockdown. Conclusion. These results provide evidence for the role of AhR in modulating cockroach allergen-induced immune responses through controlling the active TGFβ1 release, suggesting a possible synergistic effect between exposure to allergens and environmental chemicals on the development of allergic diseases.

  9. Quality Control of Biomedicinal Allergen Products - Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses.

    Directory of Open Access Journals (Sweden)

    Jelena Spiric

    Full Text Available Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied.

  10. Quality Control of Biomedicinal Allergen Products - Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses.

    Science.gov (United States)

    Spiric, Jelena; Engin, Anna M; Karas, Michael; Reuter, Andreas

    2015-01-01

    Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied.

  11. The absence of mrp4 has no effect on the recruitment of neutrophils and eosinophils into the lung after LPS, cigarette smoke or allergen challenge.

    Directory of Open Access Journals (Sweden)

    Jürgen Schymeinsky

    Full Text Available The multidrug resistance protein 4 (Mrp4 is an ATP-binding cassette transporter that is capable of exporting the second messenger cAMP from cells, a process that might regulate cAMP-mediated anti-inflammatory processes. However, using LPS- or cigarette smoke (CS-inflammation models, we found that neutrophil numbers in the bronchoalveolar lavage fluid (BALF were similar in Mrp4(-/- and Mrp4(+/+ mice treated with LPS or CS. Similarly, neutrophil numbers were not reduced in the BALF of LPS-challenged wt mice after treatment with 10 or 30 mg/kg of the Mrp1/4 inhibitor MK571. The absence of Mrp4 also had no impact on the influx of eosinophils or IL-4 and IL-5 levels in the BALF after OVA airway challenge in mice sensitized with OVA/alum. LPS-induced cytokine release in whole blood ex vivo was also not affected by the absence of Mrp4. These data clearly suggest that Mrp4 deficiency alone is not sufficient to reduce inflammatory processes in vivo. We hypothesized that in combination with PDE4 inhibitors, used at suboptimal concentrations, the anti-inflammatory effect would be more pronounced. However, LPS-induced neutrophil recruitment into the lung was no different between Mrp4(-/- and Mrp4(+/+ mice treated with 3 mg/kg Roflumilast. Finally, the single and combined administration of 10 and 30 mg/kg MK571 and the specific breast cancer resistance protein (BCRP inhibitor KO143 showed no reduction of LPS-induced TNFα release into the BALF compared to vehicle treated control animals. Similarly, LPS-induced TNFα release in murine whole blood of Mrp4(+/+ or Mrp4(-/- mice was not reduced by KO143 (1, 10 µM. Thus, BCRP seems not to be able to compensate for the absence or inhibition of Mrp4 in the used models. Taken together, our data suggest that Mrp4 is not essential for the recruitment of neutrophils into the lung after LPS or CS exposure or of eosinophils after allergen exposure.

  12. Increasing time interval and decreasing allergen dose interval improves ex vivo desensitization of human blood basophils

    DEFF Research Database (Denmark)

    Witting Christensen, Sara K; Krohn, Inge Kortekaas; Thuraiaiyah, Jani;

    2016-01-01

    BACKGROUND: Desensitization is a method for inducing temporary tolerance to allergen. The mechanism underlying desensitization is yet to be established. METHODS: Basophil granulocytes in whole blood from grass pollen allergic subjects were desensitized ex vivo by sequential addition of increasing...... allergen concentrations. At each step basophil activation (CD193(+) CD63(+) ) was monitored with and without (background activation) allergen challenge at optimal concentration. The sequential desensitization protocol was compared to a single-dose desensitization protocols with threshold and subthreshold...... allergen concentrations. Incubation intervals and allergen concentrations were varied in order to optimise the protocol. RESULTS: Sequential desensitization effectively reduced basophil response. The single-dose subthreshold protocol and single-dose threshold protocols did not reduce basophil activation...

  13. Blood flow in histamine- and allergen-induced weal and flare responses, effects of an H1 antagonist, alpha-adrenoceptor agonist and a topical glucocorticoid.

    Science.gov (United States)

    Hammarlund, A; Olsson, P; Pipkorn, U

    1990-01-01

    Allergen has previously been shown to induce a continuous increase in local dermal blood flow after a prick test in allergic subjects, whereas histamine induced, initially, similar peak increases in blood flow of much shorter duration. Blood flow changes induced by histamine and allergen have now been evaluated (i) after pretreatment with a local corticosteroid cream, clobetasole-17-propionate; (ii) after oral administration of the H1-antihistamine loratadine; and (iii) after oral pretreatment with the alpha 1-adrenoceptor agonist pseudoephedrine. Blinded placebo-controlled designs were used in the substudies. Laser doppler flowmetry was used for non-invasive recording of changes in local blood flow intermittently for 24 h after the topical corticosteroid, 6 h for the substudies on loratadine and pseudoephedrine. The size of the immediate weal and flare reactions, as well as late phase reactions, were also determined. Pretreatment with clobetasole-17-propionate cream on the skin for 1 week prior to prick tests did not affect the blood flow response elicited by histamine or allergen, in either the initial part (up to 1 h) or the protracted 24 h determinations. The size of the weal and flare reactions decreased. Loratadine and pseudoephedrine did not reduce the initial allergen-induced increase in blood flow, while lower blood flow compared with placebo pretreatment was noted for the protracted (1-6 h) determinations. Blood flow changes after histamine were unaffected. The histamine-induced weal and flare was inhibited by loratadine more effectively than the corresponding allergen-induced reaction. The weal and flare reactions after histamine and allergen were not changed after pseudoephedrine.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Allergens from fish and egg

    DEFF Research Database (Denmark)

    Poulsen, Lars K.; Hansen, T K; Nørgaard, A

    2001-01-01

    Allergens from fish and egg belong to some of the most frequent causes of food allergic reactions reported in the literature. Egg allergens have been described in both white and yolk, and the egg white proteins ovomucoid, ovalbumin, ovotransferrin and lysozyme have been adopted in the allergen...... nomenclature as Gal d1-d4. The most reported allergen from egg yolk seems to be alpha-livitin. In fish, the dominating allergen is the homologues of Gad c1 from cod, formerly described as protein M. A close cross-reactivity exists within different species of fish between this calcium-binding protein family......, denominated the parvalbumins. This cross-reactivity has been indicated to be of clinical relevance for several species, since patients with a positive double-blind, placebo-controlled food challenge to cod will also react with other fish species, such as herring, plaice and mackerel. In spite...

  15. Deficiency of nitric oxide in allergen-induced airway hyperreactivity to contractile agonists after the early asthmatic reaction : An ex vivo study

    NARCIS (Netherlands)

    deBoer, J; Meurs, H; Coers, W; Koopal, M; Bottone, AE; Visser, AC; Timens, W; Zaagsma, J

    1996-01-01

    1 Using a guinea-pig model of allergic asthma, we investigated the role of nitric oxide (NO) in allergen-induced airway hyperreactivity after the early asthmatic reaction, by examining the effects of the NO-synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on the responsiveness to me

  16. Role of L-arginine in the deficiency of nitric oxide and airway hyperreactivity after the allergen-induced early asthmatic reaction in guinea-pigs

    NARCIS (Netherlands)

    de Boer, J; Duyvendak, M; Schuurman, F.E; Pouw, F.M W; Zaagsma, Hans; Meurs, Herman

    1999-01-01

    1 Using a guinea-pig model of allergic asthma, we investigated the role of L-arginine limitation in the allergen-induced deficiency of nitric oxide (NO) and airway hyperreactivity (AHR) after the early asthmatic reaction, by examining the effects of various concentrations of the NO synthase (NOS) su

  17. Comparison of cetirizine with astemizole in the treatment of perennial allergic rhinitis and study of the concomitant effect on histamine and allergen-induced wheal responses.

    Science.gov (United States)

    Lobaton, P; Moreno, F; Coulie, P

    1990-11-01

    Thirty patients suffering from perennial allergic rhinitis took astemizole and cetirizine, 10 mg/d, under double-blind, crossover randomized conditions for 4 weeks. Four weeks washout separated the two periods. Nasal condition was improved, histamine and allergen-induced wheal responses were inhibited by both treatments with a slight advantage for cetirizine. Both treatments were well tolerated.

  18. The effects of vitamin D on allergen-induced expression of interleukin-13 and interleukin-17 in cord blood CD4⁺T cells.

    Science.gov (United States)

    Zhong, Hui; Zhou, Xiao Jian; Hong, Jian Gou

    2014-04-01

    Cytokine production in response to allergens may influence the development of atopy-predisposing immune responses, initializing the early programming of allergy and asthma. Vitamin D intake may be protective due to its immunoregulatory properties, that may contribute to influence the expression of the atopic phenotype initiated in early life. The objective of our study was to investigate the effects of 1,25-(OH)₂D₃ on allergen-stimulated expression of asthma related cytokines in cord blood T cells. Cord blood samples were collected from the umblilical vein of 24 term deliveries during labor, CD4⁺T cells derived from cord blood mononuclear cells (CBMCs), were cultured for 72 hours with ovalbumin (OVA), β-lactoglobulin (β-LG), respectively, in presence or absence of 1,25-(OH)₂D₃ to detect the levels of interleukin-13 (IL-13) and interleukin-17 (IL-17) in culture supernatants and the mRNA expressions in CD4⁺T cells. After allergens stimulation, CD4⁺T cells showed an increase of IL-13 and IL-17 production, while cultured in the presence of 1,25-(OH)₂D₃ displayed a statistically significant down-regulation of allergen-induced expression of IL-13 and IL-17 in CD4⁺T cells. These results indicated that allergens may induce changes in CD4⁺T cell function to increase inflammatory cytokine production. 1,25-(OH)₂D₃ modulated the capacity of CD4⁺T cells in response to allergens, which might be protective for allergy.

  19. Studies on BN rats model to determine the potential allergenicity of proteins from genetically modified foods

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Jia; Ning Li; Yong-Ning Wu; Xiao-Guang Yang

    2005-01-01

    AIM: To develop a Brown Norway (BN) rat model to determine the potential allergenicity of novel proteins in genetically modified food.METHODS: The allergenicity of different proteins were compared, including ovalbumin (OVA), a potent respiratory and food allergen, bovine serum albumin (BSA), a protein that is considered to have a lesser allergenic potential,and potato acid phosphatase (PAP), a non-allergenic protein when administered to BN rats via different routes of exposure (intraperitoneally or by gavage). IgG and IgE antibody responses were determined by ELISA and PCA,respectively. An immunoassay kit was used to determine the plasma histamine level. In addition, possible systemic effect of allergens was investigated by monitoring blood pressure.RESULTS: OVA provoked very vigorous protein-specific IgG and IgE responses, low grade protein-specific IgG and IgE responses were elicited by BSA, while by neither route did PAP elicit anything. In either routes of exposure,plasma histamine level in BN rats sensitized with OVA was higher than that of BSA or PAP. In addition, an oral challenge with BSA and PAP did not induce any effect on blood pressure, while a temporary drop in systolic blood pressure in few animals of each routes of exposure was found by an oral challenge with OVA.CONCLUSION: BN rat model might be a useful and predictive animal model to study the potential allergenicity of novel food proteins.

  20. IgE in the absence of allergen induces the expression of monocyte chemoattractant protein-1 in the rat basophilic cell-line RBL-2H3.

    Science.gov (United States)

    Ahn, Ki Bum; Jeon, Jun Ho; Kang, Seok-Seong; Chung, Dae Kyun; Yun, Cheol-Heui; Han, Seung Hyun

    2014-11-01

    Recently, basophils have been suggested to produce inflammatory mediators in response to IgE in the absence of allergens. Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the initiation of inflammatory responses by recruiting various immune cells to the site of allergic inflammation. In the present study, we examined whether IgE under allergen-free conditions could stimulate basophils and lead to the production of MCP-1. Exposure of the rat basophilic cell-line RBL-2H3 to IgE without allergen resulted in a dose- and time-dependent induction of MCP-1 expression at both the mRNA and protein level. Although allergen was not necessary for IgE-induced MCP-1 expression, it was essential for degranulation as determined by β-hexosaminidase release assay. IgE enhanced phosphorylation of MAP kinases including ERK, p38 kinase, and JNK. However, IgE-induced MCP-1 expression was attenuated by inhibitors for JNK and PKC. Concomitantly, IgE induced activation of AP-1, which is an important transcription factor for MCP-1 gene expression in RBL-2H3 cells. Taken together, our results suggest that IgE alone is sufficient to stimulate basophils to increase expression of MCP-1, which in turn might contribute to the inflammatory response.

  1. Cockroach protease allergen induces allergic airway inflammation via epithelial cell activation

    Science.gov (United States)

    Kale, Sagar L.; Agrawal, Komal; Gaur, Shailendra Nath; Arora, Naveen

    2017-01-01

    Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies. Per a 10 exposure also leads to secretion of IL-33, TSLP and intracellular Ca2+ dependent increase in ATP levels. Further, in vivo experiments revealed that Per a 10 administration in mice elevated allergic inflammatory parameters along with high levels of IL-33, TSLP, IL-1α and uric acid in the mice lungs. We next demonstrated that Per a 10 cleaves CD23 (low affinity IgE receptor) from the surface of PBMCs and purified B cells and CD25 (IL-2 receptor) from the surface of PBMCs and purified T cells in an activity dependent manner, which might favour Th2 responses. In conclusion, protease activity of Per a 10 plays a significant role in initiation of allergic airway inflammation at the mucosal surfaces. PMID:28198394

  2. Heat-induced alterations in cashew allergen solubility and IgE binding

    Directory of Open Access Journals (Sweden)

    Christopher P. Mattison

    2016-01-01

    Full Text Available Cashew nuts are an increasingly common cause of food allergy. We compare the soluble protein profile of cashew nuts following heating. SDS-PAGE indicate that heating can alter the solubility of cashew nut proteins. The 11S legumin, Ana o 2, dominates the soluble protein content in ready to eat and mildly heated cashew nuts. However, we found that in dark-roasted cashew nuts, the soluble protein profile shifts and the 2S albumin Ana o 3 composes up to 40% of the soluble protein. Analysis of trypsin-treated extracts by LC/MS/MS indicate changes in the relative number and intensity of peptides. The relative cumulative intensity of the 5 most commonly observed Ana o 1 and 2 peptides are altered by heating, while those of the 5 most commonly observed Ana o 3 peptides remaine relatively constant. ELISA experiments indicate that there is a decrease in rabbit IgG and human serum IgE binding to soluble cashew proteins following heating. Our findings indicate that heating can alter the solubility of cashew allergens, resulting in altered IgE binding. Our results support the use of both Ana o 2 and Ana o 3 as potential cashew allergen diagnostic targets.

  3. Hydrogen sulfide inhalation ameliorates allergen induced airway hypereactivity by modulating mast cell activation.

    Science.gov (United States)

    Roviezzo, Fiorentina; Bertolino, Antonio; Sorrentino, Rosalinda; Terlizzi, Michela; Matteis, Maria; Calderone, Vincenzo; Mattera, Valentina; Martelli, Alma; Spaziano, Giuseppe; Pinto, Aldo; D'Agostino, Bruno; Cirino, Giuseppe

    2015-10-01

    Compelling evidence suggests that hydrogen sulfide represents an important gaseous transmitter in the mammalian respiratory system. In the present study, we have evaluated the role of mast cells in hydrogen sulfide-induced effects on airways in a mouse model of asthma. Mice were sensitized to ovalbumin and received aerosol of a hydrogen sulfide donor (NaHS; 100 ppm) starting at day 7 after ovalbumin challenge. Exposure to hydrogen sulfide abrogated ovalbumin-induced bronchial hypereactivity as well as the increase in lung resistance. Concomitantly, hydrogen sulfide prevented mast cell activity as well as FGF-2 and IL-13 upregulation. Conversely, pulmonary inflammation and the increase in plasmatic IgE levels were not affected by hydrogen sulfide. A lack of hydrogen sulfide effects in mast cell deficient mice occurred. Primary fibroblasts harvested from ovalbumin-sensitized mice showed an increased proliferation rate that was inhibited by hydrogen sulfide aerosol. Furthermore, ovalbumin-induced transdifferentiation of pulmonary fibroblasts into myofibroblasts was reversed. Finally, hydrogen sulfide did abrogate in vitro the degranulation of the mast cell-like RBL-2H3 cell line. Similarly to the in vivo experiments the inhibitory effect was present only when the cells were activated by antigen exposure. In conclusion, inhaled hydrogen sulfide improves lung function and inhibits bronchial hyper-reactivity by modulating mast cells and in turn fibroblast activation.

  4. Detection of Sesame Allergen Traces with Two PCR Assays - The Challenge to Protect Food-Allergic Consumers

    Directory of Open Access Journals (Sweden)

    Dimitra Panagiotis Houhoula

    2015-01-01

    Full Text Available The purpose of this study was to investigate the possible presence of sesame in commercial foods normally carrying no warning for the allergen, but which may have been subjected to contamination during processing. One hundred units of widely consumed goods with high potential to contain allergenic substances deriving from nuts were analyzed, using sensitive and capable PCR (C-PCR and Real Time PCR (RT-PCR methodologies. Of the products examined, 15 (15.0% declared the presence of sesame, 36 (36.0% carried no food allergy label, 44 (44.0% were marked by the phrase “may contain traces of nuts” and 5 (5.0% carried the indication “may contain sesame traces”. The sesame-positive products detected using the C-PCR method were 15 (100%, 12 (33.3%, 14 (31.8% and 3 (60%, respectively. Using the RT-PCR technique, positive results were obtained for 15 (100%, 18 (50.0%, 18 (20.5% and 5 (100% samples, respectively. The results indicate that the PCR methods applied are highly sensitive and selective, which makes them suitable for the detection of sesame traces in food samples. In addition, they can be useful for monitoring the effectiveness of cleaning processes in the production units of the food industry.

  5. Occupational allergens

    NARCIS (Netherlands)

    Terwoert, J.

    2014-01-01

    Allergens are substances that may cause a hypersensitivity (allergy) of the immune system. After acquiring this hypersensitivity, further exposure to the same substance may result in allergic skin disease such as allergic contact dermatitis, or allergic airway disease such as allergic rhinitis or as

  6. Development of a new hazelnut sandwich ELISA based on detection of Cor a 9, a major hazelnut allergen

    OpenAIRE

    Trashin, Stanislav; Cucu, Tatiana; Devreese, Bart; De Meulenaer, Bruno

    2010-01-01

    The emerging health problem of food-induced allergic reactions, including life-threatening anaphylaxis, presents an important challenge to the food. In the framework of the current ALLERRISK project, analytical approaches for allergen detection are evaluated and developed. Cor a 9 is a major hazelnut protein with nutrient reservoir function, and that also known as a major food allergen. Presence of Cor a 9 indicates contamination of a product with hazelnut and, consequently, potential risk of...

  7. Immune response to allergens in sheep sensitized to house dust mite

    Directory of Open Access Journals (Sweden)

    Velden Joanne

    2008-10-01

    Full Text Available Abstract Background House dust mite (HDM allergens are a major cause of allergic asthma. Most studies using animal models of allergic asthma have used rodents sensitized with the 'un-natural' allergen ovalbumin. It has only recently been recognized that the use of animal models based on HDM provide a more relevant insight into the allergen-induced mechanisms that underpin human allergic disease. We have previously described a sheep model of human allergic asthma that uses Dermatophagoides pteronyssinus HDM. The present study extends our understanding of the immune effects of HDM and the allergens Der p 1 and Der p 2 in the sheep model of asthma. Methods Peripheral blood sera from non-sensitized (control sheep and sheep sensitized to HDM was collected to determine immunoglobulin (Ig reactivities to HDM, Der p 1 and Der p 2 by ELISA. Bronchoalveolar lavage (BAL fluid collected following allergen challenge was also assessed for the presence of HDM-specific antibodies. To examine the cellular immune response to HDM allergens, T cell proliferation and cutaneous responses were assessed in sensitized and control sheep. Results Strong HDM- and Der p 1-specific IgE, IgG1, IgG2 and IgA serum responses were observed in sensitized sheep, while detectable levels of HDM-specific IgG1 and IgA were seen in BAL fluid of allergen-challenged lungs. In contrast, minimal antibody reactivity was observed to Der p 2. Marked T cell proliferation and late phase cutaneous responses, accompanied by the recruitment of eosinophils, indicates the induction of a cellular and delayed-type hypersensitivity (DTH type II response by HDM and Der p 1 allergen, but not Der p 2. Conclusion This work characterizes the humoral and cellular immune effects of HDM extract and its major constituent allergens in sheep sensitized to HDM. The effects of allergen in HDM-sensitized sheep were detectable both locally and systemically, and probably mediated via enzymatic and immune actions of the

  8. Traffic-related air pollutants induce the release of allergen-containing cytoplasmic granules from grass pollen.

    NARCIS (Netherlands)

    Motta, A C; Marliere, M; Peltre, G; Sterenberg, P A; Lacroix, G

    2006-01-01

    BACKGROUND/AIM: Pollen cytoplasmic granules (PCG) are loaded with allergens. They are released from grass pollen grains following contact with water and can form a respirable allergenic aerosol. On the other hand, the traffic-related air pollutants NO2 and O3 are known to be involved in the current

  9. Traffic-related air pollutants induce the release of allergen-containing cytoplasmic granules from grass pollen

    NARCIS (Netherlands)

    Motta, AC; Marliere, M; Peltre, G; Sterenberg, PA; Lacroix, G

    2006-01-01

    Background/Aim: Pollen cytoplasmic granules (PCG) are loaded with allergens. They are released from grass pollen grains following contact with water and can form a respirable allergenic aerosol. On the other hand, the traffic-related air pollutants NO2 and O-3 are known to be involved in the current

  10. Impact of thermal processing on legume allergens.

    Science.gov (United States)

    Verma, Alok Kumar; Kumar, Sandeep; Das, Mukul; Dwivedi, Premendra D

    2012-12-01

    Food induced allergic manifestations are reported from several parts of the world. Food proteins exert their allergenic potential by absorption through the gastrointestinal tract and can even induce life threatening anaphylaxis reactions. Among all food allergens, legume allergens play an important role in induction of allergy because legumes are a major source of protein for vegetarians. Most of the legumes are cooked either by boiling, roasting or frying before consumption, which can be considered a form of thermal treatment. Thermal processing may also include autoclaving, microwave heating, blanching, pasteurization, canning, or steaming. Thermal processing of legumes may reduce, eliminate or enhance the allergenic potential of a respective legume. In most of the cases, minimization of allergenic potential on thermal treatment has generally been reported. Thus, thermal processing can be considered an important tool by indirectly prevent allergenicity in susceptible individuals, thereby reducing treatment costs and reducing industry/office/school absence in case of working population/school going children. The present review attempts to explore various possibilities of reducing or eliminating allergenicity of leguminous food using different methods of thermal processing. Further, this review summarizes different methods of food processing, major legumes and their predominant allergenic proteins, thermal treatment and its relation with antigenicity, effect of thermal processing on legume allergens; also suggests a path that may be taken for future research to reduce the allergenicity using conventional/nonconventional methods.

  11. Food allergens: molecular and immunological aspects, allergen databases and cross-reactivity.

    Science.gov (United States)

    Lorenz, Anne-Regine; Scheurer, Stephan; Vieths, Stefan

    2015-01-01

    The currently known food allergens are assigned to a relatively small number of protein families. Food allergens grouped into protein families share common functional and structural features that can be attributed to the allergenic potency and potential cross-reactivity of certain proteins. Molecular data, in terms of structural information, biochemical characteristics and clinical relevance for each known allergen, including isoforms and variants, are mainly compiled into four open-access databases. Allergens are designated according to defined criteria by the World Health Organization and the International Union of Immunological Societies Allergen Nomenclature Sub-committee. Food allergies are caused by primary sensitisation to the disease-eliciting food allergens (class I food allergen), or they can be elicited as a consequence of a primary sensitisation to inhalant allergens and subsequent IgE cross-reaction to homologous proteins in food (class II food allergens). Class I and class II allergens display different clinical significance in children and adults and are characterised by different molecular features. In line with this, high stability when exposed to gastrointestinal digestion and heat treatment is attributed to many class I food allergens that frequently induce severe reactions. The stability of a food allergen is determined by its molecular characteristics and can be influenced by structural (chemical) modifications due to thermal processing. Moreover, the immunogenicity and allergenicity of food allergens further depends on specific T cell and B cell epitopes. Although the T cell epitope pattern can be highly diverse for individual patients, several immuno-prominent T cell epitopes have been identified. Such conserved T cell epitopes and IgE cross-reactive B cell epitopes contribute to cross-reactivity between food allergens of the same family and to clinical cross-reactivity, similar to the birch pollen-food syndrome.

  12. Fish allergens at a glance: Variable allergenicity of parvalbumins, the major fish allergens

    OpenAIRE

    Annette eKuehn; Ines eSwoboda; Karthik eArumugam; Christiane eHilger; François eHentges

    2014-01-01

    Fish is a common trigger of severe, food-allergic reactions. Only a limited number of proteins induce specific IgE-mediated immune reactions. The major fish allergens are the parvalbumins. They are members of the calcium-binding EF-hand protein family characterized by a conserved protein structure. They represent highly cross-reactive allergens for patients with specific IgE to conserved epitopes. These patients might experience clinical reactions with various fish species. On the other hand,...

  13. Fish Allergens at a Glance: Variable Allergenicity of Parvalbumins, the Major Fish Allergens

    OpenAIRE

    Kuehn, Annette; Swoboda, Ines; Arumugam, Karthik; Hilger, Christiane; Hentges, François

    2014-01-01

    Fish is a common trigger of severe, food-allergic reactions. Only a limited number of proteins induce specific IgE-mediated immune reactions. The major fish allergens are the parvalbumins. They are members of the calcium-binding EF-hand protein family characterized by a conserved protein structure. They represent highly cross-reactive allergens for patients with specific IgE to conserved epitopes. These patients might experience clinical reactions with various fish species. On the other hand,...

  14. Hypoxia Potentiates Allergen Induction of HIF-1α, Chemokines, Airway Inflammation, TGF-β1, and Airway Remodeling in a mouse model

    OpenAIRE

    Baek, Kwang Je; Cho, Jae Youn; Rosenthal, Peter; Alexander, Laura E. Crotty; Nizet, Victor; Broide, David H.

    2013-01-01

    Whether hypoxia contributes to airway inflammation and remodeling in asthma is unknown. In this study we used mice exposed to a hypoxic environment during allergen challenge (simulating hypoxia during an asthma exacerbation) to investigate the contribution of hypoxia to airway inflammation and remodeling. Although neither hypoxia alone, nor OVA allergen alone, induced significant neutrophil influx into the lung, the combination of OVA and hypoxia induced a synergistic 27 fold increase in peri...

  15. Effect of Xiaofenghuoxue decotion on Th1 and Th2 cytokine production in BALF in allergen-induced asthma guinea pigs

    Institute of Scientific and Technical Information of China (English)

    LI Hong; XIA Ming-yu; CHIEN Li; ZHOU Lian-di; WANG Zhi-hui; HUANG Jia-nan; ZHANG Qi-hui

    2008-01-01

    Objective To investigate the effect of Xiaofenghuoxue decotion (XFHX) on the production of Th1 and Th2 cytokine in bronchoalveolar lavage fluid (BALF) in asthma guinea pigs sensitized and challenged with ovalbumin. Methods The animals were randomly divided into 5 groups: the normal control group, the asthma group, the XFHX high dose group, the XFHX low dose group and the budesonide group. 2 weeks after sensitization with a mixture of 10% OVA and 10% AI(OH)3, the drugs were given to the animals for 7 days, and then the animals were challenged with aerosol of 1% ovalbumin, the latency time for the onset of respiratory abnormalities was examined, BALF was collected 16 h after. Leukocyte in BALF was counted. The level of IFN-γ reduced by Th1 cells and IL-4 and IL-5 produced by Th2 cells were determined by EILSA. NO contents were also examined. Results The latency time for the onset of respiratory abnormalities and leukocyte infiltration in both XFHX high dose group and low dose group significantly decreased compared with the asthma group. The level of IFN-γ in both XFHX high dose group and low dose group significantly increased compared with the asthma group, the level of IL-4 and IL-5 in both XFHX high dose group and low dose group significantly decreased compared with the asthma group. The production of NO was inhibited in both XFHX high dose group and low dose group compared with the asthma group. Conclusions These results suggest that the anti-asthma effect of Xiaofenghuoxue decotion is associated with NO regulated reversal of Th1/Th2 cytokine balance in allergen-induced asthma guinea pigs.

  16. Cell-penetrating peptide derived from human eosinophil cationic protein inhibits mite allergen Der p 2 induced inflammasome activation.

    Directory of Open Access Journals (Sweden)

    Sheng-Jie Yu

    Full Text Available Newly discovered cell penetration peptides derived from human eosinophil cationic proteins (CPPecp have the characteristic of cell internalization, but the effect of CPPecp on immunomodulation has not been clarified. House dust mite (HDM major allergen, Der p 2, can induce proinflammatory cytokine production which contributes to airway inflammation and allergic asthma. However, the mechanism of Der p 2 on NLRP3 inflammasome activation remains unclear. The aim of this study was to investigate the immunomodulatory effect of CPPecp on inhibition of Der p 2 induced inflammasome activation. We showed that proinflammatory cytokines IL-1β, IL-6 and IL-8 were significantly upregulated in peripheral blood mononuclear cells (PBMCs derived from HDM allergic patients after Der p 2 stimulation. Expression of NLRP3, ASC, Caspase-1, IL-1β and Caspase-1 activity was upregulated in THP-1 cells after Der p 2 stimulation. Proinflammatory cytokine production, NLRP3 inflammasome activation and caspase-1 activity were downregulated in THP-1 cells and CD14+ cells co-cultured with Der p 2 and CPPecp. The immunomodulatory effect of CPPecp was through upregulation of IFN-α production but not induction of autophagy. These results suggested Der p 2 plays an important role in NLRP3 inflammasome activation and CPPecp has the potential to be a novel anti-inflammatory agent for allergic inflammation treatment in the future.

  17. Differences in allergen-induced T cell activation between allergic asthma and rhinitis: Role of CD28, ICOS and CTLA-4

    Directory of Open Access Journals (Sweden)

    Lacoeuille Yannick

    2011-02-01

    Full Text Available Abstract Background Th2 cell activation and T regulatory cell (Treg deficiency are key features of allergy. This applies for asthma and rhinitis. However with a same atopic background, some patients will develop rhinitis and asthma, whereas others will display rhinitis only. Co-receptors are pivotal in determining the type of T cell activation, but their role in allergic asthma and rhinitis has not been explored. Our objective was to assess whether allergen-induced T cell activation differs from allergic rhinitis to allergic rhinitis with asthma, and explore the role of ICOS, CD28 and CTLA-4. Methods T cell co-receptor and cytokine expressions were assessed by flow cytometry in PBMC from 18 house dust mite (HDM allergic rhinitics (R, 18 HDM allergic rhinitics and asthmatics (AR, 13 non allergic asthmatics (A and 20 controls, with or without anti-co-receptors antibodies. Results In asthmatics (A+AR, a constitutive decrease of CTLA-4+ and of CD4+CD25+Foxp3+ cells was found, with an increase of IFN-γ+ cells. In allergic subjects (R + AR, allergen stimulation induced CD28 together with IL-4 and IL-13, and decreased the proportion of CTLA-4+, IL-10+ and CD4+CD25+Foxp3+ cells. Anti-ICOS and anti-CD28 antibodies blocked allergen-induced IL-4 and IL-13. IL-13 production also involved CTLA-4. Conclusions T cell activation differs between allergic rhinitis and asthma. In asthma, a constitutive, co-receptor independent, Th1 activation and Treg deficiency is found. In allergic rhinitis, an allergen-induced Treg cell deficiency is seen, as well as an ICOS-, CD28- and CTLA-4-dependent Th2 activation. Allergic asthmatics display both characteristics.

  18. A randomized, double-blinded, placebo-controlled oral challenge study to evaluate the allergenicity of commercial, food-grade fish gelatin

    DEFF Research Database (Denmark)

    Hansen, Tine K; Poulsen, Lars K.; Stahl Skov, Per;

    2004-01-01

    Recent interest in the labeling of foods and food proteins derived from allergenic sources necessitates determination of the potential allergenicity of such food ingredients. Fish gelatin is extracted from the skin of fish species known to elicit allergic reactions in sensitized individuals....

  19. Assessment of the Allergenic Potential of Transgenic Wheat (Triticum aestivum) with Reduced Levels of ω5-Gliadins, the Major Sensitizing Allergen in Wheat-Dependent Exercise-Induced Anaphylaxis.

    Science.gov (United States)

    Altenbach, Susan B; Tanaka, Charlene K; Pineau, Florence; Lupi, Roberta; Drouet, Martine; Beaudouin, Etienne; Morisset, Martine; Denery-Papini, Sandra

    2015-10-28

    The ω5-gliadins are the major sensitizing allergens in wheat-dependent exercise-induced anaphylaxis (WDEIA). In this study, two-dimensional immunoblot analysis was used to assess the allergenic potential of two transgenic wheat lines in which ω5-gliadin genes were silenced by RNA interference. Sera from 7 of 11 WDEIA patients showed greatly reduced levels of immunoglobulin E (IgE) reactivity to ω5-gliadins in both transgenic lines. However, these sera also showed low levels of reactivity to other gluten proteins. Sera from three patients showed the greatest reactivity to proteins other than ω5-gliadins, either high-molecular-weight glutenin subunits (HMW-GSs), α-gliadins, or non-gluten proteins. The complexity of immunological responses among these patients suggests that flour from the transgenic lines would not be suitable for individuals already diagnosed with WDEIA. However, the introduction of wheat lacking ω5-gliadins could reduce the number of people sensitized to these proteins and thereby decrease the overall incidence of this serious food allergy.

  20. Prevention of Diabetes in NOD Mice by Repeated Exposures to a Contact Allergen Inducing a Sub-Clinical Dermatitis

    Science.gov (United States)

    Engkilde, Kaare; Buschard, Karsten; Hansen, Axel Kornerup; Menné, Torkil; Johansen, Jeanne Duus

    2010-01-01

    Background Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutanous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT) cells, since involvement of NKT cells could suggest an innate connection between the two diseases. Method NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation. Results It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004). Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine. Conclusion The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the application site. The

  1. Prevention of diabetes in NOD mice by repeated exposures to a contact allergen inducing a sub-clinical dermatitis.

    Directory of Open Access Journals (Sweden)

    Kaare Engkilde

    Full Text Available BACKGROUND: Type 1 diabetes is an autoimmune disease, while allergic contact dermatitis although immune mediated, is considered an exposure driven disease that develops due to epicutaneous contact with reactive low-molecular chemicals. The objective of the present study was to experimentally study the effect of contact allergens on the development of diabetes in NOD mice. As the link between contact allergy and diabetes is yet unexplained we also examined the effect of provocation with allergens on Natural Killer T (NKT cells, since involvement of NKT cells could suggest an innate connection between the two diseases. METHOD: NOD mice 4 weeks of age were exposed, on the ears, to two allergens, p-phenylenediamine and 2,4-dinitrochlorobenzene respectively, to investigate the diabetes development. The mice were followed for a maximum of 32 weeks, and they were either repeatedly exposed to the allergens or only sensitized a week after arrival. The stimulation of NKT cells by the two allergens were additionally studied in C57BL/6 mice. The mice were sensitized and two weeks later provocated with the allergens. The mice were subsequently euthanized at different time points after the provocation. RESULTS: It was found that repeated application of p-phenylenediamine reduced the incidence of diabetes compared to application with water (47% vs. 93%, P = 0.004. Moreover it was shown that in C57BL/6 mice both allergens resulted in a slight increment in the quantity of NKT cells in the liver. Application of the allergens at the same time resulted in an increased number of NKT cells in the draining auricular lymph node, and the increase appeared to be somewhat allergen specific as the accumulation was stronger for p-phenylenediamine. CONCLUSION: The study showed that repeated topical application on the ears with a contact allergen could prevent the development of diabetes in NOD mice. The contact allergens gave a non-visible, sub-clinical dermatitis on the

  2. The major birch pollen allergen Bet v 1 induces different responses in dendritic cells of birch pollen allergic and healthy individuals.

    Directory of Open Access Journals (Sweden)

    Ursula Smole

    Full Text Available Dendritic cells play a fundamental role in shaping the immune response to allergens. The events that lead to allergic sensitization or tolerance induction during the interaction of the major birch pollen allergen Bet v 1 and dendritic cells are not very well studied. Here, we analyzed the uptake of Bet v 1 and the cross-reactive celery allergen Api g 1 by immature monocyte-derived dendritic cells (iMoDCs of allergic and normal donors. In addition, we characterized the allergen-triggered intracellular signaling and transcriptional events. Uptake kinetics, competitive binding, and internalization pathways of labeled allergens by iMoDCs were visualized by live-cell imaging. Surface-bound IgE was detected by immunofluorescence microscopy and flow cytometry. Allergen- and IgE-induced gene expression of early growth response genes and Th1 and Th2 related cytokines and chemokines were analyzed by real-time PCR. Phosporylation of signaling kinases was analyzed by Western blot. Internalization of Bet v 1 by iMoDCs of both donor groups, likely by receptor-mediated caveolar endocytosis, followed similar kinetics. Bet v 1 outcompeted Api g 1 in cell surface binding and uptake. MoDCs of allergic and healthy donors displayed surface-bound IgE and showed a pronounced upregulation of Th2 cytokine- and NFκB-dependent genes upon non-specific Fcε receptor cross-linking. In contrast to these IgE-mediated responses, Bet v 1-stimulation increased transcript levels of the Th2 cytokines IL-4 and IL-13 but not of NFκB-related genes in MoDCs of BP allergic donors. Cells of healthy donors were either unresponsive or showed elevated mRNA levels of Th1-promoting chemokines. Moreover, Bet v 1 was able to induce Erk1/2 and p38 MAPK activation in BP allergics but only a slight p38 activation in normal donors. In conclusion, our data indicate that Bet v 1 favors the activation of a Th2 program only in DCs of BP allergic individuals.

  3. Update in the Mechanisms of Allergen-Specific Immunotheraphy

    Science.gov (United States)

    Akkoc, Tunc; Akdis, Mübeccel

    2011-01-01

    Allergic diseases represent a complex innate and adoptive immune response to natural environmental allergens with Th2-type T cells and allergen-specific IgE predominance. Allergen-specific immunotherapy is the most effective therapeutic approach for disregulated immune response towards allergens by enhancing immune tolerance mechanisms. The main aim of immunotherapy is the generation of allergen nonresponsive or tolerant T cells in sensitized patients and downregulation of predominant T cell- and IgE-mediated immune responses. During allergen-specific immunotherapy, T regulatory cells are generated, which secrete IL-10 and induce allergen-specific B cells for the production of IgG4 antibodies. These mechanisms induce tolerance to antigens that reduces allergic symptoms. Although current knowledge highlights the role of T regulatory cell-mediated immunetolerance, definite mechanisms that lead to a successful clinical outcomes of allergen-specific immunotherapy still remains an open area of research. PMID:21217920

  4. Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p I inhibits human basophil histamine release induced by natural Lol p I.

    Science.gov (United States)

    van Ree, R; Aalberse, R C

    1995-03-01

    The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a synthetic peptide of its C terminus. When allergen and antibodies were allowed to preincubate, Lol p I induced histamine release was inhibited up to 85% by the antiserum against Lol p I. By omitting preincubation, and thereby more closely mimicking an in vivo situation, up to 55% inhibition was realized. This indicates that allergen-specific IgG can act as 'blocking' antibody without preincubation. Immunization of rabbits with a synthetic C-terminal peptide of Lol p I resulted in antibodies reactive with natural Lol p I. Despite their 100-fold lower avidity for Lol p I (as compared with antinatural Lol p I), these antibodies had the capacity to inhibit Lol p I induced histamine release for > 90% (up to 50% without preincubation). This indicates that it is possible to block histamine release induced by a major allergen with low-avidity IgG antibodies directed against a minor proportion of the allergen (25 amino acids). IgE antibodies from the donors studied were unreactive with this synthetic peptide, indicating that for blocking activity identical epitope specificity of IgE and IgG is not essential. This opens interesting perspectives for application of synthetic peptides in immunotherapy, distinct from their effects on T cell reactivity.

  5. Authentication of food allergen quality by physicochemical and immunological methods

    DEFF Research Database (Denmark)

    Sancho, A I; Hoffmann-Sommergruber, K; Alessandri, S

    2010-01-01

    Purified allergens are required to detect cross-contamination with other allergenic foods and to understand allergen interaction with other components of the food matrix. Pure allergens are also used for the diagnosis and treatment of food allergies. For example, serological methods are being...... developed to improve the quality of diagnosis, and to reduce the need for food challenge tests. In addition, recombinant allergens are being evaluated as candidate vaccines for safe and efficacious specific immunotherapy. Pure allergens are indispensable as reference materials for the calibration...... and standardization of methods between different laboratories and operators for risk assessment in the food industry. Therefore, there is a need for well-defined purified food allergens. In this context, a panel of 46 food allergens from plant and animal sources has been purified, from either the food sources...

  6. Managing allergens in food

    NARCIS (Netherlands)

    Mills, C.; Wichers, H.J.; Hoffmann-Sommergruber, K.

    2007-01-01

    Controlling allergens in food is a matter of increasing importance for the food industry, especially in light of recent legislation. Effective handling of allergens depends on identifying allergenic ingredients, creating separate production lines for allergen-free products, and effective labelling t

  7. Effect of a thromboxane A2 receptor antagonist ramatroban (BAY u 3405, on inflammatory cells, chemical mediators and non-specific nasal hyperreactivity after allergen challenge in patients with perennial allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Nobuhisa Terada

    1998-01-01

    Full Text Available In some clinical studies performed in patients with perennial allergic rhinitis, ramatroban, a new thromboxane A2 receptor antagonist, significantly improved nasal symptoms. As yet the mechanism of action of this drug has not been fully elucidated. In the present study we investigated the effects of ramatroban on changes in nasal reactivity and levels of inflammatory cells and mediators in nasal lavage fluid after allergen challenge. Ramatroban was administered orally at a daily dose of 150 mg (b.i.d. for 4 weeks to 11 patients with perennial allergic rhinitis exhibiting positive responses to nasal allergen challenge with house dust mite. Analysis of variance revealed that there was a significant decrease in eosinophil counts and eosinophil cationic protein levels in nasal lavage fluid when compared with values immediately before allergen challenge before and after ramatroban treatment. Histamine, tryptase and albumin levels were significantly decreased in analysis of variance before and after ramatroban treatment. The degree of nasal reactivity to histamine was also significantly decreased after the ramatroban treatment. These findings indicate that ramatroban decreases important pathogenic factors in allergic rhinitis, resulting in an improvement in nasal symptoms.

  8. Systemic Reactions Induced by Allergen Specific Immunotherapy%变应原免疫治疗致全身反应

    Institute of Scientific and Technical Information of China (English)

    关凯; 文昭明

    2011-01-01

    目的 对变应原免疫治疗过程中发生的全身反应进行临床观察,以期找到其发生规律,便于及时发现、处理和预防.方法 回顾近15年接受变应原免疫治疗(AIT)过程中出现全身反应的29例患者,依据反应发生时间与程度按欧洲变态反应和临床免疫学会(EAACI)分类标准分为4级.结果 29例患者均为吸入变应原致呼吸道过敏性疾病,在AIT过程中共出现59例次全身反应.29例患者中男女比例17:12,开始接受AIT的平均年龄为27.3岁(6~59岁).吸入变应原致敏情况:夏秋花粉24例(蒿属花粉22例、葎草花粉1例、混合夏秋花粉1例),蚕丝4例,交链孢霉1例.皮下注射后症状出现时间:≤20 min占67.8% (40/59),≤30 min占84.7% (50/59).59例次全身反应中,荨麻疹占55.9% (33/59),哮喘占50.9% (30/59),上呼吸道过敏症状占23.7%(14/59),喉水肿占5.1% (3/59),低血容量休克占1.7%(1/59).全身反应中,较轻的Ⅰ类和Ⅱ类占76.3% (45/59),较重的Ⅲ类和Ⅳ类均发生于皮下注射后15 min内.结论 全身反应严重程度与皮试反应强度无关.AIT注射后应留院密切观察,特别是前15 min应予充分重视.%Objective Systemic reactions induced by allergen specific immunotherapy (SIT) injections can be observed in clinical practice, which are rarely life-threaten but the most dangerous reactions. Summary of the clinical features will benefit to early recognition, adequate management and prevention of systemic reactions. Methods Systemic reactions were collected and reviewed from patients who were prescribed SIT by using aqueous allergen extracts during the past fifteen years from Department of Allergy, Peking Union Medical College Hospital. All systemic reactions were graded into level I to IV based on the grading system of EAACI Immunotherapy Position Paper, according to the onset and severity of clinical symptoms. Results 59 systemic reactions were collected from 29 respiratory allergic

  9. Effect of high intensity ultrasound on the allergenicity of shrimp

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The tropomyosin fraction of shrimp proteins is potentially responsible for allergic reaction in individuals with genetic predisposition to allergy. However, there are no efficient and safe methods to reduce its allergenicity. High intensity ultrasound is known to change the structure of proteins. This study is aimed at assessing high intensity ultrasound's effect on the allergenicity of shrimp allergen. Shrimp and purified shrimp allergen were treated with high intensity ultrasound for 30~180 min. Extracts of treated samples were analyzed by enzyme-linked immunosorbent assay (ELISA) with pool serum of shrimp allergy patients and polyclonal anti-allergen antibodies and by immunoblotting after polyacrylamide gel electrophoresis. Shrimp treated with high intensity ultrasound showed a decrease in allergenicity measured with ELISA. A linear relationship between the immune response induced by treated shrimp allergen and the applied treatment time was observed. The decrease in allergenicity was confirmed by immunoblot assays with shrimp allergic patients serum. Allergenicity of shrimp allergen extracted from treated shrimp was higher than that of purified shrimp allergen with the same treatment time. Gel-filtration HPLC was applied for analysis of shrimp allergen after treatment with high intensity ultrasound. Some fractions were appeared with increasing treatment time. The results suggested that high intensity ultrasound could be used to reduce the allergenicity of shrimp.

  10. Quality Control of Biomedicinal Allergen Products – Highly Complex Isoallergen Composition Challenges Standard MS Database Search and Requires Manual Data Analyses

    Science.gov (United States)

    Spiric, Jelena; Engin, Anna M.; Karas, Michael; Reuter, Andreas

    2015-01-01

    Allergy against birch pollen is among the most common causes of spring pollinosis in Europe and is diagnosed and treated using extracts from natural sources. Quality control is crucial for safe and effective diagnosis and treatment. However, current methods are very difficult to standardize and do not address individual allergen or isoallergen composition. MS provides information regarding selected proteins or the entire proteome and could overcome the aforementioned limitations. We studied the proteome of birch pollen, focusing on allergens and isoallergens, to clarify which of the 93 published sequence variants of the major allergen, Bet v 1, are expressed as proteins within one source material in parallel. The unexpectedly complex Bet v 1 isoallergen composition required manual data interpretation and a specific design of databases, as current database search engines fail to unambiguously assign spectra to highly homologous, partially identical proteins. We identified 47 non-allergenic proteins and all 5 known birch pollen allergens, and unambiguously proved the existence of 18 Bet v 1 isoallergens and variants by manual data analysis. This highly complex isoallergen composition raises questions whether isoallergens can be ignored or must be included for the quality control of allergen products, and which data analysis strategies are to be applied. PMID:26561299

  11. 5-Aminosalicylic acid attenuates allergen-induced airway inflammation and oxidative stress in asthma.

    Science.gov (United States)

    Raju, K Rama Satyanarayana; Kumar, M N Sathish; Gupta, Saurabh; Naga, Srinivas T; Shankar, Jaya K; Murthy, Vishakantha; Madhunapanthula, Subba Rao V; Mulukutla, Shashank; Ambhore, Nilesh S; Tummala, Shashank; Vishnuvarthan, V J; Azam, Afzal; Elango, Kannan

    2014-12-01

    Pro-inflammatory cytokines regulate the magnitude of allergic reactions during asthma. Tumor necrosis factor--alpha (TNF-α), interleukin-6 (IL-6) and interleukin-13 (IL-13) play a crucial role in aggravating the inflammatory conditions during allergic asthma. In addition, oxidative stress contributes to the pathogenesis of asthma by altering the physiological condition resulting in the development of status asthmaticus. Anti-inflammatory corticosteroids are being widely used for treating allergic asthma. In the present study 5-aminosalicylic acid (5-ASA), a salicylic acid derivative, was evaluated, in vivo for its potential to suppress TNF-α, IL-6 and IL-13 using ovalbumin (OVA) induced allergic asthma in Balb/C mice. Oral administration of 65, 130 and 195 mg/kg 5-ASA significantly reduced the OVA induced total and differential leucocyte count, TNF-α, IL-6, IL-13, nitrite, nitrate, MDA, MPO and TPL levels in the lung lavage samples. Collectively, these findings suggest that 5-ASA is a potent immunomodulator and suppresses key Th2 cytokines production and oxidative stress in OVA-induced asthma.

  12. Fish allergens at a glance: variable allergenicity of parvalbumins, the major fish allergens.

    Science.gov (United States)

    Kuehn, Annette; Swoboda, Ines; Arumugam, Karthik; Hilger, Christiane; Hentges, François

    2014-01-01

    Fish is a common trigger of severe, food-allergic reactions. Only a limited number of proteins induce specific IgE-mediated immune reactions. The major fish allergens are the parvalbumins. They are members of the calcium-binding EF-hand protein family characterized by a conserved protein structure. They represent highly cross-reactive allergens for patients with specific IgE to conserved epitopes. These patients might experience clinical reactions with various fish species. On the other hand, some individuals have IgE antibodies directed against unique, species-specific parvalbumin epitopes, and these patients show clinical symptoms only with certain fish species. Furthermore, different parvalbumin isoforms and isoallergens are present in the same fish and might display variable allergenicity. This was shown for salmon homologs, where only a single parvalbumin (beta-1) isoform was identified as allergen in specific patients. In addition to the parvalbumins, several other fish proteins, enolases, aldolases, and fish gelatin, seem to be important allergens. New clinical and molecular insights advanced the knowledge and understanding of fish allergy in the last years. These findings were useful for the advancement of the IgE-based diagnosis and also for the management of fish allergies consisting of advice and treatment of fish-allergic patients.

  13. Fish allergens at a glance: Variable allergenicity of parvalbumins, the major fish allergens

    Directory of Open Access Journals (Sweden)

    Annette eKuehn

    2014-04-01

    Full Text Available Fish is a common trigger of severe, food-allergic reactions. Only a limited number of proteins induce specific IgE-mediated immune reactions. The major fish allergens are the parvalbumins. They are members of the calcium-binding EF-hand protein family characterized by a conserved protein structure. They represent highly cross-reactive allergens for patients with specific IgE to conserved epitopes. These patients might experience clinical reactions with various fish species. On the other hand, some individuals have IgE antibodies directed against unique, species-specific parvalbumin epitopes, and these patients show clinical symptoms only with certain fish species. Furthermore, different parvalbumin isoforms and isoallergens are present in the same fish and might display variable allergenicity. This was shown for salmon homologs, where only a single parvalbumin (beta-1 isoform was identified as allergen in specific patients. In addition to the parvalbumins, several other fish proteins, enolases, aldolases and fish gelatin, seem to be important allergens.New clinical and molecular insights advanced the knowledge and understanding of fish allergy in the last years. These findings will be useful for the advancement of the IgE-based diagnosis but also for the management of fish allergies consisting of advice and treatment of fish-allergic patients.

  14. 77例药物性肝损害患者过敏原检测结果分析%Allergen analysis of 77 patients with drug-induced liver injury

    Institute of Scientific and Technical Information of China (English)

    林健梅; 杨仁国; 耿晓霞; 江南

    2013-01-01

    Objective To discuss the allergic factors of drug-induced liver injury( DILI). Methods 77 cases with DILI were given test serum allergens, and 77 cases were compared with normal. Results The positive rate of serum allergens in 77 DILI was 84. 42% (65/77) ;There were no statistically significant differences between inhaled allergens and food allergen(P > 0. 05). The higher positive allergens were dust mites/powder mite,ordinary ragweed/from plants,crab/shrimp/lobster and beef/lamb. And normal serum specific allergen positive rate was only 18. 18 % ( 14/77 ) , there was statistically significant difference between DILI and normals ( P < 0.01). Conclusions DILI patients had higher allergens tested positive rate,it can help know about allergen situation through serum allergens detection, and there are some certain significance for patients to avoid or reduce exposure to the allergen.%目的 对药物性肝损害(drug induced liver injury,DILI)患者血清过敏原检测进行讨论分析.方法 选择77例临床诊断为DILI的住院患者进行血清过敏原检测,并与77例正常人进行对照.结果 77例患者血清过敏原检测阳性率84.42%(65/77);吸入性过敏原与食入性过敏原阳性率比较差异无统计学意义(P > 0.05).阳性率较高的为尘螨/粉螨、普通豚草/蒿属植物、蟹/虾/龙虾、牛肉/羊肉.而正常人血清特异性过敏原阳性率为18.18%(14/77),差异有统计学意义(P < 0.01).结论 DILI患者具有较高的过敏原检测阳性率,过敏原检测可以了解DILI患者的过敏原状况,对指导患者避免或减少接触过敏原具有一定的意义.

  15. Immunotherapy with Allergen Peptides

    OpenAIRE

    Larché Mark

    2007-01-01

    Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cro...

  16. Allergens in veterinary medicine

    OpenAIRE

    2015-01-01

    Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies pr...

  17. Allergic inflammation in the upper respiratory tract of the rat upon repeated inhalation exposure to the contact allergen dinitrochlorobenzene (DNCB).

    NARCIS (Netherlands)

    Triel, J.J. van; Arts, J.H.; Muijser, H.; Kuper, C.F.

    2010-01-01

    Previously, the contact allergen dinitrochlorobenzene (DNCB) was identified as a sensitizer by inhalation in BALB/c mice; in addition, DNCB induced a lymphocytic infiltrate in the larynx of dermally sensitized Th1-prone Wistar rats upon a single inhalation challenge. In the present study, repeated i

  18. New tree nut allergens

    Science.gov (United States)

    The 7S vicilin and 11S legumin seed storage globulins belong to the cupin protein superfamily and are major food allergens in many of the “big eight” food allergen groups. Korean pine vicilin and pecan vicilin are thus predicted to be food allergens. Recombinant vicilins were expressed in E. coli an...

  19. Allergens in veterinary medicine.

    Science.gov (United States)

    Mueller, R S; Janda, J; Jensen-Jarolim, E; Rhyner, C; Marti, E

    2016-01-01

    Allergic diseases in animals are increasingly gaining importance in veterinary practice and as research models. For intradermal testing and allergen immunotherapy, a good knowledge of relevant allergens for the individual species is of great importance. Currently, the knowledge about relevant veterinary allergens is based on sensitization rates identified by intradermal testing or serum testing for allergen-specific IgE; crude extracts are the basis for most evaluations. Only a few studies provide evidence about the molecular structure of (particularly) dust mite, insect and mould allergens in dogs and horses, respectively. In those species, some major allergens differ from those in humans. This position paper summarizes the current knowledge about relevant allergens in dogs, cats and horses.

  20. Sensitization to fungal allergens: Resolved and unresolved issues

    Directory of Open Access Journals (Sweden)

    Yuma Fukutomi

    2015-10-01

    Despite its importance in the management of allergic diseases, precise recognition of species-specific IgE sensitization to fungal allergens is often challenging because the majority of fungal extracts exhibit broad cross-reactivity with taxonomically unrelated fungi. Recent progress in gene technology has contributed to the identification of specific and cross-reactive allergen components from different fungal sources. However, data demonstrating the clinical relevance of IgE reactivity to these allergen components are still insufficient.

  1. Protective effects of the polyphenol sesamin on allergen-induced T(H2 responses and airway inflammation in mice.

    Directory of Open Access Journals (Sweden)

    Ching-Huei Lin

    Full Text Available Allergic asthma is a lifelong airway condition that affects people of all ages. In recent decades, asthma prevalence continues to increase globally, with an estimated number of 250,000 annual deaths attributed to the disease. Although inhaled corticosteroids and β-adrenergic receptor agonists are the primary therapeutic avenues that effectively reduce asthma symptoms, profound side effects may occur in patients with long-term treatments. Therefore, development of new therapeutic strategies is needed as alternative or supplement to current asthma treatments. Sesamin is a natural polyphenolic compound with strong anti-oxidative effects. Several studies have reported that sesamin is effective in preventing hypertension, thrombotic tendency, and neuroinflammation. However, it is still unknown whether sesamin can reduce asthma-induced allergic inflammation and airway hyperresponsiveness (AHR. Our study has revealed that sesamin exhibited significant anti-inflammatory effects in ovalbumin (OVA-induced murine asthma model. We found that treatments with sesamin after OVA sensitization and challenge significantly decreased expression levels of interleukin-4 (IL-4, IL-5, IL-13, and serum IgE. The numbers of total inflammatory cells and eosinophils in BALF were also reduced in the sesamin-treated animals. Histological results demonstrated that sesamin attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, mucus occlusion, and MUC5AC expression in the lung tissue. Mice administered with sesamin showed limited increases in AHR compared with mice receiving vehicle after OVA challenge. OVA increased phosphorylation levels of IκB-α and nuclear expression levels of NF-κB, both of which were reversed by sesamin treatments. These data indicate that sesamin is effective in treating allergic asthma responses induced by OVA in mice.

  2. Protective effects of the polyphenol sesamin on allergen-induced T(H)2 responses and airway inflammation in mice.

    Science.gov (United States)

    Lin, Ching-Huei; Shen, Mei-Lin; Zhou, Ning; Lee, Chen-Chen; Kao, Shung-Te; Wu, Dong Chuan

    2014-01-01

    Allergic asthma is a lifelong airway condition that affects people of all ages. In recent decades, asthma prevalence continues to increase globally, with an estimated number of 250,000 annual deaths attributed to the disease. Although inhaled corticosteroids and β-adrenergic receptor agonists are the primary therapeutic avenues that effectively reduce asthma symptoms, profound side effects may occur in patients with long-term treatments. Therefore, development of new therapeutic strategies is needed as alternative or supplement to current asthma treatments. Sesamin is a natural polyphenolic compound with strong anti-oxidative effects. Several studies have reported that sesamin is effective in preventing hypertension, thrombotic tendency, and neuroinflammation. However, it is still unknown whether sesamin can reduce asthma-induced allergic inflammation and airway hyperresponsiveness (AHR). Our study has revealed that sesamin exhibited significant anti-inflammatory effects in ovalbumin (OVA)-induced murine asthma model. We found that treatments with sesamin after OVA sensitization and challenge significantly decreased expression levels of interleukin-4 (IL-4), IL-5, IL-13, and serum IgE. The numbers of total inflammatory cells and eosinophils in BALF were also reduced in the sesamin-treated animals. Histological results demonstrated that sesamin attenuated OVA-induced eosinophil infiltration, airway goblet cell hyperplasia, mucus occlusion, and MUC5AC expression in the lung tissue. Mice administered with sesamin showed limited increases in AHR compared with mice receiving vehicle after OVA challenge. OVA increased phosphorylation levels of IκB-α and nuclear expression levels of NF-κB, both of which were reversed by sesamin treatments. These data indicate that sesamin is effective in treating allergic asthma responses induced by OVA in mice.

  3. Role of signal transducer and activator of transcription 1 in murine allergen-induced airway remodeling and exacerbation by carbon nanotubes.

    Science.gov (United States)

    Thompson, Elizabeth A; Sayers, Brian C; Glista-Baker, Ellen E; Shipkowski, Kelly A; Ihrie, Mark D; Duke, Katherine S; Taylor, Alexia J; Bonner, James C

    2015-11-01

    Asthma is characterized by a T helper type 2 phenotype and by chronic allergen-induced airway inflammation (AAI). Environmental exposure to air pollution ultrafine particles (i.e., nanoparticles) exacerbates AAI, and a concern is possible exacerbation posed by engineered nanoparticles generated by emerging nanotechnologies. Signal transducer and activator of transcription (STAT) 1 is a transcription factor that maintains T helper type 1 cell development. However, the role of STAT1 in regulating AAI or exacerbation by nanoparticles has not been explored. In this study, mice with whole-body knockout of the Stat1 gene (Stat1(-/-)) or wild-type (WT) mice were sensitized to ovalbumin (OVA) allergen and then exposed to multiwalled carbon nanotubes (MWCNTs) by oropharygneal aspiration. In Stat1(-/-) and WT mice, OVA increased eosinophils in bronchoalveolar lavage fluid, whereas MWCNTs increased neutrophils. Interestingly, OVA sensitization prevented MWCNT-induced neutrophilia and caused only eosinophilic inflammation. Stat1(-/-) mice displayed increased IL-13 in bronchoalveolar lavage fluid at 1 day compared with WT mice after treatment with OVA or OVA and MWCNTs. At 21 days, the lungs of OVA-sensitized Stat1(-/-) mice displayed increased eosinophilia, goblet cell hyperplasia, airway fibrosis, and subepithelial apoptosis. MWCNTs further increased OVA-induced goblet cell hyperplasia, airway fibrosis, and apoptosis in Stat1(-/-) mice at 21 days. These changes corresponded to increased levels of profibrogenic mediators (transforming growth factor-β1, TNF-α, osteopontin) but decreased IL-10 in Stat1(-/-) mice. Finally, fibroblasts isolated from the lungs of Stat1(-/-) mice produced significantly more collagen mRNA and protein in response to transforming growth factor-β1 compared with WT lung fibroblasts. Our results support a protective role for STAT1 in chronic AAI and exacerbation of remodeling caused by MWCNTs.

  4. A Photo-immobilized Allergen Microarray for Screening of Allergen-specific IgE

    Directory of Open Access Journals (Sweden)

    Kunio Ohyama

    2005-01-01

    Full Text Available We developed an in vitro system to diagnose allergy using an allergen microarray and photo-immobilization technique. Photo-immobilization is useful for preparing the allergen microarray because it does not require specific functional groups of the allergen and because any organic material can be immobilized by a radical reaction induced by photo-irradiation. To prepare the plates, allergen solutions were mixed with polymer and a bis- azidophenyl derivative, a photo-reactive cross-linker, the mixtures were micro-spotted on the plate, and the droplets were dried. The plate was irradiated with an ultraviolet lamp for immobilization. For the assay, human serum was added to the microarray plate. Allergen-specific immunoglobulin E (IgE adsorbed on the micro- spotted allergen was detected by peroxidase-conjugated anti-IgE antibody. The chemiluminescence intensities of the substrate decomposed by the peroxidase were detected with a sensitive CCD camera. All allergens were immobilized by this method and used to screen allergen-specific IgE.

  5. Characterization and standardization of allergen extracts.

    Science.gov (United States)

    Løwenstein, Henning

    2014-01-01

    This paper summarizes the development of the extraction and characterization of allergens responsible for the induction of immunoglobulin (lg) E-induced allergies from the beginning of the 20th century, including the nomenclature of allergens. The majority of papers characterizing allergens and allergen extracts state that the lack of standardization of allergen extracts is the reason for the paper, and so it has been for more than 100 years. A natural part of that process might be the isolation of an allergen molecule and this starts the speculation of 'what makes that allergen an allergen?' To achieve the perfect standardization is a desirable end that is still awaited. So far none of these problems have been finally solved. I started in allergy shortly after the discovery of IgE in 1967. Since that time the history as I remember it is based on the literature, my interpretation of it, and of course may be a little biased due to personal prejudice! The history of the last 10-15 years has still not matured and it might be a little early to draw conclusions. However, at the end of this chapter I do dare to make a few conclusions after having followed the development in this field for 40 years. As this is history it is not meant to be either comprehensive or technically and scientifically precise in all aspects, but rather draws on some thoughts as to what in my mind have been important developments until now. Specific techniques are only mentioned by name and not intended to be discussed in depth. This activity has, however, pushed me to reflect on my hopes and speculations at the time of my introduction to the field of allergen chemistry. To my surprise I realize that far more than I ever expected at that time has been fulfilled. It has been extremely exciting to be a part of that development.

  6. Effect of unilateral vagus blockade on allergen-induced airway obstruction: results of short- and long-term experiments.

    Science.gov (United States)

    Zimmermann, I; Ulmer, W T

    1977-01-01

    Unilateral application of ascaris extract on segment bronchus as the influence of contralateral vagus blockade on reflex bronchoconstriction was studied on four boxer dogs in a first group (A) of experiments: ascaris extract was applied in liquid form directly through a catheter into the right segment bronchus. This application was repeated after contralateral vagus blockade and once more after its lavage. All the animals showed an increase of airway resistance under local application of ascaris extract which could not be avoided by contralateral central vagus blockade. In the second group (B) isolation of unilateral vagus for reproducible performance of blockade as a long-term model was investigated in three boxer dogs for 7 weeks and the influence of this method of unilateral vagus blockade on exposure to allergen aerosol was studied. The unilateral blockade of the nerve vagus was again always successful in decreasing the reflex bronchoconstriction following allergen inhalation. The effect of unilateral section of nervus vagus 3 weeks after this vagotomy was tested on two boxer dogs. Reflex bronchoconstriction following ascaris extract inhalation can be avoided by unilateral section of the nervus vagus the first time after section. Three weeks after this unilateral vagotomy, the reflex bronchoconstriction becomes managed by the remaining vagus trunk to the same degree as observed by bilateral intact vagi.

  7. New Trends in Food Allergens Detection: Toward Biosensing Strategies.

    Science.gov (United States)

    Alves, Rita C; Barroso, M Fátima; González-García, María Begoña; Oliveira, M Beatriz P P; Delerue-Matos, Cristina

    2016-10-25

    Food allergens are a real threat to sensitized individuals. Although food labeling is crucial to provide information to consumers with food allergies, accidental exposure to allergenic proteins may result from undeclared allergenic substances by means of food adulteration, fraud or uncontrolled cross-contamination. Allergens detection in foodstuffs can be a very hard task, due to their presence usually in trace amounts, together with the natural interference of the matrix. Methods for allergens analysis can be mainly divided in two large groups: the immunological assays and the DNA-based ones. Mass spectrometry has also been used as a confirmatory tool. Recently, biosensors appeared as innovative, sensitive, selective, environmentally friendly, cheaper and fast techniques (especially when automated and/or miniaturized), able to effectively replace the classical methodologies. In this review, we present the advances in the field of food allergens detection toward the biosensing strategies and discuss the challenges and future perspectives of this technology.

  8. Immunotherapy with Allergen Peptides

    Directory of Open Access Journals (Sweden)

    Larché Mark

    2007-06-01

    Full Text Available Specific allergen immunotherapy (SIT is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases.

  9. Prevalence of food and airborne allergens in allergic patients in Kerman

    OpenAIRE

    2014-01-01

    Background: Detection of various environmental allergens is the major challenge in allergic diseases and the only treatment is avoiding these allergens. The aim of this study was to determine the prevalence of food and airborne allergens in allergic patients using Skin Prick Test (SPT). Methods: A cross-sectional study was done on clinically confirmed patients of atopic-dermatitis (n=54), allergenic-rhinitis (n=64) and chronic-urticaria (n=39) who referred to asthma and allergy clinic at ...

  10. Allergen-specific immunotherapy: from therapeutic vaccines to prophylactic approaches.

    Science.gov (United States)

    Valenta, R; Campana, R; Marth, K; van Hage, M

    2012-08-01

    Immunoglobulin E-mediated allergies affect more than 25% of the population. Allergen exposure induces a variety of symptoms in allergic patients, which include rhinitis, conjunctivitis, asthma, dermatitis, food allergy and life-threatening systemic anaphylaxis. At present, allergen-specific immunotherapy (SIT), which is based on the administration of the disease-causing allergens, is the only disease-modifying treatment for allergy. Current therapeutic allergy vaccines are still prepared from relatively poorly defined allergen extracts. However, with the availability of the structures of the most common allergen molecules, it has become possible to produce well-defined recombinant and synthetic allergy vaccines that allow specific targeting of the mechanisms of allergic disease. Here we provide a summary of the development and mechanisms of SIT, and then review new forms of therapeutic vaccines that are based on recombinant and synthetic molecules. Finally, we discuss possible allergen-specific strategies for prevention of allergic disease.

  11. Allergenicity attributes of different peanut market types.

    Science.gov (United States)

    Koppelman, Stef J; Jayasena, Shyamali; Luykx, Dion; Schepens, Erik; Apostolovic, Danijela; de Jong, Govardus A H; Isleib, Thomas G; Nordlee, Julie; Baumert, Joe; Taylor, Steve L; Cheng, Hsiaopo; Maleki, Soheila

    2016-05-01

    Four different market classes of peanut (Runner, Virginia Spanish, and Valencia) are commonly consumed in Western countries, but for some consumers peanuts are a main cause of food-induced anaphylaxis. Limited information is available on the comparative allergenicity of these distinct market classes. The aim of this study was to compare allergenicity attributes of different peanut cultivars. The protein content and protein profiles were highly comparable for all tested cultivars. All cultivar samples contained the major allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6, as assessed by SDS-PAGE and RP-HPLC, although some minor differences in major allergen content were found between samples. All samples were reactive in commercial ELISAs for detection and quantification of peanut protein. IgE-binding potency differed between samples with a maximum factor of 2, indicating a highly comparable allergenicity. Based on our observations, we conclude that peanuts from the main market types consumed in Western countries are highly comparable in their allergenicity attributes, indicating that safety considerations with regard to peanut allergy are not dependent on the peanut cultivar in question.

  12. Fluorescence of atopic allergens

    NARCIS (Netherlands)

    Berrens, L.

    1967-01-01

    Purified atopic allergens have been found to emit flue fluorescence upon irradiation with ultraviolet light of 365 mμ wavelength. The maximum of fluorescence is in the region 445–490 mμ and the intensity is of the same order of magnitude for different atopic allergens. Synthetic model compounds, inc

  13. Tree nut allergens.

    Science.gov (United States)

    Roux, Kenneth H; Teuber, Suzanne S; Sathe, Shridhar K

    2003-08-01

    Allergic reactions to tree nuts can be serious and life threatening. Considerable research has been conducted in recent years in an attempt to characterize those allergens that are most responsible for allergy sensitization and triggering. Both native and recombinant nut allergens have been identified and characterized and, for some, the IgE-reactive epitopes described. Some allergens, such as lipid transfer proteins, profilins, and members of the Bet v 1-related family, represent minor constituents in tree nuts. These allergens are frequently cross-reactive with other food and pollen homologues, and are considered panallergens. Others, such as legumins, vicilins, and 2S albumins, represent major seed storage protein constituents of the nuts. The allergenic tree nuts discussed in this review include those most commonly responsible for allergic reactions such as hazelnut, walnut, cashew, and almond as well as those less frequently associated with allergies including pecan, chestnut, Brazil nut, pine nut, macadamia nut, pistachio, coconut, Nangai nut, and acorn.

  14. Sublingual allergen immunotherapy

    DEFF Research Database (Denmark)

    Calderón, M A; Simons, F E R; Malling, Hans-Jørgen;

    2012-01-01

    To cite this article: Calderón MA, Simons FER, Malling H-J, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy 2012; 67: 302-311. ABSTRACT: Allergen immunotherapy reorients inappropriate immune responses...... in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen...... cells and eosinophils (mostly located in submucosal areas) and, in comparison with subcutaneous tissue, are less likely to give rise to anaphylactic reactions. SLIT-associated immune responses include the induction of circulating, allergen-specific Th1 and regulatory CD4+ T cells, leading to clinical...

  15. Allergen Specific Immunotherapy

    Directory of Open Access Journals (Sweden)

    Şükrü Çekiç

    2015-04-01

    Full Text Available Allergen specific immunotherapy (SIT is the only treatment that can provide a cure for allergic disorders. This treatment is based on development of immune tolerance by exposure to allergen in repetitive and increasing doses. It is tertiary to avoidance of allergen and pharmacotherapy. Allergens used for immunotherapy, must be confirmed by skin prick test or specific IgE and must be applied in supervision of allergy specialists. Studies show that immunotherapy, improve asthma symptoms, decreases drug consumption, prevent development of asthma in rhinitis patients and reduce new sensitizations. Common side effects diminished with the usage of standardized allergen solutions. It is contraindicated in severe asthma. Though it is recommended to avoid immunotherapy in patients using beta blockers and ACE inhibitors, immunotherapy can be considered in mandatory situations regarding possible benefits and harms. Most common ways of administration are subcutaneous and sublingual; new methods such as epicutaneous and intralymphatic injections are currently being studied.

  16. Advances in the quantification of relevant allergens in allergenic extracts.

    Science.gov (United States)

    Batard, T; Nony, E; Hrabina, M; Chabre, H; Frati, F; Moingeon, P

    2013-10-01

    Relevant allergens are major contributors to the safety and efficacy of allergenic extracts used in allergen immunotherapy (AIT). As such, they should be accurately quantified, as recommended by the 2008 European guidelines on allergen products. Until now, the quantification of relevant allergens was mainly performed by using immunoassays (e.g. ELISA) that relying upon specific antibodies. Although antibody-based quantification is commonly used to assess the concentration of relevant allergens in allergenic extracts, results must be taken with caution in the light of the inherent limitations of such techniques. In the present study, we discuss how those limitations can be overcome by using comprehensive mass spectrometry-based techniques.

  17. Prediction of allergenicity of gene-modified foods by serum-based testing

    DEFF Research Database (Denmark)

    Poulsen, Lars K.

    2002-01-01

    On the basis of applying the IFBC/ILSI decision tree in a number of cases, a refinement of the scheme is suggested. Large differences in allergenic potential may be obtained by altering the route of administration of an allergen. Because an inhalation allergen can induce symptoms at different thr...

  18. Hierarchy and molecular properties of house dust mite allergens.

    Science.gov (United States)

    Thomas, Wayne R

    2015-10-01

    The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 faecal allergens. The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation better than HDM extracts although discrepancies have been found in regions with complex acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5, 7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group 14 large lipid binding proteins and the recently described proteins Der f 24-33, need further investigation but with the cognoscence that other denominated allergens have been found to be minor sensitisers by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts, inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous variations.

  19. Hierarchy and molecular properties of house dust mite allergens

    Directory of Open Access Journals (Sweden)

    Wayne R. Thomas

    2015-10-01

    Full Text Available The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 faecal allergens. The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation better than HDM extracts although discrepancies have been found in regions with complex acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5, 7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group 14 large lipid binding proteins and the recently described proteins Der f 24–33, need further investigation but with the cognoscence that other denominated allergens have been found to be minor sensitisers by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts, inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10 a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous variations.

  20. Prevention of birch pollen-related food allergy by mucosal treatment with multi-allergen-chimers in mice.

    Directory of Open Access Journals (Sweden)

    Elisabeth Hoflehner

    Full Text Available BACKGROUND: Among birch pollen allergic patients up to 70% develop allergic reactions to Bet v 1-homologue food allergens such as Api g 1 (celery or Dau c 1 (carrot, termed as birch pollen-related food allergy. In most cases, specific immunotherapy with birch pollen extracts does not reduce allergic symptoms to the homologue food allergens. We therefore genetically engineered a multi-allergen chimer and tested if mucosal treatment with this construct could represent a novel approach for prevention of birch pollen-related food allergy. METHODOLOGY: BALB/c mice were poly-sensitized with a mixture of Bet v 1, Api g 1 and Dau c 1 followed by a sublingual challenge with carrot, celery and birch pollen extracts. For prevention of allergy sensitization an allergen chimer composed of immunodominant T cell epitopes of Api g 1 and Dau c 1 linked to the whole Bet v 1 allergen, was intranasally applied prior to sensitization. RESULTS: Intranasal pretreatment with the allergen chimer led to significantly decreased antigen-specific IgE-dependent β-hexosaminidase release, but enhanced allergen-specific IgG2a and IgA antibodies. Accordingly, IL-4 levels in spleen cell cultures and IL-5 levels in restimulated spleen and cervical lymph node cell cultures were markedly reduced, while IFN-γ levels were increased. Immunomodulation was associated with increased IL-10, TGF-β and Foxp3 mRNA levels in NALT and Foxp3 in oral mucosal tissues. Treatment with anti-TGF-β, anti-IL10R or anti-CD25 antibodies abrogated the suppression of allergic responses induced by the chimer. CONCLUSION: Our results indicate that mucosal application of the allergen chimer led to decreased Th2 immune responses against Bet v 1 and its homologue food allergens Api g 1 and Dau c 1 by regulatory and Th1-biased immune responses. These data suggest that mucosal treatment with a multi-allergen vaccine could be a promising treatment strategy to prevent birch pollen-related food allergy.

  1. Mechanisms of allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Fujita Hiroyuki

    2012-01-01

    Full Text Available Abstract Allergen-specific immunotherapy (allergen-SIT is a potentially curative treatment approach in allergic diseases. It has been used for almost 100 years as a desensitizing therapy. The induction of peripheral T cell tolerance and promotion of the formation of regulatory T-cells are key mechanisms in allergen-SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg cells and inducible IL-10- and TGF-β-producing type 1 Treg (Tr1 cells may prevent the development of allergic diseases and play a role in successful allergen-SIT and healthy immune response via several mechanisms. The mechanisms of suppression of different pro-inflammatory cells, such as eosinophils, mast cells and basophils and the development of allergen tolerance also directly or indirectly involves Treg cells. Furthermore, the formation of non-inflammatory antibodies particularly IgG4 is induced by IL-10. Knowledge of these molecular basis is crucial in the understanding the regulation of immune responses and their possible therapeutic targets in allergic diseases.

  2. Modifications of allergenicity linked to food technologies.

    Science.gov (United States)

    Moneret-Vautrin, D A

    1998-01-01

    The prevalence of food allergies (FA) has increased over the past fifteen years. The reasons suggested are changes in dietary behaviour and the evolution of food technologies. New cases of FA have been described with chayote, rambutan, arguta, pumpkin seeds, custard apple, and with mycoproteins from Fusarium.... Additives using food proteins are at high risk: caseinates, lysozyme, cochineal red, papaïn, alpha-amylase, lactase etc. Heating can reduce allergenicity or create neo-allergens, as well as storage, inducing the synthesis of allergenic stress or PR proteins. Aeroallergens (miles, moulds) contaminate foods and can induce allergic reactions. Involuntary contamination by peanut proteins on production lines is a problem which is not yet solved. Genetically modified plants are at risk of allergenicity, requiring methodological steps of investigations: the comparison of the amino-acid sequence of the transferred protein with the sequence of known allergens, the evaluation of thermo degradability and of the denaturation by pepsin and trypsin are required, as well as the study with sera from patients allergic to the plant producing the gene. The combination of enzymatic hydrolysis, heating, or the development of genetically modified plants may offer new alternatives towards hypoallergenic foods (57 references).

  3. Hypoxia Potentiates Allergen Induction of HIF-1α, Chemokines, Airway Inflammation, TGF-β1, and Airway Remodeling in a mouse model

    Science.gov (United States)

    Baek, Kwang Je; Cho, Jae Youn; Rosenthal, Peter; Alexander, Laura E. Crotty; Nizet, Victor; Broide, David H.

    2013-01-01

    Whether hypoxia contributes to airway inflammation and remodeling in asthma is unknown. In this study we used mice exposed to a hypoxic environment during allergen challenge (simulating hypoxia during an asthma exacerbation) to investigate the contribution of hypoxia to airway inflammation and remodeling. Although neither hypoxia alone, nor OVA allergen alone, induced significant neutrophil influx into the lung, the combination of OVA and hypoxia induced a synergistic 27 fold increase in peribronchial neutrophils, enhanced expression of HIF-1α and one of its target genes, the CXC-family neutrophil chemokine KC. The combination of hypoxia and OVA allergen increased eotaxin-1, peribronchial eosinophils, lung TGB-β1 expression, and indices of airway remodeling (fibrosis and smooth muscle) compared to either stimulus alone. As hypoxia is present in >90% of severe asthma exacerbations, these findings underscore the potential of hypoxia to potentiate the airway inflammatory response, remodeling, and accelerate the decline of lung function in asthma exacerbations. PMID:23499929

  4. Amiodarone-Induced Thyrotoxic Thyroiditis: A Diagnostic and Therapeutic Challenge

    Directory of Open Access Journals (Sweden)

    Umang Barvalia

    2014-01-01

    Full Text Available Amiodarone is an iodine-based, potent antiarrhythmic drug bearing a structural resemblance to thyroxine (T4. It is known to produce thyroid abnormalities ranging from abnormal thyroid function testing to overt hypothyroidism or hyperthyroidism. These adverse effects may occur in patients with or without preexisting thyroid disease. Amiodarone-induced thyrotoxicosis (AIT is a clinically recognized condition commonly due to iodine-induced excessive synthesis of thyroid, also known as type 1 AIT. In rare instances, AIT is caused by amiodarone-induced inflammation of thyroid tissue, resulting in release of preformed thyroid hormones and a hyperthyroid state, known as type 2 AIT. Distinguishing between the two states is important, as both conditions have different treatment implications; however, a mixed presentation is not uncommon, posing diagnostic and treatment challenges. We describe a case of a patient with amiodarone-induced type 2 hyperthyroidism and review the current literature on the best practices for diagnostic and treatment approaches.

  5. Allergens in the Lab.

    Science.gov (United States)

    Fisher, Thomas M.

    1987-01-01

    Points out the health and legal implications related to laboratory substances that could cause allergic reactions. Presents a list of potential cosmetic allergens and irritants. Includes precautionary measures dealing with allergy situations. (ML)

  6. Allergenicity of two Anisakis simplex allergens evaluated in vivo using an experimental mouse model.

    Science.gov (United States)

    Cho, Min Kyoung; Park, Mi Kyung; Kang, Shin Ae; Caballero, Maria Luisa; Perez-Pinar, Teresa; Rodriguez-Perez, Rosa; Ock, Mee Sun; Cha, Hee Jae; Hong, Yeon Chul; Yu, Hak Sun

    2014-11-01

    Anisakis (Anisakidae) is one of the most important causes of helminth-induced allergic reactions and elicits clinical responses that include urticaria, rhinitis, bronco-constriction, cough, and/or gastrointestinal symptoms. More than 13 reactive allergens have been identified in the serum of Anisakis allergy patients, but the allergenicity of only a few of these have been evaluated in vivo using a mouse model. To evaluate the allergenicity of two important allergens, Ani s 1 and Ani s 9, we induced experimental allergic airway inflammation in a mouse model by repeated intranasal administration of the allergens. Both recombinant proteins (rAni s 1 and rAni s 9) elicited increased airway hyperresponsivity, airway infiltration by inflammatory cells (especially eosinophils), bronchial epithelial cell hyperplasia, all of which are characteristic of allergic airway inflammation. These allergens significantly increased the levels of Th2-related cytokines (IL-4, IL-5, IL-13, and IL-25) and Th17 related cytokines (IL-6 and IL-17) in both splenocytes and airway (except IL-17 in airway by rAni s 9). OVA-specific IgE and total IgE were increased in rAni s 1 and rAni s 9 treated mice as compared with controls treated with OVA alone. In addition, these two allergens induced gene expression of thymic stromal lymphopoietin (TSLP) and IL-25 (initiators of the Th2 response), as well as CXCL1 (initiator of the Th17 response) in mouse lung epithelial cells. In conclusion, repeated intranasal treatments with rAni s 1 and rAni s 9 induced airway inflammation in mice by elevating of Th2 and Th17 responses in the lung.

  7. Recombinant allergens for allergen-specific immunotherapy: 10 years anniversary of immunotherapy with recombinant allergens.

    Science.gov (United States)

    Valenta, Rudolf; Linhart, B; Swoboda, I; Niederberger, V

    2011-06-01

    The broad applicability of allergen-specific immunotherapy for the treatment and eventually prevention of IgE-mediated allergy is limited by the poor quality and allergenic activity of natural allergen extracts that are used for the production of current allergy vaccines. Today, the genetic code of the most important allergens has been deciphered; recombinant allergens equalling their natural counterparts have been produced for diagnosis and immunotherapy, and a large panel of genetically modified allergens with reduced allergenic activity has been characterized to improve safety of immunotherapy and explore allergen-specific prevention strategies. Successful immunotherapy studies have been performed with recombinant allergens and hypoallergenic allergen derivatives and will lead to the registration of the first recombinant allergen-based vaccines in the near future. There is no doubt that recombinant allergen-based vaccination strategies will be generally applicable to most allergen sources, including respiratory, food and venom allergens and allow to produce safe allergy vaccines for the treatment of the most common forms of IgE-mediated allergies.

  8. Human T cell priming assay: depletion of peripheral blood lymphocytes in CD25(+) cells improves the in vitro detection of weak allergen-specific T cells.

    Science.gov (United States)

    Vocanson, Marc; Achachi, Amine; Mutez, Virginie; Cluzel-Tailhardat, Magalie; Varlet, Béatrice Le; Rozières, Aurore; Fournier, Philippe; Nicolas, Jean-François

    2014-01-01

    To develop an in vitro assay that recapitulates the key event of allergic contact dermatitis (ACD), that is the priming of effector T cells by hapten-presenting dendritic cells, and then allows for the sensitive detection of chemical allergens represents a major challenge. Classical human T cell priming assays (hTCPA) that have been developed in the past, using hapten-loaded monocyte-derived dendritic cells (MDDCs) as antigen-presenting cells and peripheral blood lymphocytes (PBLs) as responding cells, were not efficient to prime T cells to common allergens with moderate/weak sensitizing properties. Recent progress in the understanding of the effector and regulatory mechanisms of ACD have shown that T cell priming requires efficient uptake of allergens by immunogenic DCs and that it is controlled by several subsets of regulatory cells including CD25(+) Tregs. We therefore analyzed various parameters involved in allergen-specific T cell activation in vitro and showed that priming of allergen-specific T cells is hampered by several subsets of immune cells comprising CD1a(neg) DCs, CD25(+) T cells, and CD56(+) regulatory cells.CD4(+)CD25(+)FoxP3(+) Tregs prevented the in vitro T cell priming to moderate/weak allergens, and depletion of human PBLs in CD25(+) cells significantly increased specific T cell proliferation and IFN-γ secretion. CD56(+) cells exerted an additional control of T cell priming since co-depletion of both CD56(+) and CD25(+) cells improved the magnitude of chemical-specific T cell activation. Finally, CD1a(low) MDDCs were able to inhibit T cell activation obtained by allergen-pulsed CD1a(high) MDDC. Moreover, we showed that uptake by DC of allergen-encapsulated nanoparticles significantly increased their activation status and their ability to prompt specific T cell activation. Hence, by combining the different strategies, i.e., depletion of CD25(+) and CD56(+) cells, use of CD1a(high) MDDC, and nanoparticle encapsulation of allergens, it was

  9. Current Overview of Allergens of Plant Pathogenesis Related Protein Families

    Directory of Open Access Journals (Sweden)

    Mau Sinha

    2014-01-01

    Full Text Available Pathogenesis related (PR proteins are one of the major sources of plant derived allergens. These proteins are induced by the plants as a defense response system in stress conditions like microbial and insect infections, wounding, exposure to harsh chemicals, and atmospheric conditions. However, some plant tissues that are more exposed to environmental conditions like UV irradiation and insect or fungal attacks express these proteins constitutively. These proteins are mostly resistant to proteases and most of them show considerable stability at low pH. Many of these plant pathogenesis related proteins are found to act as food allergens, latex allergens, and pollen allergens. Proteins having similar amino acid sequences among the members of PR proteins may be responsible for cross-reactivity among allergens from diverse plants. This review analyzes the different pathogenesis related protein families that have been reported as allergens. Proteins of these families have been characterized in regard to their biological functions, amino acid sequence, and cross-reactivity. The three-dimensional structures of some of these allergens have also been evaluated to elucidate the antigenic determinants of these molecules and to explain the cross-reactivity among the various allergens.

  10. Current Overview of Allergens of Plant Pathogenesis Related Protein Families

    Science.gov (United States)

    Sinha, Mau; Singh, Rashmi Prabha; Kushwaha, Gajraj Singh; Iqbal, Naseer; Singh, Avinash; Kaushik, Sanket; Sharma, Sujata; Singh, Tej P.

    2014-01-01

    Pathogenesis related (PR) proteins are one of the major sources of plant derived allergens. These proteins are induced by the plants as a defense response system in stress conditions like microbial and insect infections, wounding, exposure to harsh chemicals, and atmospheric conditions. However, some plant tissues that are more exposed to environmental conditions like UV irradiation and insect or fungal attacks express these proteins constitutively. These proteins are mostly resistant to proteases and most of them show considerable stability at low pH. Many of these plant pathogenesis related proteins are found to act as food allergens, latex allergens, and pollen allergens. Proteins having similar amino acid sequences among the members of PR proteins may be responsible for cross-reactivity among allergens from diverse plants. This review analyzes the different pathogenesis related protein families that have been reported as allergens. Proteins of these families have been characterized in regard to their biological functions, amino acid sequence, and cross-reactivity. The three-dimensional structures of some of these allergens have also been evaluated to elucidate the antigenic determinants of these molecules and to explain the cross-reactivity among the various allergens. PMID:24696647

  11. Protein families: implications for allergen nomenclature, standardisation and specific immunotherapy.

    Science.gov (United States)

    Breiteneder, Heimo

    2009-01-01

    Allergens are embedded into the protein universe as members of large families and superfamilies of related proteins which is a direct consequence of their shared evolution. The classification of allergens by protein families offers a valuable frame of reference that allows the design of experiments to study cross-reactivity and allergenic potency of proteins. Information on protein family membership also complements the current official IUIS allergen nomenclature. All presently known allergens belong to one of 140 (1.4%) of the 10,340 protein families currently described by version 23.0 of the Pfam database. This is indicative of a strong bias among allergens towards certain protein architectures that are able to induce an IgE response in an atopic immune system. However, even small variations in the structure of a protein alter its immunological characteristics. Various isoforms of the major birch pollen allergen Bet v 1 were shown to possess highly variant immunogenic and allergenic properties. Ber e 1 and SFA8, two 2S albumins, were revealed to display differential capacities to polarise an immune response. Such data will be exploited in the future for the design of allergy vaccines.

  12. Food allergens and mucosal immune systems with special reference to recognition of food allergens by gut-associated lymphoid tissue

    Directory of Open Access Journals (Sweden)

    Shuichi Kaminogawa

    1999-01-01

    Full Text Available Food allergy, triggered by an aberrant immune response elicited by orally ingested food allergens, is generated through a complicated mechanism because the allergen interacts with the mucosal immune system (the gut- associated lymphoid tissue, GALT and the resulting immune response affects the generation of allergy. This review will describe the process by which antigens or allergens are recognized by the GALT and the characteristic immune responses induced thereafter. Orally administered antigens induce distinct immune responses in the Peyer's patches, lamina propria and the intestinal epithelium. In addition to these local immune responses in the gut, ingested antigens are known to affect systemic immunity. These may induce a suppressed state of systemic immune responsiveness, which is called oral tolerance, or in some cases they may elicit a systemic IgE antibody response which may lead to allergic reactions. Information on the regions on food allergens recognized by T cells and IgE antibodies is important in understanding the fates of food allergens after being recognized by the GALT. The structure of T and B cell epitopes on food allergens and the possibility of modulation of allergic reactions by amino-acid substituted analogs of allergen- derived peptides will also be discussed.

  13. Recombinant house dust mite allergens

    OpenAIRE

    2013-01-01

    House dust mites (HDM) are a globally important source of allergen responsible for the sensitization of more than 50% of allergic patients. Specific immunotherapy with HDM extracts is effective but allergen extracts cannot be fully standardized and severe side-effects can occur during the protracted course of treatment. The introduction of molecular biological techniques into allergy research allowed the indentification of more than 20 groups of HDM allergens. Recombinant HDM allergens can be...

  14. Structural insights into the IgE mediated responses induced by the allergens Hev b 8 and Zea m 12 in their dimeric forms

    Science.gov (United States)

    Mares-Mejía, Israel; Martínez-Caballero, Siseth; Garay-Canales, Claudia; Cano-Sánchez, Patricia; Torres-Larios, Alfredo; Lara-González, Samuel; Ortega, Enrique; Rodríguez-Romero, Adela

    2016-01-01

    Oligomerization of allergens plays an important role in IgE-mediated reactions, as effective crosslinking of IgE- FcεRI complexes on the cell membrane is dependent on the number of exposed B-cell epitopes in a single allergen molecule or on the occurrence of identical epitopes in a symmetrical arrangement. Few studies have attempted to experimentally demonstrate the connection between allergen dimerization and the ability to trigger allergic reactions. Here we studied plant allergenic profilins rHev b 8 (rubber tree) and rZea m 12 (maize) because they represent an important example of cross-reactivity in the latex-pollen-food syndrome. Both allergens in their monomeric and dimeric states were isolated and characterized by exclusion chromatography and mass spectrometry and were used in immunological in vitro experiments. Their crystal structures were solved, and for Hev b 8 a disulfide-linked homodimer was found. Comparing the structures we established that the longest loop is relevant for recognition by IgE antibodies, whereas the conserved regions are important for cross-reactivity. We produced a novel monoclonal murine IgE (mAb 2F5), specific for rHev b 8, which was useful to provide evidence that profilin dimerization considerably increases the IgE-mediated degranulation in rat basophilic leukemia cells. PMID:27586352

  15. Role of Allergen Source-Derived Proteases in Sensitization via Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Yasuhiro Matsumura

    2012-01-01

    Full Text Available Protease activity is a characteristic common to many allergens. Allergen source-derived proteases interact with lung epithelial cells, which are now thought to play vital roles in both innate and adaptive immune responses. Allergen source-derived proteases act on airway epithelial cells to induce disruption of the tight junctions between epithelial cells, activation of protease-activated receptor-2, and the production of thymic stromal lymphopoietin. These facilitate allergen delivery across epithelial layers and enhance allergenicity or directly activate the immune system through a nonallergic mechanism. Furthermore, they cleave regulatory cell surface molecules involved in allergic reactions. Thus, allergen source-derived proteases are a potentially critical factor in the development of allergic sensitization and appear to be strongly associated with heightened allergenicity.

  16. Allergen immunotherapy, routes of administration and cytokine networks: an update.

    Science.gov (United States)

    Cuppari, Caterina; Leonardi, Salvatore; Manti, Sara; Filippelli, Martina; Alterio, Tommaso; Spicuzza, Lucia; Rigoli, Luciana; Arrigo, Teresa; Lougaris, Vassilios; Salpietro, Carmelo

    2014-01-01

    Allergen immunotherapy is a disease-modifying therapy, effective for the treatment of allergic rhinitis, allergic asthma, conjunctivitis or stinging insect allergy. Allergen immunotherapy involves the administration of increasing doses of allergens with the aim of ameliorating the allergic response. Although precise underlying mechanisms of the induction of immune tolerance remain unclear, immunotherapy has been associated with the induction of distinct subsets of Tregs that eventually lead to peripheral tolerance by inducing a deviation from Th2 to Th1 immune responses. This review focuses on the current knowledge of the mechanisms of immunotherapy in relationship to different routes of administration and also provides a unifying view.

  17. Reduction of the in vivo allergenicity of Der p 2, the major house-dust mite allergen, by genetic engineering.

    Science.gov (United States)

    Chen, Kuan-Wei; Fuchs, Gudrun; Sonneck, Karoline; Gieras, Anna; Swoboda, Ines; Douladiris, Nikolas; Linhart, Birgit; Jankovic, Marija; Pavkov, Tea; Keller, Walter; Papadopoulos, Nikolaos G; Valent, Peter; Valenta, Rudolf; Vrtala, Susanne

    2008-05-01

    The major allergen of the house-dust mite Dermatophagoides pteronyssinus, Der p 2, is recognized by approximately 90% of mite-allergic patients. We have produced two recombinant fragments of Der p 2 comprising aa 1-53 and aa 54-129 and a hybrid molecule (aa 54-129+1-53), combining the two fragments in inverse order, by genetic engineering. The recombinant Der p 2 derivatives were expressed in E. coli and purified to homogeneity. rDer p 2 derivatives (fragments and hybrid) showed a considerably reduced beta sheet structure and IgE reactivity compared to the Der p 2 wild-type allergen. The allergenic activity of the Der p 2 derivatives was reduced more than tenfold as evaluated in vitro in basophil activation assays and in vivo by skin prick testing of mite-allergic patients. Immunization of mice and rabbits with rDer p 2 derivatives induced Der p 2-specific IgG antibodies, which inhibited the binding of allergic patients' IgE to Der p 2. Immunization of mice with rDer p 2 derivatives induced less allergenic IgE responses than immunization with rDer p 2. Thus the rDer p 2 derivatives exhibited less in vivo allergenic activity and allergenicity than the Der p 2 allergen but preserved immunogenicity and may hence represent candidates for specific immunotherapy of house-dust mite allergy.

  18. Unlocking the allergenic structure of the major house dust mite allergen der f 2 by elimination of key intramolecular interactions.

    Science.gov (United States)

    Takai, T; Ichikawa, S; Yokota, T; Hatanaka, H; Inagaki, F; Okumura, Y

    2000-11-03

    We report on the structural background of the remarkable reduction of allergenicity in engineering of the major house dust mite allergen Der f 2. Disruption of intramolecular disulfide bonds in Der f 2 caused extensive conformational change that was monitored by circular dichroism and gel-filtration analysis. The degree of conformational change correlated well with the degree of reductions in the capacity to bind IgE and to induce histamine release from basophils in mite-allergic patients. Loosening the rigid tertiary structure by elimination of key intramolecular interactions is an effective strategy to reduce the number of high affinity IgE epitopes of allergen vaccine.

  19. New Cosmetic Contact Allergens

    Directory of Open Access Journals (Sweden)

    An Goossens

    2015-02-01

    Full Text Available Allergic and photo-allergic contact dermatitis, and immunologic contact urticaria are potential immune-mediated adverse effects from cosmetics. Fragrance components and preservatives are certainly the most frequently observed allergens; however, all ingredients must be considered when investigating for contact allergy.

  20. Food processing and allergenicity

    NARCIS (Netherlands)

    Verhoeckx, K.C.M.; Vissers, Y.M.; Baumert, J.L.; Faludi, R.; Feys, M.; Flanagan, S.; Herouet-Guicheney, C.; Holzhauser, T.; Shimojo, R.; Bolt, N. van der; Wichers, H.; Kimber, I.

    2015-01-01

    Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat tre

  1. Bleach Neutralizes Mold Allergens

    Science.gov (United States)

    Science Teacher, 2005

    2005-01-01

    Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…

  2. Food Processing and Allergenicity

    NARCIS (Netherlands)

    Verhoeckx, K.; Vissers, Y.; Baumert, J.L.; Faludi, R.; Fleys, M.; Flanagan, S.; Herouet-Guicheney, C.; Holzhauser, T.; Shimojo, R.; Bolt, van der Nieke; Wichers, H.J.; Kimber, I.

    2015-01-01

    Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed.

    In this review the impact of processing (heat and non

  3. Seed-based oral vaccines as allergen-specific immunotherapies.

    Science.gov (United States)

    Takaiwa, Fumio

    2011-03-01

    Plant-based vaccines have advantages over conventional vaccines in terms of scalability, lack of requirement for cold chain logistics, stability, safety, cost-effectiveness and needle-free administration. In particular, when antigen is expressed in seeds, high production is possible and immunogenicity is not lost even if stocked at ambient temperature for several years. Induction of immune tolerance (desensitization) to allergen is a principle strategy for controlling allergic diseases, and is generally carried out by subcutaneous injection. Seed-based oral administration offers a straightforward and inexpensive alternative approach to deliver vaccines effectively to the GALT without loss of activity. Consumption of transgenic seeds containing modified hypo-allergenic tolerogen or T-cell epitope peptides derived from allergens has no or very few severe side effects and can induce immune tolerance leading to reduction of allergen-specific IgE production, T-cell proliferation and release of histamine. Suppression of allergen-specific clinical symptoms results. Thus, seed-based allergy vaccines offer an innovative and convenient allergen-specific immunotherapeutic approach as an alternative to conventional allergen-specific immunotherapy.

  4. Sublingual immunotherapy: from biological extracts to recombinant allergens.

    Science.gov (United States)

    Moingeon, P

    2006-01-01

    Sublingual vaccines based on biological extracts from various natural allergen sources are effective in the treatment of respiratory allergies. These vaccines comprise a complex mixture of proteins and glycoproteins that require dedicated standardization procedures to ensure batch-to-batch consistency. Because of the lack of correlation between the potency of an allergen extract and the quantity of major allergen content, standardization is achieved predominantly by determining the global IgE binding capacity of the extract in vitro. New proteomic technologies can be used to further characterize the most abundant proteins present in an extract. Second-generation sublingual vaccines based on recombinant allergens are under development. The aim is to produce molecularly defined vaccines that exhibit superior efficacy, while allowing for simplified immunization schedules. In this approach, recombinant DNA technology is used to express highly purified allergens in their native (i.e. wild-type) conformation. The recombinant allergens are then formulated with ad hoc adjuvants and/or mucoadhesive galenic excipients so that they specifically target oral Langerhans cells and induce allergen-specific regulatory T cells.

  5. Molecular and biochemical classification of plant-derived food allergens.

    Science.gov (United States)

    Breiteneder, H; Ebner, C

    2000-07-01

    Molecular biology and biochemical techniques have significantly advanced the knowledge of allergens derived from plant foods. Surprisingly, many of the known plant food allergens are homologous to pathogenesis-related proteins (PRs), proteins that are induced by pathogens, wounding, or certain environmental stresses. PRs have been classified into 14 families. Examples of allergens homologous to PRs include chitinases (PR-3 family) from avocado, banana, and chestnut; antifungal proteins such as the thaumatin-like proteins (PR-5) from cherry and apple; proteins homologous to the major birch pollen allergen Bet v 1 (PR-10) from vegetables and fruits; and lipid transfer proteins (PR-14) from fruits and cereals. Allergens other than PR homologs can be allotted to other well-known protein families such as inhibitors of alpha-amylases and trypsin from cereal seeds, profilins from fruits and vegetables, seed storage proteins from nuts and mustard seeds, and proteases from fruits. As more clinical data and structural information on allergenic molecules becomes available, we may finally be able to answer what characteristics of a molecule are responsible for its allergenicity.

  6. Genetic engineering of plant food with reduced allergenicity.

    Science.gov (United States)

    Scheurer, Stephan; Sonnewald, Sophia

    2009-01-01

    Food allergies are a major health concern in industrialized countries. Since a specific immunotherapy for food allergies is not available in clinical routine praxis till now, reduction of allergens in foods, either by food processing or genetic engineering are strategies to minimize the risk of adverse reactions for food allergic patients. This review summarizes biotechnological approaches, especially the RNA interference (RNAi) technology, for the reduction of selected allergens in plant foods. So far, only a limited number of reports showing proof-of-concept of this methodology are available. Using RNAi an impressive reduction of allergen accumulation was obtained which was stable in the next generations of plants. Since threshold doses for most food allergens are not known, the beneficial effect has to be evaluated by oral challenge tests in the future. The article critically addresses the potential and limitations of genetic engineering, as well as of alternative strategies to generate "low allergic" foods.

  7. The Drinking Effect of Hydrogen Water on Atopic Dermatitis Induced by Dermatophagoides farinae Allergen in NC/Nga Mice

    Directory of Open Access Journals (Sweden)

    Rosa Mistica C. Ignacio

    2013-01-01

    Full Text Available Hydrogen water (HW produced by electrolysis of water has characteristics of extremely low oxidation-reduction potential (ORP value and high dissolved hydrogen (DH. It has been proved to have various beneficial effects including antioxidant and anti-inflammatory effects; however, HW effect on atopic dermatitis (AD, an inflammatory skin disorder, is poorly documented. In the present study, we examined the immunological effect of drinking HW on Dermatophagoides farinae-induced AD-like skin in NC/Nga mice. Mice were administered with HW and purified water (PW for 25 days. We evaluated the serum concentration of pro-inflammatory (TNF-α, Th1 (IFN-γ, IL-2, and IL-12p70, Th2 (IL-4, IL-5, and IL-10, and cytokine expressed by both subsets (GM-CSF to assess their possible relationship to the severity of AD. The serum levels of cytokines such as IL-10, TNF-α, IL-12p70, and GM-CSF of mice administered with HW was significantly reduced as compared to PW group. The results suggest that HW affects allergic contact dermatitis through modulation of Th1 and Th2 responses in NC/Nga mice. This is the first note on the drinking effect of HW on AD, clinically implying a promising potential remedy for treatment of AD.

  8. Molecular characterization of recombinant T1, a non-allergenic periwinkle (Catharanthus roseus) protein, with sequence similarity to the Bet v 1 plant allergen family.

    Science.gov (United States)

    Laffer, Sylvia; Hamdi, Said; Lupinek, Christian; Sperr, Wolfgang R; Valent, Peter; Verdino, Petra; Keller, Walter; Grote, Monika; Hoffmann-Sommergruber, Karin; Scheiner, Otto; Kraft, Dietrich; Rideau, Marc; Valenta, Rudolf

    2003-07-01

    More than 25% of the population suffer from Type I allergy, an IgE-mediated hypersensitivity disease. Allergens with homology to the major birch ( Betula verrucosa ) pollen allergen, Bet v 1, belong to the most potent elicitors of IgE-mediated allergies. T1, a cytokinin-inducible cytoplasmic periwinkle ( Catharanthus roseus ) protein, with significant sequence similarity to members of the Bet v 1 plant allergen family, was expressed in Escherichia coli. Recombinant T1 (rT1) did not react with IgE antibodies from allergic patients, and failed to induce basophil histamine release and immediate-type skin reactions in Bet v 1-allergic patients. Antibodies raised against purified rT1 could be used for in situ localization of natural T1 by immunogold electron microscopy, but did not cross-react with most of the Bet v 1-related allergens. CD analysis showed significant differences regarding secondary structure and thermal denaturation behaviour between rT1 and recombinant Bet v 1, suggesting that these structural differences are responsible for the different allergenicity of the proteins. T1 represents a non-allergenic member of the Bet v 1 family that may be used to study structural requirements of allergenicity and to engineer hypo-allergenic plants by replacing Bet v 1-related allergens for primary prevention of allergy.

  9. Murine calcium-activated chloride channel family member 3 induces asthmatic airway inflammation independently of allergen exposure

    Institute of Scientific and Technical Information of China (English)

    MEI Li; HE Li; WU Si-si; ZHANG Bo; XU Yong-jian; ZHANG Zhen-xiang; ZHAO Jian-ping

    2013-01-01

    Background Expression of murine calcium-activated chloride channel family member 3 (mCLCA3) has been reported to be increased in the airway epithelium of asthmatic mice challenged with ovalbumin (OVA).However,its role in asthmatic airway inflammation under no OVA exposure has not yet been clarified.Methods mCLCA3 plasmids were transfected into the airways of normal BALB/c mice.mCLCA3 expression and airway inflammation in mouse lung tissue were evaluated.Cell differentials and cytokines in bronchoalveolar lavage fluid (BALF) were analyzed.The expression of mCLCA3 protein and mucus protein mucin-5 subtype AC (MUC5AC) were analyzed by Western blotting.The mRNA levels of mCLCA3,MUC5AC and interleukin-13 (IL-13) were determined quantitatively.Results mCLCA3 expression was not detected in the control group while strong immunoreactivity was detected in the OVA and mCLCA3 plasmid groups,and was strictly localized to the airway epithelium.The numbers of inflammatory cells in lung tissue and BALF were increased in both mCLCA3 plasmid and OVA groups.The protein and mRNA levels of mCLCA3 and MUC5AC in the lung tissue were significantly increased in the mCLCA3 plasmid and OVA groups compared to the control group.The level of IL-13,but not IL-4,IL-5,IFN-γ,CCL2,CCL5 or CCL11,was significantly increased compared with control group in BALF in the mCLCA3 plasmid and OVA groups.The level of IL-13 in the BALF in the mCLCA3 plasmid group was much higher than that in the OVA group (P <0.05).The level of mCLCA3 mRNA in lung tissue was positively correlated with the levels of MUC5AC mRNA in lung tissue,IL-13 mRNA in lung tissue,the number of eosinophils in BALF,and the content of IL-13 protein in BALF.The level of IL-13 mRNA in lung tissue was positively correlated with the number of eosinophils in BALF and the level of MUC5AC mRNA in lung tissue.Conclusion These findings suggest that increased expression of a single-gene,mCLCA3,could simulate an asthma attack,and its mechanism may

  10. Allergenicity assay of allergen from Dermatophagoides farinae in transgenic tobacco

    Institute of Scientific and Technical Information of China (English)

    TANG Mingjuan; SHEN Ye; HU Yuanlei; CAO Lei; NI Ting; ZHANG Hongyu; LIN Zhongping

    2004-01-01

    Derf2 gene for one of mite allergens in Dermatophagoides farinae has been cloned and expressed under regulation of 35S promoter in transgenic tobacco. The transcriptional analysis showed that this mite complete gene structure in genomic sequence could be spliced at prediction site. Allergenicity assay with immunological sera indicated that the extracts from the transgenic tobacco gave obvious positive IgE binding reaction with specific serum pool. This work would be of potential use in allergenicity assessment of genetically modified food.

  11. Cosmetic Contact Allergens

    Directory of Open Access Journals (Sweden)

    An Goossens

    2016-02-01

    Full Text Available This article presents trends in the frequency of cosmetics as causal factors of allergic contact dermatitis during a 26-year period in 14,911 patients patch-tested between 1990 and 2014, and discusses the cosmetic allergens identified during the last six years (2010–2015 in 603 patients out of 3105 tested. The data were retrieved from, and evaluated with, a patient database developed in-house. The results show the increasing importance of cosmetic allergies, up to 25% of the patients tested during the last five-year period. As expected, fragrance materials, preservatives, and hair dyes were the most frequent culprits, but a great variety of other allergenic ingredients were involved as well. This underlines the need of additional and extensive patch testing with the patient’s products used and their ingredients.

  12. Hazelnut Allergens: Molecular Characterization, Detection, and Clinical Relevance.

    Science.gov (United States)

    Costa, Joana; Mafra, Isabel; Carrapatoso, Isabel; Oliveira, Maria Beatriz P P

    2016-11-17

    In last few years, special attention has been given to food-induced allergies, in which hazelnut allergy is highlighted. Hazelnut is one of the most commonly consumed tree nuts, being largely used by the food industry in a variety of processed foods. It has been regarded as a food with potential health benefits, but also as a source of allergens capable of inducing mild to severe allergic reactions in sensitized individuals. Considering the great number of reports addressing hazelnut allergens, with an estimated increasing trend, this review intends to assemble all the relevant information available so far on the following main issues: prevalence of tree nut allergy, clinical threshold levels, molecular characterization of hazelnut allergens (Cor a 1, Cor a 2, Cor a 8, Cor a 9, Cor a 10, Cor a 11, Cor a 12, Cor a 14, and Cor a TLP) and their clinical relevance, and methodologies for detection of hazelnut allergens in foods. A comprehensive overview of the current data about the molecular characterization of hazelnut allergens is presented, relating to biochemical classification and biological function with clinical importance. Recent advances in hazelnut allergen detection methodologies are summarized and compared, including all the novel protein-based and DNA-based approaches.

  13. Allergen-specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Moote William

    2011-11-01

    Full Text Available Abstract Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. However, despite its proven efficacy in these conditions, it is frequently underutilized in Canada. The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, the adverse effects of pharmacological treatment, and patient preferences. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, injections must be given under medical supervision in clinics that are equipped to manage anaphylaxis. In this article, the authors review the indications and contraindications, patient selection criteria, and the administration, safety and efficacy of allergen-specific immunotherapy.

  14. Reduction of allergenicity of irradiated ovalbumin in ovalbumin-allergic mice

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Ji-Hyun; Lee, Ju-Woon; Kim, Jae-Hun [Radiation Application Research Division, Advanced Radiation Technology Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Baek [Radiation Application Research Division, Advanced Radiation Technology Institute, Jeongeup 580-185 (Korea, Republic of); Graduate School of Biotechnology, Korea University, Yeongi 339-700 (Korea, Republic of); Lee, Soo-Young [Department of Pediatrics, Ajou University School of Medicine, Suwon 442-749 (Korea, Republic of); Kang, Il-Jun [Division of Life Sciences, Hallym University, Chunchon 200-702 (Korea, Republic of); Byun, Myung-Woo [Radiation Application Research Division, Advanced Radiation Technology Institute, Jeongeup 580-185 (Korea, Republic of)], E-mail: mwbyun@kaeri.re.kr

    2007-11-15

    Egg allergy is one of the most serious of the immediate hypersensitivity reactions to foods. Such an allergic disorder is mediated by IgE antibodies stimulated by T-helper type 2 (Th2) lymphocytes. This study was undertaken to evaluate changes of allergenicity and cytokine profiles by exposure of irradiated ovalbumin (OVA), a major allergen of egg white, in the OVA-allergic mice model. OVA solutions (2 mg/ml in 0.01 M phosphate buffered saline (PBS) were gamma-irradiated to 50 and 100 kGy. The allergenicity in the OVA-allergy-induced mice model was remarkably reduced when challenged with irradiated OVA. Cultures of spleen cells harvested from OVA-sensitized mice showed a significant decrease in Th2 cytokine levels of ILs-4 and -5 with a concomitant increase in Th1 cytokine levels of IL-12 when co-cultured with irradiated OVA. However, IFN-{gamma} level decreased dependant on the radiation dose of co-cultured OVA. The levels of IgEs and Th2-cytokine were reduced dependant on the radiation dose. These data show that the irradiated OVA could downregulate the activity of Th2 lymphocytes in OVA-sensitized mice.

  15. Experimental approaches to predict allergenic potential of novel food

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard; Kroghsbo, Stine; Bøgh, Katrine Lindholm

    2013-01-01

    ’t know under what circumstances oral tolerance develops. With all these unanswered questions, it is a big challenge to designan animal model that, with relatively few animals, is able to predict if a food protein is a potential allergen. An even larger challenge is to predict its potency, a prerequisite...... of understanding of the significance of dose for the development of food allergy or its counterpart oral tolerance makes risk assessment very difficult. In addition route of exposure and digestibility are relevant variables. Examples of the use and limitations of animal models for predicting the allergenicity...

  16. Mammal-derived respiratory lipocalin allergens do not exhibit dendritic cell-activating capacity.

    Science.gov (United States)

    Parviainen, S; Kinnunen, T; Rytkönen-Nissinen, M; Nieminen, A; Liukko, A; Virtanen, T

    2013-03-01

    Most mammal-derived respiratory allergens belong to the lipocalin family of proteins. Determinants of their allergenic capacity are still unknown. Innate immune cells, in particular dendritic cells, have been shown to be involved in the allergenicity of some proteins. As recognition by dendritic cells is one of the few plausible mechanisms for the allergenicity of proteins, we wanted to investigate their role in the allergenicity of lipocalin allergens. Therefore, we first incubated human monocyte-derived dendritic cells with immunologically functional recombinant allergens mouse Mus m 1, dog Can f 1 and 2, cow Bos d 2, horse Equ c 1 and natural Bos d 2. Then, the surface marker expression and cytokine production of dendritic cells and their capacity to promote T cell proliferation and Th2 immune deviation in naïve CD4(+) T cells were examined in vitro. We found that near to endotoxin-free lipocalin allergens had no effect on the activation, allostimulatory capacity or cytokine production of dendritic cells. The dendritic cells could not induce immune deviation in naïve CD4(+) T cells. In contrast, lipopolysaccharide activated the dendritic cells efficiently. However, lipocalin allergens were not able to modify the lipopolysaccharide-induced responses. We conclude that an important group of mammal-derived respiratory allergens, lipocalins, appear not to be able to activate dendritic cells, a major component involved in the allergenicity of some proteins. It is conceivable that this incapacity of lipocalin allergens to arouse innate immunity may be associated with their poor capacity to induce a strong T cell response, verified in several studies.

  17. Chronic radiation-induced dermatitis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Spałek M

    2016-12-01

    Full Text Available Mateusz Spałek Department of Radiotherapy I, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Abstract: Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients’ quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF. RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and

  18. Pharmacological characterisation of the adenosine receptor mediating increased ion transport in the mouse isolated trachea and the effect of allergen challenge.

    Science.gov (United States)

    Kornerup, Kristin N; Page, Clive P; Moffatt, James D

    2005-04-01

    The effect of adenosine on transepithelial ion transport was investigated in isolated preparations of murine trachea mounted in Ussing chambers. The possible regulation of adenosine receptors in an established model of allergic airway inflammation was also investigated. Mucosally applied adenosine caused increases in short-circuit current (I(SC)) that corresponded to approximately 50% of the response to the most efficacious secretogogue, ATP (delta I(SC) 69.5 +/- 6.7 microA cm2). In contrast, submucosally applied adenosine caused only small (<20%) increases in I(SC), which were not investigated further. The A1-selective (N6-cyclopentyladenosine, CPA, 1 nM-10 microM), A2A-selective (2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxoamido adenosine; CGS 21680; 0.1-100 microM) and A3-selective (1-deoxy-1-[6-[[(3-iodophenyl)-methyl]amino]-9H-purin-9-yl]-N-methyl-beta-D-ribofuranuronamide; IB-MECA; 30 nM-100 microM) adenosine receptor agonists were either equipotent or less potent than adenosine, suggesting that these receptors do not mediate the response to adenosine. The A1 receptor selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10 nM-1 microM) caused a rightward shift of the adenosine concentration-effect curve only at 1 microM. The mixed A2A/A2B receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) also caused rightward shift of the adenosine concentration-effect curve, again only at micromolar concentrations, suggestive of the involvement of A2B receptors. In preparations from animals sensitised to ovalbumin and challenged over 3 days with aerosol ovalbumin, a decrease in baseline I(SC) was observed and responses to ATP were diminished. Similarly, the amplitude of responses to adenosine were attenuated although there was no change in potency. These results suggest that the A2B receptor mediates the I(SC) response to adenosine in the mouse trachea. This receptor does not appear to be

  19. Managing nut-induced anaphylaxis: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Lomas JM

    2015-10-01

    Full Text Available Jeanne M Lomas, Kirsi M Järvinen Division of Pediatric Allergy and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Abstract: The prevalence of peanut and tree nut allergy in the USA has increased, especially in the pediatric population. Nut allergy remains the leading cause of fatal anaphylactic reactions. Management of anaphylaxis includes not only treatment of symptoms during a reaction, but strict dietary avoidance and education on potential situations, which may place the patient at high risk for accidental exposure. Cross-reactivity between various nuts along with various cross-contamination sources should be discussed with all nut-allergic individuals. Exciting research continues to emerge on other potential treatments for patients allergic to nuts, including allergen immunotherapy. Results of such interventions have been encouraging, though further studies are needed regarding safety and long-term outcomes before these can be applied to clinical practice. Keywords: peanut, tree nut, anaphylaxis, cross-reactivity, avoidance, immunotherapy

  20. Reducing peanut allergens by high pressure combined with polyphenol oxidase

    Science.gov (United States)

    Chung, Si-Yin; Houska, Milan; Reed, Shawndrika

    2013-12-01

    Polyphenol oxidase (PPO) has been shown to reduce major peanut allergens. Since high pressure (HP) can increase enzyme activity, we postulated that further reduction of peanut allergens can be achieved through HP combined with PPO. Peanut extracts containing caffeic acid were treated with each of the following: (1) HP; (2) HP+PPO; (3) PPO; and (4) none. HP was conducted at 300 and 500 MPa, each for 3 and 10 min, 37 °C. After treatment, SDS-PAGE was performed and allergenic capacity (IgE binding) was determined colorimetrically in inhibition enzyme-linked immunosorbent assay and Western blots, using a pooled plasma from peanut-allergic patients. Data showed that HP alone had no effect on major peanut allergens. However, HP at 500 MPa combined with PPO (HP500/PPO) induced a higher (approximately twofold) reduction of major peanut allergens and IgE binding than PPO alone or HP300/PPO. There was no difference between treatment times. We concluded that HP500/PPO at 3-min enhanced a twofold reduction of the allergenic capacity of peanut extracts, as compared to PPO itself.

  1. Effect of processing technologies on the allergenicity of food products.

    Science.gov (United States)

    Jiménez-Saiz, Rodrigo; Benedé, Sara; Molina, Elena; López-Expósito, Iván

    2015-01-01

    Heat treatment has been used since ancient times for food processing, first to ensure the safety of food and its storage, but also to transform its characteristics (in its raw form) and obtain new textures, flavors, or novel foods. However, the transformation experienced by food components when heated, or processed, can dramatically affect the allergenicity of food, either reducing or increasing it. To date, most of the articles published dealing with the changes in the potential allergenicity of food are focused on heat treatment and the Maillard reaction. However, it is also important to give prominence to other group of new technologies developed nowadays, such as high-pressure processing, microwaves and food irradiation. These techniques are not likely to replace traditional processing methods, but they are becoming attractive for the food industry due to different reasons, and it is expected in the near future to have different products on the market processed with these new technologies at an affordable cost. Moreover, other biochemical modifications, particularly enzymatic cross-linking of proteins, have attracted wide-spread attention and will be considered as well in this review, because of its great opportunities to induce protein modification and thus affect food allergenicity. Together with the effect of processing of food allergens, this review will place special attention on gastroduodenal digestion of processed allergens, which directly affects their allergenicity.

  2. Food, novel foods, and allergenicity

    NARCIS (Netherlands)

    Loveren H van; LPI

    2002-01-01

    Certain foods lead may to allergic responses in certain individuals. Main allergenic foods are Crustacea (shrimp, lobster, crab), egg, fish, milk, peanuts, soybeans, tree nuts, and wheat, and allergens are always proteins. A wide array of symptoms can result from food allergy (gastrointestinal, ski

  3. Identification of autoclave-resistant Anisakis simplex allergens.

    Science.gov (United States)

    Carballeda-Sangiao, Noelia; Olivares, Fabiola; Rodriguez-Mahillo, Ana I; Careche, Mercedes; Tejada, Margarita; Moneo, Ignacio; González-Muñoz, Miguel

    2014-04-01

    Anisakis simplex is a fish parasite able to induce allergic reactions in humans infected when eating raw or undercooked fish parasitized with viable third-stage larvae. Some authors claim that exposure to nonviable Anisakis material can result in allergic symptoms in previously sensitized patients, indicating that parasite allergens are resistant to the thermal treatments of usual cooking procedures. Furthermore, some patients report symptoms after eating canned fish. The aim of this work was the analysis of parasite allergen stability in heating to 121 °C in an autoclave to simulate the thermal process applied to canned fish. Third-stage larvae were subjected to autoclaving for 20, 40, and 80 min, and parasite crude extracts were analyzed by electrophoresis, immunoblotting, and a flow-cytometric basophil activation test. Allergens resistant to autoclaving were separated by reversed-phase high-performance liquid chromatography and identified by ion trap mass spectrometry. Protein analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that autoclaving considerably reduced the number and intensity of identifiable protein bands in a time-dependent manner. Several allergens were detected by immunoblotting with a pool of A. simplex allergic patients' sera after autoclaving. Allergens of 9 and 14 kDa resistant to autoclaving were identified as Ani s 4 and Ani s 1 allergens, respectively. Functional analysis showed that allergens retain their capacity to activate basophils even after autoclaving for 80 min. In conclusion, some relevant A. simplex allergens retain their capacity to bind immunoglobulin E and activate basophils after being subjected to autoclaving, which is a method equivalent to that used in industrial canning processes.

  4. Structural aspects of fungal allergens.

    Science.gov (United States)

    Crameri, Reto

    2015-03-01

    Despite the increasing number of solved crystal structures of allergens, the key question why some proteins are allergenic and the vast majority is not remains unanswered. The situation is not different for fungal allergens which cover a wide variety of proteins with different chemical properties and biological functions. They cover enzymes, cell wall, secreted, and intracellular proteins which, except cross-reactive allergens, does not show any evidence for structural similarities at least at the three-dimensional level. However, from a diagnostic point of view, pure allergens biotechnologically produced by recombinant technology can provide us, in contrast to fungal extracts which are hardly producible as standardized reagents, with highly pure perfectly standardized diagnostic reagents.

  5. Prevalence of food and airborne allergens in allergic patients in Kerman

    Directory of Open Access Journals (Sweden)

    Hamed Fouladseresht

    2014-07-01

    Full Text Available Background: Detection of various environmental allergens is the major challenge in allergic diseases and the only treatment is avoiding these allergens. The aim of this study was to determine the prevalence of food and airborne allergens in allergic patients using Skin Prick Test (SPT. Methods: A cross-sectional study was done on clinically confirmed patients of atopic-dermatitis (n=54, allergenic-rhinitis (n=64 and chronic-urticaria (n=39 who referred to asthma and allergy clinic at Afzali-Pour hospital in Kerman during 2008-2010. Skin prick test was done using allergen extracts to determine the patients' sensitivity to food and airborne antigens. Results: Fifty-nine percent of patients responded to at least one allergen. Allergy to airborne and food allergens was 55.9 % and 21.7%, respectively. Chenopodiaceae (22.9% and egg white (10.2% were most prevalent airborne and food allergens. Allergy to cockroach, egg white, egg yolk and tomato was significantly higher in males than in females (P<0.05. Conclusion: The results indicated that allergy to food and airborne allergens is different depending on the nutrition and environmental conditions.

  6. Peptide immunotherapy for childhood allergy - addressing translational challenges

    Directory of Open Access Journals (Sweden)

    Mackenzie Karen J

    2011-11-01

    Full Text Available Abstract Allergic sensitisation usually begins early in life. The number of allergens a patient is sensitised to can increase over time and the development of additional allergic conditions is increasingly recognised. Targeting allergic disease in childhood is thus likely to be the most efficacious means of reducing the overall burden of allergic disease. Specific immunotherapy involves administering protein allergen to tolerise allergen reactive CD4+ T cells, thought key in driving allergic responses. Yet specific immunotherapy risks allergic reactions including anaphylaxis as a consequence of preformed allergen-specific IgE antibodies binding to the protein, subsequent cross-linking and mast cell degranulation. CD4+ T cells direct their responses to short "immunodominant" peptides within the allergen. Such peptides can be given therapeutically to induce T cell tolerance without facilitating IgE cross-linking. Peptide immunotherapy (PIT offers attractive treatment potential for allergic disease. However, PIT has not yet been shown to be effective in children. This review discusses the immunological mechanisms implicated in PIT and briefly covers outcomes from adult PIT trials. This provides a context for discussion of the challenges for the application of PIT, both generally and more specifically in relation to children.

  7. Technical advance: Langerhans cells derived from a human cell line in a full-thickness skin equivalent undergo allergen-induced maturation and migration.

    Science.gov (United States)

    Ouwehand, Krista; Spiekstra, Sander W; Waaijman, Taco; Scheper, Rik J; de Gruijl, Tanja D; Gibbs, Susan

    2011-11-01

    In this report, the construction of a functional, immunocompetent, full-thickness skin equivalent (SE) is described, consisting of an epidermal compartment containing keratinocytes, melanocytes, and human LCs derived from the MUTZ-3 cell line (MUTZ-LC) and a fibroblast-populated dermal compartment. The CD1a(+)Langerin(+)HLA-DR(+) MUTZ-LCs populate the entire epidermis at a similar density to that found in native skin. Exposure of the SE to subtoxic concentrations of the allergens NiSO(4) and resorcinol resulted in LC migration out of the epidermis toward the fibroblast-populated dermal compartment. A significant dose-dependent up-regulation of the DC maturation-related CCR7 and IL-1β transcripts and of CD83 at the protein level upon epidermal exposure to both allergens was observed, indicative of maturation and migration of the epidermally incorporated LC. We have thus successfully developed a reproducible and functional full-thickness SE model containing epidermal MUTZ-LC. This model offers an alternative to animal testing for identifying potential chemical sensitizers and for skin-based vaccination strategies and provides a unique research tool to study human LC biology in situ under controlled in vitro conditions.

  8. Recombinant allergens for pollen immunotherapy.

    Science.gov (United States)

    Wallner, Michael; Pichler, Ulrike; Ferreira, Fatima

    2013-12-01

    Specific immunotherapy (IT) represents the only potentially curative therapeutic intervention of allergic diseases capable of suppressing allergy-associated symptoms not only during treatment, but also after its cessation. Presently, IT is performed with allergen extracts, which represent a heterogeneous mixture of allergenic, as well as nonallergenic, compounds of a given allergen source. To overcome many of the problems associated with extract-based IT, strategies based on the use of recombinant allergens or derivatives thereof have been developed. This review focuses on recombinant technologies to produce allergy therapeuticals, especially for allergies caused by tree, grass and weed pollen, as they are among the most prevalent allergic disorders affecting the population of industrialized societies. The reduction of IgE-binding of recombinant allergen derivatives appears to be mandatory to increase the safety profile of vaccine candidates. Moreover, increased immunogenicity is expected to reduce the dosage regimes of the presently cumbersome treatment. In this regard, it has been convincingly demonstrated in animal models that hypoallergenic molecules can be engineered to harbor inherent antiallergenic immunologic properties. Thus, strategies to modulate the allergenic and immunogenic properties of recombinant allergens will be discussed in detail. In recent years, several successful clinical studies using recombinant wild-type or hypoallergens as active ingredients have been published and, currently, novel treatment forms with higher safety and efficacy profiles are under investigation in clinical trials. These recent developments are summarized and discussed.

  9. Sensitization to fungal allergens: Resolved and unresolved issues.

    Science.gov (United States)

    Fukutomi, Yuma; Taniguchi, Masami

    2015-10-01

    Exposure and sensitization to fungal allergens can promote the development and worsening of allergic diseases. Although numerous species of fungi have been associated with allergic diseases in the literature, the significance of fungi from the genera Alternaria, Cladosporium, Penicillium, Aspergillus, and Malassezia has been well documented. However, it should be emphasized that the contribution of different fungal allergens to allergic diseases is not identical, but species-specific. Alternaria and Cladosporium species are considered to be important outdoor allergens, and sensitization and exposure to species of these genera is related to the development of asthma and rhinitis, as well as epidemics of asthma exacerbation, including life-threatening asthma exacerbation. In contrast, xerophilic species of Penicillium and Aspergillus, excluding Aspergillus fumigatus, are implicated in allergic diseases as indoor allergens. A. fumigatus has a high capacity to colonize the bronchial tract of asthmatic patients, causing severe persistent asthma and low lung function, and sometimes leading to allergic bronchopulmonary aspergillosis. Malassezia are common commensals of healthy skin, although they are also associated with atopic dermatitis, especially on the head and neck, but not with respiratory allergies. Despite its importance in the management of allergic diseases, precise recognition of species-specific IgE sensitization to fungal allergens is often challenging because the majority of fungal extracts exhibit broad cross-reactivity with taxonomically unrelated fungi. Recent progress in gene technology has contributed to the identification of specific and cross-reactive allergen components from different fungal sources. However, data demonstrating the clinical relevance of IgE reactivity to these allergen components are still insufficient.

  10. Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity

    Directory of Open Access Journals (Sweden)

    Salome’ V. Ibba

    2016-01-01

    Full Text Available Although expression of inducible NO synthase (iNOS in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose polymerase (PARP activation. We show, for the first time, that iNOS is highly expressed in peripheral blood mononuclear cells (PBMCs of asthmatics with uncontrolled disease, which did not correspond to protein nitration. Selective iNOS inhibition with L-NIL protected against AHR upon acute, but not chronic, exposure to ovalbumin or house dust mite (HDM in mice. Supplementation of NO by nitrite administration significantly blocked AHR in chronically HDM-exposed mice that were treated with L-NIL. Protection against chronic HDM exposure-induced AHR by olaparib-mediated PARP inhibition may be associated with the partial but not the complete blockade of iNOS expression. Indeed, L-NIL administration prevented olaparib-mediated protection against AHR in chronically HDM-exposed mice. Our study suggests that the amount of iNOS and NO are critical determinants in the modulation of AHR by selective iNOS inhibitors and renews the potential of iNOS as a therapeutic target for asthma.

  11. Genetic engineering of the major timothy grass pollen allergen, Phl p 6, to reduce allergenic activity and preserve immunogenicity.

    Science.gov (United States)

    Vrtala, Susanne; Focke, Margarete; Kopec, Jolanta; Verdino, Petra; Hartl, Arnulf; Sperr, Wolfgang R; Fedorov, Alexander A; Ball, Tanja; Almo, Steve; Valent, Peter; Thalhamer, Josef; Keller, Walter; Valenta, Rudolf

    2007-08-01

    On the basis of IgE epitope mapping data, we have produced three allergen fragments comprising aa 1-33, 1-57, and 31-110 of the major timothy grass pollen allergen Phl p 6 aa 1-110 by expression in Escherichia coli and chemical synthesis. Circular dichroism analysis showed that the purified fragments lack the typical alpha-helical fold of the complete allergen. Superposition of the sequences of the fragments onto the three-dimensional allergen structure indicated that the removal of only one of the four helices had led to the destabilization of the alpha helical structure of Phl p 6. The lack of structural fold was accompanied by a strong reduction of IgE reactivity and allergenic activity of the three fragments as determined by basophil histamine release in allergic patients. Each of the three Phl p 6 fragments adsorbed to CFA induced Phl p 6-specific IgG Abs in rabbits. However, immunization of mice with fragments adsorbed to an adjuvant allowed for human use (AluGel-S) showed that only the Phl p 6 aa 31-110 induced Phl p 6-specific IgG Abs. Anti-Phl p 6 IgG Abs induced by vaccination with Phl p 6 aa 31-110 inhibited patients' IgE reactivity to the wild-type allergen as well as Phl p 6-induced basophil degranulation. Our results are of importance for the design of hypoallergenic allergy vaccines. They show that it has to be demonstrated that the hypoallergenic derivative induces a robust IgG response in a formulation that can be used in allergic patients.

  12. Molecular Characteristics of Cockroach Allergens

    Institute of Scientific and Technical Information of China (English)

    Chii-Huei Wu; Mey-Fann Lee

    2005-01-01

    Cockroaches, commonly found in urban dwellings worldwide, have long been considered vectors of various infectious diseases and cockroach allergens are one of the major etiologic risk factors for IgE-mediated allergic respiratory illness throughout the world. A high prevalence of cockroach hypersensitivity in atopic (20-55 %) and asthmatic (49-60%) populations has been documented. Cockroach allergens with molecular weights ranging from 6 to 120 kD have been identified by various standard immunochemical techniques. This article covers the characteristics of major cockroach allergens that have been purified, sequenced, cloned, and produced as recombinant proteins.

  13. Food Allergens: Is There a Correlation between Stability to Digestion and Allergenicity?

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Madsen, Charlotte Bernhard

    2016-01-01

    . This paper reviews data from digestibility studies on purified food allergens and evaluates the predictive value of digestibility tests on the allergenic potential. We point out that food allergens do not necessarily resist digestion. We discuss how the choice of in vitro digestibility assay condition...... the allergenic potential of food allergen digestion products. Studies assessing the allergenicity of digestion products, by either IgE-binding, elicitation or sensitizing capacity, shows that digestion may abolish, decrease, have no effect, or even increase the allergenicity of food allergens. Therefore...

  14. Allergen-specific immunotherapy: towards combination vaccines for allergic and infectious diseases.

    Science.gov (United States)

    Edlmayr, Johanna; Niespodziana, Katarzyna; Focke-Tejkl, Margarete; Linhart, Birgit; Valenta, Rudolf

    2011-01-01

    IgE-mediated allergies affect more than 25% of the population. Allergen-specific immunotherapy (SIT) is an antigen-specific and disease-modifying form of treatment. It is based on the therapeutic administration of the disease-causing allergens to allergic patients. However, the fact that only allergen extracts of insufficient quality are currently available and the possible occurrence of side effects during treatment limit the broad use of SIT and prophylactic vaccination is has not yet been performed. In the last 20 years the DNA sequences of the most common allergens have been isolated and the corresponding allergens have been produced as recombinant allergens. Based on the progress made in the field of allergen characterization it is possible to improve the quality and safety of allergy vaccines and to develop new, more effective strategies for a broad application of SIT and even for prophylactic treatment. Here we discuss the development of combination vaccines for allergy and infectious diseases. This approach is based on the selection of allergen-derived peptides with reduced IgE- and T cell reactivity in order to minimize IgE- and T cell-mediated side effects as well as the potential of the vaccine to induce allergic sensitization. These peptides are fused by recombinant technology onto a viral carrier protein to obtain a combination vaccine which induces protective immunity against allergy and viral infections. The application of such combination vaccines for therapy and prophylaxis of allergy and infectious diseases is discussed.

  15. Biochemical and immunological characterization of recombinant allergen Lol p 1.

    Science.gov (United States)

    Tamborini, E; Faccini, S; Lidholm, J; Svensson, M; Brandazza, A; Longhi, R; Groenlund, H; Sidoli, A; Arosio, P

    1997-11-01

    Pollen from perennial rye grass (Lolium perenne), a major cause of type-I allergy worldwide, contains a complex mixture of allergenic proteins among which Lol p 1 is one of the most important. We describe the expression, purification and characterization of a recombinant Lol p 1 overproduced in Escherichia coli. The recombinant allergen, expressed in high yields and purified in milligram amounts, bound to specific IgE antibodies from human sera, induced histamine release from sensitized human basophils, and elicited rabbit antisera that recognize specifically recombinant Lol p 1 and natural Lol p 1 of pollen extract. Recombinant Lol p 1 was used to develop ImmunoCAP assays for analysis of 150 sera that were Radioallergosorbent test positive to L. perenne pollen. In 130 of them (87%) the assay detected a significant level of IgE antibodies to Lol p 1, reaching on average 37% of the level obtained with a test for IgE to the whole grass pollen extract. To map epitopes on Lol p 1, we produced three deletion mutants [des-(116-240)-Lol p 1, des-(1-88)-Lol p 1 and des-(133-189)-Lol p 1], which were efficiently expressed in bacteria. These all showed a strong reactivity with the specific rabbit IgG antibodies, but lacked most or all the allergenic properties of recombinant Lol p 1. A study of the antigenic structure of Lol p 1 was performed using the three deletion mutants and a set of 17-18-residue overlapping synthetic peptides covering the whole allergen sequence. The results indicate that human IgE and rabbit IgG antibodies bind to distinct regions of Lol p 1, and that at least some important IgE epitopes are mainly conformational. The findings suggest that recombinant allergens constitute useful reagents for further development of serological diagnosis of allergy, and that it should be possible to produce immunogenic fragments of allergenic proteins without allergenic properties.

  16. Pollen Allergens for Molecular Diagnosis.

    Science.gov (United States)

    Pablos, Isabel; Wildner, Sabrina; Asam, Claudia; Wallner, Michael; Gadermaier, Gabriele

    2016-04-01

    Pollen allergens are one of the main causes of type I allergies affecting up to 30% of the population in industrialized countries. Climatic changes affect the duration and intensity of pollen seasons and may together with pollution contribute to increased incidences of respiratory allergy and asthma. Allergenic grasses, trees, and weeds often present similar habitats and flowering periods compromising clinical anamnesis. Molecule-based approaches enable distinction between genuine sensitization and clinically mostly irrelevant IgE cross-reactivity due to, e. g., panallergens or carbohydrate determinants. In addition, sensitivity as well as specificity can be improved and lead to identification of the primary sensitizing source which is particularly beneficial regarding polysensitized patients. This review gives an overview on relevant pollen allergens and their usefulness in daily practice. Appropriate allergy diagnosis is directly influencing decisions for therapeutic interventions, and thus, reliable biomarkers are pivotal when considering allergen immunotherapy in the context of precision medicine.

  17. Climate-change-induced range shifts of three allergenic ragweeds (Ambrosia L.) in Europe and their potential impact on human health

    Science.gov (United States)

    Muscarella, Robert; Borchsenius, Finn

    2017-01-01

    Invasive allergenic plant species may have severe health-related impacts. In this study we aim to predict the effects of climate change on the distribution of three allergenic ragweed species (Ambrosia spp.) in Europe and discuss the potential associated health impact. We built species distribution models based on presence-only data for three ragweed species, using MAXENT software. Future climatic habitat suitability was modeled under two IPCC climate change scenarios (RCP 6.0 and RCP 8.5). We quantify the extent of the increase in ‘high allergy risk’ (HAR) areas, i.e., parts of Europe with climatic conditions corresponding to the highest quartile (25%) of present day habitat suitability for each of the three species. We estimate that by year 2100, the distribution range of all three ragweed species increases towards Northern and Eastern Europe under all climate scenarios. HAR areas will expand in Europe by 27–100%, depending on species and climate scenario. Novel HAR areas will occur mostly in Denmark, France, Germany, Russia and the Baltic countries, and overlap with densely populated cities such as Paris and St. Petersburg. We conclude that areas in Europe affected by severe ragweed associated allergy problems are likely to increase substantially by year 2100, affecting millions of people. To avoid this, management strategies must be developed that restrict ragweed dispersal and establishment of new populations. Precautionary efforts should limit the spread of ragweed seeds and reduce existing populations. Only by applying cross-countries management plans can managers mitigate future health risks and economical consequences of a ragweed expansion in Europe. PMID:28321366

  18. Determination of storage conditions for shrimp extracts: analysis of specific IgE-allergen profiles.

    Science.gov (United States)

    Piboonpocanun, Surapon; Boonchoo, Siribangon; Pariyaprasert, Wipada; Visitsunthorn, Nualanong; Jirapongsananuruk, Orathai

    2010-03-01

    The consumption of shrimp is a common cause of food hypersensitivity reactions. Shrimp allergy is diagnosed using a skin prick test (SPT) as well as by food challenges. Due to the lack of a wide variety of commercial shrimp extracts for SPTs, we selected various shrimp species for the preparation of local shrimp extracts. However, optimal storage conditions for the shrimp extracts which also maintains allergenic potency has not yet been identified. The objective of the present study was to determine the potency of the shrimp extracts under different storage conditions and durations. Specific IgE-allergen profiles of eight shrimp-allergic patients were investigated by using sera incubated with extracts prepared from lyophilized raw or boiled shrimp, which were stored at 4 degress C or -20 degress C for up to 4 weeks. When stored at -20 degress C, most allergens were preserved after 4 weeks. However, storage at 4 degress C results in few allergens remaining after 2 weeks. Boiled-shrimp extracts stored at 4 degree C and -20 degress C contained higher amounts of IgE-allergen complexes than raw-shrimp extracts. Moreover, in both raw and boiled shrimp extracts, the IgE bound 36-40 kDa allergens constituted the major proteins since they were observed in all IgE-allergen profiles. In conclusion, we recommend that shrimp extracts are stored at -20 degress C for 4 weeks to prevent the loss of allergens.

  19. In vivo and in vitro techniques to determine the biological activity of food allergens

    DEFF Research Database (Denmark)

    Poulsen, Lars K.

    2001-01-01

    Methods for determination of the biological activity of food allergens comprise both determination of the allergenic potency, i.e. the capability to elicit an allergic reaction in an already sensitized individual, and the allergenic potential, i.e. the risk for sensitizing a hitherto non-allergic......Methods for determination of the biological activity of food allergens comprise both determination of the allergenic potency, i.e. the capability to elicit an allergic reaction in an already sensitized individual, and the allergenic potential, i.e. the risk for sensitizing a hitherto non......-allergic individual. Several methods are discussed for determination of potency including the double-blinded placebo-controlled food challenge, skin testing, in vitro effector cell assays such as basophil histamine release, and IgE-based techniques such as RAST and RAST inhibition. No reliable methods have yet been...... developed which can predict the allergenic potential of a food or a food allergen. The progress in the areas of stability studies and animal models for food allergy are discussed....

  20. Changes in the expression of NO synthase isoforms after ozone: the effects of allergen exposure

    Directory of Open Access Journals (Sweden)

    Lee June-Hyuk

    2004-06-01

    Full Text Available Abstract Background The functional role of nitric oxide (NO and various nitric oxide synthase (NOS isoforms in asthma remains unclear. Objective This study investigated the effects of ozone and ovalbumin (OVA exposure on NOS isoforms. Methods The expression of inducible NOS (iNOS, neuronal NOS (nNOS, and endothelial NOS (eNOS in lung tissue was measured. Enhanced pause (Penh was measured as a marker of airway obstruction. Nitrate and nitrite in bronchoalveolar lavage (BAL fluid were measured using a modified Griess reaction. Results The nitrate concentration in BAL fluid from the OVA-sensitized/ozone-exposed/OVA-challenged group was greater than that of the OVA-sensitized/saline-challenged group. Methacholine-induced Penh was increased in the OVA-sensitized/ozone-exposed/OVA-challenged group, with a shift in the dose-response curve to the left, compared with the OVA-sensitized/saline-challenged group. The levels of nNOS and eNOS were increased significantly in the OVA-sensitized/ozone-exposed/OVA-challenged group and the iNOS levels were reduced compared with the OVA-sensitized/saline-challenged group. Conclusion In mice, ozone is associated with increases in lung eNOS and nNOS, and decreases in iNOS. None of these enzymes are further affected by allergens, suggesting that the NOS isoforms play different roles in airway inflammation after ozone exposure.

  1. Crystal structure of peanut (Arachis hypogaea) allergen Ara h 5

    Science.gov (United States)

    Profilins from numerous species are known to be allergens, including food allergens, such as peanut (Arachis hypogaea) allergen Ara h 5, and pollen allergens, such as birch allergen Bet v 2. Patients with pollen allergy can also cross-react to peanut. Structural characterization of allergens will al...

  2. Categorisation of protein respiratory allergens: the case of Subtilisin.

    Science.gov (United States)

    Kimber, Ian; Basketter, David A

    2014-04-01

    Characterisation of the relative sensitizing potency of protein and chemical allergens remains challenging, particularly for materials causing allergic sensitization of the respiratory tract. There nevertheless remains an appetite, for priority setting and risk management, to develop paradigms that distinguish between individual respiratory allergens according to perceptions of the hazards and risks posed to human health. One manifestation thereof is recent listing of certain respiratory allergens as Substances of Very High Concern (SVHC) under the provisions of REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). Although priority setting is a laudable ambition, it is important the process is predicated on evidence-based criteria that are transparent, understood and owned. The danger is that in the absence of rigorous criteria unwanted precedents can be created, and confidence in the process is compromised. A default categorisation of sensitisers as SVHC requiring assessment under the authorisation process is not desirable. We therefore consider here the value and limitations of selective assignment of certain respiratory allergens as being SVHC. The difficulties of sustaining such designations in a sound and equitable way is discussed in the context of the challenges that exist with respect to assessment of potency, and information available regarding the effectiveness of exposure-based risk management.

  3. First successful reduction of clinical allergenicity of food by genetic modification : Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar

    NARCIS (Netherlands)

    Dubois, A. E. J.; Pagliarani, G.; Brouwer, R. M.; Kollen, B. J.; Dragsted, L. O.; Eriksen, F. D.; Callesen, O.; Gilissen, L. J. W. J.; Krens, F. A.; Visser, R. G. F.; Smulders, M. J. M.; Vlieg-Boerstra, B. J.; Flokstra-de Blok, B. J.; van de Weg, W. E.

    2015-01-01

    BackgroundGenetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals. MethodsWe performed oral food challenges in 21 apple-allergic individuals with Elstar apples which ha

  4. Recombinant allergens: what does the future hold?

    Science.gov (United States)

    Valenta, Rudolf; Niespodziana, Katarzyna; Focke-Tejkl, Margit; Marth, Katharina; Huber, Hans; Neubauer, Angela; Niederberger, Verena

    2011-04-01

    This year we are celebrating not only the centenary of allergen-specific immunotherapy but also the 10-year anniversary of the first administration of recombinant allergen-based vaccines to allergic patients. By using recombinant DNA technology, defined and safe allergy vaccines can be produced that allow us to overcome many, if not all, of the problems associated with the use of natural allergen extracts, such as insufficient quality, allergenic activity, and poor immunogenicity. Here we provide an update of clinical studies with recombinant allergen-based vaccines, showing that some of these vaccines have undergone successful clinical evaluation up to phase III studies. Furthermore, we introduce a strategy for allergen-specific immunotherapy based on recombinant fusion proteins consisting of viral carrier proteins and allergen-derived peptides without allergenic activity, which holds the promise of being free of side effects and eventually being useful for prophylactic vaccination.

  5. Associations between baseline allergens and polysensitization

    DEFF Research Database (Denmark)

    Carlsen, B.C.; Menne, T.; Johansen, J.D.

    2008-01-01

    : Seven allergens - parabens mix, N-isopropyl-N-phenyl-p-phenylenediamine, sesquiterpene lactone mix, wool alcohols, potassium dichromate, Myroxylon pereirae, and cobalt chloride - showed statistically significant positive associations to polysensitization. Five allergens p-phenylenediamine, neomycin...

  6. Laser-Induced Breakdown Spectroscopy: Fundamentals, Applications, and Challenges

    OpenAIRE

    Anabitarte, F.; Cobo, A.; J. M. Lopez-Higuera

    2012-01-01

    Laser-induced breakdown spectroscopy (LIBS) is a technique that provides an accurate in situ quantitative chemical analysis and, thanks to the developments in new spectral processing algorithms in the last decade, has achieved a promising performance as a quantitative chemical analyzer at the atomic level. These possibilities along with the fact that little or no sample preparation is necessary have expanded the application fields of LIBS. In this paper, we review the state of the ar...

  7. Dermatophagoides farinae Allergens Diversity Identification by Proteomics*

    OpenAIRE

    2013-01-01

    The most important indoor allergens for humans are house dust mites (HDM). Fourteen Dermatophagoides farinae allergens (Der f 1–3, 6, 7, 10, 11, 13–18, and 22) are reported although more than 30 allergens have been estimated in D. farinae. Seventeen allergens belonging to 12 different groups were identified by a procedure of proteomics combined with two-dimensional immunoblotting from D. farina extracts. Their sequences were determined by Edman degradation, mass spectrometry analysis, and cDN...

  8. Protective effects of basic fibroblast growth factor in the development of emphysema induced by interferon-γ.

    Science.gov (United States)

    Lee, Byung-Jae; Moon, Hyung-Geun; Shin, Tae-Seop; Jeon, Seong Gyu; Lee, Eun-Young; Gho, Yong Song; Lee, Chun Geun; Zhu, Zhou; Elias, Jack A; Kim, Yoon-Keun

    2011-04-30

    Recent clinical evidence indicates that the non-eosinophilic subtype of severe asthma is characterized by fixed airway obstruction, which may be related to emphysema. Transgenic studies have demonstrated that high levels of IFN-γ in the airways induce emphysema. Fibroblast growth factor 2 (FGF2), which is the downstream mediator of TGF-β, is important in wound healing. We investigated the role of FGF2 in IFN-γ-induced emphysema and the therapeutic effects of recombinant FGF2 in the prevention of emphysema in a severe non-eosinophilic asthma model. To evaluate the role of FGF2 in IFN-γ-induced emphysema, lung targeted IFN-γ transgenic mice were cross-bred with FGF2-deficient mice. A severe non-eosinophilic asthma model was generated by airway application of LPS-containing allergens twice a week for 4 weeks. To evaluate protective effects of FGF2, recombinant FGF2 (10 μg) was injected subcutaneously during allergen challenge in the severe asthma model. We found that non-eosinophilic inflammation and emphysema induced by transgenic overexpression of IFN-γ in the airways were aggravated by the absence of FGF2. Airway challenge with LPS-containing allergens induced more inflammation in mice sensitized with LPS-containing allergens compared to challenge with allergens alone. In addition, LPS-induced lung inflammation and emphysema depended on IFN-γ but not on IL-13. Interestingly, emphysema in the severe asthma model was significantly inhibited by treatment with recombinant FGF2 during allergen challenge, whereas lung inflammation was unaffected. Therefore, our present data suggest that FGF2 may help protect against IFN-γ-induced emphysema, and that recombinant FGF2 may help lessen the severity of emphysema.

  9. Prophylaxis and therapy of allergy by mucosal tolerance induction with recombinant allergens or allergen constructs.

    Science.gov (United States)

    Wiedermann, Ursula

    2005-10-01

    The mucosal immune system, present along the respiratory, gastrointestinal and genitourinary tract, has to discriminate between harmful pathogens and innocuous antigens, such as food, airborne antigens or the commensal bacterial flora. Therefore the mucosal immune system has acquired two opposing immunological functions, i.e. the induction of immunity and defence of mucosal pathogens, and the induction and maintenance of tolerance to environmental antigens and bacterial flora. As described for autoimmunity a breakdown or failure of tolerance induction is believed to lead also to allergies and food enteropathies. Based on the physiological role to prevent hypersensitivity reactions, tolerance induction via the mucosa has been proposed as a treatment strategy against inflammatory diseases, such as allergies. The aim of our research is to develop mucosal allergy vaccines based on the induction of mucosal tolerance and/or the induction of counter-regulatory immune responses with or without the use of certain mucosal antigen delivery systems, such as lactic acid bacteria. The use of recombinant allergens instead of allergen extracts with varying allergen content and composition may be essential for improvement of the treatment efficacy. In the present review we give examples of different animal models of type I allergy/asthma. Using these models we demonstrate that recombinant allergens or hypoallergenic variants thereof can be successfully used to induce mucosal tolerance in a prophylactic as well as a therapeutic treatment regime. That the concept of mucosal tolerance induction/mucosal vaccine delivery may in principal also function in humans is supported by recent clinical trials with locally (sublingual) applied immunotherapy.

  10. Chemical and Biological Properties of Food Allergens

    NARCIS (Netherlands)

    Jedrychowski, L.; Wichers, H.J.

    2009-01-01

    This book provides epidemiological data on food allergens and information on the incidence of food allergies. It discusses the link between hypersensitivity and immune system health and covers methods used for assays on allergenic components, animal models for allergen analysis, and clinical methods

  11. Hazelnut (Corylus avellana) vicilin Cor a 11: molecular characterization of a glycoprotein and its allergenic activity.

    Science.gov (United States)

    Lauer, Iris; Foetisch, Kay; Kolarich, Daniel; Ballmer-Weber, Barbara K; Conti, Amedeo; Altmann, Friedrich; Vieths, Stefan; Scheurer, Stephan

    2004-10-15

    In Europe, hazelnuts (Corylus avellana) are a frequent cause of food allergies. Several important hazelnut allergens have been previously identified and characterized. Specific N-glycans are known to induce strong IgE responses of uncertain clinical relevance, but so far the allergenic potential of glycoproteins from hazelnut has not been investigated. The aim of the study was the molecular characterization of the glycosylated vicilin Cor a 11 from hazelnut and the analysis of its allergenic activity. Although MALDI-TOF (matrix-assisted laser-desorption ionization-time-of-flight) MS showed that one of two potential glycosylation sites of Cor a 11 was glycosylated, CD spectroscopy indicated that recombinant and natural Cor a 11 share similar secondary structures. Thus to analyse the impact of the glycan residues of Cor a 11 on IgE binding, the allergenic activity of natural glycosylated Cor a 11 and recombinant Cor a 11 was compared. In addition, the IgE sensitization pattern to recombinant Cor a 11, Cor a 1, Cor a 2 and Cor a 8 of 65 hazelnut allergic patients was determined in vitro. The prevalence of IgE reactivity to hazelnut vicilin Cor a 11 was below 50%. Basophil histamine-release assays were used to determine the allergenic activity of both natural and recombinant Cor a 11 in comparison with Cor a 1, a birch (Betula verrucosa) pollen-related major hazelnut allergen. Both forms of Cor a 11 induced mediator release from basophils to a similar extent, indicating that the hazelnut allergic patients had cross-linking IgE antibodies binding to the protein backbone and not to carbohydrate structures. In comparison to Cor a 1, a 10000-fold higher concentration of Cor a 11 was required to induce similar basophil mediator release. In conclusion, the hazelnut vicilin Cor a 11 is a minor allergen both in regard to prevalence and allergenic potency, whereas its glycan does not contribute to its allergenic activity.

  12. Evidence of a novel allergenic protein Narcin in the bulbs of Narcissus tazetta

    Science.gov (United States)

    Sinha, Mau; Singh, Amar; Shokeen, Akshita; Sharma, Pradeep; Kaushik, Sanket; Mitra, Dipendra K; Kaur, Punit; Sharma, Sujata; Singh, Tej P

    2013-01-01

    Several plant-derived allergens have been identified which result in the formation of immunoglobulin E antibodies. Primarily, these allergens belong to the protein families including seed storage proteins, structural proteins and pathogenesis-related proteins. Several allergens are also reported from flower bulbs which cause contact dermatitis. Such symptoms are highly common with the bulb growers handling different species of Narcissus. Narcissus toxicity is also reported if the bulbs are consumed accidentally. The present study aimed to characterize the protein from the bulbs of Narcissus tazetta responsible for its allergenic response. A 13 kDa novel allergenic protein, Narcin was isolated from the bulbs of Narcissus tazetta. The protein was extracted using ammonium sulfate fractionation. The protein was further purified by anion exchange chromatography followed by gel filtration chromatography. The N-terminal sequence of the first 15 amino-acid residues was determined using Edman degradation. The allergenicity of the protein was measured by cytokine production using flow cytometry in peripheral blood mononuclear cells. Further estimation of total IgE was performed by ELISA method. This novel protein was found to induce pro-inflammatory cytokines and thus induce allergy by elevating total IgE level. The novel protein, Narcin isolated from Narcissus tazetta was found to exhibit allergenic properties. PMID:23936740

  13. Induced pluripotent stem cells: Challenges and opportunities for cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Patty eSachamitr

    2014-04-01

    Full Text Available Despite recent advances in cancer treatment over the past 30 years, therapeutic options remain limited and do not always offer a cure for malignancy. Given that tumour associated antigens (TAA are, by definition, self-proteins, the need to productively engage autoreactive T cells remains at the heart of strategies for cancer immunotherapy. These have traditionally focussed on the administration of autologous monocyte-derived dendritic cells (moDC pulsed with TAA, or the ex vivo expansion and adoptive transfer of tumour infiltrating lymphocytes (TIL as a source of TAA-specific cytotoxic T cells (CTL. Although such approaches have shown some efficacy, success has been limited by the poor capacity of moDC to cross-present exogenous TAA to the CD8+ T cell repertoire and the potential for exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer opportunities to generate patient-specific stem cell lines with the potential to differentiate in vitro into cell types whose properties may help address these issues. Here we review recent success in the differentiation of NK cells from human induced pluripotent stem (iPS cells as well as minor subsets of DC with therapeutic potential, including CD141+XCR1+ DC, capable of cross-presenting TAA to naïve CD8+ T cells. Furthermore, we review recent progress in the use of TIL as the starting material for the derivation of iPSC lines, thereby capturing their antigen specificity in a self-renewing stem cell line, from which potentially unlimited numbers of naïve TAA-specific T cells may be differentiated, free of the risks of exhaustion.

  14. Pectate lyase pollen allergens: sensitization profiles and cross-reactivity pattern.

    Directory of Open Access Journals (Sweden)

    Ulrike Pichler

    Full Text Available Pollen released by allergenic members of the botanically unrelated families of Asteraceae and Cupressaceae represent potent elicitors of respiratory allergies in regions where these plants are present. As main allergen sources the Asteraceae species ragweed and mugwort, as well as the Cupressaceae species, cypress, mountain cedar, and Japanese cedar have been identified. The major allergens of all species belong to the pectate lyase enzyme family. Thus, we thought to investigate cross-reactivity pattern as well as sensitization capacities of pectate lyase pollen allergens in cohorts from distinct geographic regions.The clinically relevant pectate lyase pollen allergens Amb a 1, Art v 6, Cup a 1, Jun a 1, and Cry j 1 were purified from aqueous pollen extracts, and patients' sensitization pattern of cohorts from Austria, Canada, Italy, and Japan were determined by IgE ELISA and cross-inhibition experiments. Moreover, we performed microarray experiments and established a mouse model of sensitization.In ELISA and ELISA inhibition experiments specific sensitization pattern were discovered for each geographic region, which reflected the natural allergen exposure of the patients. We found significant cross-reactivity within Asteraceae and Cupressaceae pectate lyase pollen allergens, which was however limited between the orders. Animal experiments showed that immunization with Asteraceae allergens mainly induced antibodies reactive within the order, the same was observed for the Cupressaceae allergens. Cross-reactivity between orders was minimal. Moreover, Amb a 1, Art v 6, and Cry j 1 showed in general higher immunogenicity.We could cluster pectate lyase allergens in four categories, Amb a 1, Art v 6, Cup a 1/Jun a 1, and Cry j 1, respectively, at which each category has the potential to sensitize predisposed individuals. The sensitization pattern of different cohorts correlated with pollen exposure, which should be considered for future allergy

  15. Aluminum sulfate significantly reduces the skin test response to common allergens in sensitized patients

    Directory of Open Access Journals (Sweden)

    Grier Thomas J

    2006-02-01

    Full Text Available Abstract Background Avoidance of allergens is still recommended as the first and best way to prevent allergic illnesses and their comorbid diseases. Despite a variety of attempts there has been very limited success in the area of environmental control of allergic disease. Our objective was to identify a non-invasive, non-pharmacological method to reduce indoor allergen loads in atopic persons' homes and public environments. We employed a novel in vivo approach to examine the possibility of using aluminum sulfate to control environmental allergens. Methods Fifty skin test reactive patients were simultaneously skin tested with conventional test materials and the actions of the protein/glycoprotein modifier, aluminum sulfate. Common allergens, dog, cat, dust mite, Alternaria, and cockroach were used in the study. Results Skin test reactivity was significantly reduced by the modifier aluminum sulfate. Our studies demonstrate that the effects of histamine were not affected by the presence of aluminum sulfate. In fact, skin test reactivity was reduced independent of whether aluminum sulfate was present in the allergen test material or removed prior to testing, indicating that the allergens had in some way been inactivated. Conclusion Aluminum sulfate was found to reduce the in vivo allergic reaction cascade induced by skin testing with common allergens. The exact mechanism is not clear but appears to involve the alteration of IgE-binding epitopes on the allergen. Our results indicate that it may be possible to diminish the allergenicity of an environment by application of the active agent aluminum sulfate, thus producing environmental control without complete removal of the allergen.

  16. Fish allergy and fish allergens

    DEFF Research Database (Denmark)

    Kuehn, A; Hilger, Christiane; Ollert, Markus

    2016-01-01

    Fish is one of the main elicitors for food allergies. For a long time, the clinical picture of fish allergy was reduced to the following features. First, fish-allergic patients suffer from a high IgE cross-reactivity among fishes so that they have to avoid all species. Second, clinically relevant...... review gives an overview on the clinical characteristics of fish allergy and the molecular properties of relevant fish allergens. The advancement of the IgE-based diagnosis using a panel of well-defined fish allergens from different species is in the focus of the discussion. © 2016 Dustri-Verlag Dr. Karl...

  17. Ipilimumab-Induced Enteritis without Colitis: A New Challenge

    Directory of Open Access Journals (Sweden)

    Marcus Messmer

    2016-11-01

    Full Text Available Introduction: Ipilimumab is an immune checkpoint inhibitor targeting cytotoxic T-lymphocyte associated antigen 4 (CTLA4, approved to treat metastatic melanoma. It was the first therapy shown to prolong survival in a large, randomized clinical trial. However, immune-related adverse events are common and can be severe. Enterocolitis is a common adverse event with ipilimumab, but enteritis without colitis has not been previously described. Case Report: An 83-year-old man presented to our hospital with grade 3 diarrhea for 5 days. One month prior, he had started treatment with ipilimumab for metastatic melanoma. On presentation, he was found to have severe electrolyte disturbances, including hyponatremia, hypokalemia, and acute kidney injury. Causes of infectious diarrhea were excluded, and he was treated with corticosteroids for presumed ipilimumab-associated enterocolitis. However, colonoscopy revealed normal mucosa, both grossly and on pathology of random biopsies. Steroids were weaned but his symptoms recurred. He then underwent upper endoscopy with enteroscopy. Biopsy of the duodenum was notable for acute inflammation, villous blunting, and other changes consistent with ipilimumab-associated injury. He was restarted on high-dose steroids and his symptoms resolved. Discussion: Ipilimumab-induced enteritis is a serious and potentially life-threatening immune related adverse event that warrants prompt recognition and aggressive management. As in cases of ipilimumab-associated enterocolitis, steroids are an effective therapy. Enteritis without colitis should be suspected in patients on ipilimumab who present with severe diarrhea but have a normal colonoscopy.

  18. Enzymatic hydrolysis: a method in alleviating legume allergenicity.

    Science.gov (United States)

    Kasera, Ramkrashan; Singh, A B; Lavasa, S; Prasad, Komarla Nagendra; Arora, Naveen

    2015-02-01

    Legumes are involved in IgE mediated food allergy in many countries. Avoidance of allergenic food is the only way to avoid symptomatic reaction. The present study investigated the effect of enzymatic hydrolysis on the allergenicity of three legumes - kidney bean (Phaseolus vulgaris), black gram (Vigna mungo) and peanut (Arachis hypogaea). Soluble protein extracts of the study legumes were sequentially treated by Alcalase(®) and Flavourzyme(®). Allergenicity of hydrolysates was then determined by ELISA, immunoblot, stripped basophil histamine release and skin prick test (SPT). Hydrolysis resulted in the loss of all IgE binding fractions determined by immunoblot in the three legumes. Specific IgE binding in ELISA was reduced by 62.2 ± 7.7%, 87.1 ± 9.6% and 91.8 ± 7.2% in the hydrolysates of kidney bean, black gram and peanut, respectively (p release of histamine was decreased significantly when sensitized basophils were challenged with hydrolysates as compared to raw extracts. Significant reduction in the biopotency of hydrolysates was also observed in SPT where only 1/10 kidney bean-sensitive individuals, 2/6 black gram-sensitive individuals and 1/7 peanut-sensitive individuals were found positive to their respective hydrolysates. In conclusion, enzymatic hydrolysis is effective in attenuating allergenicity of legume proteins and may be employed for preparing hypoallergenic food extracts.

  19. Dermatophagoides farinae allergens diversity identification by proteomics.

    Science.gov (United States)

    An, Su; Chen, Lingling; Long, Chengbo; Liu, Xiaoyu; Xu, Xuemei; Lu, Xingre; Rong, Mingqiang; Liu, Zhigang; Lai, Ren

    2013-07-01

    The most important indoor allergens for humans are house dust mites (HDM). Fourteen Dermatophagoides farinae allergens (Der f 1-3, 6, 7, 10, 11, 13-18, and 22) are reported although more than 30 allergens have been estimated in D. farinae. Seventeen allergens belonging to 12 different groups were identified by a procedure of proteomics combined with two-dimensional immunoblotting from D. farina extracts. Their sequences were determined by Edman degradation, mass spectrometry analysis, and cDNA cloning. Their allergenicities were assayed by enzyme-linked immunosorbent assay inhibition tests, immunoblots, basophil activation test, and skin prick tests. Eight of them are the first report as D. farinae allergens. The procedure of using a proteomic approach combined with a purely discovery approach using sera of patients with broad IgE reactivity profiles to mite allergens was an effective method to investigate a more complete repertoire of D. farinae allergens. The identification of eight new D. farinae allergens will be helpful for HDM allergy diagnosis and therapy, especially for patients without response for HDM major allergens. In addition, the current work significantly extendedthe repertoire of D. farinae allergens.

  20. The Allergen Bank: a source of extra contact allergens for the dermatologist in practice

    DEFF Research Database (Denmark)

    Andersen, Klaus Ejner; Rastogi, S C; Carlsen, L

    1996-01-01

    The Allergen Bank was established to give dermatologists easy access to special test materials in order to make early diagnoses of special cases of allergic contact dermatitis. The Allergen Bank comprises a computer system to register several hundred contact allergens in appropriate patch test...... concentrations available at the allergy laboratory and the patch test results. At the request of dermatologists in practice for Allergen Bank may supply special contact allergens for aimed patch testing of contact dermatitis patients. The organization of the Allergen Bank and the procedure of its use...... are described. During its first 23 months 28 dermatologists asked for 2,209 allergen samples for testing of 386 patients, an average of 6 allergens per patient and 14 patients per dermatologist. A total number of 164 positive reactions have been registered, and 440 of the 540 allergens have been in use. One...

  1. Studies on the Specific Degranulation of Mast Cell Sensitized by Several Allergens in vitro

    Institute of Scientific and Technical Information of China (English)

    Yongchao Guo; Zhenxing Li; Hong Lin; Haider Samee; Jamil Khalid

    2009-01-01

    Food allergy is a major health issue worldwide. Mast cells play a very important role in the immediate hypersensitivity for which mast cell degranulation needs to be studied extensively. In this study, an approach was taken to study the characteristics of sensitized mast cell degranulation in vitro, which associated with the study of mast cells and animal models. BALB/c mice were immunized respectively by several food allergens, then blood and peritoneal mast cells were collected at different time points. A dynamic determination was carried out between mast cells and serumal IgE. Comparative analysis on sequential time points showed that there was a close coincidence between mast cell degranulation and IgE antibody titers in sensitized BALB/c mice. Furthermore, it is interesting that sensitized mast cells could implement specific degranulation against the challenges in vitro, but the closely tropomyosins induced mast cell degranulation displayed cross reactions. This is very similar to IgE resisting the allergens in vivo. The study disclosed some characteristics on mast cells, coming from sensitized BALB/c mice, degranulation in vitro. Cellular & Molecular Immunology.

  2. Anthropogenic climate change and allergen exposure: The role of plant biology.

    Science.gov (United States)

    Ziska, Lewis H; Beggs, Paul J

    2012-01-01

    Accumulation of anthropogenic gases, particularly CO(2), is likely to have 2 fundamental effects on plant biology. The first is an indirect effect through Earth's increasing average surface temperatures, with subsequent effects on other aspects of climate, such as rainfall and extreme weather events. The second is a direct effect caused by CO(2)-induced stimulation of photosynthesis and plant growth. Both effects are likely to alter a number of fundamental aspects of plant biology and human health, including aerobiology and allergic diseases, respectively. This review highlights the current and projected effect of increasing CO(2) and climate change in the context of plants and allergen exposure, emphasizing direct effects on plant physiologic parameters (eg, pollen production) and indirect effects (eg, fungal sporulation) related to diverse biotic and abiotic interactions. Overall, the review assumes that future global mitigation efforts will be limited and suggests a number of key research areas that will assist in adapting to the ongoing challenges to public health associated with increased allergen exposure.

  3. [Soybean allergens and hypoallergenic germplasm enhancement].

    Science.gov (United States)

    Fang, Xu-Qian; Zhu, You-Lin; Qiu, Li-Juan

    2006-08-01

    Food allergy is a public sanitary problem which has received attention worldwide. It is becoming an increasingly interesting problem to decrease the concentration of allergens for improvement of the food security. Soybean allergens in seeds are composing of storage proteins, structure proteins, and disease-related proteins. Among them, Gly m Bd 28K, Gly m Bd 30K and Gly m Bd 60K are the major allergens located in 7S conglycinin fragments. By recognizing allergens' physicochemical property, hypersensitivity and gene structure, certain progresses had been made to reduce the concentration of allergens in soybean through food processing, traditional breeding and genetic engineering. The paper reviewed the sorts and characters of soybean allergens, the physicochemical property of the three immunodominant allergens and their gene structures. Progress in developing hypoallergenic cultivars was also discussed.

  4. New insights into ragweed pollen allergens.

    Science.gov (United States)

    Bordas-Le Floch, Véronique; Groeme, Rachel; Chabre, Henri; Baron-Bodo, Véronique; Nony, Emmanuel; Mascarell, Laurent; Moingeon, Philippe

    2015-11-01

    Pollen allergens from short ragweed (Ambrosia artemisiifolia) cause severe respiratory allergies in North America and Europe. To date, ten short ragweed pollen allergens belonging to eight protein families, including the recently discovered novel major allergen Amb a 11, have been recorded in the International Union of Immunological Societies (IUIS) allergen database. With evidence that other components may further contribute to short ragweed pollen allergenicity, a better understanding of the allergen repertoire is a requisite for the design of proper diagnostic tools and efficient immunotherapies. This review provides an update on both known as well as novel candidate allergens from short ragweed pollen, identified through a comprehensive characterization of the ragweed pollen transcriptome and proteome.

  5. Mutants of the major ryegrass pollen allergen, Lol p 5, with reduced IgE-binding capacity: candidates for grass pollen-specific immunotherapy.

    Science.gov (United States)

    Swoboda, Ines; De Weerd, Nicole; Bhalla, Prem L; Niederberger, Verena; Sperr, W R; Valent, Peter; Kahlert, Helga; Fiebig, Helmut; Verdino, Petra; Keller, Walter; Ebner, Christof; Spitzauer, Susanne; Valenta, Rudolf; Singh, Mohan B

    2002-01-01

    More than 400 million individuals are sensitized to grass pollen allergens. Group 5 allergens represent the most potent grass pollen allergens recognized by more than 80 % of grass pollen allergic patients. The aim of our study was to reduce the allergenic activity of group 5 allergens for specific immunotherapy of grass pollen allergy. Based on B- and T-cell epitope mapping studies and on sequence comparison of group 5 allergens from different grasses, point mutations were introduced by site-directed mutagenesis in highly conserved sequence domains of Lol p 5, the group 5 allergen from ryegrass. We obtained Lol p 5 mutants with low IgE-binding capacity and reduced allergenic activity as determined by basophil histamine release and by skin prick testing in allergic patients. Circular dichroism analysis showed that these mutants exhibited an overall structural fold similar to the recombinant Lol p 5 wild-type allergen. In addition, Lol p 5 mutants retained the ability to induce proliferation of group 5 allergen-specific T cell lines and clones. Our results demonstrate that a few point mutations in the Lol p 5 sequence yield mutants with reduced allergenic activity that represent potential vaccine candidates for immunotherapy of grass pollen allergy.

  6. The effect of simulated gastrointestinal digestion on shrimp Penaeus vannamei allergenicity

    Institute of Scientific and Technical Information of China (English)

    GUO Yongchao; LI Zhenxing; LIN Hong

    2009-01-01

    Pen a 1 is a major shrimp allergen that induces an allergy. The aim of this study is to assess the effect of simulated gastrointestinal fluids on the allergenicity of Pen a 1. Purified Pen a 1 from shrimp (Penaeus vannamei) was subjected to digestion in SGF (simulated gastric fluid) and SIF (simulated intestinal fluid) for a set time. The allergenicity of digestive Pen a 1 was analyzed by immunoblotting and Ci-ELISA, using pool sera from patients with shrimp specific IgE. The results showed that Pen a 1 exhibited a decrease in allergenicity with increasing digestion time in the SGF and SIF. However, Pen a l exhibited strong resistance to digestive fluids, and all yielded fragments (33 kD, 23 kD, and 14 kD) showed allergic activity. Therefore, anti-digestion may be an important factor for Pen a 1 to induce an allergy.

  7. Allergen immunotherapy for allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Dhami, Sangeeta; Nurmatov, Ulugbek; Roberts, Graham;

    2016-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT...

  8. Responsiveness of basophil granulocytes of horses suffering from chronic obstructive pulmonary disease to various allergens.

    Science.gov (United States)

    Dirscherl, P; Grabner, A; Buschmann, H

    1993-10-01

    As basophils are the major effector cells of allergic reactions, confirmation of the allergic etiology of chronic obstructive pulmonary disease (COPD) was sought by the demonstration of a specific in vitro response of equine basophilic blood cells to some potential allergens (Aspergillus, Cladosporidium, Mucor, Penicillium, extracts of dust particles of hay and straw). The allergen induced degranulation of basophils and the histamine and protease release from basophils during incubation with the allergens were tested. By evaluating the results obtained from 14 COPD horses and eight controls it could be shown that the sensitivity of the basophils of affected horses was increased, particularly against the allergen extract of Mucor mucedo and Mucor spinosus. Further a greater percentage of COPD horses reacted positively with the Mucor allergen extract. The mitogenic stimulation of lymphocytes by PHA and by the allergen extracts used gave comparable results in affected and control horses. Thus the in vitro stimulation of basophils may be an easily to perform testing device for the identification of potential allergens involved in the pathogenesis of equine COPD.

  9. [Immunoproteomics of non water-soluble allergens from 4 legumes flours: peanut, soybean, sesame and lentil].

    Science.gov (United States)

    Bouakkadia, Hayette; Boutebba, Aissa; Haddad, Iman; Vinh, Joëlle; Guilloux, Laurence; Sutra, Jean-Pierre; Sénéchal, Hélène; Poncet, Pascal

    2015-01-01

    Peanut, soybean, sesame and lentil are members of legumes worldwide consumed by human that can induce food allergy in genetically predisposed individuals. Several protein allergens, mainly water-soluble, have been described. We studied the non water-soluble fraction from these 4 food sources using immunoproteomics tools and techniques. Flour extracts were solubilized in detergent and chaotropes and analysed in 1 and 2 dimensional gel electrophoresis (2D). Results showed numerous proteins exhibiting wide ranges of isoelectric points and relative molecular masses. When IgE immunoreactivities of 18 food allergy patients were individually tested in 1 and 2D western-blots, a very diversified IgE repertoire was observed, reflecting extensive cross-reactivities but also co-sensitizations. Besides already well known and characterized allergens, mass spectrometry analysis allowed the identification of 22 allergens undescribed until now: 10 in peanut, 2 in soybean, 3 in sesame and 7 in lentil. Three allergens are legume storage proteins and the others belong to transport proteins, nucleotide binding proteins and proteins involved in the regulation of metabolism. Seven proteins are potentially similar to allergens described in plants and fungi and 11 are not related to any known allergen. Our results contribute to increase the repertoire of legume allergens that may improve the diagnosis, categorize patients and thus provide a better treatment of patients.

  10. Evaluating the in vivo Th2 priming potential among common allergens.

    Science.gov (United States)

    Camberis, Mali; Prout, Melanie; Tang, Shiau-Choot; Forbes-Blom, Elizabeth; Robinson, Marcus; Kyle, Ryan; Belkaid, Yasmine; Paul, William; Le Gros, Graham

    2013-08-30

    Exposure to allergens, both man-made and from our environment is increasingly associated with the development of significant human health issues such as allergy and asthma. Allergen induced production of the cytokine interleukin (IL-)4 by Th2 cells is central to the pathogenesis of allergic disease (Gavett et al., 1994). The development of the G4 mouse, that expresses green fluorescent protein (GFP) as a surrogate for IL-4 protein expression has made it possible to directly track the immune cells that produce IL-4. By combining a reliable intradermal immunisation technique with the transgenic G4 mouse we have been able to develop a novel & unique in vivo primary Th2 immune response model (PTh2). When allergens relevant to human disease are evaluated using the PTh2 assay a dose dependent hierarchy of allergenicity is revealed with environmental allergens (cockroach, house dust mite) the most potent and food allergens being the least. In addition, the PTh2 assay is extremely sensitive to the immunoregulatory effects of Mycobacterial extracts and immunosuppressive drugs on primary Th2 cell development. Taken together, this assay provides a standardised method for the identification of the structural and functional properties of proteins relevant to allergenicity, and is a powerful screening tool for novel lead compounds that are effective at inhibiting the primary Th2 response in allergic diseases.

  11. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients

    DEFF Research Database (Denmark)

    Howarth, P; Malling, Hans-Jørgen; Molimard, M;

    2011-01-01

    To cite this article: Howarth P, Malling H-J, Molimard M, Devillier P. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients. Allergy 2012; 67: 321-327. ABSTRACT: Background:  The assessment of allergen immunotherapy (AIT) efficacy...... in the treatment for seasonal allergic rhinoconjunctivitis (SAR) symptoms is challenging. Allergen immunotherapy differs from symptomatic therapy in that while symptomatic therapy treats patients after symptoms appear and aims to reduce symptoms, AIT is administered before symptoms are present and aims to prevent...... them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective...

  12. Mechanisms of Allergen-Specific Immunotherapy and Novel Ways for Vaccine Development

    Directory of Open Access Journals (Sweden)

    Marek Jutel

    2013-01-01

    Full Text Available Allergen-specific immunotherapy (SIT is the only available curative treatment of allergic diseases. Recent evidence provided a plausible explanation to its multiple mechanisms inducing both rapid desensitization and long-term allergen-specific immune tolerance, and suppression of allergic inflammation in the affected tissues. During SIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T cells, which suppress proliferative and cytokine responses against the allergen of interest. Regulatory T cells are characterized by IL-10 and TGF-beta secretion and expression of important cell surface suppressive molecules such as cytotoxic T lymphocyte antigen-4 and programmed death-1 that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Regulatory T cells and particularly IL-10 also have an influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies. In addition, development of allergen-specific B regulatory cells that produce IL-10 and develop into IgG4 producing plasma cells represent essential players in peripheral tolerance. These findings together with the new biotechnological approaches create a platform for development of the advanced vaccines. Moreover, reliable biomarkers could be selected and validated with the intention to select the patients who will benefit most from this immune-modifying treatment. Thus, allergen-SIT could provide a complete cure for a larger number of allergic patients and novel preventive approaches need to be elaborated.

  13. Mapping of Lol p I allergenic epitopes by using murine monoclonal antibodies.

    Science.gov (United States)

    Mourad, W; Bernier, D; Jobin, M; Hébert, J

    1989-11-01

    Murine monoclonal antibodies (MAbs) against three non-overlapping epitopes of Lol p I allergen were previously produced and subsequently used for purification of the allergen. In the present study, these MAbs were further characterized, and the biological activity of the purified allergen assessed. The three MAbs were of the IgG isotype and carried a kappa light chain. Their affinity constants were in the range of 7.4-15.1 x 10(-9) mol/l. Purified Lol p I kept its biological activity, as shown by its ability to induce histamine release by basophils of Lol p I-sensitive patients. The profiles of histamine release induced by either Lol p I or crude Lolium perenne extracts were comparable. This observation suggests that human IgE bound to basophils are polyspecific which has been confirmed by immunoblot and inhibition assay. Our data indicated also that Lol p I possesses a major allergenic epitope recognized by all human serum IgE tested. This epitope seems to be partially shared by those recognized by the three MAbs. Finally, preincubation of Lol p I with either one of the Mabs did not affect significantly the basophil-histamine release induced by the purified allergen. This suggests that Lol p I possesses allergenic sites other than the one shared by MAbs and IgE Abs.

  14. Food Allergens: Is There a Correlation between Stability to Digestion and Allergenicity?

    Science.gov (United States)

    Bøgh, Katrine Lindholm; Madsen, Charlotte Bernhard

    2016-07-03

    Food allergy is a major health problem in the Western countries, affecting 3-8% of the population. It has not yet been established what makes a dietary protein a food allergen. Several characteristics have been proposed to be shared by food allergens. One of these is resistance to digestion. This paper reviews data from digestibility studies on purified food allergens and evaluates the predictive value of digestibility tests on the allergenic potential. We point out that food allergens do not necessarily resist digestion. We discuss how the choice of in vitro digestibility assay condition and the method used for detection of residual intact protein as well as fragments hereof may greatly influence the outcome as well as the interpretation of results. The finding that digests from food allergens may retain allergenicity, stresses the importance of using immunological assays for evaluating the allergenic potential of food allergen digestion products. Studies assessing the allergenicity of digestion products, by either IgE-binding, elicitation or sensitizing capacity, shows that digestion may abolish, decrease, have no effect, or even increase the allergenicity of food allergens. Therefore, the predictive value of the pepsin resistance test for assessing the allergenic potential of novel proteins can be questioned.

  15. Maillard reaction and enzymatic browning affect the allergenicity of Pru av 1, the major allergen from cherry (Prunus avium).

    Science.gov (United States)

    Gruber, Patrick; Vieths, Stefan; Wangorsch, Andrea; Nerkamp, Jörg; Hofmann, Thomas

    2004-06-16

    The influence of thermal processing and nonenymatic as well as polyphenoloxidase-catalyzed browning reaction on the allergenicity of the major cherry allergen Pru av 1 was investigated. After thermal treatment of the recombinant protein rPru av 1 in the absence or presence of carbohydrates, SDS-PAGE, enzyme allergosorbent tests, and inhibition assays revealed that thermal treatment of rPru av 1 alone did not show any influence on the IgE-binding activity of the protein at least for 30 min, thus correlating well with the refolding of the allergen in buffer solution as demonstrated by CD spectroscopic experiments. Incubation of the protein with starch and maltose also showed no effect on IgE-binding activity, whereas reaction with glucose and ribose and, even more pronounced, with the carbohydrate breakdown products glyceraldehyde and glyoxal induced a strong decrease of the IgE-binding capacity of rPru av 1. In the second part of the study, the effect of polyphenoloxidase-catalyzed oxidation of polyphenols on food allergen activity was investigated. Incubation of rPru av 1 with epicatechin in the presence of tyrosinase led to a drastic decrease in IgE-binding activity of the protein. Variations of the phenolic compound revealed caffeic acid and epicatechin as the most active inhibitors of the IgE-binding activity of rPru av 1, followed by catechin and gallic acid, and, finally, by quercetin and rutin, showing significantly lower activity. On the basis of these data, reactive intermediates formed during thermal carbohydrate degradation as well as during enzymatic polyphenol oxidation are suggested as the active chemical species responsible for modifying nucleophilic amino acid side chains of proteins, thus inducing an irreversible change in the tertiary structure of the protein and resulting in a loss of conformational epitopes of the allergen.

  16. Aspergillus fumigatus allergen expression is coordinately regulated in response to hydrogen peroxide and cyclic AMP

    Directory of Open Access Journals (Sweden)

    Bowyer Paul

    2010-11-01

    Full Text Available Abstract Background A. fumigatus has been associated with a wide spectrum of allergic disorders such as ABPA or SAFS. It is poorly understood what allergens in particular are being expressed during fungal invasion and which are responsible for stimulation of immune responses. Study of the dynamics of allergen production by fungi may lead to insights into how allergens are presented to the immune system. Methods Expression of 17 A. fumigatus allergen genes was examined in response to various culture conditions and stimuli as well as in the presence of macrophages in order to mimic conditions encountered in the lung. Results Expression of 14/17 allergen genes was strongly induced by oxidative stress caused by hydrogen peroxide (Asp f 1, -2, -4, -5, -6, -7, -8, -10, -13, -17 and -18, all >10-fold and Asp f 11, -12, and -22, 5-10-fold and 16/17 allergen genes were repressed in the presence of cAMP. The 4 protease allergen genes (Asp f -5, -10, -13 and -18 were expressed at very low levels compared to the comparator (β-tubulin under all other conditions examined. Mild heat shock, anoxia, lipid and presence of macrophages did not result in coordinated changes in allergen gene expression. Growth on lipid as sole carbon source contributed to the moderate induction of most of the allergen genes. Heat shock (37°C > 42°C caused moderate repression in 11/17 genes (Asp f 1, -2, -4, -5, -6, -9, -10, -13, -17, -18 and -23 (2- to 9-fold, which was mostly evident for Asp f 1 and -9 (~9-fold. Anaerobic stress led to moderate induction of 13/17 genes (1.1 to 4-fold with one, Asp f 8 induced over 10-fold when grown under mineral oil. Complex changes were seen in gene expression during co-culture of A. fumigatus with macrophages. Conclusions Remarkable coordination of allergen gene expression in response to a specific condition (oxidative stress or the presence of cAMP has been observed, implying that a single biological stimulus may play a role in allergen gene

  17. High environmental ozone levels lead to enhanced allergenicity of birch pollen.

    Directory of Open Access Journals (Sweden)

    Isabelle Beck

    Full Text Available BACKGROUND: Evidence is compelling for a positive correlation between climate change, urbanisation and prevalence of allergic sensitisation and diseases. The reason for this association is not clear to date. Some data point to a pro-allergenic effect of anthropogenic factors on susceptible individuals. OBJECTIVES: To evaluate the impact of urbanisation and climate change on pollen allergenicity. METHODS: Catkins were sampled from birch trees from different sites across the greater area of Munich, pollen were isolated and an urbanisation index, NO2 and ozone exposure were determined. To estimate pollen allergenicity, allergen content and pollen-associated lipid mediators were measured in aqueous pollen extracts. Immune stimulatory and modulatory capacity of pollen was assessed by neutrophil migration assays and the potential of pollen to inhibit dendritic cell interleukin-12 response. In vivo allergenicity was assessed by skin prick tests. RESULTS: The study revealed ozone as a prominent environmental factor influencing the allergenicity of birch pollen. Enhanced allergenicity, as assessed in skin prick tests, was mirrored by enhanced allergen content. Beyond that, ozone induced changes in lipid composition and chemotactic and immune modulatory potential of the pollen. Higher ozone-exposed pollen was characterised by less immune modulatory but higher immune stimulatory potential. CONCLUSION: It is likely that future climate change along with increasing urbanisation will lead to rising ozone concentrations in the next decades. Our study indicates that ozone is a crucial factor leading to clinically relevant enhanced allergenicity of birch pollen. Thus, with increasing temperatures and increasing ozone levels, also symptoms of pollen allergic patients may increase further.

  18. Recombinant proteins from Gallibacterium anatis induces partial protection against heterologous challenge in egg-laying hens

    DEFF Research Database (Denmark)

    Pors, Susanne Elisabeth; Skjerning, Ragnhild Bager; Flachs, Esben M.

    2016-01-01

    after challenge. All birds were euthanized and subjected to a post mortem procedure including scoring of lesions and sampling for bacterial growth. Moreover, ELISA assays were used to quantify antigen-specific IgG titers in serum. The results showed that all three proteins induced protection against...

  19. Induced mutations in yeast cell populations adapting to an unforeseen challenge.

    Science.gov (United States)

    Moore, Lindsay S; Wei, Wu; Stolovicki, Elad; Benbenishty, Tamar; Wilkening, Stefan; Steinmetz, Lars M; Braun, Erez; David, Lior

    2014-01-01

    The modern evolutionary synthesis assumes that mutations occur at random, independently of the environment in which they confer an advantage. However, there are indications that cells facing challenging conditions can adapt rapidly, utilizing processes beyond selection of pre-existing genetic variation. Here, we show that a strong regulatory challenge can induce mutations in many independent yeast cells, in the absence of general mutagenesis. Whole genome sequencing of cell lineages reveals a repertoire of independent mutations within a single lineage that arose only after the cells were exposed to the challenging environment, while other cells in the same lineage adapted without any mutation in their genomes. Thus, our experiments uncovered multiple alternative routes for heritable adaptation that were all induced in the same lineage during a short time period. Our results demonstrate the existence of adaptation mechanisms beyond random mutation, suggesting a tight connection between physiological and genetic processes.

  20. Allergenicity and allergens of amphipods found in nori (dried laver).

    Science.gov (United States)

    Motoyama, Kanna; Hamada, Yuki; Nagashima, Yuji; Shiomi, Kazuo

    2007-09-01

    Gammaridean and caprellid amphipods, crustaceans of the order Amphipoda, inhabit laver culture platforms and, hence, are occasionally found in nori (dried laver) sheets. Amphipods mixed in nori may cause allergic reactions in sensitized patients, as is the case with other crustaceans, such as shrimp and crab, members of the order Decapoda. In this study, dried samples of amphipods (unidentified) found in nori and fresh samples of gammaridean amphipod (Gammarus sp., not accurately identified) and caprellid amphipod (Caprella equilibra) were examined for allergenicity and allergens using two species of decapods (black tiger prawn and spiny lobster) as references. When analyzed by ELISA, sera from crustacean-allergic patients reacted to extracts from amphipod samples, although less potently than to the extracts from decapods. In IgE-immunoblotting, a 37-kDa protein was found to be the major allergen in amphipods. Based on the molecular mass and the cross-reactivity with decapod tropomyosin evidenced by inhibition ELISA and inhibition immunoblotting, the 37-kDa protein was identified as amphipod tropomyosin.

  1. Sensitising capacity of peptides from food allergens

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm

    , MALDI-TOF mass spectrometry, amino acid analysis and GPC. To study the sensitising capacity groups of BN rats were immunised with the intact allergen or digestion products hereof by i.p. immunisation and specific antibody responses were examined by ELISAs, RBL-assay or avidity measurements. Comparison...... of peptide fragments of up to Mr 2,000, yet both the peptide fragments in the gastric as well as in the gastro-duodenal digests were aggregated to complexes of larger sizes. After separation of the digested Ara h 1 into fractions the sensitising capacity was lost, though the IgE-binding capacity was retained...... found for both the intact as well as the digested Ara h 1. Digested BLG with peptide sizes of up to Mr 4,500 could on the other hand not induce any sensitisation response in the BN rats. They were instead suggested to possess tolerogenic capacity when co-administered together with intact BLG...

  2. Protein contact dermatitis: allergens, pathogenesis, and management.

    Science.gov (United States)

    Levin, Cheryl; Warshaw, Erin

    2008-01-01

    Protein contact dermatitis is an allergic skin reaction induced principally by proteins of either animal or plant origin. The clinical presentation is that of a chronic dermatitis, and it is often difficult to differentiate between allergic contact dermatitis and other eczematous dermatoses. One distinguishing clinical feature is that acute flares of pruritus, urticaria, edema, or vesiculation are noted minutes after contact with the causative substances. Additionally, the patch-test result is typically negative, and the scratch- or prick-test result is positive. The pathogenesis of protein contact dermatitis is unclear but may involve a type I (immunoglobulin E [IgE], immediate) hypersensitivity reaction, type IV (cell-mediated delayed) hypersensitivity reaction, and/or a delayed reaction due to IgE-bearing Langerhans' cells. Management involves avoidance of the allergen.

  3. Sensitising capacity of peptides from food allergens

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm

    to be a general characteristic of food allergens is resistance to digestion. This is based on studies showing that allergenic dietary proteins in general are more resistant to digestion than dietary proteins with no proven allergenicity, concluding that a correlation between stability to digestion and allergenic......, MALDI-TOF mass spectrometry, amino acid analysis and GPC. To study the sensitising capacity groups of BN rats were immunised with the intact allergen or digestion products hereof by i.p. immunisation and specific antibody responses were examined by ELISAs, RBL-assay or avidity measurements. Comparison...... of aggregates is suggested by the epitope mapping study, where survival of conformational epitopes is demonstrated. This together with the findings, that fractionation of digestion products leads to a loss of the sensitising potential, reveals that the allergenicity had to be more than simply a result...

  4. Cross-reactivity between aeroallergens and food allergens

    Science.gov (United States)

    Popescu, Florin-Dan

    2015-01-01

    In patients with respiratory allergy, cross-reactivity between aeroallergens and foods may induce food allergy, symptoms ranging from oral allergy syndrome to severe anaphylaxis. Clinical entities due to IgE sensitization to cross-reactive aeroallergen and food allergen components are described for many sources of plant origin (pollen-food syndromes and associations, such as birch-apple, cypress-peach and celery-mugwort-spice syndromes, and mugwort-peach, mugwort-chamomile, mugwort-mustard, ragweed-melon-banana, goosefoot-melon associations), fungal origin (Alternaria-spinach syndrome), and invertebrate, mammalian or avian origin (mite-shrimp, cat-pork, and bird-egg syndromes). Clinical cases of allergic reactions to ingestion of food products containing pollen grains of specific plants, in patients with respiratory allergy to Asteraceae pollen, especially mugwort and ragweed, are also mentioned, for honey, royal jelly and bee polen dietary supplements, along with allergic reactions to foods contaminated with mites or fungi in patients with respiratory allergy to these aeroallergens. Medical history and diagnosis approach may be guided by the knowledge about the diverse cross-reacting allergens involved, and by the understanding of these clinical entities which may vary significantly or may be overlapping. The association between primary IgE sensitization with respiratory symptoms to inhaled allergens and food allergy due to cross-reactive allergen components is important to assess in allergy practice. The use of molecular-based diagnosis improves the understanding of clinically relevant IgE sensitization to cross-reactive allergen components from aeroallergen sources and foods. PMID:26140270

  5. Biochemical and molecular biological aspects of silverfish allergens.

    Science.gov (United States)

    Barletta, Bianca; Di Felice, Gabriella; Pini, Carlo

    2007-01-01

    Insects and insect-derived materials have been implicated as a risk factor for sensitization and subsequent elicitation of allergic rhinitis and allergic bronchial asthma. During the last decades, insects other than those known as allergenic, were investigated for their potential role in inducing and triggering an IgE immune response. Among these, the silverfish, an insect belonging to the Thysanura order, appeared to be of particular interest. Silverfish (Lepisma saccharina) is the most primitive living insect, and represents a descendent of the ancestral wingless insects. They are 3-12 mm long, have three tail feelers and are covered with shiny scales. They shun light and need a humid environment and their diet consists of carbohydrate materials such as paper and book-binding glue, crumbs of bread and flour. Because of these features, silverfish finds an optimal habitat both in dwellings and workplaces and in spite of its antiquity, silverfish has succeeded in exploiting the new opportunity created by man. Although its importance significantly increased when it has been demonstrated that house dust contains significant silverfish levels even in houses where the inhabitants were unaware of its presence, no silverfish extract for diagnosis of allergic diseases is commercially available yet. Identification of optimal extraction conditions and characterization of allergenic extracts are the first steps to obtain an effective allergen preparation suitable for diagnosis and therapy, and will be useful as a reference preparation for assessing silverfish exposure in different indoor environments. It has been cloned and characterized a silverfish tropomyosin, named Lep s 1, which represents the first allergen identified in silverfish extract and can be regarded as a molecule cross-reactive among inhalant and edible invertebrates allergenic sources. rLep s 1 displayed biological activity, suggesting that it could be regarded as a useful tool to study the role of silverfish

  6. Characterization of Allergen Exposure in Homes

    Science.gov (United States)

    1991-01-17

    dust mixture.6 Dust mite allergens have been associated causatively with asthma, atopic dermatitis , and rhini- tis. 7 Studies from several countries...Asthma: A Controlled Trial. The Lancet 1976; ***:333-335. 10. Tuft L. Importance of Inhalant Allergens in Atopic Dermatitis . The Journal of Investigative...Monoclonal Antibodies to the Major Feline Allergen Fel d 1. 1I. Single Step Affinity Purification of Fel d 1, N-Terminal Sequence Analysis, and Development of

  7. Legumin allergens from peanuts and soybeans: Effects of denaturation and aggregation on allergenicity

    NARCIS (Netherlands)

    Boxtel, E.L. van; Broek, L.A.M. van den; Koppelman, S.J.; Gruppen, H.

    2008-01-01

    Legumin proteins Ara h 3 from peanuts and glycinin from soybeans are increasingly described as important allergens. The stability of an allergen's IgE binding capacity towards heating and digestion is considered an important characteristic for food allergens. We investigated the effects of heating a

  8. Legumin allergens from peanuts and soybeans : Effects of denaturation and aggregation on allergenicity

    NARCIS (Netherlands)

    Boxtel, van E.L.; Broek, van den L.A.M.; Koppelman, S.J.; Gruppen, H.

    2008-01-01

    Legumin proteins Ara h 3 from peanuts and glycinin from soybeans are increasingly described as important allergens. The stability of an allergen's IgE binding capacity towards heating and digestion is considered an important characteristic for food allergens. We investigated the effects of heating a

  9. Peanut Allergens Attached With p-Aminobenzamidine Are More Resistant to Digestion than Native Allergens

    Science.gov (United States)

    Undigested foods are excreted rather than absorbed and therefore, peanut allergens, if undigested, may not cause an allergic reaction in peanut-allergic individuals. Our objective was to make peanut allergens more resistant to digestion by preparing allergen conjugates and demonstrating that the con...

  10. Effective Allergen Management : Precautionary (may contain) allergen labeling; when to apply?

    NARCIS (Netherlands)

    Zandvoort. M.M.J. van

    2013-01-01

    When do you label food products as having been possibly cross contaminated by allergens? TNO can help you to develop a quantitative risk management guidance for food allergens, based on a unique method that quantifies the risk of food allergen traces in products and validated data on thresholds. Thi

  11. Variability of Corylus avellana, L. CorA and profilin pollen allergens expression.

    Science.gov (United States)

    Ražná, Katarína; Bežo, Milan; Nikolaieva, Natalia; Garkava, Katerina; Brindza, Ján; Ziarovská, Jana

    2014-01-01

    Corylus avellana is the source of inhalant allergies induced by hazel pollen as well as food allergies induced after ingestion of hazelnuts. In this study, real-time PCR approach was used to analyse expression of hazel pollen allergens on the molecular level. Relative quantity of hazelnut allergens Corylus avellana, L. CorA and Corylus avellana, L. pollen profiling in samples from different Ukraine areas were determining and comparing. Differences among the levels of both analysed allergen transcripts were found for hazel CorA and profillin. In both cases, the expression within the urbanized growth conditions was higher when compared to the sample from village area. The average expression for CorA was 0.84 times higher than for profilin and the results are very variable depending on the place of growth. Expression levels here were within the range of 2.957 up to the 52.936. Profilin expression was the highest in the sample from the polluted place of growth-cement plant area with the value of 52 times higher when compared to the sample from the village area. In this study, comparison of expression levels of hazel CorA and profiling pollen allergens was performed for the first time. Real-time PCR assay developed in this study proved the sensitivity for detection of the changes of the hazel pollen allergens expression levels and could benefit labs by fast and reproducible detection method of these allergens.

  12. Indoor allergens: identification and quantification

    Energy Technology Data Exchange (ETDEWEB)

    Reed, C.E.; Swanson, M.C.

    1986-01-01

    A large number of allergens occur in the air of the home and many work sites. Almost any organic dust or volatile chemical reactive with proteins can cause allergic respiratory disease: allergic rhinitis, asthma, and hypersensitivity pneumonitis (extrinsic allergic alveolitis). If the exposure continues several years after the disease begins there may be permanent disability, so recognition and control of exposure are important. Techniques now exist to sample the particulate antigens suspended in the air and assay them by sensitive immunochemical methods.

  13. Recombinant expression systems for allergen vaccines.

    Science.gov (United States)

    Singh, Mohan B; Bhalla, Prem L

    2006-01-01

    Allergen immunotherapy of future is likely to be based on allergy vaccines that contain engineered allergens modified to abolish or substantially reduce their IgE-binding activity in order to remove the risk of unwanted anaphylactic responses. The development of efficient systems for the production of recombinant allergens in sufficient quantities is requirement for establishing use of engineered allergens as components of allergy vaccines. This review outlines relative advantages and disadvantages of various heterologous systems for production of recombinant allergens. Microbial systems are most convenient and cost effective platforms for the production of recombinant allergens. However, lack of post-translational processing implies that some allergens have to be expressed in eukaryotic systems for proper folding and post-translational modifications such as glycosylation. Yeast systems can yield high levels of recombinant allergens but often are associated with hyper- glycosylation problems. Mammalian cell culture systems offer suitable post -translational modifications but are nearly hundred fold more expensive than microbial systems. The use of plants as bio-factories for production of recombinant allergens is emerging as a very attractive option as plants-based production system offer several advantages over other expression systems such as post translational processing of proteins, low production costs, scale up ability and enhanced safety due to absence of animal or human pathogens.

  14. Protective effect of the DNA vaccine encoding the major house dust mite allergens on allergic inflammation in the murine model of house dust mite allergy

    Directory of Open Access Journals (Sweden)

    Lee Jaechun

    2006-02-01

    Full Text Available Abstract Background Vaccination with naked DNA encoding antigen induces cellular and humoral immunity characterized by the activation of specific Th1 cells. Objective To evaluate the effects of vaccination with mixed naked DNA plasmids encoding Der p 1, Der p 2, Der p 3, Der f 1, Der f 2, and Der f 3, the major house dust mite allergens on the allergic inflammation to the whole house dust mites (HDM crude extract. Methods Three hundred micrograms of these gene mixtures were injected into muscle of BALB/c mice. Control mice were injected with the pcDNA 3.1 blank vector. After 3 weeks, the mice were actively sensitized and inhaled with the whole house dust mite extract intranasally. Results The vaccinated mice showed a significantly decreased synthesis of total and HDM-specific IgE compared with controls. Analysis of the cytokine profile of lymphocytes after challenge with HDM crude extract revealed that mRNA expression of interferon-γ was higher in the vaccinated mice than in the controls. Reduced infiltration of inflammatory cells and the prominent infiltration of CD8+ T cells were observed in histology of lung tissue from the vaccinated mice. Conclusion Vaccination with DNA encoding the major house dust mite allergens provides a promising approach for treating allergic responses to whole house dust mite allergens.

  15. Electrochemical Affinity Biosensors Based on Disposable Screen-Printed Electrodes for Detection of Food Allergens.

    Science.gov (United States)

    Vasilescu, Alina; Nunes, Gilvanda; Hayat, Akhtar; Latif, Usman; Marty, Jean-Louis

    2016-11-05

    Food allergens are proteins from nuts and tree nuts, fish, shellfish, wheat, soy, eggs or milk which trigger severe adverse reactions in the human body, involving IgE-type antibodies. Sensitive detection of allergens in a large variety of food matrices has become increasingly important considering the emergence of functional foods and new food manufacturing technologies. For example, proteins such as casein from milk or lysozyme and ovalbumin from eggs are sometimes used as fining agents in the wine industry. Nonetheless, allergen detection in processed foods is a challenging endeavor, as allergen proteins are degraded during food processing steps involving heating or fermentation. Detection of food allergens was primarily achieved via Enzyme-Linked Immuno Assay (ELISA) or by chromatographic methods. With the advent of biosensors, electrochemical affinity-based biosensors such as those incorporating antibodies and aptamers as biorecognition elements were also reported in the literature. In this review paper, we highlight the success achieved in the design of electrochemical affinity biosensors based on disposable screen-printed electrodes towards detection of protein allergens. We will discuss the analytical figures of merit for various disposable screen-printed affinity sensors in relation to methodologies employed for immobilization of bioreceptors on transducer surface.

  16. In vivo allergenic activities of eleven purified members of a major allergen family from wheat and barley flour.

    Science.gov (United States)

    Armentia, A; Sanchez-Monge, R; Gomez, L; Barber, D; Salcedo, G

    1993-05-01

    Eleven purified members of the alpha-amylase/trypsin inhibitor family from wheat and barley that showed very different IgE-binding capacities when previously assayed in vitro, were used in double blind in vivo diagnostic tests to further evaluate their allergenic activity. These tests were carried out in 31 patients who showed allergic sensitization to wheat flour as verified by skin test, RAST and challenge test. The three members of the protein family with highest IgE binding in vitro (the glycosylated subunits of tetrameric alpha-amylase inhibitors CM16* from wheat and CMb* from barley, and the barley monomeric inhibitor BMAI-1) were found to be the strongest allergens as indicated by skin sensitivity in prick tests.

  17. Carbohydrates as food allergens

    OpenAIRE

    SOH, Jian Yi; Huang, Chiung Hui; Lee, Bee Wah

    2015-01-01

    The literature supports the notion that carbohydrate epitopes, on their own, do not contribute significantly to the induction of allergic reactions. They bind weakly to IgE antibodies and have been termed as cross reactive carbohydrate determinants. These epitopes cause confusion in in vitro IgE testing through nonspecific cross-reactivity. Coincident with the rising trends in food allergy prevalence, there has recently been reports of anaphylaxis induced by carbohydrate epitopes. There are t...

  18. Characterization of apple 18 and 31 kd allergens by microsequencing and evaluation of their content during storage and ripening.

    Science.gov (United States)

    Hsieh, L S; Moos, M; Lin, Y

    1995-12-01

    Patients with tree pollinosis frequently report allergic reactions after ingestion of apples. The severity of apple allergy has been related to the variety of apples and their degree of maturity. To generate a serum pool that is representative of various IgE-binding patterns of apple-allergic sera, serum samples from 34 patients allergic to tree pollens were screened. Only 24 serum samples reacted to the apple extract. Pooled serum was used to identify allergens in apples. An efficient and consistent extraction method for apple fruits was used to compare the immunoreactivities of extracts of different varieties (McIntosh, Red Delicious, Granny Smith, and Golden Delicious) of freshly picked and store-purchased apples. We found that Golden Delicious apples had the greatest amount of the 18 kd allergen, which has been reported to be a potent IgE-binding apple allergen. Store-purchased apples contained higher concentrations of the 18 kd allergen than freshly picked apples. In our study only 37.5% of sera reacted to the 18 kd protein, whereas 75% of the sera reacted to a 31 kd allergen. Other immunoreactive bands in apple extracts included proteins of 50, 38, 16, 14, and 13 kd. The amino-terminal amino acid sequences of the two major allergens, 18 kd and 31 kd, were determined. These sequences shared approximately 50% identity with disease resistance proteins of various plants or Bet v 1 in birch tree pollens. The appearance of various allergens was also investigated in mature apples during storage. The amount of 18 kd allergen increased significantly when apples were stored at 4 degrees C. However, under controlled atmospheric conditions in which oxygen- and carbon dioxide-induced ripening were regulated, the amount of 18 kd allergen remained unaffected. Because ripening and maturation were not associated with increases in 18 kd allergen content, the observed changes might be induced by factors related to disease resistance.

  19. Influence of Ultrasonic Treatment on the Allergenic Properties of Shrimp (Penaeus vannamei ) Allergen

    Institute of Scientific and Technical Information of China (English)

    LI Zhenxing; LIN Hong; CAO Limin

    2006-01-01

    The present study was undertaken to determine whether high intensity ultrasound could reduce the allergic properties of shrimp allergens. Reducing the allergenic properties of these allergens will be beneficial to allergic individuals. Samples of shrimp protein extract and shrimp muscle were treated by high-intensity ultrasound with water bathing at 0 ℃ or 50 ℃for different time periods. The treated and untreated samples were then analyzed by SDS-PAGE, Western blots and competitive inhibition ELISA (Ci-ELISA) to determine the shrimp allergenicity. The results show that high-intensity ultrasound has no effect on allergenicity when the extracts were treated at 0 ℃. However, a significant decrease was observed in the level of the major shrimp allergen, Pen a 1, when the samples were treated at 50 ℃. In the determination of allergenicity with CiELISA, a reduction in IgE binding was also observed.

  20. Central Diabetes Insipidus and Cisplatin-Induced Renal Salt Wasting Syndrome: A Challenging Combination.

    Science.gov (United States)

    Cortina, Gerard; Hansford, Jordan R; Duke, Trevor

    2016-05-01

    We describe a 2-year-old female with a suprasellar primitive neuroectodermal tumor and central diabetes insipidus (DI) who developed polyuria with natriuresis and subsequent hyponatremia 36 hr after cisplatin administration. The marked urinary losses of sodium in combination with a negative sodium balance led to the diagnosis of cisplatin-induced renal salt wasting syndrome (RSWS). The subsequent clinical management is very challenging. Four weeks later she was discharged from ICU without neurological sequela. The combination of cisplatin-induced RSWS with DI can be confusing and needs careful clinical assessment as inaccurate diagnosis and management can result in increased neurological injury.

  1. The allergenic significance of certain fungi rarely reported as allergens.

    Science.gov (United States)

    Giannini, E H; Northey, W T; Leathers, C R

    1975-12-01

    The allergenic significance of seven different species of fungi was investigated. Included were Chlorophyllum molybdites, Podaxis pistillaris, Stemonitis ferruginea, Lycogala epidendrum, Fuligo septica, Ustilago maydis and Puccinia cynodontis. All of these fungi have wide distribution patterns and aerially disseminated spores but, because of their unique growth characteristics, are usually not reported in atmospheric fungal surveys. Seventy-eight patients were treated for dermal sensitivity to extracts of the organisms after the spores were extracted in 50% glycerinated Coca's solution. The results represent a six-month test period. Forty-four patients, representing 56% of the total number tested, demonstrated dermal reactivity toward one or more of the extracts.

  2. Diet-induced obesity attenuates cytokine production following an immune challenge

    OpenAIRE

    2014-01-01

    Obesity increases susceptibility for numerous diseases and neurological disorders including cardiovascular disease, metabolic syndrome, and dementia. One factor that may contribute to the increased risk for these conditions is the development of chronic inflammation. The current study evaluated whether diet-induced obesity (DIO) affects cognitive performance by increasing neuroinflammation and prolonging the behavioral and inflammatory response to an immune challenge. Adult male C57BL/6J mice...

  3. Carbohydrates as allergens.

    Science.gov (United States)

    Commins, Scott P

    2015-01-01

    Complex carbohydrates are effective inducers of Th2 responses, and carbohydrate antigens can stimulate the production of glycan-specific antibodies. In instances where the antigen exposure occurs through the skin, the resulting antibody production can contain IgE class antibody. The glycan-stimulated IgE may be non-specific but may also be antigen specific. This review focuses on the production of cross-reactive carbohydrate determinants, the recently identified IgE antibody response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), as well as discusses practical implications of carbohydrates in allergy. In addition, the biological effects of carbohydrate antigens are reviewed in setting of receptors and host recognition.

  4. Airway responses towards allergens - from the airway epithelium to T cells.

    Science.gov (United States)

    Papazian, D; Hansen, S; Würtzen, P A

    2015-08-01

    The prevalence of allergic diseases such as allergic rhinitis is increasing, affecting up to 30% of the human population worldwide. Allergic sensitization arises from complex interactions between environmental exposures and genetic susceptibility, resulting in inflammatory T helper 2 (Th2) cell-derived immune responses towards environmental allergens. Emerging evidence now suggests that an epithelial dysfunction, coupled with inherent properties of environmental allergens, can be responsible for the inflammatory responses towards allergens. Several epithelial-derived cytokines, such as thymic stromal lymphopoietin (TSLP), IL-25 and IL-33, influence tissue-resident dendritic cells (DCs) as well as Th2 effector cells. Exposure to environmental allergens does not elicit Th2 inflammatory responses or any clinical symptoms in nonatopic individuals, and recent findings suggest that a nondamaged, healthy epithelium lowers the DCs' ability to induce inflammatory T-cell responses towards allergens. The purpose of this review was to summarize the current knowledge on which signals from the airway epithelium, from first contact with inhaled allergens all the way to the ensuing Th2-cell responses, influence the pathology of allergic diseases.

  5. Profilins: Mimickers of Allergy or Relevant Allergens?

    NARCIS (Netherlands)

    A. Santos; R. van Ree

    2011-01-01

    Profilins are ubiquitous proteins, present in all eukaryotic cells and identified as allergens in pollen, latex and plant foods. The highly conserved structure justifies the cross-reactive nature of IgE antibodies against plant profilins and their designation as pan-allergens. Primary sensitization

  6. 21 CFR 680.1 - Allergenic Products.

    Science.gov (United States)

    2010-04-01

    ... ADDITIONAL STANDARDS FOR MISCELLANEOUS PRODUCTS § 680.1 Allergenic Products. (a) Definition. Allergenic... (b). (ii) Mold cultures shall be free of contaminating materials (including microorganisms) prior to... individual, that will ensure the identity of the seed culture, prescribe adequate processing of the mold,...

  7. New structural information on food allergens (abstract)

    Science.gov (United States)

    A small number of protein families are responsible for food allergies suffered by the majority of allergy patients. What properties of these proteins make them allergens is not clear at present. Reliable methods for allergen prediction and mitigation are lacking. Most the immediate type of food alle...

  8. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  9. Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors.

    Science.gov (United States)

    Braun, Andrea; Engel, Tabea; Aguilar-Pimentel, Juan Antonio; Zimmer, Andreas; Jakob, Thilo; Behrendt, Heidrun; Mempel, Martin

    2011-04-01

    The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB(1) and CB(2) receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB(1/2) receptors in this setting, we used pharmacological blockade of CB(1) and/or CB(2) receptors by the selective antagonists and moreover CB(1)/CB(2) receptor double-knockout mice (CB(1)(-/-)/CB(2)(-/-)) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB(1)/CB(2) receptor-independent signalling seems likely in the observed results.

  10. A histamine release assay to identify sensitization to Culicoides allergens in horses with skin hypersensitivity.

    Science.gov (United States)

    Wagner, Bettina; Childs, Bronwen A; Erb, Hollis N

    2008-12-15

    Skin hypersensitivity is an allergic disease induced in horses by allergens of Culicoides midges. The condition is typically diagnosed by clinical signs and in some horses in combination with allergy testing such as intradermal skin testing or serological allergen-specific IgE determination. Here, we describe an alternative method for allergy testing: a histamine release assay (HRA) that combines the functional aspects of skin testing with the convenience of submitting a blood sample. The assay is based on the principle that crosslinking of allergen-specific IgE bound via high-affinity IgE receptors to the surfaces of mast cells and basophils induces the release of inflammatory mediators. One of these mediators is histamine. The histamine was then detected by a colorimetric enzyme-linked immunosorbent assay. The histamine assay was used to test 33 horses with skin hypersensitivity and 20 clinically healthy control animals for histamine release from their peripheral blood basophils after stimulation with Culicoides allergen extract or monoclonal anti-IgE antibody. An increased histamine release was observed in the horses with skin hypersensitivity compared to the control group after allergen-specific stimulation with Culicoides extract (p=0.023). In contrast, stimulation with anti-IgE induced similar amounts of released histamine in both groups (p=0.46). For further evaluation of the HRA, we prepared a receiver operating-characteristic (ROC) curve and performed a likelihood-ratio analysis for assay interpretation. Our results suggested that the assay is a valuable diagnostic tool to identify sensitization to Culicoides allergens in horses. Because some of the clinically healthy horses also showed sensitization to Culicoides extract, the assay cannot be used to distinguish allergic from non-allergic animals. The observation that sensitization is sometimes detectable in non-affected animals suggested that clinically healthy horses use immune mechanisms to control the

  11. From allergen genes to allergy vaccines.

    Science.gov (United States)

    Valenta, Rudolf; Ferreira, Fatima; Focke-Tejkl, Margarete; Linhart, Birgit; Niederberger, Verena; Swoboda, Ines; Vrtala, Susanne

    2010-01-01

    IgE-mediated allergy is a hypersensitivity disease affecting more than 25% of the population. The structures of the most common allergens have been revealed through molecular cloning technology in the past two decades. On the basis of this knowledge of the sequences and three-dimensional structures of culprit allergens, investigators can now analyze the immune recognition of allergens and the mechanisms of allergic inflammation in allergic patients. Allergy vaccines have been constructed that are able to selectively target the aberrant immune responses in allergic patients via different pathways of the immune system. Here we review various types of allergy vaccines that have been developed based on allergen structures, results from their clinical application in allergic patients, and future strategies for allergen-specific immunotherapy and allergy prophylaxis.

  12. The impact of structural integrity and route of administration on the antibody specificity against three cow's milk allergens - a study in Brown Norway rats

    DEFF Research Database (Denmark)

    Madsen, Jeanette Lund; Kroghsbo, Stine; Madsen, Charlotte Bernhard;

    2014-01-01

    This study showed that the three-dimensional (3D) structure has a significant impact on the antibodies raised for both systemic and orally administered allergens. A remarkable difference in the antibody binding patterns against linear and conformational epitope was seen between the allergens......, indicating that the structural characteristics of proteins may heavily affect the induced antibody response....

  13. Application of recombinant latex allergens in diagnostics of occupational latex allergy

    Directory of Open Access Journals (Sweden)

    Ewa Nowakowska-Świrta

    2015-02-01

    Full Text Available Over many years, allergy to natural rubber latex has been a major problem among health care workers (HCW. The diagnosis of occupational allergy requires methods of high diagnostic accuracy in view of certification implications (e.g., a sick worker quits a job. With the development of molecular methods, the frequency of application of recombinant allergens in the diagnostics of allergic diseases continues to increase. This paper reviews the applicability of laboratory tests which use recombinant allergens in the diagnostics of occupational allergy. The diagnosis of latex allergy is based on the presence of clinical symptoms linked with exposure to latex allergens, positive skin prick tests and detection of specific IgE antibodies to latex in serum. Moreover, in some cases specific challenge tests are conducted. The analysis of literature indicates that applying the panel of recombinant latex allergens in diagnostic tests, cross-reactivity can very likely be excluded and/or sensitization can be confirmed without the need for specific challenge tests, which in case of latex allergens carries a potential risk of generalized reactions. Med Pr 2015;66(1:85–97

  14. Indoor Dust Allergen Levels in the Homes of Patients with Childhood Asthma: An Experience From Southwestern Iran

    Directory of Open Access Journals (Sweden)

    Mozhgan Moghtaderi

    2016-04-01

    Full Text Available Exposure to indoor allergens plays an important role in the etiology of asthma. This study was designed to quantify indoor allergens from homes of families that had at least one case of childhood asthma at home in a southwestern city of Iran. The relationship between the indoor allergen levels and home characteristics was also investigated. Dust samples were collected from the bedrooms and the kitchens of 35 homes where children with persistent asthma were living. The levels of indoor allergens were measured by enzyme linked immunosorbent assay (ELISA. Detectable amounts of mite, mouse and cockroach allergens were found in all evaluated places. None of our patients were exposed to a threshold concentration of indoor allergen for sensitizing at home. Regarding of mite allergens, the levels of Der f1 were significantly higher than Der p1 and a direct correlation was observed between living in an apartment and Der f1 levels. Moreover, Fel d1 (cat and Bla g1 (cockroach allergens were found in the children’s bedrooms more frequently than those in the kitchens. In this study, direct associations were obtained between Bla g1 allergen and the duration of occupancy and between Fel d1 and average home size. A total of 34.2% of the patients showed positive skin reactions to at least one of the tested allergens as 17.1% of them showed reactivity to D. pteronyssinus. Proper controlling of cockroaches and mice by public health officials would be a practical approach to avoid inducing asthma or worsening the symptoms.

  15. Specific IgE response to different grass pollen allergen components in children undergoing sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    Marcucci Francesco

    2012-06-01

    Full Text Available Abstract Background Grass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized. Methods We investigated in 30 children (19 males and 11 females, mean age 11.3 years, 19 treated with sublingual immunotherapy (SLIT by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components. Results Significant increases (p  Conclusions These findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure.

  16. Effects of NO2 and ozone on pollen allergenicity

    Directory of Open Access Journals (Sweden)

    Ulrike eFrank

    2016-02-01

    Full Text Available This mini-review summarizes the available data of the air pollutants NO2 and ozone on allergenic pollen from different plant species, focusing on potentially allergenic components of the pollen, such as allergen content, protein release, IgE-binding or protein modification. Various in vivo and in vitro studies on allergenic pollen are shown and discussed.

  17. Properties of tree and grass pollen allergens: reinvestigation of the linkage between solubility and allergenicity.

    Science.gov (United States)

    Vrtala, S; Grote, M; Duchêne, M; van Ree, R; Kraft, D; Scheiner, O; Valenta, R

    1993-01-01

    In this study we reinvestigated the kinetics of allergen release from birch pollen (Betula verrucosa) and timothy grass pollen (Phleum pratense) using different protein extraction procedures, immunoblotting with specific antibodies and immune electron microscopy. Pollen allergens such as the major birch pollen allergen, Bet v I, the major timothy grass pollen allergens, Phl p I and Phl p V, group-II/III allergens from timothy grass and profilins were released rapidly and in large amounts from hydrated pollen. Within a few minutes pollen allergens could be detected in aqueous supernatants prepared from birch and grass pollen with serum IgE or specific antibodies. In parallel the allergen content in the pollen pellet fractions decreased. A nonallergenic protein such as heat shock protein 70 can be extracted in sufficient amounts only with harsh extraction procedures. Immune electron microscopy of dry and rehydrated birch pollens showed that after short hydration, the major birch pollen allergen, Bet v I, migrated into the exine and to the surface of intact pollen grains, whereas profilin, against which a lower percentage of patients is sensitized, was retained in the pollen grain. Comparing the amino acid composition and hydrophilicity of the tested allergens with a nonallergenic protein such as heat shock protein 70, no significant difference was noted. In agreement with earlier observations we conclude that the allergenic properties of proteins are rather linked to the amount and speed of solubility from airborne particles than to intrinsic properties.

  18. Safety of allergen-specific immunotherapy. Relation between dosage regimen, allergen extract, disease and systemic side-effects during induction treatment

    DEFF Research Database (Denmark)

    Mellerup, M T; Hahn, G W; Poulsen, Lars K.;

    2000-01-01

    Allergen-specific immunotherapy is a well-documented treatment for allergic rhinitis, asthma, and allergy to Hymenoptera venoms. The drawbacks of injection immunotherapy are related to the risk of inducing systemic side-effects (especially during the induction phase), the time used to reach...

  19. Combined fluticasone propionate and salmeterol reduces RSV infection more effectively than either of them alone in allergen-sensitized mice

    Directory of Open Access Journals (Sweden)

    Ledford Dennis

    2006-05-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV infection is the major cause of bronchiolitis in infants and is a risk factor for the development of asthma. Allergic asthmatics are more susceptible to RSV infection and viral exacerbation. Methods Since the effectiveness of corticosteroids in treating RSV infection has been controversial, we tested fluticasone propionate (FP and salmeterol (Sal alone versus FP plus Sal (FPS on RSV-induced airway inflammation. Mice were sensitized and challenged with ovalbumin (OVA and infected with RSV. Following infection they were treated with FP, Sal, or FPS intranasally and airway hyperreactivity (AHR, inflammation and RSV titers were examined. Results The group treated with FPS showed significantly lower AHR compared to the group treated with FP or Sal alone. The group treated with FP alone showed slightly decreased (non-significant AHR compared to controls. Treatment with FPS resulted in significant decreases in the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid and in lung pathology compared to FP or Sal. FP alone decreased eosinophils but not neutrophils or lymphocytes, while Sal alone decreased eosinophils and neutrophils but not lymphocytes. FPS treatment of mice infected with RSV in the absence of allergen sensitization resulted in a 50% decrease of RSV titer in the lung and a reduction in neutrophils compared to FP or Sal. Conclusion Together, these results indicate that fluticasone in combination with salmeterol is a more effective treatment for decreasing airway hyperreactivity and inflammation than either of them alone in allergen-sensitized, RSV-infected mice.

  20. Requirements for acquiring a high-quality house dust mite extract for allergen immunotherapy

    Directory of Open Access Journals (Sweden)

    Frati F

    2012-05-01

    Full Text Available Franco Frati,1 Cristoforo Incorvaia,2 Marie David,3 Silvia Scurati,3 Simona Seta,4 Guglielmo Padua,4 Eleonora Cattaneo,1 Carlo Cavaliere,5 Alessia Di Rienzo,6 Ilaria Dell'Albani,1 Paola Puccinelli11Medical and Scientific and Regulatory Department, Stallergenes, Milan, Italy; 2Allergy/Pulmonary Rehabilitation, ICP Hospital, Milan, Italy; 3Laboratoire Stallergenes, Antony, France; 4Marketing Department, Stallergenes, Milan, Italy; 5Ear, Nose and Throat Department, University Sapienza, Rome, Italy; 6Azienda Sanitaria Locale, Allergology Service, Frosinone, ItalyAbstract: The house dust mite is a major cause of respiratory allergy worldwide. The management of mite allergy is based on avoidance measures, drug treatment, and allergen immunotherapy, but only allergen immunotherapy is able to modify the natural history of the disease. Injectable subcutaneous immunotherapy was introduced a century ago, while sublingual immunotherapy was proposed in the 1980s and emerged in the ensuing years as an effective and safe option to subcutaneous immunotherapy. However, the quality of the extracts to be used in allergen immunotherapy is crucial for the success of treatment. The mite extract for sublingual immunotherapy known as Staloral 300 was developed to offer optimal characteristics concerning the mite culture medium, standardization, and allergen dose. Double-blind, placebo-controlled trials with Staloral 300 have provided a substantial part of the clinical evidence analyzed in a meta-analysis of the efficacy of allergen immunotherapy in mite-induced rhinitis and asthma. Safety and tolerability are very good, mild local reactions in the mouth being the most common side effect. This makes it feasible to carry out sublingual immunotherapy for the 3–5-year duration needed to achieve long-lasting tolerance to the specific allergen. The performance of Staloral 300 may provide optimal conditions for an effective and safe sublingual immunotherapy in patients with

  1. Enhanced approaches for identifying Amadori products:application to peanut allergens

    Science.gov (United States)

    The dry roasting of peanuts is suggested to influence allergenic sensitization due to formation of advanced glycation end products (AGE) on peanut proteins. Identifying AGEs is technically challenging. The AGE composition of peanut proteins was probed with nanoLC-ESI-MS and MS/MS analyses. Amadori ...

  2. Will genetically modified foods be allergenic?

    Science.gov (United States)

    Taylor, S L; Hefle, S L

    2001-05-01

    Foods produced through agricultural biotechnology, including such staples as corn, soybeans, canola, and potatoes, are already reaching the consumer marketplace. Agricultural biotechnology offers the promise to produce crops with improved agronomic characteristics (eg, insect resistance, herbicide tolerance, disease resistance, and climatic tolerance) and enhanced consumer benefits (eg, better taste and texture, longer shelf life, and more nutritious). Certainly, the products of agricultural biotechnology should be subjected to a careful and complete safety assessment before commercialization. Because the genetic modification ultimately results in the introduction of new proteins into the food plant, the safety, including the potential allergenicity, of the newly introduced proteins must be assessed. Although most allergens are proteins, only a few of the many proteins found in foods are allergenic under the typical circumstances of exposure. The potential allergenicity of the introduced proteins can be evaluated by focusing on the source of the gene, the sequence homology of the newly introduced protein to known allergens, the expression level of the novel protein in the modified crop, the functional classification of the novel protein, the reactivity of the novel protein with IgE from the serum of individuals with known allergies to the source of the transferred genetic material, and various physicochemical properties of the newly introduced protein, such as heat stability and digestive stability. Few products of agricultural biotechnology (and none of the current products) will involve the transfer of genes from known allergenic sources. Applying such criteria provides reasonable assurance that the newly introduced protein has limited capability to become an allergen.

  3. The hammock: a reservoir of allergens

    Directory of Open Access Journals (Sweden)

    Francisca X. M. Rego

    2011-01-01

    Full Text Available INTRODUCTION: Asthma affects approximately 10% of the world's population. Sensitization to allergens is an important risk factor, and exposure to allergens is associated with disease severity. METHODS: We performed skin tests to evaluate allergen sensitization to mites, cockroaches, cats, dogs, and molds in 73 asthmatic patients. Enzyme Linked Immunosorbent Assay was used to assay the mite and cockroach allergens found in dust from the bedding, hammocks, bedroom floors, living rooms, and kitchens of 29 patients and 14 controls. RESULTS: Fifty patients (68.5% had positive skin test responses. There were positive responses to D. pteronyssinus (52.0%, B. tropicalis (53.4%, T. putrescentiae (15.0%, E. maynei (12.3%, L. destructor (8.2%, B. germanica (20.5%, P. americana (21.9%, Felis catus (10.9%, C. herbarium (2.7%, A. alternata (4.1%, and P. notatun (1.3%. The exposure to mite and cockroach allergens was similar in the patients and the controls. The Dermatophagoides pteronyssinus Group 1 levels were highest in the beds and hammocks. The Blattella germanica Group 1 levels were highest in the kitchens, living rooms and hammocks. DISCUSSION: The positive skin tests to mites, cockroaches and cats were consistent with previous studies. D pteronyssinus was the most prevalent home dust mite, and hammocks were a source of allergens. To improve asthma prophylaxis, it is important to determine its association with mite allergen exposure in hammocks.

  4. Classification of contact allergens according to potency: proposals.

    Science.gov (United States)

    Kimber, I; Basketter, D A; Butler, M; Gamer, A; Garrigue, J-L; Gerberick, G F; Newsome, C; Steiling, W; Vohr, H-W

    2003-12-01

    It is clear that contact allergens vary substantially with regard to the relative potency with which they are able to induce skin sensitisation. Considerations of potency will in the future become a significant factor in the classification of skin sensitising chemicals. It is therefore appropriate to establish what is known of potency and thresholds in the induction of skin sensitisation and the elicitation of allergic contact dermatitis, and to identify approaches that might be available for assessment of relative potency for the purposes of categorising chemical allergens. This paper was prepared by an ECETOC (European Centre for Ecotoxicology and Toxicology) Task Force that had the objective of recommending approaches for the measurement of potency and definition of thresholds for both the induction and elicitation of contact sensitisation. The deliberations recorded here build upon recommendations made previously by an ECETOC Task Force that considered the conduct of standard skin sensitisation test methods for the purposes of hazard identification and risk assessment (ECETOC, Monograph No. 29, Brussels, 2000). The emphasis in this present paper is also on standard and accepted methods for the assessment of skin sensitisation, and for which OECD guidelines are available: the local lymph node assay (LLNA), the guinea pig maximisation test and the occluded patch test of Buehler. For various reasons, discussed in detail herein, attention focused primarily upon consideration of categorisation of chemical allergens and the identification of thresholds with respect to the induction of skin sensitisation, rather than the elicitation of allergic contact dermatitis. It is concluded that although the LLNA is the method of choice for the determination of skin sensitisation potency for the purposes of categorisation, if data are already available from appropriate guinea pig tests then their judicious interpretation may provide information of value in determinations of

  5. Tetrahydrobiopterin restores endothelial dysfunction induced by an oral glucose challenge in healthy subjects

    DEFF Research Database (Denmark)

    Ihlemann, Nikolaj; Rask-Madsen, Christian; Perner, Anders;

    2003-01-01

    cofactor of eNOS. Therefore, we examined whether an acute supplement of BH4 could restore endothelial dysfunction induced by an oral glucose challenge. Healthy subjects were examined in 53 experiments. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies were obtained......An oral glucose challenge causes transient impairment of endothelial function, probably because of increased oxidative stress. During oxidative stress, endothelial nitric oxide (NO) synthase (eNOS) becomes uncoupled because of decreased bioavailability of tetrahydrobiopterin (BH4), an essential...... (n = 10) and SNP (n = 8). On different days (6R)-5,6,7,8-tetrahydro-l-biopterin dihydrochloride (6R-BH4; n = 10), the active cofactor of eNOS or its stereoisomer (6S)-5,6,7,8-tetrahydro-l-biopterin sulfate (6S-BH4; n = 10), which is inactive as a cofactor, was added 10 min (500 microg/min) before...

  6. Fuzzy logic for personalized healthcare and diagnostics: FuzzyApp--a fuzzy logic based allergen-protein predictor.

    Science.gov (United States)

    Saravanan, Vijayakumar; Lakshmi, P T V

    2014-09-01

    The path to personalized medicine demands the use of new and customized biopharmaceutical products containing modified proteins. Hence, assessment of these products for allergenicity becomes mandatory before they are introduced as therapeutics. Despite the availability of different tools to predict the allergenicity of proteins, it remains challenging to predict the allergens and nonallergens, when they share significant sequence similarity with known nonallergens and allergens, respectively. Hence, we propose "FuzzyApp," a novel fuzzy rule based system to evaluate the quality of the query protein to be an allergen. It measures the allergenicity of the protein based on the fuzzy IF-THEN rules derived from five different modules. On various datasets, FuzzyApp outperformed other existing methods and retained balance between sensitivity and specificity, with positive Mathew's correlation coefficient. The high specificity of allergen-like putative nonallergens (APN) revealed the FuzzyApp's capability in distinguishing the APN from allergens. In addition, the error analysis and whole proteome dataset analysis suggest the efficiency and consistency of the proposed method. Further, FuzzyApp predicted the Tropomyosin from various allergenic and nonallergenic sources accurately. The web service created allows batch sequence submission, and outputs the result as readable sentences rather than values alone, which assists the user in understanding why and what features are responsible for the prediction. FuzzyApp is implemented using PERL CGI and is freely accessible at http://fuzzyapp.bicpu.edu.in/predict.php . We suggest the use of Fuzzy logic has much potential in biomarker and personalized medicine research to enhance predictive capabilities of post-genomics diagnostics.

  7. Sensitization patterns to food and inhalant allergens in childhood: a comparison of non-sensitized, monosensitized, and polysensitized children.

    Science.gov (United States)

    de Jong, Adriana Baatenburg; Dikkeschei, Lambert D; Brand, Paul L P

    2011-03-01

    The clinical interpretation of children sensitized to numerous allergens is challenging. We examined differences between children sensitized to zero, one, or more allergens. This was a retrospective analysis of all specific IgE tests in children 0-18 yrs of age sent to our laboratory by general practitioners and hospital-based specialists for allergy testing between 1990 and 2003. Of all 9044 children tested, 5439 (60.1%) were not sensitized to any of the aeroallergens or food allergens tested. Three thousand six hundred and five children (39.9%) had one or more positive specific IgE tests, 1120 of which (31.1%) were monosensitized (73% to aeroallergens and 27% to food allergens), 1709 (47.4%) were sensitized to two to four allergens, and 776 (21.5%) to five or more allergens (polysensitization). Polysensitization was more common in children 4-11 yrs of age (24.8%) than in younger (18.7%) or older children (18.3%, p food allergens (hen's egg 9.7%, peanut 4.6%, wheat 0.8%, soy 0.7%). Between 55.7% (cow's milk) and 87.9% (soy) of children sensitized to food were cosensitized to aeroallergens, while only 25.4% (house dust mite) to 39.5% (dog) of children sensitized to aeroallergens were cosensitized to food. Polysensitization is common in children, in particular in boys. It is most common in school-aged children. The strong association with total serum IgE values and the striking cosensitization between biologically unrelated allergens suggest that polysensitization is the expression of a distinct clinical, more severe, atopic phenotype, and not of biologic cross-reactivity to similar allergens.

  8. Contact Dermatitis, Patch Testing, and Allergen Avoidance.

    Science.gov (United States)

    Burkemper, Nicole M

    2015-01-01

    In patients presenting with a complaint of rash, contact dermatitis is often the underlying diagnosis making it an entity with which health care providers should be familiar. Contact dermatitis can be divided into irritant contact dermatitis and allergic contact dermatitis. In a patient suspected of having allergic contact dermatitis, patch testing can be done to identify specific allergens. Education focused on allergen avoidance and safe products is an integral part of treatment for the contact dermatitis patient. Knowledge of the most common allergens is helpful for clinicians to be able to provide this education.

  9. Allergenic fragments of ryegrass (Lolium perenne) pollen allergen Lol p IV.

    Science.gov (United States)

    Jaggi, K S; Ekramoddoullah, A K; Kisil, F T

    1989-01-01

    To facilitate studies on establishing the nature of structure/function relationships of allergens, ryegrass pollen allergen, Lol p IV, was cleaved into smaller fragments by cyanogen bromide (CNBr) and the resulting peptides were further digested with trypsin. The resulting peptides were then fractionated by high performance liquid chromatography (HPLC) on a C-18 reverse phase column. The allergenic activity of the HPLC fractions was evaluated in terms of their ability to inhibit the binding of 125I-Lol p IV to serum IgE antibodies of a grass-allergic patient. Many of these fractions inhibited the binding between the native allergen and IgE antibodies in a dose-dependent manner. The inhibitions were specific, i.e., the fractions did not inhibit the binding between 125I-Lol p I (a group-I ryegrass pollen allergen) and the IgE antibodies present in the allergic human serum. The possibility that the allergenic peptide fractions were contaminated by the native undegraded allergen, which might have accounted for the observed inhibition, was ruled out by the fact that the native allergen could not be detected by SDS-PAGE and the elution profiles of allergenically active peptides did not coincide with that of native allergen. One of the allergenic sites recognized by monoclonal antibody (Mab) 90, i.e., site A, was located in HPLC fractions 90-100 while another allergenic site B (recognized by Mab 12) appeared to be lost following the sequential digestion of Lol p IV with CNBr and trypsin.

  10. Beneficial cross-protection of allergen-specific immunotherapy on airway eosinophilia using unrelated or a partial repertoire of allergen(s) implicated in experimental feline asthma.

    Science.gov (United States)

    Reinero, Carol; Lee-Fowler, Tekla; Chang, Chee-Hoon; Cohn, Leah; Declue, Amy

    2012-06-01

    The study hypothesis was that in experimentally asthmatic cats rush immunotherapy (RIT) using allergens not completely matched with sensitizing allergen(s) would at least partially attenuate the asthmatic phenotype and modulate the aberrant immune response. In phase I, cats sensitized to Bermuda grass allergen (BGA), house dust mite allergen (HDMA) or placebo received BGA RIT. In phase II, cats dually sensitized to BGA and HDMA received RIT using BGA, HDMA or placebo. Efficacy of RIT was assessed using percentage bronchoalveolar lavage fluid (BALF) eosinophils. Additionally, a variety of immunologic assays were performed. Eosinophilic airway inflammation significantly decreased over time in asthmatic cats given RIT using sensitizing allergen or unrelated allergen (P<0.001). In dually sensitized cats, single allergen RIT but not placebo reduced airway eosinophilia (P=0.038). Differences in allergen-specific lymphocyte proliferation, in the number of IL-10 producing cells and in the percentage T regulatory cells were detected between asthmatic cats getting RIT and controls. Cross-protection manifested by reduced airway eosinophilia was noted in cats treated with RIT allergens which did not completely match allergen used in asthma induction. However, the mechanism of immunologic tolerance may differ when improperly matched allergens to the sensitizing allergens are used in RIT.

  11. Allergenic properties of apples – molecular basis, factors determining level of allergens

    Directory of Open Access Journals (Sweden)

    Maria Trzcińska

    2015-09-01

    Full Text Available Approximately 2% of the northern and central European population is allergic to apples. This explains why there is a lot of interest in allergenic properties of apples. This study presents four major identified allergens. Three of them – Mal d 1, Mal d 2, Mal d 3 – are pathogenesis-related proteins. The fourth – Mal d 4 – is categorized as a profilin. This paper describes the influence of different factors such as apple variety, cultivation method and long term storage on the allergen content and synthesis of allergens in apples. The article describes attempts at growing hypoallergenic apples, safe for consumers with mild allergy.

  12. Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducing myo-inositol biosynthesis.

    Science.gov (United States)

    Gardell, Alison M; Yang, Jun; Sacchi, Romina; Fangue, Nann A; Hammock, Bruce D; Kültz, Dietmar

    2013-12-15

    This study aimed to determine the regulation of the de novo myo-inositol biosynthetic (MIB) pathway in Mozambique tilapia (Oreochromis mossambicus) brain following acute (25 ppt) and chronic (30, 60 and 90 ppt) salinity acclimations. The MIB pathway plays an important role in accumulating the compatible osmolyte, myo-inositol, in cells in response to hyperosmotic challenge and consists of two enzymes, myo-inositol phosphate synthase and inositol monophosphatase. In tilapia brain, MIB enzyme transcriptional regulation was found to robustly increase in a time (acute acclimation) or dose (chronic acclimation) dependent manner. Blood plasma osmolality and Na(+) and Cl(-) concentrations were also measured and significantly increased in response to both acute and chronic salinity challenges. Interestingly, highly significant positive correlations were found between MIB enzyme mRNA and blood plasma osmolality in both acute and chronic salinity acclimations. Additionally, a mass spectrometry assay was established and used to quantify total myo-inositol concentration in tilapia brain, which closely mirrored the hyperosmotic MIB pathway induction. Thus, myo-inositol is a major compatible osmolyte that is accumulated in brain cells when exposed to acute and chronic hyperosmotic challenge. These data show that the MIB pathway is highly induced in response to environmental salinity challenge in tilapia brain and that this induction is likely prompted by increases in blood plasma osmolality. Because the MIB pathway uses glucose-6-phosphate as a substrate and large amounts of myo-inositol are being synthesized, our data also illustrate that the MIB pathway likely contributes to the high energetic demand posed by salinity challenge.

  13. Exposure to Allergen Causes Changes in NTS Neural Activities after Intratracheal Capsaicin Application, in Endocannabinoid Levels and in the Glia Morphology of NTS.

    Science.gov (United States)

    Spaziano, Giuseppe; Luongo, Livio; Guida, Francesca; Petrosino, Stefania; Matteis, Maria; Palazzo, Enza; Sullo, Nikol; de Novellis, Vito; Di Marzo, Vincenzo; Rossi, Francesco; Maione, Sabatino; D'Agostino, Bruno

    2015-01-01

    Allergen exposure may induce changes in the brainstem secondary neurons, with neural sensitization of the nucleus solitary tract (NTS), which in turn can be considered one of the causes of the airway hyperresponsiveness, a characteristic feature of asthma. We evaluated neurofunctional, morphological, and biochemical changes in the NTS of naive or sensitized rats. To evaluate the cell firing activity of NTS, in vivo electrophysiological experiments were performed before and after capsaicin challenge in sensitized or naive rats. Immunohistochemical studies, endocannabinoid, and palmitoylethanolamide quantification in the NTS were also performed. This study provides evidence that allergen sensitization in the NTS induced: (1) increase in the neural firing response to intratracheal capsaicin application, (2) increase of endocannabinoid anandamide and palmitoylethanolamide, a reduction of 2-arachidonoylglycerol levels in the NTS, (3) glial cell activation, and (4) prevention by a Group III metabotropic glutamate receptor activation of neural firing response to intratracheal application of capsaicin in both naïve and sensitized rats. Therefore, normalization of ovalbumin-induced NTS neural sensitization could open up the prospect of new treatments based on the recovery of specific brain nuclei function and for extensive studies on acute or long-term efficacy of selective mGlu ligand, in models of bronchial hyperreactivity.

  14. Induced pluripotent stem cells for retinal degenerative diseases: a new perspective on the challenges

    Indian Academy of Sciences (India)

    Zi-Bing Jin; Satoshi Okamoto; Michiko Mandai; Masayo Takahashi

    2009-12-01

    Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, are the prodominant causes of human blindness in the world; however, these diseases are difficult to treat. Currently, knowledge on the mechanisms of these diseases is still very limited and no radical drugs are available. Induced pluripotent stem (iPS) cells are an innovative technology that turns somatic cells into embryonic stem (ES)-like cells with pluripotent potential via the exogenous expression of several key genes. It can be used as an unlimited source for cell differentiation or tissue engineering, either of which is a promising therapy for human degenerative diseases. Induced pluripotent cells are both an unlimited source for retinal regeneration and an expectant tool for pharmaprojects and developmental or disease modelling. In this review, we try to summarize the advancement of iPS-based technologies and the potential utility for retinal degenerative diseases. We also discuss the challenges of using this technology in the retinology field.

  15. Limitations and possibilities of animal models for human allergenic risk evaluation

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard; Kroghsbo, Stine; Bøgh, Katrine Lindholm

    2012-01-01

    evaluation. One of the pitfalls may be the premise that an animal model needs to mimic the disease. Chemical contact sensitizers may be predicted in an animal test, the Local Lymph Node Assay (LLNA). This assay is based on detailed mechanistic knowledge of contact sensitization including knowledge on dose......-response relationship. The outcome of the test is sensitization measured as cell proliferation in the regional lymph node. Animal models in food allergy can be used to increase our understanding of food allergens and food allergy sensitization e.g. the influence of digestion or processing or to compare closely related......’t know under what circumstances oral tolerance develops. With all these unanswered questions, it is a big challenge to design an animal model that, with relatively few animals, is able to predict if a food allergen is not only a potential allergen but also predict its potency, a prerequisite for risk...

  16. Ethosome formulation of contact allergens may enhance patch test reactions in patients

    DEFF Research Database (Denmark)

    Madsen, Jakob Torp; Vogel, Stefan; Karlberg, Ann-Therese;

    2010-01-01

    Background: Ethosomes and liposomes are ultra-small vesicles capable of encapsulating drugs and cosmetic ingredients for topical use, thereby potentially increasing bioavailability and clinical efficacy. So far, few reports have suggested that formulation of cosmetic ingredients in vesicular......, a repeated open application test (ROAT) was performed in a subset of 16 patients, and lag time until a positive response was recorded. Results: Both contact allergens encapsulated in ethosomes showed significantly enhanced patch test reactions as compared with the allergen preparation in ethanol....../water without ethosomes. No significant difference in the median lag time was recorded between preparations in the ROAT. Conclusions: Encapsulating potential contact allergens in ethosomes may increase the challenge response as compared with the same concentrations in an ethanol/water base without ethosomes....

  17. Skin Barrier Function and Allergens

    DEFF Research Database (Denmark)

    Engebretsen, Kristiane Aasen; Thyssen, Jacob Pontoppidan

    2016-01-01

    The skin is an important barrier protecting us from mechanical insults, microorganisms, chemicals and allergens, but, importantly, also reducing water loss. A common hallmark for many dermatoses is a compromised skin barrier function, and one could suspect an elevated risk of contact sensitization...... and skin barrier status. Psoriasis has traditionally been regarded a Th1-dominated disease, but the discovery of Th17 cells and IL-17 provides new and interesting information regarding the pathogenesis of the disease. Research suggests an inverse relationship between psoriasis and CA, possibly due......) and Th2 (AD) have been proposed as an explanation. Finally, there is convincing evidence that exposure to irritants increases the risk of CS, and patients with ICD are, therefore, at great risk of developing CA. Skin irritation leads to the release of IL-1 and TNF-α, which affects the function of antigen...

  18. Allergen immunotherapy for allergic rhinoconjunctivitis

    DEFF Research Database (Denmark)

    Dhami, Sangeeta; Nurmatov, Ulugbek; Roberts, Graham;

    2016-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT...... in the management of allergic rhinoconjunctivitis. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically...... appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. CONCLUSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT....

  19. Thioredoxin from the Indianmeal moth Plodia interpunctella: cloning and test of the allergenic potential in mice.

    Directory of Open Access Journals (Sweden)

    Elisabeth Hoflehner

    Full Text Available BACKGROUND/OBJECTIVE: The Indianmeal moth Plodia interpunctella is a highly prevalent food pest in human dwellings, and has been shown to contain a number of allergens. So far, only one of these, the arginine kinase (Plo i 1 has been identified. OBJECTIVE: The aim of this study was to identify further allergens and characterise these in comparison to Plo i 1. METHOD: A cDNA library from whole adult P. interpunctella was screened with the serum of a patient with indoor allergy and IgE to moths, and thioredoxin was identified as an IgE-binding protein. Recombinant thioredoxin was generated in E. coli, and tested together with Plo i 1 and whole moth extracts in IgE immunoblots against a large panel of indoor allergic patients' sera. BALB/c mice were immunised with recombinant thioredoxin and Plo i 1, and antibody production, mediator release from RBL cells, T-cell proliferation and cytokine production were measured. RESULT: For the first time a thioredoxin from an animal species was identified as allergen. About 8% of the sera from patients with IgE against moth extracts reacted with recombinant P. interpunctella thioredoxin, compared to 25% reacting with recombinant Plo i 1. In immunised BALB/c mice, the recombinant allergens both induced classical Th2-biased immune responses such as induction IgE and IgG1 antibodies, upregulation of IL-5 and IL-4 and basophil degranulation. CONCLUSION: Thioredoxin from moths like Plo i 1 acts like a classical Type I allergen as do the thioredoxins from wheat or corn. This clearly supports the pan-allergen nature of thioredoxin. The designation Plo i 2 is suggested for the new P. interpunctella allergen.

  20. Allergen immunotherapy for the prevention of allergy

    DEFF Research Database (Denmark)

    Kristiansen, Maria; Dhami, Sangeeta; Netuveli, Gopal

    2017-01-01

    Background: There is a need to establish the effectiveness, cost-effectiveness and safety of allergen immunotherapy (AIT) for the prevention of allergic disease. Methods:Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using ran...

  1. Re-challenge with Etanercept in patients with Etanercept-induced Neutropenia.

    LENUS (Irish Health Repository)

    Haroon, Muhammad

    2011-08-05

    TNF blockers have rarely been associated with haematological complications; however, there are scattered case reports of marked neutropenia with their use and necessitating in their withdrawal. We would like to report a series of five patients who developed neutropenia with etanercept use; however, all these patients were re-challenged with etanercept with a mean follow up of 30 months. These patients developed neutropenia within 2 months of starting etanercept. Two patients were eventually taken off etanercept; one of them needed switching to a different form of TNF blockers, and the second patient is in clinical remission with low-dose corticosteroids. All our patients continued to have mild-moderate degree of neutropenia; however, they are being monitored very closely and they are enjoying complete disease remission. It was interesting to note that none of our patients had increased infections during the re-challenge phase, even though they had grade 2 to grade 4 neutropenia. We have re-challenged these patients without any clinical complications, revealing that patients with mild to moderate neutropenia can be safely exposed to TNF blockers as long as they are monitored with regular cell count checks. Although largely noted to be clinically insignificant in our patient series, the potential of drug-induced neutropenia in causing higher rate of infections do exist. Careful clinical and hematologic monitoring is the best way to recognize this adverse event.

  2. Assessment of allergen specific response in humans

    OpenAIRE

    Archila Diaz, Luis Diego

    2015-01-01

    [eng] Allergies are emerging as a major public health concern in the westernized world as they are increasing for reasons that remain poorly understood. Allergies involving polysensitization and multiple organ involvement result in decreased quality of life, increased morbidity and mortality. Allergic subjects can be poly-sensitized to different allergens due to phylogenetic relatedness; several species contain shared allergenic epitopes. This phenomenon occurs both at the IgE as the T cell ...

  3. Allergen specific immunotherapy in nasobronchial allergy.

    Directory of Open Access Journals (Sweden)

    Joshi S

    2003-12-01

    Full Text Available BACKGROUND: More than one antigen has been used for immunotherapy of allergic disorders. So far less than five antigens have been employed with variable results. AIM: To evaluate effect of multiple antigens up to six in the immunotherapy of nasobronchial allergy. SETTING AND DESIGN: Based on clinical history, symptoms present for at least 3 years with set criteria of immunomodulation for asthma and rhinitis: documented IgE mediated asthma and rhinitis, failure in allergen avoidance and moderate to severe clinical manifestations. MATERIAL AND METHODS: Five hundred cases of various allergic disorders attending allergy clinic of Bombay hospital were screened. Allergen specific immunotherapy was initiated in 131 subjects (56 -rhinitis and 75 asthma with prior consent. Patients suffering from allergic disorders secondary to diseases or drug therapy were excluded. Multiple allergen immunotherapy was given at specific intervals up to a period of one year. Allergen extracts were prepared as per standard technique. For statistical analysis "students′t test" was used. RESULTS AND CONCLUSIONS: Significant improvement in PEFR, reduction in skin sensitivity to allergens used in immunotherapy formulation and symptomatic relief without any untoward reaction show that multiple allergen immunotherapy is as effective as monoallergen immunotherapy in nasobronchial allergy.

  4. High pressure effects on allergen food proteins.

    Science.gov (United States)

    Somkuti, Judit; Smeller, László

    2013-12-15

    There are several proteins, which can cause allergic reaction if they are inhaled or ingested. Our everyday food can also contain such proteins. Food allergy is an IgE-mediated immune disorder, a growing health problem of great public concern. High pressure is known to affect the structure of proteins; typically few hundred MPa pressure can lead to denaturation. That is why several trials have been performed to alter the structure of the allergen proteins by high pressure, in order to reduce its allergenicity. Studies have been performed both on simple protein solutions and on complex food systems. Here we review those allergens which have been investigated under or after high pressure treatment by methods capable of detecting changes in the secondary and tertiary structure of the proteins. We focus on those allergenic proteins, whose structural changes were investigated by spectroscopic methods under pressure in correlation with the observed allergenicity (IgE binding) changes. According to this criterion we selected the following allergen proteins: Mal d 1 and Mal d 3 (apple), Bos d 5 (milk), Dau c 1 (carrot), Gal d 2 (egg), Ara h 2 and Ara h 6 (peanut), and Gad m 1 (cod).

  5. Sweat-inducing physiological challenges do not result in acute changes in hair cortisol concentrations.

    Science.gov (United States)

    Grass, Juliane; Kirschbaum, Clemens; Miller, Robert; Gao, Wei; Steudte-Schmiedgen, Susann; Stalder, Tobias

    2015-03-01

    Hair cortisol concentrations (HCC) are assumed to provide a stable, integrative marker of long-term systemic cortisol secretion. However, contrary to this assumption, some recent observations have raised the possibility that HCC may be subject to acute influences, potentially related to cortisol incorporation from sweat. Here, we provide a first detailed in vivo investigation of this possibility comprising two independent experimental studies: study I (N=42) used a treadmill challenge to induce sweating together with systemic cortisol reactivity while in study II (N=52) a sauna bathing challenge induced sweating without systemic cortisol changes. In both studies, repeated assessments of HCC, salivary cortisol, cortisol in sweat and individuals' sweating rate (single assessment) were conducted on the experimental day and at a next-day follow-up. Results across the two studies consistently revealed that HCC were not altered by the acute interventions. Further, HCC were found to be unrelated to acute salivary cortisol reactivity, sweat cortisol levels, sweating rate or the time of examination. In line with previous data, cortisol levels in sweat were strongly related to total salivary cortisol output across the examined periods. The present results oppose recent case report data by showing that single sweat-inducing interventions do not result in acute changes in HCC. Our data also tentatively speak against the notion that cortisol in sweat may be a dominant source of HCC. Further, our findings also indicate that HCC are not subject to diurnal variation. This research provides further support for hair cortisol analysis as a marker of integrated long-term systemic cortisol secretion.

  6. House dust mites: a risk factor to be considered for occupational safety or source of work-related allergens.

    Science.gov (United States)

    Saleh, Ahmed Megahed Ahmed; Ali, Hisham Abd El-Raouf; Ahmed, Salwa Abdalla Mohamed; Mohammad, Naema Mahmoud; Morsy, Tosson A

    2013-12-01

    House dust mites (HDM) can be found worldwide where human beings live independent from the climate and are a major source of multiple allergens. Mite allergens sensitize and induce perennial rhinitis, asthma, or atopic dermatitis in a large portion of patients with allergic disease particularly children. There is convincing evidence that avoidance of mite allergen can effectively reduce allergic symptoms. This study examined dust from a military hospital and the private home of some nursing staff. A total of seven species of mites belonging to six genera were recovered. The commonest species was Dermatophagoides farinae followed by D. pteronyssinus and the lowest Laelaps nuttalli. Besides, the 7th mite or Parasitus consanguineous live free on dust as a bio-control agent of mites. The presence of mites in and out doors in a hospital and dwellings of medical personnel pave the way to consider HDM as occupational or nosocomial Allergens.

  7. Optical diagnostics of vascular reactions triggered by weak allergens using laser speckle-contrast imaging technique

    Energy Technology Data Exchange (ETDEWEB)

    Kuznetsov, Yu L; Kalchenko, V V [Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, 76100 (Israel); Astaf' eva, N G [V.I.Razumovsky Saratov State Medical University, Saratov (Russian Federation); Meglinski, I V [N.G. Chernyshevsky Saratov State University, Saratov (Russian Federation)

    2014-08-31

    The capability of using the laser speckle contrast imaging technique with a long exposure time for visualisation of primary acute skin vascular reactions caused by a topical application of a weak contact allergen is considered. The method is shown to provide efficient and accurate detection of irritant-induced primary acute vascular reactions of skin. The presented technique possesses a high potential in everyday diagnostic practice, preclinical studies, as well as in the prognosis of skin reactions to the interaction with potentially allergenic materials. (laser biophotonics)

  8. Optical diagnostics of vascular reactions triggered by weak allergens using laser speckle-contrast imaging technique

    Science.gov (United States)

    Kuznetsov, Yu L.; Kalchenko, V. V.; Astaf'eva, N. G.; Meglinski, I. V.

    2014-08-01

    The capability of using the laser speckle contrast imaging technique with a long exposure time for visualisation of primary acute skin vascular reactions caused by a topical application of a weak contact allergen is considered. The method is shown to provide efficient and accurate detection of irritant-induced primary acute vascular reactions of skin. The presented technique possesses a high potential in everyday diagnostic practice, preclinical studies, as well as in the prognosis of skin reactions to the interaction with potentially allergenic materials.

  9. Allergenicity assessment of genetically-modified tobacco expressing salt tolerance cbl gene.

    Science.gov (United States)

    Verma, Alok Kumar; Kumar, Sandeep; Chaudhari, Bhushan P; Tuteja, Narendra; Das, Mukul; Dwivedi, Premendra D

    2014-09-01

    It is mandatory to assess the allergenic potential of genetically modified (GM) crops before their commercialization. Recently, a transgene [Calcineurin B-like (CBL) protein] has been introduced into tobacco plant to make the crop salt resistance. Therefore, it was felt necessary to assess the allergenic potential of the cbl gene product, which was introduced and expressed in Nicotiana tabacum (tobacco) plant and compared the allergenic effects with the wild-type (WT) counterpart. Bioinformatic analysis revealed that there was no significant sequence homology with known allergens. Also, no difference between the protein digestibility profiles of GM and WT tobacco was found. Rapid digestion of CBL protein (Mol Wt 35 kDa) by simulated gastric fluid (SGF) indicated reduced chances of this protein to induce allergenicity. In addition, BALB/c mice sensitized by intraperitoneal administration of WT and GM tobacco protein showed comparable levels of clinical score, specific IgE, IgG1, histamine level, similar effect on different organs as well as IgE binding proteins. These findings indicate that insertion of cbl gene in tobacco did not cause any additional allergic risk to consumer and the GM and native tobacco proteins behave similarly in both in vitro and in vivo situations even after genetic modification.

  10. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis

    NARCIS (Netherlands)

    Dahl, Ronald; Kapp, Alexander; Colombo, Giselda; deMonchy, Jan G. R.; Rak, Sabina; Emminger, Waltraud; Rivas, Montserrat Fernandez; Ribel, Mette; Durham, Stephen R.

    2006-01-01

    Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. Obje

  11. Effect of oleic acid on the allergenic properties of peanut and cashew allergens

    Science.gov (United States)

    Oleic acid is the major fatty acid in peanuts and cashews. There is limited information about its effect on peanut and cashew allergens during heating. The objective was to determine if heat treatment with oleic acid changes the allergenic properties of these nut proteins. Peanut and cashew protein...

  12. Effects of phytic acid on peanut allergens and allergenic properties of extracts.

    Science.gov (United States)

    Chung, Si-Yin; Champagne, Elaine T

    2007-10-31

    Phytic acid would form soluble and insoluble complexes with proteins. Our objective was to determine if phytic acid forms insoluble complexes with major peanut allergens, and if such reaction results in a peanut extract with a lower level of soluble allergens and allergenic property. Extracts from raw and roasted peanuts were treated with and without phytic acid at various pH values and then analyzed by SDS-PAGE and a competitive inhibition ELISA (ciELISA). The ciELISA measured IgE binding using a pooled serum from peanut-allergic individuals. Results showed that phytic acid formed complexes with the major peanut allergens (Ara h 1 and Ara h 2), which were insoluble in acidic and neutral conditions. Succinylation of the allergens inhibited complex formation, indicating that lysine residues were involved. A 6-fold reduction in IgE binding or allergenic potency of the extract was observed after treatment with phytic acid. It was concluded that phytic acid formed insoluble complexes with the major peanut allergens, and resulted in a peanut extract with reduced allergenic potency. Application of phytic acid to a peanut butter slurry presented a similar result, indicating that phytic acid may find use in the development of hypoallergenic peanut-based products.

  13. Is high pressure treatment able to modify the allergenicity of the largemouth bass allergens?

    Science.gov (United States)

    Liu, Chu-Yi; Tao, Sha; Liu, Rong; Chen, Fu-Sheng; Xue, Wen-Tong

    2012-12-01

    The aim of this paper is to study the influence of high pressure treatment on the structural changes and allergenicity of largemouth bass. We treated the allergens at 100, 200, 300 and 400 MPa for 15 min and at 300 MPa for 5, 10, 15, 20 and 30 min at 20 °C. The treated samples from largemouth bass were tested for their IgE-binding properties by combining Sodium dodecyl sulfate-Polyacrylamide gel electrophoresis (SDS-PAGE) with western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Circular dichroism analysis was performed to characterize the structural change. In summary, we can determine that the greatest structure changes were found for samples treated by 400 MPa for 15 min. High pressure treatment did change the structure, subunit composition and molecular weight of largemouth bass allergens, but it did not change the allergenicity of the allergens.

  14. Sensitive detection of major food allergens in breast milk: first gateway for allergenic contact during breastfeeding.

    Science.gov (United States)

    Pastor-Vargas, C; Maroto, A S; Díaz-Perales, A; Villaba, M; Casillas Diaz, N; Vivanco, F; Cuesta-Herranz, J

    2015-08-01

    Food allergy is recognized as a major public health issue, especially in early childhood. It has been hypothesized that early sensitization to food allergens maybe due to their ingestion as components dissolved in the milk during the breastfeeding, explaining reaction to a food, which has never been taken before. Thus, the aim of this work has been to detect the presence of the food allergens in breast milk by microarray technology. We produced a homemade microarray with antibodies produced against major food allergens. The antibody microarray was incubated with breast milk from 14 women collected from Fundación Jiménez Díaz Hospital. In this way, we demonstrated the presence of major foods allergens in breast milk. The analysis of allergens presented in breast milk could be a useful tool in allergy prevention and could provide us a key data on the role of this feeding in tolerance induction or sensitization in children.

  15. Endogenous allergens and compositional analysis in the allergenicity assessment of genetically modified plants.

    Science.gov (United States)

    Fernandez, A; Mills, E N C; Lovik, M; Spoek, A; Germini, A; Mikalsen, A; Wal, J M

    2013-12-01

    Allergenicity assessment of genetically modified (GM) plants is one of the key pillars in the safety assessment process of these products. As part of this evaluation, one of the concerns is to assess that unintended effects (e.g. over-expression of endogenous allergens) relevant for the food safety have not occurred due to the genetic modification. Novel technologies are now available and could be used as complementary and/or alternative methods to those based on human sera for the assessment of endogenous allergenicity. In view of these developments and as a step forward in the allergenicity assessment of GM plants, it is recommended that known endogenous allergens are included in the compositional analysis as additional parameters to be measured.

  16. Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor.

    Science.gov (United States)

    Bae, Ok-Nam; Ahn, Seyeon; Jin, Sun Hee; Hong, Soo Hyun; Lee, Jinyoung; Kim, Eun-Sun; Jeong, Tae Cheon; Chun, Young-Jin; Lee, Ai-Young; Noh, Minsoo

    2015-03-01

    Allergic contact dermatitis (ACD) is a cell-mediated immune response that involves skin sensitization in response to contact with various allergens. Angiogenesis and lymphangiogenesis both play roles in the allergic sensitization process. Epidermal keratinocytes can produce vascular endothelial growth factor (VEGF) in response to UV irradiation and during wound healing. However, the effect of haptenic chemical allergens on the VEGF production of human keratinocytes, which is the primary contact site of toxic allergens, has not been thoroughly researched. We systematically investigated whether immune-regulatory cytokines and chemical allergens would lead to the production of VEGF in normal human keratinocytes (NHKs) in culture. VEGF production significantly increased when NHKs were treated with IFNγ, IL-1α, IL-4, IL-6, IL-17A, IL-22 or TNFα. Among the human sensitizers listed in the OECD Test Guideline (TG) 429, we found that CMI/MI, DNCB, 4-phenylenediamine, cobalt chloride, 2-mercaptobenzothiazole, citral, HCA, cinnamic alcohol, imidazolidinyl urea and nickel chloride all significantly upregulated VEGF production in NHKs. In addition, common human haptenic allergens such as avobenzone, formaldehyde and urushiol, also induced the keratinocyte-derived VEGF production. VEGF upregulation by pro-inflammatory stimuli, IFNγ, DNCB or formaldehyde is preceded by the production of IL-8, an acute inflammatory phase cytokine. Lymphangiogenic VEGF-C gene transcription was significantly increased when NHKs were treated with formaldehyde, DNCB or urushiol, while transcription of VEGF-A and VEGF-B did not change. Therefore, the chemical allergen-induced VEGF upregulation is mainly due to the increase in lymphangiogenic VEGF-C transcription in NHKs. These results suggest that keratinocyte-derived VEGF may regulate the lymphangiogenic process during the skin sensitization process of ACD.

  17. Inter-laboratory comparisons of assessment of the allergenic potential of proteins in mice.

    Science.gov (United States)

    Herouet-Guicheney, C; Aldemir, H; Bars, R; de Barbeyrac, D; Kennel, P; Rouquié, D; Stahl, B U; Kimber, I; Dearman, R J

    2009-03-01

    Assessment of the potential allergenicity of novel proteins, including those expressed in genetically modified plants, is an important issue. In previous studies, we have shown that the IgE measurement induced by systemic exposure of BALB/c mice to a range of proteins correlates broadly with what is known of their allergenic potential in humans. The approach used a homologous passive cutaneous anaphylaxis (PCA) assay that reflects IgE-dependent biological activity and is of sufficient sensitivity to detect IgE production in the absence of adjuvant. In previous studies, the immunization phase was conducted independently in two separate facilities, and the subsequent analytical work (PCA) conducted in a single facility. The purpose here was to further evaluate the transferability of this approach. To this end, BALB/c mice were exposed to a range of doses of peanut agglutinin or ovalbumin, allergenic proteins of peanut and hen's egg, respectively, in two independent laboratories. Serial doubling dilutions of serum pooled for each treatment group were analyzed for specific IgE. At higher doses of allergen very similar, or identical, IgE titers were achieved in both laboratories, although at lower doses, responses were somewhat more variable. These data demonstrate that, although technically demanding, the measurement of protein allergen-induced IgE antibody production in mice using PCA is relatively robust and is transferable and reproducible between laboratories. This approach may provide a useful tool for the safety assessment of novel proteins and suggests that continued evaluation of the approach with a wider range of protein allergens and non-sensitising proteins is justified.

  18. Allergenic Proteins in Foods and Beverages

    Directory of Open Access Journals (Sweden)

    Fernanda Cosme

    2013-01-01

    Full Text Available Food allergies can be defined as immunologically mediated hypersensitivity reactions; therefore, a food allergy is also known as food hypersensitivity. The reactions are caused by the immune system response to some food proteins. The eight most common food allergens are proteins from milk, eggs, peanuts, tree nuts, soya, wheat, fish and shellfish. However, many other foods have been identified as allergens for some people, such as certain fruits or vegetables and seeds. It is now recognized that food allergens are an important food safety issue. A food allergy occurs when the body’s immune system reacts to otherwise harmless substances in certain foods. For these reasons, one of the requirements from the European Union is that allergenic food ingredients should be labelled in order to protect allergic consumers. According to the European Federation of Allergy and Airways Diseases Patients’ Associations, about 8 % of children and 4 % of adults suffer from some type of food allergy. Food allergies often develop during infant or early childhood ages, affecting mainly the gastrointestinal tract (stomach and intestines. In some cases, the allergy may persist in adult age, for example, coeliac disease, which is an abnormal immune response to certain proteins present in gluten, a type of protein composite found in wheat and barley. Almost all allergens are proteins, and highly sensitive analytical methods have been developed to detect traces of these compounds in food, such as electrophoretic and immunological methods, enzyme-linked immunosorbent assay (ELISA and polyacrylamide gel electrophoresis. The purpose of this review is to describe the allergenic components of the most common causes of food allergies, followed by a brief discussion regarding their importance in the food industry and for consumer safety. The most important methods used to detect allergenicity in food will also be discussed.

  19. Allergens of the entomopathogenic fungus Beauveria bassiana

    Directory of Open Access Journals (Sweden)

    Keyhani Nemat O

    2005-01-01

    Full Text Available Abstract Background Beauveria bassiana is an important entomopathogenic fungus currently under development as a bio-control agent for a variety of insect pests. Although reported to be non-toxic to vertebrates, the potential allergenicity of Beauveria species has not been widely studied. Methods IgE-reactivity studies were performed using sera from patients displaying mould hypersensitivity by immunoblot and immunoblot inhibition. Skin reactivity to B. bassiana extracts was measured using intradermal skin testing. Results Immunoblots of fungal extracts with pooled as well as individual sera showed a distribution of IgE reactive proteins present in B. bassiana crude extracts. Proteinase K digestion of extracts resulted in loss of IgE reactive epitopes, whereas EndoH and PNGaseF (glycosidase treatments resulted in minor changes in IgE reactive banding patterns as determined by Western blots. Immunoblot inhibitions experiments showed complete loss of IgE-binding using self protein, and partial inhibition using extracts from common allergenic fungi including; Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum, Candida albicans, Epicoccum purpurascens, and Penicillium notatum. Several proteins including a strongly reactive band with an approximate molecular mass of 35 kDa was uninhibited by any of the tested extracts, and may represent B. bassiana specific allergens. Intradermal skin testing confirmed the in vitro results, demonstrating allergenic reactions in a number of individuals, including those who have had occupational exposure to B. bassiana. Conclusions Beauveria bassiana possesses numerous IgE reactive proteins, some of which are cross-reactive among allergens from other fungi. A strongly reactive potential B. bassiana specific allergen (35 kDa was identified. Intradermal skin testing confirmed the allergenic potential of B. bassiana.

  20. Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Ok-Nam [College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791 (Korea, Republic of); Ahn, Seyeon; Jin, Sun Hee; Hong, Soo Hyun; Lee, Jinyoung [College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Eun-Sun [College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 426-791 (Korea, Republic of); Jeong, Tae Cheon [College of Pharmacy, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Chun, Young-Jin [College of Pharmacy, Chung-Ang University, Seoul 156-756 (Korea, Republic of); Lee, Ai-Young, E-mail: leeay@duih.org [Department of Dermatology, Dongguk University Ilsan Hospital, Goyang 410-773 (Korea, Republic of); Noh, Minsoo, E-mail: minsoo@alum.mit.edu [College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2015-03-01

    Allergic contact dermatitis (ACD) is a cell-mediated immune response that involves skin sensitization in response to contact with various allergens. Angiogenesis and lymphangiogenesis both play roles in the allergic sensitization process. Epidermal keratinocytes can produce vascular endothelial growth factor (VEGF) in response to UV irradiation and during wound healing. However, the effect of haptenic chemical allergens on the VEGF production of human keratinocytes, which is the primary contact site of toxic allergens, has not been thoroughly researched. We systematically investigated whether immune-regulatory cytokines and chemical allergens would lead to the production of VEGF in normal human keratinocytes (NHKs) in culture. VEGF production significantly increased when NHKs were treated with IFNγ, IL-1α, IL-4, IL-6, IL-17A, IL-22 or TNFα. Among the human sensitizers listed in the OECD Test Guideline (TG) 429, we found that CMI/MI, DNCB, 4-phenylenediamine, cobalt chloride, 2-mercaptobenzothiazole, citral, HCA, cinnamic alcohol, imidazolidinyl urea and nickel chloride all significantly upregulated VEGF production in NHKs. In addition, common human haptenic allergens such as avobenzone, formaldehyde and urushiol, also induced the keratinocyte-derived VEGF production. VEGF upregulation by pro-inflammatory stimuli, IFNγ, DNCB or formaldehyde is preceded by the production of IL-8, an acute inflammatory phase cytokine. Lymphangiogenic VEGF-C gene transcription was significantly increased when NHKs were treated with formaldehyde, DNCB or urushiol, while transcription of VEGF-A and VEGF-B did not change. Therefore, the chemical allergen-induced VEGF upregulation is mainly due to the increase in lymphangiogenic VEGF-C transcription in NHKs. These results suggest that keratinocyte-derived VEGF may regulate the lymphangiogenic process during the skin sensitization process of ACD. - Highlights: • Pro-inflammatory cytokines induced VEGF production in normal human

  1. Mass spectrometry-based identification of allergens from Curvularia pallescens, a prevalent aerospore in India.

    Science.gov (United States)

    Dey, Debarati; Saha, Bodhisattwa; Sircar, Gaurab; Ghosal, Kavita; Bhattacharya, Swati Gupta

    2016-07-01

    The worldwide prevalence of fungal allergy in recent years has augmented mining allergens from yet unexplored ones. Curvularia pallescens (CP) being a dominant aerospore in India and a major sensitiser on a wide range of allergic population, pose a serious threat to human health. Therefore, we aimed to identify novel allergens from CP in our present study. A cohort of 22 CP-sensitised patients was selected by positive Skin prick grade. Individual sera exhibited elevated specific IgE level and significant histamine release on a challenge with antigenic extract of CP. First gel-based profiling of CP proteome was done by 1- and 2-dimensional gel. Parallel 1- and 2-dimensional immunoblot were performed applying individual as well as pooled patient sera. Identification of the sero-reactive spots from the 2-dimensional gel was found to be challenging as CP was not previously sequenced. Hence, mass spectrometry-based proteomic workflow consisting of conventional database search was not alone sufficient. Therefore, de novo sequencing preceded homology search was implemented for further identification. Altogether 11 allergenic proteins including Brn-1, vacuolar protease, and fructose-bis-phosphate aldolase were identified with high statistical confidence (pallergens from CP. This kind of proteome-based analysis provided a catalogue of CP allergens that would lead an improved way of diagnosis and therapy of CP-related allergy.

  2. Developing a preventive immunization approach against insect bite hypersensitivity using recombinant allergens: A pilot study.

    Science.gov (United States)

    Jonsdottir, Sigridur; Hamza, Eman; Janda, Jozef; Rhyner, Claudio; Meinke, Andreas; Marti, Eliane; Svansson, Vilhjalmur; Torsteinsdottir, Sigurbjorg

    2015-07-15

    Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by bites of midges (Culicoides spp.). IgE-mediated reactions are often involved in the pathogenesis of this disease. IBH does not occur in Iceland due to the absence of Culicoides, but it occurs with a high frequency in Icelandic horses exported to mainland Europe, where Culicoides are present. We hypothesize that immunization with the Culicoides allergens before export could reduce the incidence of IBH in exported Icelandic horses. The aim of the present study was therefore to compare intradermal and intralymphatic vaccination using four purified recombinant allergens, in combination with a Th1 focusing adjuvant. Twelve horses were vaccinated three times with 10μg of each of the four recombinant Culicoides nubeculosus allergens. Six horses were injected intralymphatically, three with and three without IC31(®), and six were injected intradermally, in the presence or absence of IC31(®). Antibody responses were measured by immunoblots and ELISA, potential sensitization in a sulfidoleukotriene release test and an intradermal test, cytokine and FoxP3 expression with real time PCR following in vitro stimulation of PBMC. Immunization with the r-allergens induced a significant increase in levels of r-allergen-specific IgG1, IgG1/3, IgG4/7, IgG5 and IgG(T). Application of the r-allergens in IC31(®) adjuvant resulted in a significantly higher IgG1, IgG1/3, IgG4/7 allergen-specific response. Intralymphatic injection was slightly more efficient than intradermal injection, but the difference did not reach significance. Testing of the blocking activity of the sera from the horses immunized intralymphatically with IC31(®) showed that the generated IgG antibodies were able to partly block binding of serum IgE from an IBH-affected horse to these r-allergens. Furthermore, IgG antibodies bound to protein bands on blots of C. nubeculosus salivary gland extract. No allergen-specific IgE was induced and

  3. A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A.

    Science.gov (United States)

    Jonsdottir, Sigridur; Svansson, Vilhjalmur; Stefansdottir, Sara Bjork; Schüpbach, Gertraud; Rhyner, Claudio; Marti, Eliane; Torsteinsdottir, Sigurbjorg

    2016-04-01

    Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides insects, not indigenous to Iceland. Horses born in Iceland and exported to Culicoides-rich areas are frequently affected with IBH. The aims of the study were to compare immunization with recombinant allergens using the adjuvant aluminum hydroxide (Alum) alone or combined with monophosphoryl lipid A (MPLA) for development of a preventive immunization against IBH. Twelve healthy Icelandic horses were vaccinated intralymphatically three times with 10 μg each of four recombinant Culicoides nubeculosus allergens in Alum or in Alum/MPLA. Injection with allergens in both Alum and Alum/MPLA resulted in significant increase in specific IgG subclasses and IgA against all r-allergens with no significant differences between the adjuvant groups. The induced antibodies from both groups could block binding of allergen specific IgE from IBH affected horses to a similar extent. No IgE-mediated reactions were induced. Allergen-stimulated PBMC from Alum/MPLA horses but not from Alum only horses produced significantly more IFNγ and IL-10 than PBMC from non-vaccinated control horses. In conclusion, intralymphatic administration of small amounts of pure allergens in Alum/MPLA induces high IgG antibody levels and Th1/Treg immune response and is a promising approach for immunoprophylaxis and immunotherapy against IBH.

  4. Induced Pluripotent Stem Cell-derived Cardiomyocytes: Cardiac Applications, Opportunities and Challenges.

    Science.gov (United States)

    Moreau, Adrien; Boutjdir, Mohamed; Chahine, Mohamed

    2017-03-28

    Chronic diseases are the primary cause of mortality worldwide, accounting for 67% of deaths. One of the major challenges in developing new treatments is the lack of understanding of the exact underlying biological and molecular mechanisms. Chronic cardiovascular diseases are the single most common cause of death worldwide, and sudden deaths due to cardiac arrhythmias account for approximately 50% of all such cases. Traditional genetic screening for genes involved in cardiac disorders is laborious and frequently fails to detect the mutation that explains or causes the disorder. However, when mutations are identified, human induced pluripotent stem cells (hiPSCs) derived from affected patients make it possible to address fundamental research questions directly relevant to human health. As such, hiPSC technology has recently been used to model human diseases and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) thus offer a unique opportunity to investigate potential disease-causing genetic variants in their natural environment. The purpose of this review is to present the current state of knowledge regarding hiPSC-CMs, including their potential, limitations, and challenges and to discuss future prospects.

  5. Prevalence of Exercise-Induced Bronchospasm by laboratory exercise challenge among Ragunan Sport School athletes

    Directory of Open Access Journals (Sweden)

    Ignatio Rika

    2008-03-01

    Full Text Available Exercise-induced bronchospasm (EIB is a common condition among adolescent athletes. There has been no study examining the prevalence of EIB among adolescent athletes in Indonesia. This study aimed to get the prevalence of EIB among Ragunan Sport School athletes by laboratory exercise challenge. Subjects performed static cycle ergometer exercise (Monark, Sweden to reach minimal workload of 90% maximal heart rate. Force expiratory ventilation (FEV₁ was examined by spirometry (Minato AS-PAL, Japan at minute 0, 5, 10 and 20 post exercise. The EIB was defined as a decline of FEV₁ as much as 10% or more from baseline value. Room temperature and humidity were 28°C-31°C and 74%-82% respectively. There were 168 athletes from 12 sport types who participated in this study. Among them, 23 athletes (13.7% were EIB positive. The highest percentage of EIB was in taekwondo (54.5%. Sixteen athletes with EIB (70% were from less asthmogenic sports. Athletes with EIB consisted of 17 (17.5% females and 6 (8.4% males. In conclusion, the prevalence of EIB among adolescent athletes was moderately high, and was more prevalent in female. More over, laboratory exercise challenge could elicit EIB in less asthmogenic sport. (Med J Indones 2008; 17: 33-6Keywords: adolescent athlete, asthmogenic sports

  6. Evaluation of the Allergenicity Potential of TcPR-10 Protein from Theobroma cacao

    Science.gov (United States)

    Cardoso, Thyago Hermylly Santana; Pirovani, Carlos Priminho; Micheli, Fabienne; Noronha, Fátima Soares Motta; Alves, Andréa Catão; Faria, Ana Maria Caetano; da Silva Gesteira, Abelmon

    2012-01-01

    Background The pathogenesis related protein PR10 (TcPR-10), obtained from the Theobroma cacao-Moniliophthora perniciosa interaction library, presents antifungal activity against M. perniciosa and acts in vitro as a ribonuclease. However, despite its biotechnological potential, the TcPR-10 has the P-loop motif similar to those of some allergenic proteins such as Bet v 1 (Betula verrucosa) and Pru av 1 (Prunus avium). The insertion of mutations in this motif can produce proteins with reduced allergenic power. The objective of the present work was to evaluate the allergenic potential of the wild type and mutant recombinant TcPR-10 using bioinformatics tools and immunological assays. Methodology/Principal Findings Mutant substitutions (T10P, I30V, H45S) were inserted in the TcPR-10 gene by site-directed mutagenesis, cloned into pET28a and expressed in Escherichia coli BL21(DE3) cells. Changes in molecular surface caused by the mutant substitutions was evaluated by comparative protein modeling using the three-dimensional structure of the major cherry allergen, Pru av 1 as a template. The immunological assays were carried out in 8–12 week old female BALB/c mice. The mice were sensitized with the proteins (wild type and mutants) via subcutaneous and challenged intranasal for induction of allergic airway inflammation. Conclusions/Significance We showed that the wild TcPR-10 protein has allergenic potential, whereas the insertion of mutations produced proteins with reduced capacity of IgE production and cellular infiltration in the lungs. On the other hand, in vitro assays show that the TcPR-10 mutants still present antifungal and ribonuclease activity against M. perniciosa RNA. In conclusion, the mutant proteins present less allergenic potential than the wild TcPR-10, without the loss of interesting biotechnological properties. PMID:22768037

  7. Evaluation of the allergenicity potential of TcPR-10 protein from Theobroma cacao.

    Directory of Open Access Journals (Sweden)

    Sara Pereira Menezes

    Full Text Available BACKGROUND: The pathogenesis related protein PR10 (TcPR-10, obtained from the Theobroma cacao-Moniliophthora perniciosa interaction library, presents antifungal activity against M. perniciosa and acts in vitro as a ribonuclease. However, despite its biotechnological potential, the TcPR-10 has the P-loop motif similar to those of some allergenic proteins such as Bet v 1 (Betula verrucosa and Pru av 1 (Prunus avium. The insertion of mutations in this motif can produce proteins with reduced allergenic power. The objective of the present work was to evaluate the allergenic potential of the wild type and mutant recombinant TcPR-10 using bioinformatics tools and immunological assays. METHODOLOGY/PRINCIPAL FINDINGS: Mutant substitutions (T10P, I30V, H45S were inserted in the TcPR-10 gene by site-directed mutagenesis, cloned into pET28a and expressed in Escherichia coli BL21(DE3 cells. Changes in molecular surface caused by the mutant substitutions was evaluated by comparative protein modeling using the three-dimensional structure of the major cherry allergen, Pru av 1 as a template. The immunological assays were carried out in 8-12 week old female BALB/c mice. The mice were sensitized with the proteins (wild type and mutants via subcutaneous and challenged intranasal for induction of allergic airway inflammation. CONCLUSIONS/SIGNIFICANCE: We showed that the wild TcPR-10 protein has allergenic potential, whereas the insertion of mutations produced proteins with reduced capacity of IgE production and cellular infiltration in the lungs. On the other hand, in vitro assays show that the TcPR-10 mutants still present antifungal and ribonuclease activity against M. perniciosa RNA. In conclusion, the mutant proteins present less allergenic potential than the wild TcPR-10, without the loss of interesting biotechnological properties.

  8. Allergen avoidance: does it work?

    Science.gov (United States)

    Woodcock, A; Custovic, A

    2000-01-01

    The first recorded example of allergen avoidance in the treatment of allergic disorders dates from the 16th century. The Italian physician Gerolamo Cardano (1501-1576) was invited to Scotland by John Hamilton, Archbishop of St Andrews (and brother of the Regent), to give advice on the treatment of his asthma. Cardano recommended that the Archbishop should get rid of his feather bedding, which was followed by a 'miraculous' remission of otherwise troublesome symptoms. The first controlled attempts to treat asthma by environmental manipulation date to the beginning of 20th century. In 1925, the Leopold brothers treated patients with asthma and other allergic disorders by moving them into a dust free room. Storm van Leeuwen created a 'climate' chamber in The Netherlands in 1927 and demonstrated that asthmatic patients improved when moved from their homes into the chamber. One year later, Dekker observed that measures aimed at reducing the amount of dust in bedrooms had a beneficial effect on asthma symptoms in patients allergic to house dust. Van Leeuwen wrote: 'In our endeavours to find the cause of the attack ... we utilised the known fact that the environment of the asthmatic patient is, as a rule, of primary importance in determining the intensity and frequency of his attacks'. Nowadays, more than ever, it is essential to address the environmental influences on the increasing prevalence of asthma and allergic disorders.

  9. Domestic cat allergen and allergic sensitisation in young children

    NARCIS (Netherlands)

    Chen, Chih-Mei; Gehring, Ulrike; Wickman, Magnus; Hoek, Gerard; Giovannangelo, Mariella; Nordling, Emma; Wijga, Alet; de Jongste, Johan; Pershagen, Goeran; Almqvist, Catarina; Kerkhof, Marjan; Bellander, Tom; Wichmann, H. -Erich; Brunekreef, Bert; Heinrich, Joachim

    2008-01-01

    Studies have presented conflicting associations between cat allergen exposure and sensitisation and atopic disease. We therefore investigated the association between the observed domestic cat allergen level and cat sensitisation in young children in four study populations from three European countri

  10. 78 FR 66011 - Allergenic Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-11-04

    ..., perennial rye, Timothy, and Kentucky bluegrass mixed pollens allergen extract tablet for sublingual use... recommendations on the safety and efficacy of Grastek, a Timothy grass pollen allergen extract tablet...

  11. 76 FR 59406 - Allergenic Products Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-09-26

    ... medical literature concerning the use of non-standardized allergen extracts in the diagnosis and treatment... Scientific and Medical Literature and Information on Non-Standardized Allergen Extracts in the Diagnosis...

  12. ROLE OF ENVIRONMENTAL ALLERGENS ON ATOPIC DERMATITIS

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    M. Wardhana

    2014-01-01

    Full Text Available Background: Atopic dermatitis (AD is a chronic eczematous skin disease that develops in a patient with atopic diathesis, which is characterized by an increased liability to produce IgE antibodies for allergens mostly derived from environmental or inhalant allergens and food allergens. They are produced by cell-mediated allergic contact reactions, and recently contact sensitivity to various environmental allergens has been demonstrated in patients with AD. Atopic patients are recognized by their ability to produce large amounts of specific IgE antibodies to common substances as environmental allergens, i.e. house dust mites, grass pollens, animal danders, molds, food, etc. These antibodies can be detected by skin prick test. The aim of this study was to identify the sensitization against environmental or inhalants allergens through skin prick tests in the patients with atopic dermatitis. Material and Methods: This is a retrospective, descriptive study. We revised all medical records of patients with AD since January 2002 to December 2004 in the Out Patients Unit of Sanglah General Hospital, Bali-Indonesia. The variables studied were: gender, age, work related, diagnosis associates to AD, and prick test of environmental allergens. Results: In 3 years periods we had revised 46 of patients with AD that was done skin prick tests. The median age was 38 years (range 29-54 years, 34/46 (73.9 % of these were male and 12 (26.1 % female. Twenty nine patients presented pure AD, and 17 patients had AD with asthma and allergic rhinitis. Only 16 (34.7% of patients had no history of allergic disease. Thirsty six of 46 (78.20% of all tested AD patients had a positive skin prick tests against inhalant (aeroallergens 16 patients and food allergens 21 patients. Sixteen patients with positive of skin test include; dust mite in 12 patients, animal dander in 10 patients, grass pollen in 9 patients and cockroach in 6 patients. Conclusion: We concluded that

  13. HYMENOPTERA ALLERGENS: FROM VENOM TO VENOME

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    Edzard eSpillner

    2014-02-01

    Full Text Available In Western Europe hymenoptera venom allergy primarily relates to venoms of the honeybee and the common yellow jacket. In contrast to other allergen sources, only a few major components of hymenoptera venoms had been characterized until recently. Improved expression systems and proteomic detection strategies have allowed the identification and characterization of a wide range of additional allergens. The field of hymenoptera venom allergy research has moved rapidly from focusing on venom extract and single major allergens to a molecular understanding of the entire venome as a system of unique and characteristic components. An increasing number of such components has been identified, characterized regarding function and assessed for allergenic potential. Moreover, advanced expression strategies for recombinant production of venom allergens allow selective modification of molecules and provide insight into different types of IgE reactivities and sensitization patterns. The obtained information contributes to an increased diagnostic precision in hymenoptera venom allergy and may serve for monitoring, reevaluation and improvement of current therapeutic strategies.

  14. Indoor determinants of dustborne allergens in Mexican homes.

    Science.gov (United States)

    Hernández-Cadena, Leticia; Zeldin, Darryl C; Barraza-Villarreal, Albino; Sever, Michelle L; Sly, Peter D; London, Stephanie J; Escamilla-Nuñez, María Consuelo; Romieu, Isabelle

    2015-01-01

    Exposure to indoor allergens represents a significant risk factor for allergies and asthma in several parts of the world. In Mexico, few studies have evaluated indoor allergens, including cat, dog, and mouse allergens and the factors that predict their presence. This study evaluates the main environmental and household predictors of high prenatal allergen levels and multiple allergen exposures in a birth cohort from Mexico City. A cross-sectional study was conducted as part of a birth cohort study of 1094 infants recruited during pregnancy and followed until delivery. We collected dust samples in a subset of 264 homes and assessed environmental factors. Der p 1, Der f 1, dust mite group 2, Fel d 1, Can f 1, Rat n 1, Mus m 1, and Bla g 2 concentrations in dust samples were measured using immunoassays. To define detectable allergen levels, the lowest limits of detection for each allergen were taken as cutoff points. Overall allergen exposure was considered high when four or more allergens exceeded detectable levels in the same household. Logistic regression was used for predictive models. Eighty-five percent of homes had at least one allergen in dust over the detection limit, 52.1% had high exposure (four or more allergens above detectable limits), and 11.7% of homes had detectable levels for more than eight allergens. Der p 1, Der p 2, Mus m 1, and Fel d 1 were the most frequent allergens detected. Each allergen had both common and distinct predictors. The main predictors of a high multiple allergen index were the size of the home, pesticide use, mother's age, mother as homemaker, and season. Increased indoor environmental allergen exposure is mainly related to sociodemographic factors and household cleaning.

  15. The current state of recombinant allergens for immunotherapy

    DEFF Research Database (Denmark)

    Pauli, Gabrielle; Malling, H-J

    2010-01-01

    Subcutaneous immunotherapy is a well documented treatment of allergic rhinitis and asthma. The majority of the disadvantages of the treatment are related to the poor quality of the natural allergen extracts which can contain varying amounts of individual allergens including allergens to which...

  16. Oxazolone (OXA) is a respiratory allergen in Brown Norway rats

    NARCIS (Netherlands)

    Kuper, C.F.; Radonjic, M.; Triel, J. van; Stierum, R.; Groot, R.J. de; Arts, J.H.E.

    2011-01-01

    Oxazolone (OXA) is a potent contact allergen in man, and it is used as a model Th1-allergen to test (Q)SAR's and screening assays for allergenic potential of chemicals. However, it elevates serum IgE levels and Thelper2 cytokines at relatively low doses in test animals, suggesting that it has also r

  17. An alternative inhibition method for determining cross-reactive allergens

    NARCIS (Netherlands)

    Schmidt-Hieltjes, Yvonne; Teodorowicz, Malgorzata; Jansen, Ad; Hartog, Den Gerco; Elfvering-Berendsen, Lisette; Jong, De Nicolette W.; Savelkoul, Huub F.J.; Ruinemans-Koerts, Janneke

    2017-01-01

    Inhibition assays are an useful tool to identify the allergen of primary sensitization of cross-reactive allergens. Classical ELISA-based inhibition assays are limited by both the availability of commercial standardized allergen extracts and the experience and knowledge needed for making home-made e

  18. Diesel exhaust particles and allergenicity of pollen grains of Lilium martagon.

    Science.gov (United States)

    Chehregani, Abdolkarim; Kouhkan, Fatemeh

    2008-03-01

    Diesel exhaust particles are considered as the most important parts of air pollutants. Diesel exhaust particles have been shown to express both adjuvant activity for sensitization against common allergens and enhancing effects on allergic symptoms in sensitized individuals. In this research, pollen grains of Lilium martagon that are known as a non-allergic substance were collected and exposed to DEP 5 and 10 days. The allergy potency of different pollen extracts were compared by means of skin test, as well as analyses blood eosinophil numbers and IgE levels in the treated animals. Normal and DEP-exposed pollen grains were examined by scanning electron microscopy. Pollen extracts were also studied by SDS-PAGE for DEP-induced changes in protein profiles. Allergic bands were also studied and checked by using immunoblotting method. The results of the investigated allergy tests showed that DEP-exposed pollen grains are effective in inducing allergic symptoms. According to our microscopic observations, organic substances that exist in the DEP, mediate agglomeration of particles on the pollen surface. In appropriate conditions, water-soluble components of DEP may induce changes that affect the release of pollen proteins. SDS-PAGE showed protein profiles of pollen grains were changed and some new bands appeared in DEP-exposed pollen grains. Immunoblotting studies showed a new band in DEP-exposed pollen grains that react strongly with anti-IgE, but there is no allergenic band in normal pollen grains. On the other hand, diesel exhaust particles can carry pollen allergen molecules, induce new proteins (allergens), and also act as adjuvant for allergens.

  19. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

    NARCIS (Netherlands)

    Bøgh, Katrine Lindholm; Bilsen, van Jolanda; Głogowski, Robert; López-Expósito, Iván; Bouchaud, Grégory; Blanchard, Carine; Bodinier, Marie; Smit, Joost; Pieters, Raymond; Bastiaan-Net, Shanna; Wit, de Nicole; Untersmayr, Eva; Adel-Patient, Karine; Knippels, Leon; Epstein, Michelle M.; Noti, Mario; Nygaard, Unni Cecilie; Kimber, Ian; Verhoeckx, Kitty; O'Mahony, Liam

    2016-01-01

    Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced

  20. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

    NARCIS (Netherlands)

    Bøgh, Katrine Lindholm; Bilsen, Jolanda van; Głogowski, Robert; López‑Expósito, Iván; Bouchaud, Grégory; Blanchard, Carine; Bodinier, Marie; Smit, Joost; Pieters, Raymond; Bastiaan‑Net, Shanna; Wit, Nicole de; Untersmayr, Eva; Adel‑Patient, Karine; Knippels, Leon; Epstein, Michelle M.; Noti, Mario; Nygaard, Unni Cecilie; Kimber, Ian; Verhoeckx, Kitty; O’Mahony, Liam

    2016-01-01

    From the article: Abstract Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovat

  1. Allergenic proteins of natural rubber latex.

    Science.gov (United States)

    Yeang, H Y; Arif, Siti Arija M; Yusof, Faridah; Sunderasan, E

    2002-05-01

    As the living cytoplasm of laticiferous cells, Hevea brasiliensis latex is a rich blend of organic substances that include a mélange of proteins. A small number of these proteins have given rise to the problem of latex allergy. The salient characteristics of H. brasiliensis latex allergens that are recognized by the International Union of Immunological Societies (IUIS) are reviewed. These are the proteins associated with the rubber particles, the cytosolic C-serum proteins and the B-serum proteins that originate mainly from the lutoids. Procedures for the isolation and purification of latex allergens are discussed, from latex collection in the field to various preparative approaches adopted in the laboratory. As interest in recombinant latex allergens increases, there is a need to validate recombinant proteins to ascertain equivalence with their native counterparts when used in immunological studies, diagnostics, and immunotherapy.

  2. Multiplex Assay for Protein Profiling and Potency Measurement of German Cockroach Allergen Extracts.

    Directory of Open Access Journals (Sweden)

    Taruna Khurana

    Full Text Available German cockroach (GCr allergens induce IgE responses and may cause asthma. Commercial GCr allergen extracts are variable and existing assays may not be appropriate for determining extract composition and potency.Our aim was to develop a multiplex antibody/bead-based assay for assessment of GCr allergen extracts.Single chain fragment variable (scFv antibodies against GCr were obtained by screening libraries derived from naïve human lymphocytes and hyperimmunized chicken splenocytes and bone marrow. Selected clones were sequenced and characterized by immunoblotting. Eighteen scFv antibodies (17 chicken, 1 human coupled to polystyrene beads were used in this suspension assay; binding of targeted GCr allergens to antibody-coated beads was detected using rabbit antisera against GCr, and against specific allergens rBla g 1, rBla g 2, and rBla g 4. The assay was tested for specificity, accuracy, and precision. Extracts were also compared by IgE competition ELISA.Chicken scFv's generated eight different binding patterns to GCr proteins from 14 to 150 kDa molecular weight. Human scFv's recognized a 100 kDa GCr protein. The multiplex assay was found to be specific and reproducible with intra-assay coefficient of variation (CV of 2.64% and inter-assay CV of 10.0%. Overall potencies of various GCr extracts were calculated using mean logEC50s for eight selected scFvs. Overall potency measures were also analyzed by assessing the contributions to potency of each target.An scFv antibody-based multiplex assay has been developed capable of simultaneously measuring different proteins in a complex mixture, and to determine the potencies and compositions of allergen extracts.

  3. Quantification of Anisakis simplex allergens in fresh, long-term frozen, and cooked fish muscle.

    Science.gov (United States)

    Rodríguez-Mahillo, Ana Isabel; González-Muñoz, Miguel; de las Heras, Cristina; Tejada, Margarita; Moneo, Ignacio

    2010-08-01

    Fish-borne parasitic zoonoses such as Anisakiasis were once limited to people living in countries where raw or undercooked fish is traditionally consumed. Nowadays, several factors, such as the growing international markets, the improved transportation systems, the population movements, and the expansion of ethnic ways of cooking in developed countries, have increased the population exposed to these parasites. Improved diagnosis technology and a better knowledge of the symptoms by clinicians have increased the Anisakiasis cases worldwide. Dietary recommendations to Anisakis-sensitized patients include the consumption of frozen or well-cooked fish, but these probably do not defend sensitized patients from allergen exposure. The aim of our work was to develop a sensitive and specific method to detect and quantify Anisakis simplex allergens in fish muscle and its derivatives. Protein extraction was made in saline buffer followed by preparation under acid conditions. A. simplex antigens were detected by IgG immunoblot and quantified by dot blot. The allergenic properties of the extracts were assessed by IgE immunoblotting and basophil activation test. We were able to detect less than 1 ppm of A. simplex antigens, among them the allergen Ani s 4, in fish muscle with no cross-reactions and with a recovery rate of 82.5%. A. simplex antigens were detected in hakes and anchovies but not in sardines, red mullets, or shellfish. We detected A. simplex allergens in cooked hakes and also in hake stock. We proved that A. simplex allergens are preserved in long-term frozen storage (-20 degrees C +/- 2 degrees C for 11 months) of parasitized hakes. Basophil activation tests have proven the capability of the A. simplex-positive fish extracts to induce allergic symptoms.

  4. Comparison of Allergenicity at Gly m 4 and Gly m Bd 30K of Soybean after Genetic Modification.

    Science.gov (United States)

    Tsai, Jaw-Ji; Chang, Ching-Yun; Liao, En-Chih

    2017-02-15

    Despite rapid growth of genetically modified (GM) crops, effective evaluations of genetic modification on allergenicity are still lacking. Gly m Bd 30K is cross-reactive with cow's milk protein casein, Gly m 4, and with birch pollen allergen Bet v 1. Here we compared the allergenicity between GM and non-GM soybeans with respect to the foci Gly m 4 and Gly m Bd 30K. Recombinant allergens of Gly m Bd 30K and Gly m 4 were generated and polyclonal antibodies raised to identify these two allergenic components in soybeans. GM soybean was first PCR-confirmed using 35S promoter. A total of 20 soybeans (half GM, half non-GM) obtained from a food market were used to assess their allergenicity based on IgE-binding and histamine release. The concentrations of Gly m Bd 30K and Gly m 4 in soybeans were then determined. Most soybean-allergic patients (9 of 10) showed IgE-positive reactions to the allergen of 30 kDa in molecular weight. That allergen turned out to be Glycine max Gly m Bd 30K based on LC-MS/MS analyses. Gly m Bd 30K is therefore the major allergen in the soybean. An increase in the transcription of both the Gly m 4 (stress-induced protein SAM22) and Gly m Bd 28K (soybean allergen precursor) was found after genetic modification. The protein concentrations of Gly m 4 and Gly m Bd 30K were not statistically significant different between non-GM and GM soybeans. There were also no statistical significances between them in the tests of IgE binding and histamine release. In conclusion, soybeans showed similar concentrations of Gly m Bd 30K and Gly m 4 regardless of genetic modification or absence thereof. The allergenicity of both Gly m Bd 30K and Gly m 4 was therefore not altered after genetic modification. Patients showing hypersensitivity to soybeans and who had pre-existing allergy to birch pollen and cow's milk casein might not further increase their allergic reactions following exposures to the GM soybeans.

  5. Search for Allergens from the Pollen Proteome of Sunflower (Helianthus annuus L.: A Major Sensitizer for Respiratory Allergy Patients.

    Directory of Open Access Journals (Sweden)

    Nandini Ghosh

    Full Text Available Respiratory allergy triggered by pollen allergens is increasing at an alarming rate worldwide. Sunflower pollen is thought to be an important source of inhalant allergens. Present study aims to identify the prevalence of sunflower pollinosis among the Indian allergic population and characterizes the pollen allergens using immuno-proteomic tools.Clinico-immunological tests were performed to understand the prevalence of sensitivity towards sunflower pollen among the atopic population. Sera from selected sunflower positive patients were used as probe to detect the IgE-reactive proteins from the one and two dimensional electrophoretic separated proteome of sunflower pollen. The antigenic nature of the sugar moiety of the glycoallergens was studied by meta-periodate modification of IgE-immunoblot. Finally, these allergens were identified by mass-spectrometry.Prevalence of sunflower pollen sensitization was observed among 21% of the pollen allergic population and associated with elevated level of specific IgE and histamine in the sera of these patients. Immunoscreening of sunflower pollen proteome with patient sera detected seven IgE-reactive proteins with varying molecular weight and pI. Hierarchical clustering of 2D-immunoblot data highlighted three allergens characterized by a more frequent immuno-reactivity and increased levels of IgE antibodies in the sera of susceptible patients. These allergens were considered as the major allergens of sunflower pollen and were found to have their glycan moiety critical for inducing IgE response. Homology driven search of MS/MS data of these IgE-reactive proteins identified seven previously unreported allergens from sunflower pollen. Three major allergenic proteins were identified as two pectate lyases and a cysteine protease.Novelty of the present report is the identification of a panel of seven sunflower pollen allergens for the first time at immuno-biochemical and proteomic level, which substantiated the

  6. Generation of an allergy vaccine by disruption of the three-dimensional structure of the cross-reactive calcium-binding allergen, Phl p 7.

    Science.gov (United States)

    Westritschnig, Kerstin; Focke, Margarete; Verdino, Petra; Goessler, Walter; Keller, Walter; Twardosz, Anna; Mari, Adriano; Horak, Friedrich; Wiedermann, Ursula; Hartl, Arnulf; Thalhamer, Josef; Sperr, Wolfgang R; Valent, Peter; Valenta, Rudolf

    2004-05-01

    The grass pollen allergen, Phl p 7, belongs to a family of highly cross-reactive calcium-binding pollen allergens. Because Phl p 7 contains most of the disease-eliciting epitopes of pollen-derived calcium-binding allergens, hypoallergenic variants were engineered according to the x-ray crystal structure of Phl p 7 for allergy vaccination. In three recombinant variants, amino acids essential for calcium binding were mutated, and two peptides comprising the N- and C-terminal half were obtained by synthetic peptide chemistry. As determined by circular dichroism analysis and size exclusion chromatography coupled to mass spectrometry, recombinant mutants showed altered structural fold and lacked calcium-binding capacity, whereas the two synthetic peptides had completely lost their structural fold. Allergic patients' IgE Ab binding was strongest reduced to the variant containing two mutations in each of the two calcium-binding sites and to the peptides. Basophil histamine release and skin test experiments in allergic patients identified the peptides as the vaccine candidates with lowest allergenic activity. Immunization of rabbits with the peptides induced IgG Abs that blocked allergic patients' IgE binding to Phl p 7 and inhibited allergen-induced basophil degranulation. Our results indicate that disruption of an allergen's three-dimensional structure represents a general strategy for the generation of hypoallergenic allergy vaccines, and demonstrate the importance of allergen-specific IgG Abs for the inhibition of immediate allergic symptoms.

  7. 1H, 13C and 15N resonance assignments and second structure information of Fag s 1: Fagales allergen from Fagus sylvatica.

    Science.gov (United States)

    Moraes, A H; Asam, C; Batista, A; Almeida, F C L; Wallner, M; Ferreira, F; Valente, A P

    2016-04-01

    Fagales allergens belonging to the Bet v 1 family account responsible for the majority of spring pollinosis in the temperate climate zones in the Northern hemisphere. Among them, Fag s 1 from beech pollen is an important trigger of Fagales pollen associated allergic reactions. The protein shares high similarity with birch pollen Bet v 1, the best-characterized member of this allergen family. Of note, recent work on Bet v 1 and its homologues found in Fagales pollen demonstrated that not all allergenic members of this family have the capacity to induce allergic sensitization. Fag s 1 was shown to bind pre-existing IgE antibodies most likely primarily directed against other members of this multi-allergen family. Therefore, it is especially interesting to compare the structures of Bet v 1-like pollen allergens, which have the potential to induce allergic sensitization with allergens that are mainly cross-reactive. This in the end will help to identify allergy eliciting molecular pattern on Bet v 1-like allergens. In this work, we report the (1)H, (15)N and (13)C NMR assignment of beech pollen Fag s 1 as well as the secondary structure information based on backbone chemical shifts.

  8. Multiplex detection of food allergens and gluten.

    Science.gov (United States)

    Cho, Chung Y; Nowatzke, William; Oliver, Kerry; Garber, Eric A E

    2015-05-01

    To help safeguard the food supply and detect the presence of undeclared food allergens and gluten, most producers and regulatory agencies rely on commercial test kits. Most of these are ELISAs with a few being PCR-based. These methods are very sensitive and analyte specific, requiring different assays to detect each of the different food allergens. Mass spectrometry offers an alternative approach whereby multiple allergens may be detected simultaneously. However, mass spectrometry requires expensive equipment, highly trained analysts, and several years before a quantitative approach can be achieved. Using multianalyte profiling (xMAP®) technology, a commercial multiplex test kit based on the use of established antibodies was developed for the simultaneous detection of up to 14 different food allergens plus gluten. The assay simultaneously detects crustacean seafood, egg, gluten, milk, peanut, soy, and nine tree nuts (almond, Brazil nut, cashew, coconut, hazelnut, macadamia, pine nut, pistachio, and walnut). By simultaneously performing multiple tests (typically two) for each analyte, this magnetic bead-based assay offers built-in confirmatory analyses without the need for additional resources. Twenty-five of the assays were performed on buffer extracted samples, while five were conducted on samples extracted using reduced-denatured conditions. Thus, complete analysis for all 14 allergens and gluten requires only two wells of a 96-well microtiter plate. This makes it possible to include in a single analytical run up to 48 samples. All 30 bead sets in this multiplex assay detected 5 ng/mL of food allergen and gluten with responses greater than background. In addition, 26 of the bead sets displayed signal/noise ratios of five or greater. The bead-based design makes this 30-plex assay expandable to incorporate new antibodies and capture/detector methodologies by ascribing these new detectors to any of the unassigned bead sets that are commercially available.

  9. Parvalbumin--the major tropical fish allergen.

    Science.gov (United States)

    Lim, Dawn Li-Chern; Neo, Keng Hwee; Yi, Fong Cheng; Chua, Kaw Yan; Goh, Denise Li-Meng; Shek, Lynette Pei-Chi; Giam, Yoke Chin; Van Bever, Hugo P S; Lee, Bee Wah

    2008-08-01

    Fish allergy is common in countries where consumption is high. Asian nations are amongst the world's largest consumers of fish but the allergen profiles of tropical fish are unknown. This study sought to evaluate the allergenicity of four commonly consumed tropical fish, the threadfin (Polynemus indicus), Indian anchovy (Stolephorus indicus), pomfret (Pampus chinensis) and tengirri (Scomberomorus guttatus). Immunoglobulin E (IgE) cross-reactivity with parvalbumin of cod fish (Gad c 1), the major fish allergen, was also studied. Detection of tropical fish and cod specific-IgE was performed by UniCap assay, and skin prick tests were also carried out. The IgE-binding components of tropical fish were identified using IgE immunoblot techniques, and cross-reactivity with Gad c 1 was assessed by ELISA inhibition and IgE immunoblot inhibition. Clinically, nine of 10 patients studied were allergic to multiple fish. All patients exhibited detectable specific-IgE to cod fish (10 of 10 skin prick test positive, eight of 10 UniCap assay positive) despite lack of previous exposure. The major allergen of the four tropical fish was the 12-kDa parvalbumin. IgE cross-reactivity of these allergens to Gad c 1 was observed to be moderate to high in the tropical fish studied. Parvalbumins are the major allergens in commonly consumed tropical fish. They are cross-reactive with each other as well as with Gad c 1. Commercial tests for cod fish appear to be sufficient for the detection of tropical fish specific-IgE.

  10. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Greiff Lennart

    2012-06-01

    Full Text Available Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779. In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003. Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.

  11. Novel Approaches and Perspectives in Allergen Immunotherapy

    DEFF Research Database (Denmark)

    Hoffmann, Hans Jürgen; Valovirta, Erkka; Pfaar, Oliver;

    2017-01-01

    In this review we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the 1(st) Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December, 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium...... have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments like peptide immunotherapy, intralymphatic immunotherapy and use of recombinant allergens herald a new age in which AIT may address treatment of allergy as a public health issue by reaching a large...

  12. Citral a fragrance allergen and irritant

    DEFF Research Database (Denmark)

    Heydorn, S; Menné, T; Andersen, Klaus Ejner;

    2003-01-01

    Citral is a well known contact allergen and a contact irritant. Routine patch testing in the past may have been restricted because of possible irritant (IR) patch test responses. 586 consecutive patients, with hand eczema, were patch tested with a selection of fragrances including citral 2...... and positive patch test reactions to other fragrances compared with IR reactions (n = 82) was established. The difference regarding fragrance history found between those with IR and positive reactions to citral was not significant. Citral could be an allergen and/or irritant, worthy of further more extensive...

  13. The current state of recombinant allergens for immunotherapy

    DEFF Research Database (Denmark)

    Pauli, Gabrielle; Malling, H-J

    2010-01-01

    Subcutaneous immunotherapy is a well documented treatment of allergic rhinitis and asthma. The majority of the disadvantages of the treatment are related to the poor quality of the natural allergen extracts which can contain varying amounts of individual allergens including allergens to which...... the patient may not be sensitized. Recombinant allergens offer a possibility to use well defined molecules with consistent pharmaceutical quality defined in mass units. The proof of concept of the clinical efficacy of recombinant allergens is based on two studies published as full articles....

  14. Prioritisation of allergenic foods with respect to public health relevance: Report from an ILSI Europe Food Allergy Task Force Expert Group.

    Science.gov (United States)

    Houben, Geert; Burney, Peter; Chan, Chun-Han; Crevel, René; Dubois, Anthony; Faludi, Roland; Klein Entink, Rinke; Knulst, André; Taylor, Steve; Ronsmans, Stefan

    2016-03-01

    Regulators and risk managers in general need to decide whether an allergenic food or ingredient is of such public health importance that it needs to be actively managed. There is therefore a need to scale the relative allergenicity of foods and ingredients according to the hazards they pose. Objective criteria increase transparency and trust in this decision-making process and its conclusions. This paper proposes a framework that allows categorisation and prioritisation of allergenic foods according to their public health importance. The challenge is to find a basis on which the allergenicity of foods can best be described and a method to combine the relevant measures of allergenicity into a scoring system that prioritises allergenic foods on the basis of their public health relevance. The framework is designed in accordance with the generic risk analysis principles used in food safety and can be used by regulators to decide whether or not a specific allergenic food or ingredient is of sufficient public health importance that it warrants regulation (i.e. mandatory labelling) when used in the production of food products.

  15. Mutant Brucella abortus membrane fusogenic protein induces protection against challenge infection in mice.

    Science.gov (United States)

    de Souza Filho, Job Alves; de Paulo Martins, Vicente; Campos, Priscila Carneiro; Alves-Silva, Juliana; Santos, Nathalia V; de Oliveira, Fernanda Souza; Menezes, Gustavo B; Azevedo, Vasco; Cravero, Silvio Lorenzo; Oliveira, Sergio Costa

    2015-04-01

    Brucella species can cause brucellosis, a zoonotic disease that causes serious livestock economic losses and represents a public health threat. The mechanism of virulence of Brucella spp. is not yet fully understood. Therefore, it is crucial to identify new molecules that serve as virulence factors to better understand this host-pathogen interplay. Here, we evaluated the role of the Brucella membrane fusogenic protein (Mfp) and outer membrane protein 19 (Omp19) in bacterial pathogenesis. In this study, we showed that B. abortus Δmfp::kan and Δomp19::kan deletion mutant strains have reduced persistence in vivo in C57BL/6 and interferon regulatory factor 1 (IRF-1) knockout (KO) mice. Additionally, 24 h after macrophage infection with a Δmfp::kan or Δomp19::kan strain expressing green fluorescent protein (GFP) approximately 80% or 65% of Brucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP-1, respectively, whereas around 60% of BCVs containing wild-type S2308 were found in LAMP-1-negative compartments. B. abortus Δomp19::kan was attenuated in vivo but had a residual virulence in C57BL/6 and IRF-1 KO mice, whereas the Δmfp::kan strain had a lower virulence in these same mouse models. Furthermore, Δmfp::kan and Δomp19::kan strains were used as live vaccines. Challenge experiments revealed that in C57BL/6 and IRF-1 KO mice, the Δmfp::kan strain induced greater protection than the vaccine RB51 and protection similar that of vaccine S19. However, a Δomp19::kan strain induced protection similar to that of RB51. Thus, these results demonstrate that Brucella Mfp and Omp19 are critical for full bacterial virulence and that the Δmfp::kan mutant may serve as a potential vaccine candidate in future studies.

  16. Fatigue of airway obstruction during long-term exposure to allergen aerosol.

    Science.gov (United States)

    Zimmermann, I; Curschmann, P; Kowalski, J; Ulmer, W T

    1977-12-15

    The response to prolonged antigen exposure and the potentiation of airway resistance increase to ACH challenge, after this exposure, were studied on sixteen boxer dogs. One group of animals presented fatigue to A.E. after 3 hours of exposure. This group developed an increased response to ACH aerosol after fatigue to antigen was present. In a second group of dogs, absence of fatigue during prolonged exposure to allergen was observed. A growing tendency of Edyn (as an index of airway resistance) was observed after 5 hours of exposure. The therapeutical influence of bilateral vagus blockade was tested in these last animals. Blockade of nervus vagus released airway obstruction during prolonged allergen exposure and no bronchoconstriction was observed after ACH challenge during blockade.

  17. Animal allergens and their presence in the environment

    Directory of Open Access Journals (Sweden)

    Eva eZahradnik

    2014-03-01

    Full Text Available Exposure to animal allergens is a major risk factor for sensitization and allergic diseases. Besides mites and cockroaches, the most important animal allergens are derived from mammals. Cat and dog allergies affect the general population; whereas, allergies to rodents or cattle is an occupational problem. Exposure to animal allergens is not limited to direct contact to animals. Based on their aerodynamic properties, mammalian allergens easily become airborne, attach to clothing and hair, and can be spread from one environment to another. For example, the major cat allergen Fel d 1 was frequently found in homes without pets and in public buildings, including schools, day care centers and hospitals. Allergen concentrations in a particular environment showed high variability depending on numerous factors.Assessment of allergen exposure levels is a stepwise process that involves dust collection, allergen quantification and data analysis. Whereas a number of different dust sampling strategies are used, ELISA assays have prevailed in the last years as the standard technique for quantification of allergen concentrations. This review focuses on allergens arising from domestic, farm and laboratory animals and describes the ubiquity of mammalian allergens in the human environment. It includes an overview of exposure assessment studies carried out in different indoor settings (homes, schools, workplaces using numerous sampling and analytical methods and summarizes significant factors influencing exposure levels. However, methodological differences among studies have contributed to the variability of the findings and make comparisons between studies difficult. Therefore, a general standardization of methods is needed and recommended.

  18. Induced Pluripotency and Gene Editing in Disease Modelling: Perspectives and Challenges

    Directory of Open Access Journals (Sweden)

    Yu Fen Samantha Seah

    2015-12-01

    Full Text Available Embryonic stem cells (ESCs are chiefly characterized by their ability to self-renew and to differentiate into any cell type derived from the three main germ layers. It was demonstrated that somatic cells could be reprogrammed to form induced pluripotent stem cells (iPSCs via various strategies. Gene editing is a technique that can be used to make targeted changes in the genome, and the efficiency of this process has been significantly enhanced by recent advancements. The use of engineered endonucleases, such as homing endonucleases, zinc finger nucleases (ZFNs, transcription activator-like effector nucleases (TALENs and Cas9 of the CRISPR system, has significantly enhanced the efficiency of gene editing. The combination of somatic cell reprogramming with gene editing enables us to model human diseases in vitro, in a manner considered superior to animal disease models. In this review, we discuss the various strategies of reprogramming and gene targeting with an emphasis on the current advancements and challenges of using these techniques to model human diseases.

  19. Immunological and physical properties of allergen solutions. Effects of nebulization

    DEFF Research Database (Denmark)

    Frølund, L; Poulsen, L K; Heinig, J H;

    1991-01-01

    Lyophilised birch pollen allergen extracts, reconstituted with different diluents (H2O, saline, Albumin diluent (AD] were investigated to determine whether the allergen activity and quality of the extracts deteriorated by nebulization with different nebulizers (Pari, Wright, and Sandoz). Allergen...... activity was measured by IgG4 RAST inhibition technique and allergen quality was analysed by crossed immunoelectrophoresis (CIE). The distribution of particle sizes of aerosols of different allergen solutions was determined by a TSI Aerodynamic Particle Sizer. A significant difference (P less than 0.......05) in allergen activity was found between the AD and H2O diluents before and after using a Sandoz nebulizer and a Wright nebulizer equipped with a small chamber. This suggested greater allergen activity in AD-diluted solutions, and the pattern was repeated with the other two nebulizers, but was not statistically...

  20. A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

    DEFF Research Database (Denmark)

    Taylor, S. L.; Hefle, S. L.; Bindslev-Jensen, C.

    2004-01-01

    Background While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an a...

  1. Allergen immunotherapy: routes, safety,efficacy, and mode of action

    Directory of Open Access Journals (Sweden)

    Hochfelder JL

    2013-07-01

    Full Text Available Jillian Leigh Hochfelder, Punita PondaDivision of Allergy and Immunology, North Shore–Long Island Jewish Health System, New Hyde Park, NY, USAAbstract: Allergic rhinitis, allergic conjunctivitis, and allergic asthma have been steadily increasing in prevalence in recent years. These allergic diseases have a major impact on quality of life and are a major economic burden in the US. Although allergen avoidance and pharmacotherapy are currently the mainstays of therapy, they are not always successful in treating patients’ symptoms effectively. If a patient fails allergen avoidance and medical therapy, immunotherapy may be indicated. Furthermore, immunotherapy is the only therapy that may change the course of the disease and induce long-term remission. Though subcutaneous administration has been the standard route for immunotherapy for many decades, there are several other routes of administration that have been and are currently being studied. The goal of utilizing alternative routes of immunotherapy is to improve safety without decreasing the efficacy of treatment. This paper will review the novel routes of immunotherapy, including sublingual, oral, local nasal, epicutaneous, and intralymphatic.Keywords: immunotherapy, allergic rhinitis, allergic asthma, sublingual, intralymphatic

  2. Recombinant allergen Lol p II: expression, purification and characterization.

    Science.gov (United States)

    Tamborini, E; Brandazza, A; De Lalla, C; Musco, G; Siccardi, A G; Arosio, P; Sidoli, A

    1995-05-01

    Pollen from perennial rye grass (Lolium perenne) is a major cause of type I allergies worldwide. It contains complex mixtures of proteins, among which Lol p II is a major allergen. Previously, we have reported the cloning and sequencing of Lol p II and its expression in fusion with the heavy chain of human ferritin as carrier polypeptide (Sidoli et al., 1993, J. biol. Chem. 268, 21819-21825). Here, we describe the expression, purification and characterization of a recombinant Lol p II overproduced as a non-fusion protein in the periplasm of E. coli. The recombinant allergen was expressed in high yields and was easily purified in milligram amounts. It competed with the natural Lol p II for binding to specific IgE, and it induced allergic responses in skin prick tests, indicating to be immunologically analogous to the natural protein. Biochemical analyses indicate that recombinant Lol p II is a highly stable and soluble monomeric molecule which behaves like a small globular protein.

  3. Is food allergen analysis flawed? Health and supply chain risks and a proposed framework to address urgent analytical needs.

    Science.gov (United States)

    Walker, M J; Burns, D T; Elliott, C T; Gowland, M H; Mills, E N Clare

    2016-01-07

    Food allergy is an increasing problem for those affected, their families or carers, the food industry and for regulators. The food supply chain is highly vulnerable to fraud involving food allergens, risking fatalities and severe reputational damage to the food industry. Many facets are being pursued to ameliorate the difficulties including better food labelling and the concept of thresholds of elicitation of allergy symptoms as risk management tools. These efforts depend to a high degree on the ability reliably to detect and quantify food allergens; yet all current analytical approaches exhibit severe deficiencies that jeopardise accurate results being produced particularly in terms of the risks of false positive and false negative reporting. If we fail to realise the promise of current risk assessment and risk management of food allergens through lack of the ability to measure food allergens reproducibly and with traceability to an international unit of measurement, the analytical community will have failed a significant societal challenge. Three distinct but interrelated areas of analytical work are urgently needed to address the substantial gaps identified: (a) a coordinated international programme for the production of properly characterised clinically relevant reference materials and calibrants for food allergen analysis; (b) an international programme to widen the scope of proteomics and genomics bioinformatics for the genera containing the major allergens to address problems in ELISA, MS and DNA methods; (c) the initiation of a coordinated international programme leading to reference methods for allergen proteins that provide results traceable to the SI. This article describes in more detail food allergy, the risks of inapplicable or flawed allergen analyses with examples and a proposed framework, including clinically relevant incurred allergen concentrations, to address the currently unmet and urgently required analytical requirements. Support for the

  4. Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivity.

    Science.gov (United States)

    Focke, M; Swoboda, I; Marth, K; Valenta, R

    2010-03-01

    Allergen-specific immunotherapy (SIT) is the only specific and disease-modifying approach for the treatment of allergy but several disadvantages have limited its broad applicability. We argue that the majority of the possible disadvantages of SIT such as unwanted effects, poor efficacy and specificity as well as inconvenient application are related to the poor quality of natural allergen extracts, which are the active ingredients of all currently available allergy vaccines. Because of the progress made in the field of molecular allergen characterization, new allergy vaccines based on recombinant allergens, recombinant hypoallergenic allergen derivatives and allergen-derived T cell peptides have entered clinical testing and hold promise to reduce the side-effects and to increase the specificity as well as the efficacy of SIT. Here, we present a refined immunotherapy concept, which is based on the use of peptides derived from allergen surfaces that exhibit reduced, allergen-specific IgE as well as T cell reactivity. These peptides when fused to non-allergenic carriers give rise to allergen-specific protective IgG responses with T cell help from a non-allergenic carrier molecule. We summarize the experimental data demonstrating that such peptide vaccines can bypass allergen-specific IgE as well as T cell activation and may be administered at high doses without IgE- and T cell-mediated side-effects. Should these peptide vaccines prove efficacious and safe in clinical trials, it may become possible to develop convenient, safe and broadly applicable forms of SIT as true alternatives to symptomatic, drug-based allergy treatment.

  5. De allergene potentie van geneesmiddelen: literatuurstudie

    NARCIS (Netherlands)

    van Amsterdam JGC; Vleeming W; de Wildt DJ; van der Laan JW; de Waal EJ; van Loveren H; Garssen J; TOX; LGM; PAT

    1995-01-01

    Dit rapport geeft een overzicht van de allergische reacties, die het gevolg zijn van geneesmiddelengebruik. De nadruk is gelegd op ernstige allergische reacties. Een overzicht -ingedeeld volgens de classificatie van Gell en Coombs wordt gegeven van geneesmiddelen met een allergene potentie. Daarn

  6. Effect of thermal processing on mealworm allergenicity

    NARCIS (Netherlands)

    Broekman, H.; Knulst, A.; Hartog Jager, S. den; Monteleone, F.; Gaspari, M.; Jong, G. de; Houben, G.; Verhoeckx, K.

    2015-01-01

    Scope: The growing world population requires the exploration of new sustainable protein sources to ensure food security. Insects such as mealworm are promising candidates. For safety reasons, a risk assessment, including allergy risks, is needed. Since allergenicity can be influenced by thermal proc

  7. Innate immune responses to environmental allergens

    NARCIS (Netherlands)

    Kauffman, HF

    2006-01-01

    Aero-allergens, including plant pollens, house dust mite particles, fungal spores, and mycelium fragments, are continuously inhaled and deposited on the airway mucosa. These particles and their soluble components actively interact with innate recognition systems present in the mucosal layer (e.g., s

  8. Kiwifruit as a food allergen source

    Directory of Open Access Journals (Sweden)

    Popović Milica

    2013-01-01

    Full Text Available Since its first appearance on the market kiwifruit has become very popular in the human diet due to its pleasant taste, low caloric value and high content of vitamin C. However, kiwifruit allergy has become a frequent cause of type I hypersensitivity in the western society. Molecular basis for kiwifruit allergy has been ascribed to up-to-now 11 identified IgE reactive molecules. They are proteins and glycoproteins with a molecular mass between 50 and 10 kDa. The major kiwifruit allergen is a cysteine protease denoted as Act d 1, which represents 50% of the soluble protein extract. Due to a difference in the abundance of protein components and biological activity, the quality of kiwifruit extracts intended for allergy diagnosis can vary in content and amount of IgE reactive molecules. In addition, the quality of allergen extracts for allergy diagnosis depends on the fruit ripening stage and storage conditions. In terms of clinical reactivity it has become evident that kiwifruit allergy is not a homogeneous disorder. Different patterns of IgE reactivity accompany several clinical subgroups that have been identified in different geographical regions. In the last decade an enormous progress has been made in isolation and characterization of kiwifruit allergens. This paper will give an overview of the structural features of kiwifruit allergens. [Projekat Ministarstva nauke Republike Srbije, br. 172049

  9. PROTEOMIC ANALYSIS OF ALLERGENS FROM METARHIZIUM ANISOPLIAE

    Science.gov (United States)

    IntroductionThe goal of this project is the identification and characterization of allergens from the fungus Metarhizium anisopliae, using mass spectrometry (MS). The US EPA, under the "Children at Risk" program, is currently addressing the problem of indoor fungal bioaer...

  10. PROTEOMIC ANALYSIS OF ALLERGENS FROM METARHIZIUM ANISOPLIEA

    Science.gov (United States)

    The goal of this project is the identification and characterization of allergens from the fungus M. Anisopliae, using mass spectrometry (MS). The US EPA, under the "Children at Risk" program, is currently addressing the problem of indoor fungal bioaerosol contamination. One of ...

  11. Differential allergenicity of mature and immature pollen grains in Shasta daisy (Chrysanthemum maximum Ramond.

    Directory of Open Access Journals (Sweden)

    Maryam Sharif Shoushtari

    2013-06-01

    Full Text Available Weed pollen grains belonging to  the  Asteraceae  family contain  a variety of  allergens inducing type I  and IV allergies in susceptible people. The  aim of this research was to compare  the  allergenic properties  of  immature  and  mature  Shasta  daisy pollen  grains (Chrysanthemum maximum Ramond to define the potential role of the maturation process on the allergenicity of Asteraceae pollen grains.The  immature (IP and mature  pollen (MP grains were first studied by optical and scanning electron microscopand their protein contents were quantitatively and qualitatively analyzed. Pollen extracts were finally used to sensitize guinea pigs in order to obtain IP and MP specific antibodies. Nasal provocation tests using IP and MP crude extracts were also performed on pre-sensitized guinea pigs.The  MP  extract  induced  IgE  and  eosinophilia in  blood  and  positive skin  tests  in sensitized guinea pigs. Moreover, high number of eosinophils was found in the nasal mucosa of MP sensitized guinea pigs. SDS-PAGE analysis of the IP and MP protein content showed seven and five apparent bands ranging from 7 to 66kDa respectively.According to immunoblot analysis, MP extract contained a single allergen of 66kDa. The overall results showed developmental processes of Shasta daisy pollen grains towards both morphological and molecular changes increasing their allergenic potency.

  12. The human skin/chick chorioallantoic membrane model accurately predicts the potency of cosmetic allergens.

    Science.gov (United States)

    Slodownik, Dan; Grinberg, Igor; Spira, Ram M; Skornik, Yehuda; Goldstein, Ronald S

    2009-04-01

    The current standard method for predicting contact allergenicity is the murine local lymph node assay (LLNA). Public objection to the use of animals in testing of cosmetics makes the development of a system that does not use sentient animals highly desirable. The chorioallantoic membrane (CAM) of the chick egg has been extensively used for the growth of normal and transformed mammalian tissues. The CAM is not innervated, and embryos are sacrificed before the development of pain perception. The aim of this study was to determine whether the sensitization phase of contact dermatitis to known cosmetic allergens can be quantified using CAM-engrafted human skin and how these results compare with published EC3 data obtained with the LLNA. We studied six common molecules used in allergen testing and quantified migration of epidermal Langerhans cells (LC) as a measure of their allergic potency. All agents with known allergic potential induced statistically significant migration of LC. The data obtained correlated well with published data for these allergens generated using the LLNA test. The human-skin CAM model therefore has great potential as an inexpensive, non-radioactive, in vivo alternative to the LLNA, which does not require the use of sentient animals. In addition, this system has the advantage of testing the allergic response of human, rather than animal skin.

  13. From Allergen Back to Antigen:. a Rational Approach to New Forms of Immunotherapy

    Science.gov (United States)

    Colombo, Paolo; Trapani, Antonino; Geraci, Domenico; Golino, Massimiliano; Gianguzza, Fabrizio; Bonura, Angela

    2007-12-01

    Mapping an epitope on a protein by gene fragmentation and/or point mutations is often expensive and time consuming. Analysis of a 3D model can be utilized to detect the amino acids residues which are exposed to the solvent surface and thus represent potential epitope residues. Parj1 and Parj2 are the two major allergens of the Parietaria judaica pollen belonging to the Lipid Transfer Protein family. Using their three-dimensional structures as a guide, a head to tail dimer expressing disulphide bond variants of the major allergens was generated by means of DNA recombinant technology. The hybrid was expressed in E.coli and its immunological activity studied in vivo and in vitro. Our results demonstrate that a hybrid polypeptide expressing disulphide bond variants of the major allergens of the Parietaria pollen displayed reduced allergenicity and enhanced T cell reactivity for induction of protective antibodies able to block human IgE induced during the natural course of sensitization against the Parietaria pollen.

  14. Chironomid midges as allergens: evidence from two species from West Bengal, Kolkata, India

    Directory of Open Access Journals (Sweden)

    Soumi Nandi

    2014-01-01

    Full Text Available Background & objectives: Arthropods of different taxonomic identity including chironomid midges are known to induce allergic response in humans. The present study was done to access two common chironomid species Chironomus circumdatus and Polypedilum nubifer for their sensitizing potential as an allergen in atopic patients and controls. Methods: Following preparation of allergenic extracts of the two chironomid species separately, 198 atopic patients attending an allergy clinic and 50 age matched controls were tested along with a routine panel of allergens to assess sensitization. Results: The skin prick test (SPT results revealed that 189 of the 198 patients (95.4% demonstrated sensitization to both the chironomid species. Higher levels of total IgE was observed in atopic subjects than in the control group. Interpretation & conclusions: The results suggest that the chironomid midges Chironomus circumdatus and Polypedilum nubifer can elicit sensitization in humans. A potential risk for allergic reactions by susceptible individuals exists due to these chironomid species, owing to their abundance and chances of contact with human beings. Further studies may be initiated to characterize the nature of the allergens and to assess their clinical relevance.

  15. Impacts of air pollution exposure on the allergenic properties of Arizona cypress pollens

    Energy Technology Data Exchange (ETDEWEB)

    Shahali, Y; Pourpak, Z; Moin, M; Zare, A [Immunology, Asthma and Allergy Research Institute, Medical Sciences/ University of Tehran (Iran, Islamic Republic of); Majd, A, E-mail: youcef.shahali@espci.f [Department of Biology, Faculty of Sciences, Islamic Azad University, North Tehran Branch (Iran, Islamic Republic of)

    2009-02-01

    Epidemiological studies have demonstrated that urbanization and high levels of vehicle emissions correlated with the increasing trend of pollen-induced respiratory allergies. Numerous works have investigated the role of pollutants in the pathogenesis of respiratory diseases but impacts of anthropogenic pollution on pollen allergenic properties are still poorly understood. The objective of this survey was to evaluate impacts of the traffic-related pollution on the structure and allergenic protein content of Arizona cypress (Cupressus arizonica, CA) pollens, recognized as a rising cause of seasonal allergy in various regions worldwide. According to our results, traffic-related air pollution by its direct effects on the elemental composition of pollens considerably increased the fragility of the pollen exine, causing numerous cracks in its surface and facilitating pollen content liberation. Pollen grains were also covered by numerous submicronic orbicules which may act as effective vectors for pollen-released components into the lower regions of respiratory organs. On the other hand, this study provides us reliable explications about the low efficiency of standard commercial allergens in the diagnosis of the Arizona cypress pollen allergy in Tehran. Although traffic related pollution affects the allergenic components of CA pollens, the repercussions on the respiratory health of urban populations have yet to be clarified and need further investigations.

  16. Protocol for simultaneous isolation of three important banana allergens.

    Science.gov (United States)

    Nikolic, Jasna; Mrkic, Ivan; Grozdanovic, Milica; Popovic, Milica; Petersen, Arnd; Jappe, Uta; Gavrovic-Jankulovic, Marija

    2014-07-01

    Banana fruit (Musa acuminata) has become an important food allergen source in recent years. So far, 5 IgE reactive banana proteins have been identified, and the major allergens are: Mus a 2 (a class I chitinase, 31kDa), Mus a 4 (thaumatin-like protein, 21kDa), and Mus a 5 (β-1,3-glucanase, 33kDa). Due to variations in allergen expression levels, diagnostic reagents for food allergy can be improved by using individual allergen components instead of banana allergen extracts. The purpose of this study was to optimize the purification protocol of the three major allergens present in banana fruit: Mus a 2, Mus a 4 and Mus a 5. By employing a three-step purification protocol (a combination of anion-exchange, cation-exchange and reversed-phase chromatography) three important banana allergens were obtained in sufficient yield and high purity. Characterization of the purified proteins was performed by both biochemical (2-D PAGE, mass fingerprint and N-terminal sequencing) and immunochemical (immunoblot) methods. IgE reactivity to the purified allergens was tested by employing sera of five allergic patients. The purified allergens displayed higher sensitivity in IgE detection than the routinely used extracts. The three purified allergens are good candidates for reagents in component-based diagnosis of banana allergy.

  17. GC-MS and NMR analysis of the bioactive compounds from the crude extracts of Waltheria indica and the histopathological changes induced in albino rats challenged with Naja nigricollis venom

    Directory of Open Access Journals (Sweden)

    Philip Ilani

    2016-05-01

    Full Text Available Objective: To develop a characteristic fingerprint of the different chemical compounds of plant by gas chromatography-mass spectrometer (GC-MS and nuclear magnetic resonance (NMR analysis and assess the effect of the crude extract on histological changes induced in Naja nigricollis (N. nigricollis envenomed albino rats. Methods: The coarsely powdered Waltheria indica (W. indica whole plant material was extracted using 70% methanol. GC-MS analysis was carried out using a Shimadzu GC-MS QP 2010 plus system of gas chromatography interfaced to a mass spectrometer. The identification of components was based on National Institute of Standard and Technology-08 and Willey-8 libraries. Hydrogen-NMR spectra of the extracts was performed using Bruker Biospin Avance 400-MHz NMR spectrophotometer with a 5 mm broad inverse probe head, equipped with shielded z-gradient accessories and C-13 NMR hetero-nuclear single quantum correction was carried out using the Brucker’s standard pulse library. The efficacy of the crude extract of W. indica whole plant was tested and the lesions induced in the liver, brain and kidney of albino rats challenged with N. nigricollis were analyzed by light microscopy. Results: The identification of the bioactive compounds from W. indica by GC-MS analysis revealed 41 peaks. A total of 38 compounds were identified with majority having important pharmacological activities that included anti-microbial, anti-cancer, anti-oxidant antiinflammatory, anti-allergenic, anti-ageing, anti-arthritic, larvicidal, anti-convulsant and herbicidal activities. C-13 and hydrogen-NMR analysis of W. indica elucidated key bioactive compounds in the whole plant that were consistent with the classes of bioactive compounds detected by GC-MS analysis. The efficacy of the crude extract of W. indica whole plant in ameliorating histopathological lesions induced in the liver, brain and kidney of albino rats challenged with N. nigricollis venom revealed the

  18. GC-MS and NMR analysis of the bioactive compounds from the crude extracts ofWaltheria indica and the histopathological changes induced in albino rats challenged withNaja nigricollis venom

    Institute of Scientific and Technical Information of China (English)

    Philip Ilani; Nicholas Ajodo; Folashade Adewusi; Samirat Yakubu; Victor Yakubu Cosmos; Ache Eunice; Atonila Kayode Ezekiel; Oshiedu Sarah; Emmanuel Amlabu

    2016-01-01

    Objective:To develop a characteristic fingerprint of the different chemical compounds of plant by gas chromatography-mass spectrometer (GC-MS) and nuclear magnetic resonance (NMR) analysis and assess the effect of the crude extract on histological changes induced inNaja nigricollis(N. nigricollis)envenomed albino rats. Methods: The coarsely powderedWaltheria indica (W. indica) whole plant material was extracted using 70% methanol.GC-MS analysis was carried out using a ShimadzuGC-MS QP 2010 plus system of gas chromatography interfaced to a mass spectrometer. The identification of components was based on National Institute of Standard and Technology-08 and Willey-8 libraries. Hydrogen-NMR spectra of the extracts was performed using Bruker Biospin Avance 400-MHzNMR spectrophotometer with a 5 mm broad inverse probe head, equipped with shielded z-gradient accessories andC-13 NMR hetero-nuclear single quantum correction was carried out using the Brucker’s standard pulse library. The efficacy of the crude extract ofW. indica whole plant was tested and the lesions induced in the liver, brain and kidney of albino rats challenged withN. nigricollis were analyzed by light microscopy. Results:The identification of the bioactive compounds fromW. indica byGC-MS analysis revealed 41 peaks. A total of 38 compounds were identified with majority having important pharmacological activities that included anti-microbial, anti-cancer, anti-oxidant anti-inflammatory, anti-allergenic, anti-ageing, anti-arthritic, larvicidal, anti-convulsant and herbicidal activities.C-13 and hydrogen-NMR analysis ofW. indica elucidated key bioactive compounds in the whole plant that were consistent with the classes of bioactive compounds detected byGC-MS analysis. The efficacy of the crude extract ofW. indica whole plant in ameliorating histopathological lesions induced in the liver, brain and kidney of albino rats challenged withN. nigricollis venom revealed the abrogation of tissue degeneration when

  19. Allergen-specific regulation of allergic rhinitis in mice by intranasal exposure to IgG1 monoclonal antibody Fab fragments against pathogenic allergen.

    Science.gov (United States)

    Matsuoka, Daiko; Mizutani, Nobuaki; Sae-Wong, Chutha; Yoshino, Shin

    2014-09-01

    Fab fragments (Fabs) have the ability to bind to specific antigens but lack the Fc portion for binding to receptors on immune and inflammatory cells that play a critical role in allergic diseases. In the present study, we investigated whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) inhibited allergic rhinitis in mice. BALB/c mice sensitized by intraperitoneal injections of ovalbumin (OVA) plus alum on days 0 and 14 were intranasally challenged with OVA on days 28-30, and 35. Fabs prepared by the digestion of an anti-OVA IgG1 mAb (O1-10) with papain were also intranasally administered 15min before each OVA challenge. The results showed that treatment with O1-10 Fabs significantly suppressed the sneezing frequency, associated with decrease of OVA-specific IgE in the serum and infiltration by mast cells in the nasal mucosa seen following the fourth antigenic challenge; additionally, the level of mouse mast cell protease-1, a marker of mast cell activation, in serum was decreased. Furthermore, infiltration of eosinophils and goblet cell hyperplasia in the nasal mucosa at the fourth challenge were inhibited by treatment with O1-10 Fabs. In conclusion, these results suggest that intranasal exposure to Fabs of a pathogenic antigen-specific IgG1 mAb may be effective in regulating allergic rhinitis through allergen capture by Fabs in the nasal mucosa before the interaction of the intact antibody and allergen.

  20. Experimental extrinsic allergic alveolitis and pulmonary angiitis induced by intratracheal or intravenous challenge with Corynebacterium parvum in sensitized rats.

    Science.gov (United States)

    Yi, E S; Lee, H; Suh, Y K; Tang, W; Qi, M; Yin, S; Remick, D G; Ulich, T R

    1996-10-01

    Extrinsic allergic alveolitis and pulmonary sarcoidosis are granulomatous diseases of the lung for which clinical presentation and anatomic site of granuloma formation differ. Extrinsic allergic alveolitis is caused by inhaled antigens, whereas the nature and source of the inciting antigen in sarcoidosis is unknown. To test the hypothesis that the route via which antigen is introduced to the lung contributes to the clinicopathological presentation of pulmonary granulomatous disease, rats immunized with intravenous (i.v.) Corynebacterium parvum were challenged after 2 weeks with either intratracheal (i.t.) or i.v. C. parvum. The granulomatous inflammation elicited by i.t. challenge predominantly involved alveolar spaces and histologically simulated extrinsic allergic alveolitis. In contrast, the inflammation induced by i.v. challenge was characterized by granulomatous angiitis and interstitial inflammation simulating sarcoidosis. Elevations of leukocyte counts and TNF levels in bronchoalveolar fluid, which reflect inflammation in the intra-alveolar compartment, were much more pronounced after i.t. than after i.v. challenge. Tumor necrosis factor, interleukin-6, CC chemokine, CXC chemokine, and adhesion molecule mRNA and protein expression occurred in each model. In conclusion, i.t. or i.v. challenge with C. parvum in sensitized rats caused pulmonary granulomatous inflammation that was histologically similar to human extrinsic allergic alveolitis and sarcoidosis, respectively. Although the soluble and cellular mediators of granulomatous inflammation were qualitatively similar in both disease models, the differing anatomic source of the same antigenic challenge was responsible for differing clinicopathological presentations.

  1. Comparison of four variants of a major allergen in hazelnut (Corylus avellana) Cor a 1.04 with the major hazel pollen allergen Cor a 1.01

    DEFF Research Database (Denmark)

    Lüttkopf, D; Müller, U; Skov, P S

    2002-01-01

    The aim of this study was to produce the Bet v 1-related major hazelnut allergen Cor a 1.0401 and variants thereof as recombinant allergens, and to compare their immuno-reactivity with the major hazel pollen allergen using sera of patients whose hazelnut allergy recently was confirmed by double......-blind placebo-controlled food challenges (DBPCFC) in a multicenter study. Total RNA was isolated from immature hazelnuts and transcribed into cDNA. Full length coding DNA obtained by PCR-strategy was subcloned into pTYB11 vector and expressed in E. coli ER2566 cells. Native non-fusion target proteins were...... residue in position 99. Surprisingly, only 63% identity was revealed with hazel pollen Cor a 1. EAST with 43 sera of patients with positive DBPCFC to hazelnut indicated IgE reactivity to Cor a 1.0401 in 95% of the sera, to Cor a 1.0402 in 93%, to Cor a 1.0403 in 91%, and in only 74% of the sera...

  2. Reducing LPS content in cockroach allergens increases pulmonary cytokine production without increasing inflammation: A randomized laboratory study

    Directory of Open Access Journals (Sweden)

    Cruikshank William

    2011-02-01

    Full Text Available Abstract Background Endotoxins are ubiquitously present in the environment and constitute a significant component of ambient air. These substances have been shown to modulate the allergic response, however a consensus has yet to be reached whether they attenuate or exacerbate asthmatic responses. The current investigation examined whether reducing the concentration of lipopolysaccharide (LPS in a house dust extract (HDE containing high concentrations of both cockroach allergens 1 and LPS would attenuate asthma-like pulmonary inflammation. Methods Mice were sensitized with CRA and challenged with the intact HDE, containing 182 ng of LPS, or an LPS-reduced HDE containing 3 ng LPS, but an equivalent amount of CRA. Multiple parameters of asthma-like pulmonary inflammation were measured. Results Compared to HDE challenged mice, the LPS-reduced HDE challenged mice had significantly reduced TNFα levels in the bronchoalveolar lavage fluid. Plasma levels of IgE and IgG1 were significantly reduced, however no change in CRA-specific IgE was detected. In HDE mice, plasma IgG2a levels were similar to naïve mice, while LPS-reduced HDE mice had significantly greater concentrations. Reduced levels of LPS in the HDE did not decrease eosinophil or neutrophil recruitment into the alveolar space. Equivalent inflammatory cell recruitment occurred despite having generally higher pulmonary concentrations of eotaxins and CXC chemokines in the LPS-reduced HDE group. LPS-reduced HDE challenge induced significantly higher concentrations of IFNγ, and IL-5 and IL-13 in the BAL fluid, but did not decrease airways hyperresponsiveness or airway resistance to methacholine challenge. Conclusion: These data show that reduction of LPS levels in the HDE does not significantly protect against the severity of asthma-like pulmonary inflammation.

  3. Spectrum of allergens for Japanese cedar pollinosis and impact of component-resolved diagnosis on allergen-specific immunotherapy.

    Science.gov (United States)

    Fujimura, Takashi; Kawamoto, Seiji

    2015-10-01

    The high prevalence of Japanese cedar pollinosis in Japan is associated with a negative impact on the quality of life of patients, as well as significant loss of productivity among the workforce in early spring, thus representing a serious social problem. Furthermore, the prevalence is increasing, and has risen by more than 10% in this decade. Cry j 1 and Cry j 2 were identified as the major allergens in Japanese cedar pollen (JCP), and in 2004, the existence of other major and minor allergens were revealed by a combination of two-dimensional electrophoresis and immunoblotting analysis. Allergenome analysis identified a chitinase, a lipid transfer protein, a serine protease, and an aspartic protease as novel IgE-reactive allergens in patients with JCP allergy. Thaumatin-like protein (Cry j 3) was shown to be homologous to Jun a 3, a major allergen from mountain cedar pollen. Isoflavone reductase-like protein was also characterized in a study of a JCP cDNA library. The characterization of component allergens is required to clarify the sensitizer or cross-reactive elicitor allergens for component-resolved diagnosis (CRD). Increasing evidence from numerous clinical trials indicates that CRD can be used to design effective allergen-specific immunotherapy. In this review, we summarize the eight characterized JCP allergens and discuss the impact of CRD and characterization of novel allergens on allergen-specific immunotherapy.

  4. Understanding chemical allergen potency: role of NLRP12 and Blimp-1 in the induction of IL-18 in human keratinocytes.

    Science.gov (United States)

    Papale, Angela; Kummer, Elena; Galbiati, Valentina; Marinovich, Marina; Galli, Corrado L; Corsini, Emanuela

    2016-09-01

    Keratinocytes (KCs) play a key role in all phases of skin sensitization. We recently identified interleukin-18 (IL-18) production as useful end point for determination of contact sensitization potential of low molecular weight chemicals. The aim of this study was to identify genes involved in skin sensitizer-induced inflammasome activation and to establish their role in IL-18 production. For gene expression analysis, cells were treated for 6 h with p-phenylenediamine (PPD) as reference contact allergen; total RNA was extracted and examined with a commercially available Inflammasome Polymerase Chain Reaction (PCR) array. Among genes induced, NLRP12 (Nod-like receptor P12) was selected for further investigation. NLRP12 promoter region contains Blimp-1 (B-lymphocyte-induced maturation protein-1)/PRDM1 binding site, and from the literature, it is reported that Blimp-1 reduces NLRP12 activity and expression in monocytes/macrophages. Their expression and role in KCs are currently unknown. To confirm NLRP12 expression and to investigate its relationship with Blimp-1, cells were exposed for different times (3, 6 and 24 h) to the extreme sensitizer 2,4-dinitrochlorobenzene (DNCB) and the strong sensitizer PPD. Allergens were able to induce both genes, however, with different kinetic, with DNCB more rapidly upregulating Blimp-1 and inducing IL-18 production, compared to PPD. NLRP12 and Blimp-1 expression appeared to be inversely correlated: Blimp-1 silencing resulted in increased NLRP12 expression and reduced contact allergen-induced IL-18 production. Overall results indicate that contact allergens of different potency differently modulate Blimp-1/NLRP12 expression, with strong allergen more rapidly downregulating NLRP12, thus more rapidly inducing IL-18 production. Data confirm that also in KCs, NLRP12 has an inhibitory effect on inflammasome activation assessed by IL-18 maturation.

  5. First successful reduction of clinical allergenicity of food by genetic modification: Mal d 1-silenced apples cause fewer allergy symptoms than the wild-type cultivar

    DEFF Research Database (Denmark)

    Dubois, A. E. J.; Pagliarani, G.; Brouwer, R. M.;

    2015-01-01

    BACKGROUND: Genetic modification of allergenic foods such as apple has the potential to reduce their clinical allergenicity, but this has never been studied by oral challenges in allergic individuals. METHODS: We performed oral food challenges in 21 apple-allergic individuals with Elstar apples...... which had undergone gene silencing of the major allergen of apple, Mal d 1, by RNA interference. Downregulation of Mal d 1 gene expression in the apples was verified by qRT-PCR. Clinical responses to the genetically modified apples were compared to those seen with the wild-type Elstar using a visual...... analogue scale (VAS). RESULTS: Gene silencing produced two genetically modified apple lines expressing Mal d 1.02 and other Mal d 1 gene mRNA levels which were extensively downregulated, that is only 0.1-16.4% (e-DR1) and 0.2-9.9% (e-DR2) of those of the wild-type Elstar, respectively. Challenges...

  6. [Evaluation of the total biological activity and allergenic composition of allergenic extracts].

    Science.gov (United States)

    Lombardero, M; González, R; Duffort, O; Juan, F; Ayuso, R; Ventas, P; Cortés, C; Carreira, J

    1986-01-01

    In the present study, a complete procedure is presented in order to standardize allergenic extracts, the meaning of which is the measurement of the total allergenic activity and the determination of the allergenic composition. The measurement of the biological activity comprises 2 steps: Preparation of Reference Extracts and determination of their "in vivo" activity. Evaluation of the total allergenic activity of extracts for clinical use. Reference extracts were prepared from the main allergens and their "in vivo" biological activity was determined by a quantitative skin prick test in a sample of at least 30 allergic patients. By definition, the protein concentration of Reference Extract that produces, in the allergic population, a geometric mean wheal of 75 mm.2 has an activity of 100 biological units (BUs). The determination of the biological activity of a problem extract is made by RAST inhibition. The sample is compared with the corresponding Reference Extract by this technique and, from this comparison, it is possible to quantify the activity of the problem extract in biologic units (BUs) with clinical significance. Likewise, different techniques have been used to determine the allergenic composition of extracts. These techniques comprise 2 steps: Separation of the components of the extract. Identification of the components that bind specific human IgE. The separation of the components of the extract has been carried out by isoelectric focusing (IEF) and electrophoresis in the presence of sodium dodecyl sulphate (SDS-PAGE). In order to identify the allergenic components, an immunoblotting technique has been employed. The separated components in the IEF gel or SDS-PAGE gel are transferred to a nitrocellulose sheet and later on, this membrane is overlaid with a serum pool from allergic patients and a mouse monoclonal anti-human IgE, labelled with 125I. Finally, the autoradiography of the nitrocellulose membrane is obtained. In this way it is possible to compare

  7. Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives.

    Science.gov (United States)

    Linhart, Birgit; Valenta, Rudolf

    2012-06-19

    Hundred years ago therapeutic vaccination with allergen-containing extracts has been introduced as a clinically effective, disease-modifying, allergen-specific and long-lasting form of therapy for allergy, a hypersensitivity disease affecting more than 25% of the population. Today, the structures of most of the disease-causing allergens have been elucidated and recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during allergen-specific immunotherapy (SIT). These recombinant hypoallergens have been characterized in vitro, in experimental animal models and in clinical trials in allergic patients. This review provides a summary of the molecular, immunological and preclinical evaluation criteria applied for this new generation of allergy vaccines. Furthermore, we summarize the mechanisms underlying SIT with recombinant hypoallergens which are thought to be responsible for their therapeutic effect.

  8. Common food allergens and their IgE-binding epitopes.

    Science.gov (United States)

    Matsuo, Hiroaki; Yokooji, Tomoharu; Taogoshi, Takanori

    2015-10-01

    Food allergy is an adverse immune response to certain kinds of food. Although any food can cause allergic reactions, chicken egg, cow's milk, wheat, shellfish, fruit, and buckwheat account for 75% of food allergies in Japan. Allergen-specific immunoglobulin E (IgE) antibodies play a pivotal role in the development of food allergy. Recent advances in molecular biological techniques have enabled the efficient analysis of food allergens. As a result, many food allergens have been identified, and their molecular structure and IgE-binding epitopes have also been identified. Studies of allergens have demonstrated that IgE antibodies specific to allergen components and/or the peptide epitopes are good indicators for the identification of patients with food allergy, prediction of clinical severity and development of tolerance. In this review, we summarize our current knowledge regarding the allergens and IgE epitopes in the well-researched allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.

  9. Allergen extracts for immunotherapy: to mix or not to mix?

    Science.gov (United States)

    Nony, Emmanuel; Martelet, Armelle; Jain, Karine; Moingeon, Philippe

    2016-01-01

    Allergen immunotherapy (AIT) is established as a curative treatment for allergic rhinitis, asthma, as well as insect venom allergy. AIT is based on the administration of natural allergen extracts via the subcutaneous or sublingual routes to reorient the immune system towards tolerogenic mechanisms. In this regard, since many patients are poly-allergic, mixtures of allergen extracts are often used with a potential risk to cause allergen degradation, thereby affecting treatment efficacy. Herein, we discuss the advantages and drawbacks of mixing homologous (i.e., related) or heterogeneous (i.e., unrelated) allergen extracts. We provide evidence for incompatibilities between mixes of grass pollen and house dust mite extracts containing bodies and feces, and summarize critical points to consider when mixing allergen extracts for AIT.

  10. A DNA vaccine directed against a rainbow trout rhabdovirus induces early protection against a nodavirus challenge in turbot

    DEFF Research Database (Denmark)

    Sommerset, I.; Lorenzen, Ellen; Lorenzen, Niels;

    2003-01-01

    A DNA vaccine encoding the envelope glycoprotein from a fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), has previously been shown to induce both early and long time protection against the virus in rainbow trout. Challenge experiments have revealed that the immunity established shortly...... after vaccination is cross-protective against heterologous fish rhabdoviruses. In this study, we show that the DNA vaccine encoding the VHSV glycoprotein also induces early protection against a non-enveloped, positive-sense RNA vir-us belonging to the Nodavirus family, the Atlantic halibut nodavirus...... (AHNV). In a vaccine. efficacy test using juvenile turbot as model fish, the fish injected with the VHSV vaccine were completely protected against a nodavirus challenge performed 8 days post vaccination, while the cumulative mortality in the control group reached 54%. A DNA vaccine carrying the gene...

  11. Prospects and challenges for practical application of rhizobacteria-mediated induced systemic resistance

    NARCIS (Netherlands)

    Loon, L.C. van; Bakker, P.A.H.M.; Pieterse, C.M.J.

    2002-01-01

    Selected strains of plant growth-promoting rhizobacteria are able to induce a systemic resistance (ISR) in plants, which is phenotypically similar to pathogen-induced systemic acquired resistance (SAR). The generally non-specific character of induced resistance constitutes an increase in the level o

  12. Immunoproteomic characterization of Ambrosia artemisiifolia pollen allergens in canine atopic dermatitis.

    Science.gov (United States)

    Ognjenovic, Jana; Milcic-Matic, Natalija; Smiljanic, Katarina; Vuckovic, Olga; Burazer, Lidija; Popovic, Nikola; Stanic-Vucinic, Dragana; Velickovic, Tanja Cirkovic

    2013-09-01

    Canine atopic dermatitis (CAD) is an immune system disorder that affects 10-15% of the canine population. Short ragweed (Ambrosia artemisiifolia) pollen represents one of the major seasonal sources of allergenic pollen proteins in Europe, particularly in the Pannonian valley of the Balkan region. In Serbia, about 66% of atopic dogs showed a positive intradermal skin test with its pollen extract, which is second to house dust mites. Therefore, characterization of Ambrosia artemisiifolia pollen components, in terms of defining major and minor allergens that induce clinically manifested allergic reaction in dogs, is important for valid diagnosis and efficient therapy. This study has, for the first time, characterized and identified major Ambrosia artemisiifolia allergens in CAD, using an immunoproteomic approach. To assess the prevalence of specific IgE in electrophoretically separated ragweed pollen proteins, individual reactivity of sera from dogs with CAD was analyzed and compared to the reactivity of sera from healthy dogs in the non-reducing conditions, which were found optimal for specific canine IgE detection. A specific IgE band (38 kDa) was recognized as the most dominant allergen in CAD, occurring in 81% of positive dog's sera. 2-D immunoblotting followed by a mass spectrometry peptide fingerprint analyses with pooled canine and human atopic sera, revealed that 38 kDa major Ambrosia atremisiifolia allergens in CAD were all five isoallergens of the Amb a 1 group (antigen E), including the previously named Amb a 2 (antigen K). In contrast to canine sera, human atopic sera also recognized lower mass allergens such as the β fragment of Amb a 1 and profilins (Amb a 8 variants). The most prominent ragweed proteins in CAD, represent, as in humans, variants of all five isoallergens of the Amb a 1 group (pectate lyase): Amb a 1.0101 and its natural variant E1XUL2, Amb a 1.0202, 1.0304, 1.0402 and the natural variant of Amb a 1.0501, E1XUM0, as well as the

  13. Exertional-induced bronchoconstriction: Comparison between cardiopulmonary exercise test and methacholine challenging test

    Directory of Open Access Journals (Sweden)

    Mostafa Ghanei

    2015-01-01

    Full Text Available Introduction: Exertional-induced bronchoconstriction is a condition in which the physical activity causes constriction of airways in patients with airway hyper- responsiveness. In this study, we tried to study and evaluate any relationship between the findings of cardiopulmonary exercise testing (CPET and the response to methacholine challenge test (MCT in patients with dyspnea after activity. Materials and Methods: Thirty patients with complaints of dyspnea following activity referred to "Lung Clinic" of Baqiyatallah Hospital but not suffering from asthma were entered into the study. The subjects were excluded from the study if: Suffering from any other pulmonary diseases, smoking more than 1 cigarette a week in the last year, having a history of smoking more than 10 packets of cigarettes/year, having respiratory infection in the past 4 weeks, having abnormal chest X-ray or electrocardiogram, and cannot discontinue the use of medicines interfering with bronchial provocation. Baseline spirometry was performed for all the patients, and the values of forced expiratory volume in 1 second (FEV1, forced vital capacity (FVC, and FEV/FVC were recorded. The MCT and then the CPET were performed on all patients. Results: The mean VO 2 (volume oxygen in patients with positive methacholine test (20.45 mL/kg/min was significantly lower than patients with negative MCT (28.69 mL/kg/min (P = 0.000. Respiratory rates per minute (RR and minute ventilation in the group with positive MCT (38.85 and 1.636 L were significantly lower than the group with negative methacholine test (46.78 and 2.114 L (P < 0.05. Also, the O 2 pulse rate in the group with negative methacholine test (116.27 mL/beat was significantly higher than the group with positive methacholine test (84.26 mL/beat (P < 0.001. Conclusion: Pulmonary response to exercise in patients with positive methacholine test is insufficient. The dead space ventilation in these patients has increased. Also, dynamic

  14. Footwear dermatitis - Clinical patterns and contact allergens

    Directory of Open Access Journals (Sweden)

    Handa S

    1991-01-01

    Full Text Available Thirty patients suspected of contact dermatitis to footwear studied to evaluate various clinical presentations and possible sensitizers. ′V′ chappals and sandals were suspected alone in 12, a combination of open and closed shoes in 15 and closed shoes alone in 3 patients. Commonest affected sites were dorsa of feet and toes in 14 and dorsa of feet corresponding to the shape of footwear in 12 patients. Patch tests were done using a battery of sixteen allergens. Positive patch tests were seen in 29 patients. Rubber chemicals were the commonest allergens detected in 26 patients, dyes in 10,leather in 6, glues and neoprene cements in 4 and rubber material from suspected footwear as such in 4 patients respectively.

  15. Aluminium in Allergies and Allergen immunotherapy.

    Science.gov (United States)

    Jensen-Jarolim, Erika

    2015-01-01

    Aluminium is a hot topic in the current debate. Exposure occurs due to environmental, dietary and intentional exposure to aluminium, such as in vaccines where it was introduced in 1926. In spite of the fact that it is a typical Th2 adjuvant, aluminium redirects the immune response in systemic allergen immunotherapy (SIT) upon prolonged immunization. SIT in the US, and SLIT in general, are at present non-adjuvanted therapies, but in Europe aluminium is used as adjuvant in most SIT preparations. It enhances the safety of SIT by local deposition of the allergen. Undesired properties of aluminium adjuvants comprise acute and chronic inflammation at the injection site, its Th2 immune stimulatory capacity, its accumulation besides biodistribution in the body. The adjuvant and safety profile of aluminium adjuvants in allergy vaccines are discussed, as well as the need for putting modern delivery systems and adjuvants on the fast track.

  16. The major allergen of Dendropanax trifidus Makino.

    Science.gov (United States)

    Oka, K; Saito, F; Yasuhara, T; Sugimoto, A

    1997-05-01

    Dendropanax trifidus Makino (family Araliaceae, syn. Gilibertia trifida Makino) has been reported as causing allergic contact dermatitis in Japan. To identify the major allergen, fractionated extracts of fresh leaves of Dendropanax trifidus were patch tested on 2 patients with hypersensitivity to the plant. Cis-9,17-octadecadiene-12,14-diyne-1, 16-diol (I), an analog of falcarinol, was identified as an active component. 18 normal control subjects were patch tested with the leaf of Dendropanax trifidus and I diluted to 0.05% in pet. 4 of them showed active sensitization to the leaf of Dendropanax trifidus and I. Our results suggest that I is the major allergen of Dendropanax trifidus and is a strong sensitizer. The results of patch testing on patients and control subjects with the leaves of Fatsia japonica Decne. et Planch. and Hedera helix L., which also belong to the Araliaceae family, and urushiol are also shown.

  17. Wheat allergens associated with Baker's asthma.

    Science.gov (United States)

    Salcedo, G; Quirce, S; Diaz-Perales, A

    2011-01-01

    Baker's asthma is a frequent occupational allergic disease caused mainly by inhalation of cereal flour, particularly wheat flour. This review deals with the current diagnosis and immunomodulatory treatments, as well as the role of wheat allergens as molecular tools to enhance management and knowledge of this disease. The review also discusses the current status of several salt-soluble proteins (albumins and globulins)--cereal alpha-amylase/trypsin inhibitors, peroxidase, thioredoxin, nonspecific lipid transfer protein, serine proteinase inhibitor, and thaumatin-like protein-as well as salt-insoluble storage proteins (prolamins, namely, gliadins and glutenins) as allergens associated with baker's asthma. Finally, current limitations to using these proteins as molecular tools for diagnosis and immunotherapy are highlighted.

  18. Challenge assay: A functional biomarker for exposure-induced DNA repair deficiency and for risk of cancer.

    Science.gov (United States)

    Au, William W; Giri, Ashok K; Ruchirawat, Mathuros

    2010-01-01

    A variety of biomarkers have been used to monitor exposed populations to determine potential health hazards from their exposure to environmental toxic agents. However, the majority of these biomarkers have been focused onto the identification of biological damage from the exposure. Therefore, there is a need to develop functional biomarkers that can identify exposure-induced functional deficiencies. More importantly, these deficiencies should be positioned along pathways that are responsible for the development of specific diseases. One of such pathways belongs to the extensive and complex DNA-repair machinery. The machinery thus becomes a large target for damage from environmental toxic agents. The hypothesis is that damage to any component of a repair pathway will interfere with the pathway-specific repair activities. Therefore, when cells from exposed populations are challenged with a DNA-damaging agent in vitro, the in vivo exposure-induced repair deficiency will be dramatically amplified and the deficiency will be detectable in a challenge assay as increased chromosome aberrations, micronuclei or un-repaired DNA strand breaks. The challenge assay has been used in different laboratories to show that a variety of exposed populations (with exposure to air pollutants, arsenic, benzene, butadiene, cigarette smoke, incense smoke, lead, mercury, pesticides, uranium or xylene but not to low concentrations of air pollutants or butadiene) expressed abnormal challenge response. The predicted health consequences of some of these studies have also been validated. Therefore, the challenge assay is a useful functional biomarker for population studies. Details of the challenge assay and its application will be presented in this review.

  19. Allergen uptake, activation, and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice.

    Directory of Open Access Journals (Sweden)

    Ian P Lewkowich

    Full Text Available Maladaptive, Th2-polarized inflammatory responses are integral to the pathogenesis of allergic asthma. As regulators of T cell activation, dendritic cells (DCs are important mediators of allergic asthma, yet the precise signals which render endogenous DCs "pro-asthmatic", and the extent to which these signals are regulated by the pulmonary environment and host genetics, remains unclear. Comparative phenotypic and functional analysis of pulmonary DC populations in mice susceptible (A/J, or resistant (C3H to experimental asthma, revealed that susceptibility to airway hyperresponsiveness is associated with preferential myeloid DC (mDC allergen uptake, and production of Th17-skewing cytokines (IL-6, IL-23, whereas resistance is associated with increased allergen uptake by plasmacytoid DCs. Surprisingly, adoptive transfer of syngeneic HDM-pulsed bone marrow derived mDCs (BMDCs to the lungs of C3H mice markedly enhanced lung IL-17A production, and rendered them susceptible to allergen-driven airway hyperresponsiveness. Characterization of these BMDCs revealed levels of antigen uptake, and Th17 promoting cytokine production similar to that observed in pulmonary mDCs from susceptible A/J mice. Collectively these data demonstrate that the lung environment present in asthma-resistant mice promotes robust pDC allergen uptake, activation, and limits Th17-skewing cytokine production responsible for driving pathologic T cell responses central to the development of allergen-induced airway hyperresponsiveness.

  20. Allergen specificity is relevant for immunotherapy prescription in polysensitised children

    Directory of Open Access Journals (Sweden)

    Ciprandi Giorgio

    2012-09-01

    Full Text Available Abstract The sensitization to more allergens, such as polysenitization, is becoming a frequent characteristic of allergic patients, since the childhood. However, this phenomenon is considered an obstacle to prescribe immunotherapy by many doctors. This study investigated the relevance of polysensitization in a cohort of allergic children and evaluated the number of allergen extracts prescribed for these children. There are allergens that are frequent, but not prescribed. This issue should be matter of adequate debate for Italian paediatricians.

  1. Messenger RNA expression of IL-6 and IL-8 in allergen-induced late-phase cutaneous reactions (LPR) in Schneiderian membrane subjects%白细胞介素6(IL-6)和IL-8mRNA在变应原诱导的鼻粘膜晚期反应标本的表达

    Institute of Scientific and Technical Information of China (English)

    吕俊华; 宇丽; 孙英

    2001-01-01

    目的:测定IL-6和IL-8变应原诱导的鼻粘膜晚期反应标本中mRNA的表达。方法:采用原位杂交技术,测定变应原诱导的10例变态反应性鼻炎病人的鼻粘膜标本表达IL-6和IL-8mRNA阳性细胞数。结果:在10例标本中,2种细胞因子的阳性表达率分别为9/10和10/10。与对照相比,变应原诱导的鼻粘膜标本表达IL-6和IL-8mRNA阳性细胞数明显增加(P<0.05和P<0.01)。结论:IL-6和IL-8mRNA表达增加可作为变态反应性鼻炎晚期的标志。%Objective:To detect mRNA expression of IL-6 and IL-8 in allergen-induced late-phase cutaneous reactions in schneiderian membrane subjects. Methods:Cryostat sections from rhinitis biopsies from 24 h allergen-induced late-phase cutaneous reactions (LPR) in 10human atopic subjects were hybridization with 35S-labeled RNA probes for IL-6 and IL-8.Results:mRNA was detected for IL-6 (9/10) and IL8 (10/10).Compared with the control, there were significant increases in the numbers of ce11 expreasing mRNA expression for IL-6 and IL-8(P<0.05, P<0.01). Conclusion: The augmentation of mRNA expression of IL-6 and IL-8 maybe regarded as the mark of rhinits in IL PR.

  2. An SPR based sensor for allergens detection.

    Science.gov (United States)

    Ashley, J; Piekarska, M; Segers, C; Trinh, L; Rodgers, T; Willey, R; Tothill, I E

    2017-02-15

    A simple, sensitive and label-free optical sensor method was developed for allergens analysis using α-casein as the biomarker for cow's milk detection, to be used directly in final rinse samples of cleaning in place systems (CIP) of food manufacturers. A Surface Plasmon Resonance (SPR) sensor chip consisting of four sensing arrays enabling the measurement of samples and control binding events simultaneously on the sensor surface was employed in this work. SPR offers several advantages in terms of label free detection, real time measurements and superior sensitivity when compared to ELISA based techniques. The gold sensor chip was used to immobilise α-casein-polyclonal antibody using EDC/NHS coupling procedure. The performance of the assay and the sensor was first optimised and characterised in pure buffer conditions giving a detection limit of 58ngmL(-1) as a direct binding assay. The assay sensitivity can be further improved by using sandwich assay format and amplified with nanoparticles. However, at this stage this is not required as the detection limit achieved exceeded the required allergens detection levels of 2µgmL(-1) for α-S1-casein. The sensor demonstrated good selectivity towards the α-casein as the target analyte and adequate recoveries from CIP final rinse wash samples. The sensor would be useful tool for monitoring allergen levels after cleaning procedures, providing additional data that may better inform upon wider food allergen risk management decision(s) that are made by food manufacturer. In particular, this sensor could potentially help validate or optimise cleaning practices for a given food manufacturing process.

  3. Diagnostic test allergens used for in vivo diagnosis of allergic diseases are at risk: a European Perspective.

    Science.gov (United States)

    Klimek, L; Hoffmann, H J; Renz, H; Demoly, P; Werfel, T; Matricardi, P M; Muraro, A; Schmid-Grendelmeier, P; Cardona, V; Papadopoulos, N G

    2015-10-01

    In the European Union (EU), allergens used for diagnostic tests (TAs) are defined as medicinal products and have to be registered by national authorities. The current situation is not homogeneous. Existing authorizations need to be kept in the market in some EU states, while others need complete new authorizations requiring clinical trials, quality assurance methods, stability studies, and periodic safety update reports. Allergen manufacturers argue that offering a comprehensive panel of TAs may be economically disastrous. Expenses for initiation and maintenance of TA authorizations far exceed their related revenues and manufacturers may be forced to significantly limit their allergen portfolios. The availability of a wide range of high-quality TAs is very important for in vivo diagnoses of IgE-mediated allergies. Increased regulatory demands induce costs that need to be covered by public health organizations or reimbursed by health insurance companies.

  4. Analysis of regulated suspected allergens in waters.

    Science.gov (United States)

    Becerril, Elias; Lamas, J Pablo; Sanchez-Prado, Lucia; Llompart, Maria; Lores, Marta; Garcia-Jares, Carmen

    2010-12-15

    Fragrance suspected allergens including those regulated by the EU Directive 76/768/EEC have been determined in different types of waters using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). The procedure was based on headspace sampling (HS-SPME) using polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibers and has been optimized by an experimental design approach. The method performance has been studied showing good linearity (R ≥ 0.994) as well as good intra-day and inter-day precision (RSD ≤ 12%). Detection limits (S/N=3) ranged from 0.001 to 0.3 ng mL(-1). Reliability was demonstrated through the quantitative recoveries of the compounds in real water samples, including baby bathwaters, swimming pool waters, and wastewaters. The absence of matrix effects allowed quantification of the compounds by external aqueous calibration. The analysis of 35 samples of different types of waters showed the presence of suspected allergens in all the analyzed samples. All targets were found in the samples, with the exception of methyl eugenol and amyl cinnamic alcohol. Highest concentrations of suspected allergens were present in baby bathwaters, containing from 5 to 15 of the compounds at concentrations ranging from few pg mL(-1) to several hundreds of ng mL(-1).

  5. The Level of Sensitivity of Food Allergens

    Directory of Open Access Journals (Sweden)

    Iris Rengganis

    2011-06-01

    Full Text Available In recent years, the occurrence of allergy continues to increase rapidly both domestically and globally. World Allergy Organization (WAO revealed that 22% of the world population suffers from allergies, and this number increases every year. Food allergy is a condition caused by the reaction of IgE against substances (chemicals in food. Food allergy can interfere with brain function and body organ systems as well as affect the quality of life. The purpose of this study is to know the level of sensitivity of food allergens in the Immunology Allergy Poly RSCM in 2007. Data were collected from 208 patients who have medical records and went through skin prick tests in the Immunology Allergy Clinic RSCM in 2007. Univariate analysis was performed to describe the types of food allergens within groups of children and adults. Around 49% of the respondents were sensitive to food allergens. The types of foods that caused the most allergies for children and adults are respectively shrimp, egg white and cornstarch. Cow's milk and wheat flour are the types of food that caused most allergies for children only, whereas for adults, the food that caused the most allergies is crab.

  6. Wind-pollination and the roles of pollen allergenic proteins.

    Science.gov (United States)

    Songnuan, Wisuwat

    2013-12-01

    Over the past few decades, there has been an explosion of understanding of the molecular nature of major allergens contained within pollens from the most important allergenic plant species. Most major allergens belong to only a few protein families. Protein characteristics, cross-reactivity, structures, and IgE binding epitopes have been determined for several allergens. These efforts have led to significant improvements in specific immunotherapy, yet there has been little discussion about the physiological functions of these proteins. Even with large amounts of available information about allergenic proteins from pollens, the incidence of pollen allergy continuously increases worldwide. The reason for this increase is unclear and is most likely due to a combination of factors. One important culprit might be a change in the pollen itself. Knowledge about pollen biology and how pollen is changing as a result of more extreme environmental conditions might improve our understanding of the disease. This review focuses on the characteristics of plants producing allergenic pollens that are relevant to pollen allergy, including the phylogenetic relationships, pollen dispersal distances, amounts of pollen produced, amounts of protein in each type of pollen, and how allergenic proteins are released from pollens. In addition, the physiological roles of major allergenic protein families will be discussed to help us understand why some of these proteins become allergens and why GMO plants with hypoallergenic pollens may not be successful.

  7. Preparation of patient-related allergens for hyposensitization. Qualitative aspects

    DEFF Research Database (Denmark)

    Poulsen, L K; Søndergaard, I; Weeke, B

    1988-01-01

    An affinity chromatography method for preparation of patient-related antigens from commercially available allergen extracts has been investigated. IgG1,2,4 from a patient previously hyposensitized with dog hair and dandruff allergen was bound to protein A-sepharose. Secondly, commercial allergen...... found in immune complexes with a molecular weight of greater than 300 kdalton equivalent to 2 or more molecules of IgG. The possibility of employing a similar method with IgE instead of IgG for preparation of patient-related allergens instead of antigens, is discussed....

  8. Endogenous allergen upregulation: transgenic vs. traditionally bred crops.

    Science.gov (United States)

    Herman, Rod A; Ladics, Gregory S

    2011-10-01

    The safety assessment for transgenic food crops currently includes an evaluation of the endogenous allergy potential (via serum IgE screening) when the non-transgenic counterpart is a commonly allergenic food. The value of this analysis in the safety assessment of transgenic crops, especially with reference to recent requests to quantify individual allergen concentrations in raw commodities, is examined. We conclude that the likelihood of upregulating an endogenous allergen due to transgenesis is no greater than from traditional breeding which has a history of safety and is largely unregulated. The potential consequences of upregulating an endogenous allergen are also unclear.

  9. Functional Genomics of Allergen Gene Families in Fruits

    Directory of Open Access Journals (Sweden)

    Fatemeh Maghuly

    2009-10-01

    Full Text Available Fruit consumption is encouraged for health reasons; however, fruits may harbour a series of allergenic proteins that may cause discomfort or even represent serious threats to certain individuals. Thus, the identification and characterization of allergens in fruits requires novel approaches involving genomic and proteomic tools. Since avoidance of fruits also negatively affects the quality of patients’ lives, biotechnological interventions are ongoing to produce low allergenic fruits by down regulating specific genes. In this respect, the control of proteins associated with allergenicity could be achieved by fine tuning the spatial and temporal expression of the relevant genes.

  10. Immunochemical estimations of allergenic activities from outdoor aero-allergens, collected by a high-volume air sampler

    DEFF Research Database (Denmark)

    Jensen, J; Poulsen, L K; Mygind, K;

    1989-01-01

    To quantify airborne allergens in amorphus and morphological particles, a survey with collection of aero-allergens on glass fibre filters by means of a high-volume air-sampler (HIVOL) was conducted. In preliminary laboratory experiments we compared various filter elution techniques......, and the pulverizing elution technique was found to be optimal with regard to yield and convenience. When a surfactant, Tween 20 (0.5% v/v), was added to the elution buffer, a recovery of 80% could be obtained. Allergens in eluates were analysed by means of an IgG-subclass RAST inhibition assay. This immunochemical...... method for quantification of airborne allergens was validated, as a high recovery of timothy grass pollen allergens was eluted from air filters, and eluates were shown specific by RAST inhibition. The amount of immunochemically measured airborne timothy and birch allergens collected by means of the HIVOL...

  11. 东北地区10年螨变应原诱发的过敏性疾病调查分析%Investigation and analysis of ten years mite allergen-induced anaphylactic disease in the northeast of China

    Institute of Scientific and Technical Information of China (English)

    柴若楠; 谢华; 林小平; 宋薇薇

    2012-01-01

    目的 了解东北地区十年螨变应原诱发的过敏性疾病病种及特征,为东北地区过敏性疾病的防治提供依据.方法 本研究采用我科信息系统数据库,统计自2001年1月-2010年12月共10年的过敏性疾病人数,并结合数据库中皮肤点刺试验(SPT)结果,对尘螨变应原诱发的过敏性疾病的病种、性别、年龄、职业、环境等进行统计及分析研究.结果 10年中来我科就诊的总人数为156 800人次,就诊病种主要为哮喘、鼻炎、荨麻疹、皮炎、湿疹、结膜炎、过敏性结肠炎等.由尘螨变应原引起的过敏性疾病最多的是过敏性哮喘,其次是变应性鼻炎、荨麻疹、皮炎.结论 东北地区尘螨孳生多见,易引起过敏,且患者四季均可发病.加强居室环境尘螨类控制,是减轻尘螨病症状和减少过敏发作的重要预防措施.%Objective To understand ten years mite allergen-induced disease and its characteristics in the northeast of China, provide scientific basis for the control and prevention of local allergic diseases. Methods The utilisation of the database of our information system, statistically from January 2001 to December 2010, a number of allergic diseases cases for 10 years period, combined with the skin prick test (SPT) result in our database, studied and analyzed allergic house dust mite allergen-induced diseases based on different species, sex, age, occupation, environment, statistics, etc. Results For the 10 years period our department have received a number of 156 800 patients, types mainly for retrospective asthma, rhinitis, urticaria, dermatitis, eczema, conjunctivitis and allergic colitis. Among those diseases the most cases caused by dust mite allergens is allergic asthma, followed by allergic rhinitis, urticaria and dermatitis. Conclusion Dust mite breed easily in the Northeast area of China, which can cause allergies in all four seasons. The improvement of the control of room environment is critical

  12. Mammalian-derived respiratory allergens - implications for diagnosis and therapy of individuals allergic to furry animals.

    Science.gov (United States)

    Nilsson, Ola B; van Hage, Marianne; Grönlund, Hans

    2014-03-01

    Furry animals cause respiratory allergies in a significant proportion of the population. A majority of all mammalian allergens are spread as airborne particles, and several have been detected in environments where furry animals are not normally kept. The repertoire of allergens from each source belongs to a restricted number of allergen families. Classification of allergen families is particularly important for the characterization of allergenicity and cross-reactivity of allergens. In fact, major mammalian allergens are taken from only three protein families, i.e. the secretoglobin, lipocalin and kallikrein families. In particular, the lipocalin superfamily harbours major allergens in all important mammalian allergen sources, and cross-reactivity between lipocalin allergens may explain cross-species sensitization between mammals. The identification of single allergen components is of importance to improve diagnosis and therapy of allergic patients using component-resolved diagnostics and allergen-specific immunotherapy (ASIT) respectively. Major disadvantages with crude allergen extracts for these applications emphasize the benefits of careful characterization of individual allergens. Furthermore, detailed knowledge of the characteristics of an allergen is crucial to formulate attenuated allergy vaccines, e.g. hypoallergens. The diverse repertoires of individual allergens from different mammalian species influence the diagnostic potential and clinical efficacy of ASIT to furry animals. As such, detailed knowledge of individual allergens is essential for adequate clinical evaluation. This review compiles current knowledge of the allergen families of mammalian species, and discusses how this information may be used for improved diagnosis and therapy of individuals allergic to mammals.

  13. Perilla frutescens leaf extract inhibits mite major allergen Der p 2-induced gene expression of pro-allergic and pro-inflammatory cytokines in human bronchial epithelial cell BEAS-2B.

    Directory of Open Access Journals (Sweden)

    Jer-Yuh Liu

    Full Text Available Perilla frutescens has been used in traditional medicine for respiratory diseases due to its anti-bacterial and anti-inflammatory activity. This study aimed to investigate effects of Perilla frutescens leaf extract (PFE on expression of pro-allergic and pro-inflammatory cytokines in airway epithelial cells exposed to mite major allergen Der p 2 (DP2 and the underlying mechanisms. Our results showed that PFE up to 100 µg/mL had no cytotoxic effect on human bronchial epithelial cell BEAS-2B. Further investigations revealed that PFE dose-dependently diminished mRNA expression of pro-allergic cytokine IL-4, IL-5, IL-13 and GM-CSF, as well as pro-inflammatory cytokine IL-6, IL-8 and MCP-1 in BEAS-2B cells treated with DP2. In parallel to mRNA, the DP-2-elevated levels of the tested cytokines were decreased. Further investigation showed that DP2-indued phosphorylation of p38 MAPK (P38 and JNK, but not Erk1/2, was also suppressed by PFE. In addition, PFE elevated cytosolic IκBα level and decreased nuclear NF-κB level in DP2-stimulated BEAS-2B cells. Taken together, these findings revealed that PFE significantly diminished both mRNA expression and protein levels of pro-allergic and pro-inflammatory cytokines in response to DP2 through inhibition of P38/JNK and NK-κB activation. These findings suggest that PFE should be beneficial to alleviate both allergic and inflammatory responses on airway epithelium in response to aeroallergens.

  14. Immunoproteomic tools are used to identify masked allergens: Ole e 12, an allergenic isoflavone reductase from olive (Olea europaea) pollen.

    Science.gov (United States)

    Castro, Lourdes; Crespo, Jesús F; Rodríguez, Julia; Rodríguez, Rosalía; Villalba, Mayte

    2015-12-01

    Proteins performing important biochemical activities in the olive tree (Olea europaea) pollen have been identified as allergens. One novel 37-kDa protein seems to be associated to the IgE-binding profile of a group of patients suffering allergy to peach and olive pollen. Three previously described olive pollen allergens exhibit very similar molecular mass. Our objective was to identify this allergen by using immunoproteomic approaches. After 2D-electrophoresis and mass spectrometry, peptide sequences from several IgE-binding spots, allowed identifying this new allergen, as well as cloning and DNA sequencing of the corresponding gene. The allergen, named Ole e 12, is a polymorphic isoflavone reductase-like protein of 308 amino acids showing 80% and 74% identity with birch and pear allergens, Bet v 6 and Pyr c 5, respectively. A prevalence of 33% in the selected population is in contrast to 4%-10% in groups of subjects suffering from pollinosis. Recombinant allergen was produced in Escherichia coli, and deeply characterised. Immunoblotting and ELISA detection as well as inhibition experiments were performed with polyclonal antisera and allergic patients' sera. The recombinant allergen retains the IgE reactivity of its natural counterpart. Close structural and immunological relationships between members of this protein family were supported by their IgG recognition in vegetable species. In summary, Ole e 12 is a minor olive pollen allergen, which gains relevance in patients allergic to peach with olive pollinosis. Proteomic approaches used to analyse this allergen provide useful tools to identify hidden allergens, relevant for several allergic populations and thus complete allergenic panels.

  15. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure.

    Science.gov (United States)

    Kosten, Ilona J; Spiekstra, Sander W; de Gruijl, Tanja D; Gibbs, Susan

    2015-08-15

    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a(+) MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a(-)/CD14(+)/CD68(+) which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets.

  16. B cells play key roles in th2-type airway immune responses in mice exposed to natural airborne allergens.

    Science.gov (United States)

    Drake, Li Yin; Iijima, Koji; Hara, Kenichiro; Kobayashi, Takao; Kephart, Gail M; Kita, Hirohito

    2015-01-01

    Humans are frequently exposed to various airborne allergens. In addition to producing antibodies, B cells participate in immune responses via various mechanisms. The roles of B cells in allergic airway inflammation and asthma have been controversial. We examined the functional importance of B cells in a mouse model of asthma, in which mice were exposed repeatedly to common airborne allergens. Naïve wild-type BALB/c mice or B cell-deficient JH-/- mice were exposed intranasally to a cocktail of allergen extracts, including Alternaria, Aspergillus, and house dust mite, every other day for two weeks. Ovalbumin was included in the cocktail to monitor the T cell immune response. Airway inflammation, lung pathology, and airway reactivity were analyzed. The airway exposure of naïve wild type mice to airborne allergens induced robust eosinophilic airway inflammation, increased the levels of Th2 cytokines and chemokines in the lung, and increased the reactivity to inhaled methacholine. These pathological changes and immune responses were attenuated in B cell-deficient JH-/- mice. The allergen-induced expansion of CD4+ T cells was impaired in the lungs and draining lymph nodes of JH-/- mice. Furthermore, lymphocytes from JH-/- mice failed to produce Th2 cytokines in response to ovalbumin re-stimulation in vitro. Our results suggest that B cells are required for the optimal development of Th2-type immune responses and airway inflammation when exposed to common airborne allergens. The therapeutic targeting of B cells may be beneficial to treat asthma in certain patients.

  17. B cells play key roles in th2-type airway immune responses in mice exposed to natural airborne allergens.

    Directory of Open Access Journals (Sweden)

    Li Yin Drake

    Full Text Available Humans are frequently exposed to various airborne allergens. In addition to producing antibodies, B cells participate in immune responses via various mechanisms. The roles of B cells in allergic airway inflammation and asthma have been controversial. We examined the functional importance of B cells in a mouse model of asthma, in which mice were exposed repeatedly to common airborne allergens. Naïve wild-type BALB/c mice or B cell-deficient JH-/- mice were exposed intranasally to a cocktail of allergen extracts, including Alternaria, Aspergillus, and house dust mite, every other day for two weeks. Ovalbumin was included in the cocktail to monitor the T cell immune response. Airway inflammation, lung pathology, and airway reactivity were analyzed. The airway exposure of naïve wild type mice to airborne allergens induced robust eosinophilic airway inflammation, increased the levels of Th2 cytokines and chemokines in the lung, and increased the reactivity to inhaled methacholine. These pathological changes and immune responses were attenuated in B cell-deficient JH-/- mice. The allergen-induced expansion of CD4+ T cells was impaired in the lungs and draining lymph nodes of JH-/- mice. Furthermore, lymphocytes from JH-/- mice failed to produce Th2 cytokines in response to ovalbumin re-stimulation in vitro. Our results suggest that B cells are required for the optimal development of Th2-type immune responses and airway inflammation when exposed to common airborne allergens. The therapeutic targeting of B cells may be beneficial to treat asthma in certain patients.

  18. Use of humanised rat basophilic leukaemia cell line RS-ATL8 for the assessment of allergenicity of Schistosoma mansoni proteins.

    Directory of Open Access Journals (Sweden)

    Daniel Wan

    2014-09-01

    Full Text Available Parasite-specific IgE is thought to correlate with protection against Schistosoma mansoni infection or re-infection. Only a few molecular targets of the IgE response in S. mansoni infection have been characterised. A better insight into the basic mechanisms of anti-parasite immunity could be gained from a genome-wide characterisation of such S. mansoni allergens. This would have repercussions on our understanding of allergy and the development of safe and efficacious vaccinations against helminthic parasites.A complete medium- to high-throughput amenable workflow, including important quality controls, is described, which enables the rapid translation of S. mansoni proteins using wheat germ lysate and subsequent assessment of potential allergenicity with a humanised Rat Basophilic Leukemia (RBL reporter cell line. Cell-free translation is completed within 90 minutes, generating sufficient amounts of parasitic protein for rapid screening of allergenicity without any need for purification. Antigenic integrity is demonstrated using Western Blotting. After overnight incubation with infected individuals' serum, the RS-ATL8 reporter cell line is challenged with the complete wheat germ translation mixture and Luciferase activity measured, reporting cellular activation by the suspected allergen. The suitability of this system for characterization of novel S. mansoni allergens is demonstrated using well characterised plant and parasitic allergens such as Par j 2, SmTAL-1 and the IgE binding factor IPSE/alpha-1, expressed in wheat germ lysates and/or E. coli. SmTAL-1, but not SmTAL2 (used as a negative control, was able to activate the basophil reporter cell line.This method offers an accessible way for assessment of potential allergenicity of anti-helminthic vaccine candidates and is suitable for medium- to high-throughput studies using infected individual sera. It is also suitable for the study of the basis of allergenicity of helminthic proteins.

  19. Responsiveness of the major birch allergen Bet v 1 scaffold to the gastric environment: Impact on structure and allergenic activity

    DEFF Research Database (Denmark)

    Sancho, Ana I; Wangorsch, Andrea; Jensen, Bettina M

    2011-01-01

    Four Bet v 1 homologous food allergens from celeriac (rApi g 1), apple (rMal d 1), peach (rPru p 1) and hazelnut (rCor a 1), were used to probe the structural responsiveness of the Bet v 1 scaffold to gastric digestion conditions and its impact on allergenicity.......Four Bet v 1 homologous food allergens from celeriac (rApi g 1), apple (rMal d 1), peach (rPru p 1) and hazelnut (rCor a 1), were used to probe the structural responsiveness of the Bet v 1 scaffold to gastric digestion conditions and its impact on allergenicity....

  20. Proteomic and immunochemical characterization of glutathione transferase as a new allergen of the nematode Ascaris lumbricoides.

    Directory of Open Access Journals (Sweden)

    Nathalie Acevedo

    Full Text Available Helminth infections and allergy have evolutionary and clinical links. Infection with the nematode Ascaris lumbricoides induces IgE against several molecules including invertebrate pan-allergens. These antibodies influence the pathogenesis and diagnosis of allergy; therefore, studying parasitic and non-parasitic allergens is essential to understand both helminth immunity and allergy. Glutathione transferases (GSTs from cockroach and house dust mites are clinically relevant allergens and comparative studies between them and the GST from A. lumbricoides (GSTA are necessary to evaluate their allergenicity. We sought to analyze the allergenic potential of GSTA in connection with the IgE response to non-parasitic GSTs. IgE to purified GSTs from Ascaris (nGSTA and rGSTA, house dust mites (rDer p 8, nBlo t 8 and rBlo t 8, and cockroach (rBla g 5 was measured by ELISA in subjects from Cartagena, Colombia. Also, multidimensional proteomic approaches were used to study the extract of A. lumbricoides and investigate the existence of GST isoforms. We found that among asthmatics, the strength of IgE levels to GSTA was significantly higher than to mite and cockroach GSTs, and there was a strong positive correlation between IgE levels to these molecules. Specific IgE to GSTA was found in 13.2% of controls and 19.5% of asthmatics. In addition nGSTA induced wheal and flare in skin of sensitized asthmatics indicating that it might be of clinical relevance for some patients. Frequency and IgE levels to GSTA were higher in childhood and declined with age. At least six GST isoforms in A. lumbricoides bind human IgE. Four isoforms were the most abundant and several amino acid substitutions were found, mainly on the N-terminal domain. In conclusion, a new allergenic component of Ascaris has been discovered; it could have clinical impact in allergic patients and influence the diagnosis of mite and cockroach allergy in tropical environments.

  1. Proteomic and immunochemical characterization of glutathione transferase as a new allergen of the nematode Ascaris lumbricoides.

    Science.gov (United States)

    Acevedo, Nathalie; Mohr, Jens; Zakzuk, Josefina; Samonig, Martin; Briza, Peter; Erler, Anja; Pomés, Anna; Huber, Christian G; Ferreira, Fatima; Caraballo, Luis

    2013-01-01

    Helminth infections and allergy have evolutionary and clinical links. Infection with the nematode Ascaris lumbricoides induces IgE against several molecules including invertebrate pan-allergens. These antibodies influence the pathogenesis and diagnosis of allergy; therefore, studying parasitic and non-parasitic allergens is essential to understand both helminth immunity and allergy. Glutathione transferases (GSTs) from cockroach and house dust mites are clinically relevant allergens and comparative studies between them and the GST from A. lumbricoides (GSTA) are necessary to evaluate their allergenicity. We sought to analyze the allergenic potential of GSTA in connection with the IgE response to non-parasitic GSTs. IgE to purified GSTs from Ascaris (nGSTA and rGSTA), house dust mites (rDer p 8, nBlo t 8 and rBlo t 8), and cockroach (rBla g 5) was measured by ELISA in subjects from Cartagena, Colombia. Also, multidimensional proteomic approaches were used to study the extract of A. lumbricoides and investigate the existence of GST isoforms. We found that among asthmatics, the strength of IgE levels to GSTA was significantly higher than to mite and cockroach GSTs, and there was a strong positive correlation between IgE levels to these molecules. Specific IgE to GSTA was found in 13.2% of controls and 19.5% of asthmatics. In addition nGSTA induced wheal and flare in skin of sensitized asthmatics indicating that it might be of clinical relevance for some patients. Frequency and IgE levels to GSTA were higher in childhood and declined with age. At least six GST isoforms in A. lumbricoides bind human IgE. Four isoforms were the most abundant and several amino acid substitutions were found, mainly on the N-terminal domain. In conclusion, a new allergenic component of Ascaris has been discovered; it could have clinical impact in allergic patients and influence the diagnosis of mite and cockroach allergy in tropical environments.

  2. Chemically induced Salmonella enteritidis ghosts as a novel vaccine candidate against virulent challenge in a rat model.

    Science.gov (United States)

    Vinod, Nagarajan; Oh, Sung; Kim, Seongdae; Choi, Chang Won; Kim, Sei Chang; Jung, Cheong-Hwan

    2014-05-30

    Salmonella enteritidis ghosts (SEGs), non-living empty bacterial cell envelopes were generated by using the minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH) and investigated as a vaccine candidate in rats. To determine the immunogenicity and protective efficacy of SEG vaccine, rats were divided into four groups: group A (non-vaccinated control), group B (orally vaccinated), group C (intramuscularly vaccinated) and group D (intramuscularly vaccinated with complete Freund's adjuvant). Vaccination of rats with SEGs induced significant immune responses before and after virulent challenge. Rats vaccinated with SEGs showed significant increases in serum IgG antibodies after challenging with virulent S. enteritidis on week 8 and week 10 (P<0.01). During the vaccination period, groups B, C and D showed significantly higher serum bactericidal activity (SBA) compared to group A (P<0.01). Most importantly, bacterial loads in vaccinated groups were significantly lower than in the non-vaccinated group (P<0.01). In conclusion, these results show that the chemically induced SEGs as a vaccine candidate against virulent challenge.

  3. Air pollution and allergy: experimental studies on modulation of allergen release from pollen by air pollutants.

    Science.gov (United States)

    Behrendt, H; Becker, W M; Fritzsche, C; Sliwa-Tomczok, W; Tomczok, J; Friedrichs, K H; Ring, J

    1997-01-01

    The fact that allergic diseases increase in prevalence is a generally accepted and worldwide phenomenon. The causes for this increase are not known: only hypothetical concepts exist. Epidemiological studies comparing Eastern and Western European populations have shown a striking difference in the prevalence of respiratory atopic diseases, which is lower in the East. At the same time, different patterns of air pollution have been described, namely 'classical' type I, characterized by SO2 and dust prevailing in the East, and 'modern' type II, characterized by organic compounds, fine particles and ozone, which is more prominent in the West. Type II was associated in multivariate regression analysis with increased prevalence of IgE-mediated allergy. Pollen grains collected from industrial regions with high polyaromatic hydrocarbon load in West Germany, but not in East Germany, were shown to be agglomerated with airborne particles. In vitro exposure of pollen to particles indicated morphological changes and increased allergen release from the pollen. In vitro exposure of pollen to gaseous pollutants (SO2 and NO2) under different conditions of humidity resulted in SO2-induced, but not NO2-induced reduction of allergen release from pollen. It is concluded that the bioavailability of grass pollen allergens may be modulated by air pollutants, supporting the concept of an interaction between pollen and pollutants in the atmosphere outside the organism which in turn may affect allergy-relevant phenomena.

  4. Pyrosequencing analysis of Salinomycin and Eimeria spp. challenge-induced changes in broiler cecal microbial communities

    Science.gov (United States)

    Eimeria spp. invade and damage the intestinal cell lining of broilers, resulting in cell necrosis and secondary bacterial infections. The current work investigates the effect of anticoccidial agents, salinomycin in combination with roxarsone, and Eimeria challenge on the composition of broiler ceca...

  5. Recombinant proteins from Gallibacterium anatis induces partial protection against heterologous challenge in egg-laying hens

    DEFF Research Database (Denmark)

    Pors, Susanne Elisabeth; Skjerning, Ragnhild Bager; Flachs, Esben M.;

    2016-01-01

    are urgently required. The aim of the present study was to evaluate the cross-protective capacity of three recombinant proteins recently identified as potential vaccine candidates; GtxA-N, GtxA-C, and FlfA, in an in vivo challenge model. Nine groups of birds were immunized twice with each protein, respectively...

  6. Side effects induced by the acute levodopa challenge in Parkinson’s Disease and atypical parkinsonisms

    Science.gov (United States)

    Mostile, Giovanni; Dibilio, Valeria; Sciacca, Giorgia; Contrafatto, Donatella; Cicero, Calogero Edoardo; Raciti, Loredana; Luca, Antonina; Zappia, Mario

    2017-01-01

    Introduction Acute levodopa challenge may be performed to predict levodopa chronic responsiveness. The aim of the study was to investigate frequency of side effects during the acute levodopa challenge in PD and atypical parkinsonisms. Methods We enrolled 34 de novo PD patients and 29 patients affected by atypical parkinsonisms (Multiple System Atrophy, MSA, n = 10; Progressive Supranuclear Palsy, PSP, n = 12 and Corticobasal Degeneration, CBD, n = 7) who underwent an acute levodopa challenge. Side effects occurring during test were recorded. Results Side effects were more frequent among atypical parkinsonisms as unique group when compared to PD patients (64.3% versus 23.5%; p-value 0.002) with an adjusted OR of 4.36 (95%CI 1.40–13.5). Each atypical parkinsonisms showed almost double occurrence of side effects (MSA 90%, PSP 41.7% and CBD 57%). Conclusions Side effects during acute levodopa challenge may be frequent in atypical parkinsonisms. This information could be useful in order to better prepare the patient for the test. Furthermore, it could represent a useful cue in differential diagnosis with PD. PMID:28207803

  7. Could an experimental dengue virus infection fail to induce solid immunity against homologous viral challenge in non-human primates?

    Science.gov (United States)

    Valdés, Iris; Gil, Lázaro; Lazo, Laura; Marcos, Ernesto; Martín, Jorge; Suzarte, Edith; Castro, Jorge; Romero, Yaremis; Guillén, Gerardo; Hermida, Lisset

    2016-02-01

    There are several dengue vaccine candidates at advanced stages of development, but none of them are licensed. Despite the reactogenicity and immunogenicity profile in humans of the tetravalent ChimeriVax™ dengue vaccine candidate, in efficacy trials, it has failed to confer complete protection against dengue virus (DENV)-1 and DENV-2. However, full protection against the four serotypes had been observed previously in monkeys immunized with this vaccine candidate. Some authors have tried to explain this contradiction by hypothesizing that protection rates in non-human primates (NHPs) are associated with a lack of post-challenge anamnestic immune responses. Here, we studied the protection and anamnestic response patterns after homologous challenge in NHPs previously infected with DENV-2. Two immunization schemes were used, varying the viral doses and the intervals between them. Animals developed immunity against DENV-2 that provided full protection against reinfection with a homologous virus. However, all monkeys showed a significant increase in antiviral and neutralizing antibody titers after challenge. Our results suggest that sterilizing immunity could not be induced by infection with the virus despite the lack of detectable viremia in some animals in which an increase in antibody titer was observed. For this reason, we propose that the lack of an anamnestic neutralizing antibody response after challenge, as suggested by some authors, should be carefully reviewed as a criterion for evaluating the functionality of vaccine candidates.

  8. A protein allergen microarray detects specific IgE to pollen surface, cytoplasmic, and commercial allergen extracts.

    Directory of Open Access Journals (Sweden)

    Katinka A Vigh-Conrad

    Full Text Available Current diagnostics for allergies, such as skin prick and radioallergosorbent tests, do not allow for inexpensive, high-throughput screening of patients. Additionally, extracts used in these methods are made from washed pollen that lacks pollen surface materials that may contain allergens.We sought to develop a high-throughput assay to rapidly measure allergen-specific IgE in sera and to explore the relative allergenicity of different pollen fractions (i.e. surface, cytoplasmic, commercial extracts. To do this, we generated a protein microarray containing surface, cytoplasmic, and commercial extracts from 22 pollen species, commercial extracts from nine non-pollen allergens, and five recombinant allergenic proteins. Pollen surface and cytoplasmic fractions were prepared by extraction into organic solvents and aqueous buffers, respectively. Arrays were incubated with <25 uL of serum from 176 individuals and bound IgE was detected by indirect immunofluorescence, providing a high-throughput measurement of IgE. We demonstrated that the allergen microarray is a reproducible method to measure allergen-specific IgE in small amounts of sera. Using this tool, we demonstrated that specific IgE clusters according to the phylogeny of the allergen source. We also showed that the pollen surface, which has been largely overlooked in the past, contained potent allergens. Although, as a class, cytoplasmic fractions obtained by our pulverization/precipitation method were comparable to commercial extracts, many individual allergens showed significant differences.These results support the hypothesis that protein microarray technology is a useful tool for both research and in the clinic. It could provide a more efficient and less painful alternative to traditionally used skin prick tests, making it economically feasible to compare allergen sensitivity of different populations, monitor individual responses over time, and facilitate genetic studies on pollen allergy.

  9. Localization of candidate allergen genes on the apple (Malus domestica) genome and their putative allergenicity

    NARCIS (Netherlands)

    Gao Zhongshan,

    2005-01-01

    Apple is generally considered as a healthy food, but 2-3% European people can not eat this fruit because it provokes allergy reaction. Four classes of apple allergen genes have been identified, they are Mal d 1, Mal d 2, Mal d 3 and Mal d 4 . This thesis focuses on the genomic characterization of th

  10. Serological response of cattle to Brucella allergen after repeated intradermal applications of this allergen

    NARCIS (Netherlands)

    Muskens, J.A.M.; Bercovich, Z.; Damen, C.P.R.M.

    1996-01-01

    A study was conducted to determine whether an allergen that has been prepared from a mucoid strain of Brucella abortus triggers a serum antibody response that interferes with the interpretation of serologic tests results. Fifteen cattle seronegative for Brucella antigen were tested with the SDTH tes

  11. Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

    Directory of Open Access Journals (Sweden)

    Juliana De Souza Rebouças

    2012-01-01

    Full Text Available In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  12. Authentication of food allergen quality by physicochemical and immunological methods

    DEFF Research Database (Denmark)

    Sancho, A I; Hoffmann-Sommergruber, K; Alessandri, S

    2010-01-01

    and standardization of methods between different laboratories and operators for risk assessment in the food industry. Therefore, there is a need for well-defined purified food allergens. In this context, a panel of 46 food allergens from plant and animal sources has been purified, from either the food sources...

  13. Precautionary allergen labelling: perspectives from key stakeholder groups

    NARCIS (Netherlands)

    DunnGalvin, A.; Chun-Han, C.; Crevel, R.; Grimshaw, K.; Poms, R.; Schnadt, S.; Taylor, S.L.; Turner, P.; Allen, K,J.; Austin, M.; Baka, A.; Baumert, J.L.; Baumgartner, S.; Beyer, K.; Bucchini, L; Fernández-Rivas, M.; Grinter, K.; Houben, G.F.; Hourihane, J.; Kenna, F.; Kruizinga, AG; Lack, G; Madsen, CB; Mills, EN; Papadopoulos, N.G.; Alldrick, A.; Regent, L.; Sherlock, R.; Wal, J.M.; Roberts, G.

    2015-01-01

    Precautionary allergen labelling (PAL) was introduced by the food industry to help manage and communicate the possibility of reaction from the unintended presence of allergens in foods. However, in its current form, PAL is counter-productive for consumers with food allergies. This review aims to sum

  14. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy.

    Science.gov (United States)

    De Souza Rebouças, Juliana; Esparza, Irene; Ferrer, Marta; Sanz, María Luisa; Irache, Juan Manuel; Gamazo, Carlos

    2012-01-01

    In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  15. An overview of fruit allergy and the causative allergens.

    Science.gov (United States)

    Hassan, A K G; Venkatesh, Y P

    2015-11-01

    Plant allergens, being one of the most widespread allergenic substances, are hard to avoid. Hence, their identification and characterization are of prime importance for the diagnosis and treatment of food allergy. The reported allergies to fruits mainly evoke oral allergy syndrome caused by the presence of cross-reactive IgE to certain pollens and thus, allergy to fruits has also been linked to particular pollens. Many fruit allergies are being studied for their causative allergens, and are being characterized. Some tropical or exotic fruits are responsible for region-specific allergies for which only limited information is available, and generally lack allergen characterization. From a survey of the literature on fruit allergy, it is clear that some common fruits (apple, peach, musk melon, kiwi fruit, cherry, grape, strawberry, banana, custard apple, mango and pomegranate) and their allergens appear to be at the center of current research on food allergy. The present review focuses on common fruits reported as allergenic and their identified allergens; a brief description of allergens from six rare/tropical fruits is also covered.

  16. Development and evolution of risk assessment for food allergens

    NARCIS (Netherlands)

    Crevel, R.W.R.; Baumert, J.L.; Baka, A.; Houben, G.F.; Knulst, A.C.; Kruizinga, A.G.; Luccioli, S.; Taylor, S.L.; Madsen, C.B.

    2014-01-01

    The need to assess the risk from food allergens derives directly from the need to manage effectively this food safety hazard. Work spanning the last two decades dispelled the initial thinking that food allergens were so unique that the risk they posed was not amenable to established risk assessment

  17. Enzymatic treatment of soy protein isolates: effects on the potential allergenicity, technofunctionality, and sensory properties.

    Science.gov (United States)

    Meinlschmidt, Pia; Sussmann, Daniela; Schweiggert-Weisz, Ute; Eisner, Peter

    2016-01-01

    Soybean allergy is of great concern and continues to challenge both consumer and food industry. The present study investigates the enzyme-assisted reduction in major soybean allergens in soy protein isolate using different food-grade proteases, while maintaining or improving the sensory attributes and technofunctional properties. SDS-PAGE analyses showed that hydrolysis with Alcalase, Pepsin, and Papain was most effective in the degradation of the major soybean allergens with proteolytic activities of 100%, 100%, and 95.9%, respectively. In the course of hydrolysis, the degree of hydrolysis increased, and Alcalase showed the highest degree of hydrolysis (13%) among the proteases tested. DSC analysis confirmed the degradation of major soybean allergens. The sensory experiments conducted by a panel of 10 panelists considered the overall improved sensory properties as well as the bitterness of the individual hydrolysates. In particular, Flavourzyme and Papain were attractive due to a less pronounced bitter taste and improved sensory profile (smell, taste, mouthfeeling). Technofunctional properties showed a good solubility at pH 7.0 and 4.0, emulsifying capacity up to 760 mL g(-1) (Flavourzyme) as well as improved oil-binding capacities, while the water-binding properties were generally decreased. Increased foaming activity for all proteases up to 3582% (Pepsin) was observed, whereas lower foaming stability and density were found. The hydrolysates could potentially be used as hypoallergenic ingredients in a variety of food products due to their improved technofunctional properties and a pleasant taste.

  18. Allergic contact dermatitis in dermatologic surgery: review of common allergens.

    Science.gov (United States)

    Butler, Lara; Mowad, Christen

    2013-01-01

    With the growing number of dermatologic surgeries performed each year comes an increased potential for patient exposure and sensitization to allergens. Patients are exposed to many well-documented allergens in the preoperative, intraoperative, and postoperative settings during surgery. Postoperative skin complications of allergic contact dermatitis increase health care costs and cause patient suffering. Early recognition, diagnosis, and treatment by dermatologic surgeons are essential to decrease morbidity related to medically necessary and elective cutaneous surgeries. While a specific standard screening panel for cutaneous surgery-related allergens is not well established, we propose several categories of allergens be strongly considered and tested if a patient is suspected of having allergic contact dermatitis in an attempt to reveal pertinent allergens and prevent future exposures.

  19. Aspects of food processing and its effect on allergen structure.

    Science.gov (United States)

    Paschke, Angelika

    2009-08-01

    The article summarizes current physical and chemical methods in food processing as storage, preparation, separation, isolation or purification and thermal application on the one hand as well as enzymatic treatment on the other and their impact on the properties of food proteins. Novel methods of food processing like high pressure, electric field application or irradiation and their impact on food allergens are presented. The EU project REDALL (Reduced Allergenicity of Processed Foods, Containing Animal Allergens: QLK1-CT-2002-02687) showed that by a combination of enzyme and heat treatment the allergic potential of hen's egg decreased about 100 fold. Clinical reactions do not appear anymore. An AiF-FV 12024 N project worked with fruits like mango, lychee and apple. Processed mango and lychee had no change in allergenic potential during heating while e. g. canning. Apple almost lost its allergenic potential after pasteurization in juice production.

  20. Controlling allergens in animal rooms by using curtains

    DEFF Research Database (Denmark)

    Krohn, Thomas Cæcius; Itter, Gabi; Fosse, Richard

    2006-01-01

    . The experimental situation we studied provides some information regarding allergen disposition in animal rooms but is clearly artificial and does not reflect a typical, ‘real-world’ environment in terms of preventing exposure of workers to allergens. Plastic curtains with holes were placed in front of racks......The reduction and control of allergens in the animal facility is important for staff working with laboratory animals. This study was designed to evaluate the efficiency of perforated Makrolon curtains in front of racks as a method to reduce the amount of allergen in the animal room...... the curtains and prevents its spread from the cages into the aisle. The present study shows that the use of curtains in front of the cage racks is an efficient way to prevent spread of allergens from rodent cages to the entire animal room....

  1. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

    Directory of Open Access Journals (Sweden)

    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  2. Allergen immunotherapy for insect venom allergy

    DEFF Research Database (Denmark)

    Dhami, S; Zaman, H; Varga, Eva-Maria

    2017-01-01

    BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety...... of AIT in the management of insect venom allergy. METHODS: We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were...

  3. [New pets, allergens and allergic dermatitis].

    Science.gov (United States)

    Brajon, D; Waton, J; Schmutz, J-L; Barbaud, A

    2014-10-01

    The number of household pets increased greatly during the twentieth century, with the numbers of new pets (NP, i.e. any pet other than cats and dogs) rising especially sharply over the last decade. Contact with such animals, whose owners do not always know how to look after them properly, expose the population to new risks such as trauma, infection and allergy. While the most common allergies are respiratory, allergic skin reactions, both immediate and delayed, may also result from contact with these new allergens. The animal itself or its environment may be the cause. Herein, we review NPs and reports of allergic dermatitis associated with them.

  4. Solution structure of allergenic 2 S albumins.

    Science.gov (United States)

    Pantoja-Uceda, D; Bruix, M; Santoro, J; Rico, M; Monsalve, R; Villalba, M

    2002-11-01

    The NMR solution structures at different levels of refinement of three different 2 S albumin seed proteins, the recombinant pronapin precursor from Brassica napus, the recombinant RicC3 from Ricinus communis and the methionine-rich protein from sunflower ( Helianthus annuus ), are described. The resulting common structure consists of a bundle of five alpha-helices, folded in a right-handed superhelix. The structure is very similar to that of other plant proteins: the hydrophobic protein from soybean, non-specific lipid transfer proteins and amylase/trypsin inhibitors. Analogies and differences in the structures of these families, as well as their possible relationship to allergenicity, are discussed.

  5. MUTZ-3 derived Langerhans cells in human skin equivalents show differential migration and phenotypic plasticity after allergen or irritant exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kosten, Ilona J.; Spiekstra, Sander W. [Department of Dermatology, VU University Medical Center, Amsterdam (Netherlands); Gruijl, Tanja D. de [Department of Dermatology Medical Oncology, VU University Medical Center, Amsterdam (Netherlands); Gibbs, Susan, E-mail: s.gibbs@acta.nl [Department of Dermatology, VU University Medical Center, Amsterdam (Netherlands); Department of Oral Cell Biology, Academic Center for Dentistry (ACTA), Amsterdam (Netherlands)

    2015-08-15

    After allergen or irritant exposure, Langerhans cells (LC) undergo phenotypic changes and exit the epidermis. In this study we describe the unique ability of MUTZ-3 derived Langerhans cells (MUTZ-LC) to display similar phenotypic plasticity as their primary counterparts when incorporated into a physiologically relevant full-thickness skin equivalent model (SE-LC). We describe differences and similarities in the mechanisms regulating LC migration and plasticity upon allergen or irritant exposure. The skin equivalent consisted of a reconstructed epidermis containing primary differentiated keratinocytes and CD1a{sup +} MUTZ-LC on a primary fibroblast-populated dermis. Skin equivalents were exposed to a panel of allergens and irritants. Topical exposure to sub-toxic concentrations of allergens (nickel sulfate, resorcinol, cinnamaldehyde) and irritants (Triton X-100, SDS, Tween 80) resulted in LC migration out of the epidermis and into the dermis. Neutralizing antibody to CXCL12 blocked allergen-induced migration, whereas anti-CCL5 blocked irritant-induced migration. In contrast to allergen exposure, irritant exposure resulted in cells within the dermis becoming CD1a{sup −}/CD14{sup +}/CD68{sup +} which is characteristic of a phenotypic switch of MUTZ-LC to a macrophage-like cell in the dermis. This phenotypic switch was blocked with anti-IL-10. Mechanisms previously identified as being involved in LC activation and migration in native human skin could thus be reproduced in the in vitro constructed skin equivalent model containing functional LC. This model therefore provides a unique and relevant research tool to study human LC biology in situ under controlled in vitro conditions, and will provide a powerful tool for hazard identification, testing novel therapeutics and identifying new drug targets. - Highlights: • MUTZ-3 derived Langerhans cells integrated into skin equivalents are fully functional. • Anti-CXCL12 blocks allergen-induced MUTZ-LC migration.

  6. Lung-derived innate cytokines: new epigenetic targets of allergen-specific sublingual immunotherapy

    Directory of Open Access Journals (Sweden)

    Abbas Pishdadian

    2016-01-01

    Full Text Available Objective(s:Sublingual allergen-specific immunotherapy is a safe and effective method for treatment of IgE-mediated respiratory allergies; however, the underlying mechanisms are not fully understood. This study was planned to test whether sublingual immunotherapy (SLIT can exert epigenetic mechanisms through which the airway allergic responses can be extinguished. Materials and Methods:BALB/c mice were sensitized intraperitoneally and challenged intranasally. Then, they received sublingual treatment with recombinant Che a 2 (rChe a 2, a major allergen of Chenopodium album. After SLIT, allergen-specific antibodies in sera, cytokine profiles of spleen cell cultures, mRNA and protein expression of lung-derived IL-33, IL-25, and TSLP (thymic stromal lymphopoietin, and histone modifications of these three genes were assessed. Results:Following Immunotherapy, systemic immune responses shifted from Th2 to Th1 profile as demonstrated by significant decrease in IgE and IL-4 and substantial increase in IgG2a and IFN-γ. At local site, mRNA and protein levels of lung-derived pro-inflammatory cytokines IL-33 and TSLP were markedly down-regulated following SLIT that was associated with marked enrichment of trimethylated lysine 27 of histone H3 at promoter regions of these two cytokines. Conclusion:In our study, sublingual immunotherapy with recombinant allergen effectively attenuated allergic immune responses, at least partly, by induction of distinct histone modifications at specific loci. Additionally, the lung-derived pro-allergic cytokines IL-33 and TSLP could be promising mucosal candidates for either monitoring allergic conditions or therapeutic approaches.

  7. Study on allergen in 1 538 eczema of children%儿童湿疹1538例过敏原分析

    Institute of Scientific and Technical Information of China (English)

    李静; 兰凤荣; 陈亚秋; 陈昱; 赵利媛; 邵平; 李卫芹; 冷峻宏

    2013-01-01

    ,with the growth of the age,inhaled allergen was the main allergen in elder children eczema.[Conclusion] The inducing factor of eczema can be found out by the detection of allergen,which providing the foundation for the prevention and treatment of eczema.

  8. Methotrexate-induced necrolysis in tumoral-stage mycosis fungoides: a challenging diagnosis.

    Science.gov (United States)

    Mna, Amira Ben; Souissi, Asmahene; Halouani, Slim; El Euch, Dalenda; Zahani, Alia; Kchir, Nidham; Zaraa, Ines; Mokni, Mourad

    2016-01-01

    Methotrexate-induced cutaneous ulceration is a rare but potentially serious drug adverse reaction. This adverse reaction of methotrexate therapy has been initially described in psoriasis patients and is unusual in patients with cutaneous T-cell lymphoma. In 1978, Mc Donald et al reported the first three cases of cutaneous ulcerations in patients treated for a mycosis fungoides with intravenous infusions of methotrexate. Since then, few cases of methotrexate-induced skin ulcers in patients with mycosis fungoides have been published. We report an additional patient with erythrodermic mycosis fungoides who developed cutaneous ulcerations as a sole manifestation of methotrexate toxicity.

  9. 27 CFR 5.32a - Voluntary disclosure of major food allergens.

    Science.gov (United States)

    2010-04-01

    ... major food allergens. 5.32a Section 5.32a Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... Labeling Requirements for Distilled Spirits § 5.32a Voluntary disclosure of major food allergens. (a... allergen. Major food allergen means any of the following: (i) Milk, egg, fish (for example, bass,...

  10. Making peanut allergens indigestible: a model system for reducing or preventing an allergic reaction

    Science.gov (United States)

    Peanut allergens are not totally resistant to digestion as previously known. Creating peanut allergen conjugates that are more resistant to digestion may prevent absorption of the allergens into the bloodstream, and thereby, an allergic reaction. Peanut allergen conjugates were prepared by covalen...

  11. 27 CFR 7.22a - Voluntary disclosure of major food allergens.

    Science.gov (United States)

    2010-04-01

    ... major food allergens. 7.22a Section 7.22a Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX... Labeling Requirements for Malt Beverages § 7.22a Voluntary disclosure of major food allergens. (a... allergen. Major food allergen means any of the following: (i) Milk, egg, fish (for example, bass,...

  12. Reduction of the Number of Major Representative Allergens: From Clinical Testing to 3-Dimensional Structures

    Directory of Open Access Journals (Sweden)

    Ying He

    2014-01-01

    Full Text Available Vast amounts of allergen sequence data have been accumulated, thus complicating the identification of specific allergenic proteins when performing diagnostic allergy tests and immunotherapy. This study aims to rank the importance/potency of the allergens so as to logically reduce the number of allergens and/or allergenic sources. Meta-analysis of 62 allergenic sources used for intradermal testing on 3,335 allergic patients demonstrated that in southern China, mite, sesame, spiny amaranth, Pseudomonas aeruginosa, and house dust account for 88.0% to 100% of the observed positive reactions to the 62 types of allergenic sources tested. The Kolmogorov-Smironov Test results of the website-obtained allergen data and allergen family featured peptides suggested that allergen research in laboratories worldwide has been conducted in parallel on many of the same species. The major allergens were reduced to 21 representative allergens, which were further divided into seven structural classes, each of which contains similar structural components. This study therefore has condensed numerous allergenic sources and major allergens into fewer major representative ones, thus allowing for the use of a smaller number of allergens when conducting comprehensive allergen testing and immunotherapy treatments.

  13. Unintended allergens in precautionary labelled and unlabelled products pose significant risks to UK allergic consumers

    NARCIS (Netherlands)

    Remington, B.C.; Baumert, J.L.; Blom, W.M.; Houben, G.F.; Taylor, S.L.; Kruizinga, A.G.

    2015-01-01

    Background Allergens in food may pose a risk to allergic consumers. While there is EU regulation for allergens present as an ingredient, this is not the case for unintended allergen presence (UAP). Food companies use precautionary allergen labels to inform allergic individuals of a potential risk fr

  14. Mouse allergen, lung function, and atopy in Puerto Rican children.

    Directory of Open Access Journals (Sweden)

    Erick Forno

    Full Text Available To examine the relation between mouse allergen exposure and asthma in Puerto Rican children.Mus m 1, Der p 1, Bla g 2, and Fel d 1 allergens were measured in dust samples from homes of Puerto Rican children with (cases and without (controls asthma in Hartford, CT (n = 449 and San Juan (SJ, Puerto Rico (n = 678. Linear or logistic regression was used for the multivariate analysis of mouse allergen (Mus m 1 and lung function (FEV(1 and FEV(1/FVC and allergy (total IgE and skin test reactivity (STR to ≥1 allergen measures.Homes in SJ had lower mouse allergen levels than those in Hartford. In multivariate analyses, mouse allergen was associated with higher FEV(1 in cases in Hartford (+70.6 ml, 95% confidence interval (CI = 8.6-132.7 ml, P = 0.03 and SJ (+45.1 ml, 95% CI =  -0.5 to 90.6 ml, P = 0.05. In multivariate analyses of controls, mouse allergen was inversely associated with STR to ≥1 allergen in non-sensitized children (odds ratio [OR] for each log-unit increment in Mus m 1 = 0.7, 95% CI = 0.5-0.9, P<0.01. In a multivariate analysis including all children at both study sites, each log-increment in mouse allergen was positively associated with FEV(1 (+28.3 ml, 95% CI = 1.4-55.2 ml, P = 0.04 and inversely associated with STR to ≥1 allergen (OR for each log-unit increment in Mus m 1 = 0.8, 95% CI = 0.6-0.9, P<0.01.Mouse allergen is associated with a higher FEV(1 and lower odds of STR to ≥1 allergen in Puerto Rican children. This may be explained by the allergen itself or correlated microbial exposures.

  15. Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future.

    Science.gov (United States)

    Valenta, Rudolf; Campana, Raffaela; Focke-Tejkl, Margit; Niederberger, Verena

    2016-02-01

    In the past, the development of more effective, safe, convenient, broadly applicable, and easy to manufacture vaccines for allergen-specific immunotherapy (AIT) has been limited by the poor quality of natural allergen extracts. Progress made in the field of molecular allergen characterization has now made it possible to produce defined vaccines for AIT and eventually for preventive allergy vaccination based on recombinant DNA technology and synthetic peptide chemistry. Here we review the characteristics of recombinant and synthetic allergy vaccines that have reached clinical evaluation and discuss how molecular vaccine approaches can make AIT more safe and effective and thus more convenient. Furthermore, we discuss how new technologies can facilitate the reproducible manufacturing of vaccines of pharmaceutical grade for inhalant, food, and venom allergens. Allergy vaccines in clinical trials based on recombinant allergens, recombinant allergen derivatives, and synthetic peptides allow us to target selectively different immune mechanisms, and certain of those show features that might make them applicable not only for therapeutic but also for prophylactic vaccination.

  16. Papain-induced occupational rhinoconjunctivitis and asthma - A case report.

    Science.gov (United States)

    Tymoszuk, Diana; Wiszniewska, Marta; Walusiak-Skorupa, Jolanta

    2016-01-01

    This report presents a case of occupational asthma, rhinitis and conjunctivitis to papain in a 50-year-old herbs and spices packer, with documented increased eosinophilia in induced sputum and in the nasal lavage fluids after a specific inhalation challenge test (SICT) and specific nasal challenge test (SNCT) with this enzyme. Immunoglobulin E-mediated (IgE) sensitization to papain was confirmed by positive results of a skin prick test with specific solution. Specific inhalation and nasal challenge tests demonstrated a direct and significant link between the exposure to this protease and the allergic response from the respiratory system. Additionally, the SNCT induced a severe reaction of the conjunctivae and a significant increase in the count of eosinophils in tears, despite the lack of direct contact of the allergen with the conjunctiva.

  17. Effects of the recombinant allergen rDer f 2 on neuro-endocrino-immune network in asthmatic mice.

    Science.gov (United States)

    Jiang, Yong-Qian; Zhou, Zhi-Xiang; Ji, You-Lin

    2014-01-01

    Severe and life-threatening side effects can occur in patients receiving allergen-specific immunotherapy (SIT), and recombinant allergens made from cDNA have been used in clinical trials for ten years and appear promising for SIT. The aim of this study is to explore the effects of the recombinant allergen Der f 2 (the group 2 allergen from Dermatophagoides farinae) on the neuro-endocrino-immune network in asthmatic mice. Twenty-eight mice were divided into four groups - A, B, C and D. To induce asthma, a crude extract of D. farinae was injected intraperitoneally into the mice in groups B, C and D. Later, the crude extract or recombinant allergen rDer f 2 was given to groups C and D, respectively. Normal saline was given to groups A and B. Serum corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), interleukin 4 (IL-4), and interferon γ (IFN-γ) were detected by immunoassay and the pathological change of lung tissue was observed by hematoxylin and eosin (HE) staining. Serum CRH, ACTH, CORT, and IFN-γ were highest in healthy group A but lowest in asthma group B. Treatment with the crude extract or recombinant allergen rDer f 2 significantly attenuated this response in asthmatic mice, but there was no difference between the two treatments (p > 0.05). Serum IL-4 was elevated in asthma group B but lowest in healthy group A. Treatment with the crude extract or recombinant allergen rDer f 2 significantly attenuated this response in asthmatic mice, but there was no significant difference between the two treatments (p > 0.05). However, lung pathology as measured histologically (Underwood Score) showed that rDer f 2-treatment was significantly better than crude extract treatment (p < 0.05). In brief, recombinant allergen Der f 2 can strengthen the function of hypothalamus-pituitary-adrenal (HPA) axis, affect the balance of Th1 and Th2 cytokines, and reduce pulmonary inflammation in asthmatic mice.

  18. Evaluation of subcutaneous versus mucosal (intranasal) allergen-specific rush immunotherapy in experimental feline asthma.

    Science.gov (United States)

    Lee-Fowler, Tekla M; Cohn, Leah A; DeClue, Amy E; Spinka, Christine M; Reinero, Carol R

    2009-05-15

    Rush immunotherapy (RIT) is effective for the treatment of experimental feline allergic asthma. In humans, the safety profile of immunotherapy is improved by delivering allergen by a mucosal route. We hypothesized that mucosal (intranasal) RIT would have similar efficacy to subcutaneous RIT with improved safety. Twelve cats sensitized and challenged with Bermuda grass allergen (BGA) were randomized to receive subcutaneous (SC) or intranasal (IN) RIT. Increasing doses of BGA (20-200 microg) were administered over 24h followed by 200 microg BGA weekly as maintenance. Adverse reactions were recorded. Clinical respiratory scores after BGA aerosol challenge, bronchoalveolar lavage fluid (BALF) % eosinophils, and cytokine concentrations were measured before RIT (day 1) and at months 1, 3 and 6 (M1, M3, M6). More adverse events were recorded with SC RIT (n=12) compared with IN RIT (n=6). Respiratory scores were lower by M6 compared with D1 in both the groups. The % BALF eosinophils declined significantly after RIT for both groups (mean+/-SEM, SC RIT D1 62+/-12, M6 9+/-4; IN RIT D1 54+/-9, M6 14+/-6). The BALF IL-4:IFN-gamma ratio significantly decreased over time in the IN RIT group (mean+/-SEM, D1 2.4+/-0.2, M6 1.0+/-0.2). While both protocols decreased eosinophilic airway inflammation, the SC RIT protocol did not cause life-threatening adverse events and demonstrated more consistent resolution of clinical signs after allergen challenge. Either protocol could be considered for the treatment of feline allergic asthma.

  19. What is the source of serum allergen-specific IgE?

    Science.gov (United States)

    Eckl-Dorna, Julia; Niederberger, Verena

    2013-06-01

    Immunoglobulin E (IgE), the key effector element in the induction and propagation of allergic diseases, is the least abundant antibody class. In allergic patients, class switch recombination to IgE in B cells is induced by allergen contact in conjunction with T cell interaction and a Th2 cytokine environment. With regard to future therapeutic approaches, the sites of IgE production in human subjects and the nature and characteristics of IgE-producing cells are of great interest. In this context, it has been shown that allergen-specific IgE levels can be boosted by contact with allergens via the respiratory mucosa of the nose. Also, it has been proposed that allergy effector organs (e.g., the nasal mucosa and the lung) may be important sites of IgE production in allergic patients. IgE-producing cells have also been found in the blood, but their numbers are extremely low. Transfer of specific sensitization during bone marrow transplantation indicates the presence of IgE-producing B memory cells or plasma cells also in the bone marrow. This review summarizes data on the induction of IgE production, IgE memory and the sites of IgE production in human allergic patients.

  20. Allergy and asthma: Effects of the exposure to particulate matter and biological allergens.

    Science.gov (United States)

    Baldacci, S; Maio, S; Cerrai, S; Sarno, G; Baïz, N; Simoni, M; Annesi-Maesano, I; Viegi, G

    2015-09-01

    The prevalence of asthma and allergies including atopy has increased during the past decades, particularly in westernized countries. The rapid rise in the prevalence of such diseases cannot be explained by genetic factors alone. Rapid urbanization and industrialization throughout the world have increased air pollution and population exposures, so that most epidemiologic studies are focusing on possible links between air pollution and respiratory diseases. Furthermore, a growing body of evidence shows that chemical air pollution may interact with airborne allergens enhancing the risk of atopic sensitization and exacerbation of symptoms in sensitized subjects. These phenomena are supported by current in vitro and animal studies showing that the combined exposure to air pollutants and allergens may have a synergistic or additive effect on asthma and allergies, although there is an insufficient evidence about this link at the population level. Further research is needed in order to elucidate the mechanisms by which pollutants and biological allergens induce damage in exposed subjects. The abatement of the main risk factors for asthma and allergic diseases may achieve huge health benefits. Thus, it is important to raise awareness of respiratory allergies as serious chronic diseases which place a heavy burden on patients and on society as a whole.

  1. Isolation and full characterisation of a potentially allergenic lipid transfer protein (LTP) in almond.

    Science.gov (United States)

    Buhler, Sofie; Tedeschi, Tullia; Faccini, Andrea; Garino, Cristiano; Arlorio, Marco; Dossena, Arnaldo; Sforza, Stefano

    2015-01-01

    Non-specific lipid transfer proteins (nsLTP) were shown to be among the most significant allergens, in particular in several fruits belonging to the Rosaceae family. The molecular features of LTPs, such as the presence of eight cysteine residues forming four disulfide bridges, confer a compact structure, decreasing the probability of degradation due to cooking or digestion, thereby increasing the chance of systemic absorption and severe allergic reactions. Few studies on LTP-induced allergies regarding almond (Prunus dulcis L) are available in the literature. In the present work, we describe for the first time the extraction and purification of an almond LTP, achieving its full characterisation by using liquid chromatography and exact mass spectrometry; the full sequence was identified by means of LC-ESI-Orbitrap-MS applying a bottom-up approach. The characterised protein consists of 92 amino acids and has a calculated exact MW of 9579.0. The presence of four disulfide bridges was confirmed after reduction, as shown by a mass increment of 8 Da. Finally, its potential allergenicity was confirmed via an in silico approach. The results presented here demonstrate the enormous potential of advanced MS techniques for obtaining high-quality structural and functional data of allergenic proteins in a short time.

  2. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Directory of Open Access Journals (Sweden)

    Thomas R Hird

    Full Text Available Inactivated poliovirus vaccine (IPV may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24. In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11] or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]. There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  3. Systematic review of mucosal immunity induced by oral and inactivated poliovirus vaccines against virus shedding following oral poliovirus challenge.

    Science.gov (United States)

    Hird, Thomas R; Grassly, Nicholas C

    2012-01-01

    Inactivated poliovirus vaccine (IPV) may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV) after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5-30 days after a "challenge" dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08-0.24)). In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59-1.11]) or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82-1.58]). There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.

  4. Management of phenytoin induced gingival enlargement associated with cerebral palsy: A challenge to the clinician

    Directory of Open Access Journals (Sweden)

    Anupama Shriram Rao

    2013-01-01

    Full Text Available Phenytoin, which is the drug of choice for treatment of grandmal, psychomotor seizures associated with cerebral palsy, has serious side effect like gingival enlargement. Drug induced gingival enlargement is not only esthetically disfiguring but often impairs speech, mastication, nutrition and plaque control measures. In addition, poor oral hygiene, lack of motor coordination and muscular limitations in mentally disabled individuals results in increased susceptibility to periodontal disease. The present case report unfolds a complex nature of the management of phenytoin induced gingival enlargement, secondarily complicated by inflammation, and in the cerebral palsy patient. A supportive team work of periodontist, neurophysician, and general anesthetist plays a significant role in maintaining the quality of life in mentally disabled patient.

  5. Management of phenytoin induced gingival enlargement associated with cerebral palsy: A challenge to the clinician

    OpenAIRE

    Anupama Shriram Rao; Amit K Walvekar; Rao, Subramaniam M; Biju Thomas

    2013-01-01

    Phenytoin, which is the drug of choice for treatment of grandmal, psychomotor seizures associated with cerebral palsy, has serious side effect like gingival enlargement. Drug induced gingival enlargement is not only esthetically disfiguring but often impairs speech, mastication, nutrition and plaque control measures. In addition, poor oral hygiene, lack of motor coordination and muscular limitations in mentally disabled individuals results in increased susceptibility to periodontal disease. T...

  6. A B Cell Epitope Peptide Derived from the Major Grass Pollen Allergen Phl p 1 Boosts Allergen-Specific Secondary Antibody Responses without Allergen-Specific T Cell Help

    Science.gov (United States)

    Narayanan, Meena; Freidl, Raphaela; Focke-Tejkl, Margarete; Baranyi, Ulrike; Wekerle, Thomas; Valenta, Rudolf

    2017-01-01

    More than 40% of allergic patients suffer from grass pollen allergy. Phl p 1, the major timothy grass pollen allergen, belongs to the cross-reactive group 1 grass pollen allergens that are thought to initiate allergic sensitization to grass pollen. Repeated allergen encounter boosts allergen-specific IgE production and enhances clinical sensitivity in patients. To investigate immunological mechanisms underlying the boosting of allergen-specific secondary IgE Ab responses and the allergen epitopes involved, a murine model for Phl p 1 was established. A B cell epitope–derived peptide of Phl p 1 devoid of allergen-specific T cell epitopes, as recognized by BALB/c mice, was fused to an allergen-unrelated carrier in the form of a recombinant fusion protein and used for sensitization. This fusion protein allowed the induction of allergen-specific IgE Ab responses without allergen-specific T cell help. Allergen-specific Ab responses were subsequently boosted with molecules containing the B cell epitope–derived peptide without carrier or linked to other allergen-unrelated carriers. Oligomeric peptide bound to a carrier different from that which had been used for sensitization boosted allergen-specific secondary IgE responses without a detectable allergen-specific T cell response. Our results indicate that allergen-specific secondary IgE Ab responses can be boosted by repetitive B cell epitopes without allergen-specific T cell help by cross-linking of the B cell epitope receptor. This finding has important implications for the design of new allergy vaccines. PMID:28093528

  7. Disulfiram-induced de novo convulsions without alcohol challenge: Case series and review of literature

    Directory of Open Access Journals (Sweden)

    Ranganath Ramarao Kulkarni

    2015-01-01

    Full Text Available Seizure induction by disulfiram (DSF an adverse effect of therapeutic dosages of DSF is less understood. In our prospective case series of eight subjects with alcohol dependence a temporal, dose-dependent, and reversible epileptogenic potential due to DSF was noted. Mean duration of onset of first seizure was 2.13 ± 1.13 weeks after initiation of DSF therapy (125-500 mg/day with no other detectable causes of seizures. Presence of alcohol withdrawal seizures (50%, DSF-induced hypertension (HTN (37.5%, psychosis (12.5% were noted, that may suggest common neurobiological underpinnings like dopamine-beta-hydroxylase inhibition. Various types of DSF-induced generalized seizures (tonic-clonic, 62.5%; myoclonic and tonic-clonic, 25%; myoclonic, 12.5% were effectively managed by halving initial DSF dose (37.5% even after cessation of antiepileptics, or stopping DSF (37.5%. Presence of alcohol withdrawal seizures, DSF-induced HTN/psychosis during DSF therapy may be early risk factors for dose-dependent and reversible adverse effect of DSF therapy - seizure induction, emphasizing caution.

  8. Disulfiram-Induced De Novo Convulsions without Alcohol Challenge: Case Series and Review of Literature.

    Science.gov (United States)

    Kulkarni, Ranganath Ramarao; Bairy, Bhavya K

    2015-01-01

    Seizure induction by disulfiram (DSF) an adverse effect of therapeutic dosages of DSF is less understood. In our prospective case series of eight subjects with alcohol dependence a temporal, dose-dependent, and reversible epileptogenic potential due to DSF was noted. Mean duration of onset of first seizure was 2.13 ± 1.13 weeks after initiation of DSF therapy (125-500 mg/day) with no other detectable causes of seizures. Presence of alcohol withdrawal seizures (50%), DSF-induced hypertension (HTN) (37.5%), psychosis (12.5%) were noted, that may suggest common neurobiological underpinnings like dopamine-beta-hydroxylase inhibition. Various types of DSF-induced generalized seizures (tonic-clonic, 62.5%; myoclonic and tonic-clonic, 25%; myoclonic, 12.5%) were effectively managed by halving initial DSF dose (37.5%) even after cessation of antiepileptics, or stopping DSF (37.5%). Presence of alcohol withdrawal seizures, DSF-induced HTN/psychosis during DSF therapy may be early risk factors for dose-dependent and reversible adverse effect of DSF therapy - seizure induction, emphasizing caution.

  9. [Hidden allergens in processed food. The consumer perspective].

    Science.gov (United States)

    Schnadt, S

    2012-03-01

    Despite improved allergen-labeling and careful avoidance strategies, hidden allergens in food are a substantial risk for unintended reactions in food allergy sufferers. Unpublished data from a survey of the German Allergy and Asthma Association (Deutscher Allergie- und Asthmabund, DAAB) show that 85% of 738 questioned food allergic patients have experienced at least one allergic reaction from each prepacked products as well as food sold loose. Almost half of the participants said to have not received information of a food allergen as an ingredient or possible trace on the label. Different possibilities are discussed under which food allergens can be hidden in processed products, like incomprehensible labeling, labeling gaps, unexpected occurrence of allergens as well as cross contaminations or allergens in loose products. To each of the seven highlighted sources of hidden allergens in food, practical examples are given as well as proposals for the improvement of the situation from consumer view. The aim is to indicate possibilities and measures for politics and industry by which allergic consumers and their social circle are able to make an informed choice concerning the safe consumption of a certain product and to protect themselves from unintentional reactions.

  10. [Alpha-amylase as an occupational allergen in baking industry employees].

    Science.gov (United States)

    De Zotti, R; Larese, F; Molinari, S

    1994-01-01

    In a group of 226 bakers and pastry makers and in 88 students of a training school for bakers, we evaluated skin sensitization to the common allergens, wheat and alpha amylase. Skin prick tests were positive to the enzyme in 17 exposed subjects (7.5%) and in one student with previous occupational exposure as a baker; 27 exposed subjects (11.9%) and 2 students were sensitized to wheat. Among the 42 exposed workers who complained of work-related symptoms, 12 (28.6%) cases were skin positive to amylase and 17 (42.9%) to wheat. Among the 17 workers who were positive to amylase, 16 were also sensitized to wheat and/or common allergens, 12 complained of symptoms at work but since in many cases there was a positive response to wheat, too, it is impossible to speculate on the role of each allergen in inducing symptoms. One case, with work-related rhinoconjunctivitis, had skin sensitization only to alpha amylase but no specific IgE in the serum. These findings confirm that bakers are at risk of sensitization not only to wheat allergen but also to amylase from Aspergillus oryzae. The enzyme should be included in the list of substances to be tested among bakers in whom an occupational allergy is suspected, but particular care should be taken in evaluating the cutaneous response, especially if compared to wheat wheals. Further investigations are also needed to identify the source of risk and to better define the characteristics of the enzyme and the relationship between skin reaction to amylase, sensitization to wheat and atopy.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Crystal Structure of a Dimerized Cockroach Allergen Bla g 2 Complexed with a Monoclonal Antibody

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mi; Gustchina, Alla; Alexandratos, Jerry; Wlodawer, Alexander; Wünschmann, Sabina; Kepley, Christopher L.; Chapman, Martin D.; Pomes, Anna (INDOOR Bio.); (VCU); (NIH)

    2008-09-03

    The crystal structure of a 1:1 complex between the German cockroach allergen Bla g 2 and the Fab' fragment of a monoclonal antibody 7C11 was solved at 2.8-{angstrom} resolution. Bla g 2 binds to the antibody through four loops that include residues 60-70, 83-86, 98-100, and 129-132. Cation-{pi} interactions exist between Lys-65, Arg-83, and Lys-132 in Bla g 2 and several tyrosines in 7C11. In the complex with Fab', Bla g 2 forms a dimer, which is stabilized by a quasi-four-helix bundle comprised of an {alpha}-helix and a helical turn from each allergen monomer, exhibiting a novel dimerization mode for an aspartic protease. A disulfide bridge between C51a and C113, unique to the aspartic protease family, connects the two helical elements within each Bla g 2 monomer, thus facilitating formation of the bundle. Mutation of these cysteines, as well as the residues Asn-52, Gln-110, and Ile-114, involved in hydrophobic interactions within the bundle, resulted in a protein that did not dimerize. The mutant proteins induced less {beta}-hexosaminidase release from mast cells than the wild-type Bla g 2, suggesting a functional role of dimerization in allergenicity. Because 7C11 shares a binding epitope with IgE, the information gained by analysis of the crystal structure of its complex provided guidance for site-directed mutagenesis of the allergen epitope. We have now identified key residues involved in IgE antibody binding; this information will be useful for the design of vaccines for immunotherapy.

  12. Proteomic profile of hemolymph and detection of induced antimicrobial peptides in response to microbial challenge in Diatraea saccharalis (Lepidoptera: Crambidae).

    Science.gov (United States)

    Rocha, Iara Fernanda; Maller, Alexandre; de Cássia Garcia Simão, Rita; Kadowaki, Marina Kimiko; Angeli Alves, Luis Francisco; Huergo, Luciano Fernandes; da Conceição Silva, José Luis

    2016-04-29

    Insects are organisms extremely well adapted to diverse habitats, primarily due to their innate immune system, which provides them with a range of cellular and humoral responses against microorganisms. Lepidoptera hemolymph proteins involved in humoral responses are well known; however, there is a lack of knowledge about the sugarcane borer Diatraea saccharalis. In this present work, the hemolymph proteins of this pest insect were studied by applying proteomic methodologies. Two-dimensional electrophoresis (2-DE) gels of proteins extracted from naive larvae and larvae challenged with Escherichia coli (ATCC 11224) and Bacillus subtilis (ATCC 6623) showed an average of 300 spots, and 92 of these spots corresponded in all three 2-DE gels. Forty-one spots were excised and digested with trypsin and analyzed using mass spectrometry. After analysis, 10 proteins were identified, including some proteins of the immune system: β-defensin-like protein, Turandot A-like protein, attacin-like protein, peptidoglycan recognition protein and cyclophilin-like protein. Nine proteins were present in both experimental conditions; however, β-defensin-like protein was present only in hemolymph challenged by B. subtilis. Notably, attacin-like protein was strongly induced by challenge with E. coli, suggesting an immune response against the infection. However, antimicrobial activity was observed in the test zone of microbial growth inhibition of B. subtilis solely with the hemolymph extract of the larvae challenged with B. subtilis. We made for the first time a proteomic profile of the hemolymph of D. saccharalis in which it was possible to identify the presence of important proteins involved in the immune response.

  13. Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.

    Directory of Open Access Journals (Sweden)

    Noam Cohen

    Full Text Available Mice are exceedingly sensitive to intra-peritoneal (IP challenge with some virulent pneumococci (LD50 = 1 bacterium. To investigate how peripheral contact with bacterial capsular polysaccharide (PS antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1 The PS co-localized with MHC molecules on the BMDC surface; 2 PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3 Type-specific resistance to lethal IP challenge was manifested only after day 5; 4 Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5 Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6 Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18-20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination.

  14. Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.

    Science.gov (United States)

    Cohen, Noam; Margalit, Raanan; Pevsner-Fischer, Meirav; Yona, Simon; Jung, Steffen; Eisenbach, Lea; Cohen, Irun R

    2012-01-01

    Mice are exceedingly sensitive to intra-peritoneal (IP) challenge with some virulent pneumococci (LD50 = 1 bacterium). To investigate how peripheral contact with bacterial capsular polysaccharide (PS) antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC) of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP) and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1) The PS co-localized with MHC molecules on the BMDC surface; 2) PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3) Type-specific resistance to lethal IP challenge was manifested only after day 5; 4) Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5) Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6) Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18-20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination.

  15. Optimal strategies for virtual screening of induced-fit and flexible target in the 2015 D3R Grand Challenge

    Science.gov (United States)

    Ye, Zhaofeng; Baumgartner, Matthew P.; Wingert, Bentley M.; Camacho, Carlos J.

    2016-09-01

    Induced fit or protein flexibility can make a given structure less useful for docking and/or scoring. The 2015 Drug Design Data Resource (D3R) Grand Challenge provided a unique opportunity to prospectively test optimal strategies for virtual screening in these type of targets: heat shock protein 90 (HSP90), a protein with multiple ligand-induced binding modes; and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a kinase with a large flexible pocket. Using previously known co-crystal structures, we tested predictions from methods that keep the receptor structure fixed and used (a) multiple receptor/ligand co-crystals as binding templates for minimization or docking ("close"), (b) methods that align or dock to a single receptor ("cross"), and (c) a hybrid approach that chose from multiple bound ligands as initial templates for minimization to a single receptor ("min-cross"). Pose prediction using our "close" models resulted in average ligand RMSDs of 0.32 and 1.6 Å for HSP90 and MAP4K4, respectively, the most accurate models of the community-wide challenge. On the other hand, affinity ranking using our "cross" methods performed well overall despite the fact that a fixed receptor cannot model ligand-induced structural changes,. In addition, "close" methods that leverage the co-crystals of the different binding modes of HSP90 also predicted the best affinity ranking. Our studies suggest that analysis of changes on the receptor structure upon ligand binding can help select an optimal virtual screening strategy.

  16. Categorization of fragrance contact allergens for prioritization of preventive measures

    DEFF Research Database (Denmark)

    Uter, Wolfgang; Johansen, Jeanne D; Börje, Anna;

    2013-01-01

    of substances as contact allergens. A total of 54 individual chemicals and 28 natural extracts (essential oils) can be categorized as established contact allergens in humans, including all 26 substances previously identified as contact allergens (SCCNFP/0017/98). Twelve of the 54 individual chemicals...... of 11 substances of special concern should be limited to 100 ppm. The substance hydroxyisohexyl 3-cyclohexene carboxaldehyde and the two ingredients chloroatranol and atranol in the natural extracts Evernia prunastri and Evernia furfuracea should not be present in cosmetic products....

  17. What do we know about plant food allergens?

    DEFF Research Database (Denmark)

    Jenkins, J. A.; Sancho, A. I.; Madsen, Charlotte Bernhard

    2005-01-01

    Food allergies are a topic of interest and concern for both consumers and the Agro-Food industry which is reflected in the plethora of internet-based information resources now available. The development of a reliable credible resource through the EU-funded InformAll project is described, along...... with other related credible internet resources with information on food allergies and allergens. The InformAll database is unique as it combines refereed information on the clinical aspects of food allergies with details of individual allergens. The collection of allergenic protein sequences into online...

  18. Expression analysis of chitinase upon challenge inoculation to Alternaria wounding and defense inducers in Brassica juncea

    Directory of Open Access Journals (Sweden)

    Sandhya Rawat

    2017-03-01

    Full Text Available Chitinases are the hydrolytic enzymes which belong to the pathogenesis-related (PR protein family and play an important role not only in plant defense but also in various abiotic stresses. However, only a limited number of chitinase genes have been characterised in B. juncea. In this study, we have characterised B. juncea class IV chitinase gene (accession no EF586206 in response to fungal infection, salicylic acid (SA, jasmonic acid (JA treatments and wounding. Gene expression studies revealed that the transcript levels of Bjchitinase (BjChp gene increases significantly both in local and distal tissues after Alternaria infection. Bjchitinase gene was also induced by jasmonic acid and wounding but moderately by salicylic acid. A 2.5 kb class IV chitinase promoter of this gene was isolated from B. juncea by Genome walking (accession no KF055403.1. In-silico analysis of this promoter revealed a number of conserved cis-regulatory elements related to defense, wounding and signalling molecules like SA, and JA. For validation, chitinase promoter was fused to the GUS gene, and the resultant construct was then introduced into Arabidopsis plants. Histochemical analysis of T2 transgenic Arabidopsis plants showed that higher GUS activity in leaves after fungal infection, wounding and JA treatment but weakly by SA. GUS activity was seen in meristematic tissues, young leaves, seeds and siliques. Finally investigation has led to the identification of a pathogen-inducible, developmentally regulated and organ-specific promoter. Present study revealed that Bjchitinase (BjChp promoter is induced during biotic and environmental stress and it can be used in developing finely tuned transgenics.

  19. [Placebo effect in clinical trials with allergen-specific immunotherapy with inhalant allergens].

    Science.gov (United States)

    Wedi, B; Wieczorek, D; Kapp, A

    2017-04-01

    Placebo effects play an important role in the treatment of allergic diseases. Therefore, in this study, we analysed the described effects of placebo in all double-blind placebo-controlled clinical trials of allergen-specific immunotherapy (ASIT) with inhalant allergens (birch, grass, house dust mites) listed in the tables (updated July 2016) attached to the German S2k guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases. The most common placebo consisted of verum without allergen, but when the subcutaneous route was used, histamine was sometimes added. From the 33 studies analysed no conclusions could be drawn regarding the pure placebo effect. The symptom medication score (SMS) from an adequate baseline period was described in one single study. An untreated population was not included in any study. Indirect evidence points to substantial placebo effects in up to 77% of the subjects with respect to retrospective, subjective parameters. Well-known factors influencing the placebo effect such as age, gender, application route/composition of the placebo, individual and cultural differences, severity of symptoms at the beginning and the probability of receiving verum have not been addressed regarding ASIT and could not be estimated from available data. Taken together regarding ASIT the placebo effect has been investigated inadequately. In spite of significant expenditure of time and costs future ASIT studies should include assessment of the SMS in an adequate baseline period and preferably include an untreated trial arm. A better understanding of placebo effects in ASIT trials will improve the design of clinical trials and the assessment of therapeutic effects.

  20. Enlarging the toolbox for allergen epitope definition with an allergen-type model protein.

    Directory of Open Access Journals (Sweden)

    Hanna Berkner

    Full Text Available Birch pollen-allergic subjects produce polyclonal cross-reactive IgE antibodies that mediate pollen-associated food allergies. The major allergen Bet v 1 and its homologs in plant foods bind IgE in their native protein conformation. Information on location, number and clinical relevance of IgE epitopes is limited. We addressed the use of an allergen-related protein model to identify amino acids critical for IgE binding of PR-10 allergens.Norcoclaurine synthase (NCS from meadow rue is structurally homologous to Bet v 1 but does not bind Bet v 1-reactive IgE. NCS was used as the template for epitope grafting. NCS variants were tested with sera from 70 birch pollen allergic subjects and with monoclonal antibody BV16 reported to compete with IgE binding to Bet v 1.We generated an NCS variant (Δ29NCSN57/I58E/D60N/V63P/D68K harboring an IgE epitope of Bet v 1. Bet v 1-type protein folding of the NCS variant was evaluated by 1H-15N-HSQC NMR spectroscopy. BV16 bound the NCS variant and 71% (50/70 sera of our study population showed significant IgE binding. We observed IgE and BV16 cross-reactivity to the epitope presented by the NCS variant in a subgroup of Bet v 1-related allergens. Moreover BV16 blocked IgE binding to the NCS variant. Antibody cross-reactivity depended on a defined orientation of amino acids within the Bet v 1-type conformation.Our system allows the evaluation of patient-specific epitope profiles and will facilitate both the identification of clinically relevant epitopes as biomarkers and the monitoring of therapeutic outcomes to improve diagnosis, prognosis, and therapy of allergies caused by PR-10 proteins.

  1. Identification of novel allergen in edible insect, Gryllus bimaculatus and its cross-reactivity with Macrobrachium spp. allergens.

    Science.gov (United States)

    Srinroch, Chutima; Srisomsap, Chantragan; Chokchaichamnankit, Daranee; Punyarit, Phaibul; Phiriyangkul, Pharima

    2015-10-01

    Edible insects have recently been promoted as a source of protein and have a high nutrition value. Identification of allergens and cross-reactivity between Macrobrachium spp. and the field cricket (Gryllus bimaculatus) is necessary for food safety control and to assist in the diagnosis and therapy of allergy symptoms. Denaturing polyacrylamide gel electrophoresis (SDS-PAGE) was used to separate proteins. Allergens were determined and identified by IgE-immunoblotting with pooled sera from prawn-allergic patients (n=16) and LC-MS/MS. Arginine kinase (AK) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were determined as the important allergens in muscle of Macrobrachium rosenbergii whereas, hemocyanin (HC) was identified as an allergen in Macrobrachium spp. The allergens in Macrobrachium lanchesteri were identified as AK and HC. In addition, hexamerin1B (HEX1B) was identified as a novel and specific allergen in G. bimaculatus. The important allergen in G. bimaculatus and Macrobrachium spp. is AK and was found to cross-react between both species.

  2. House dust mite allergen Der f enhanced bronchial epithelial cell cytokine expression

    Institute of Scientific and Technical Information of China (English)

    BAO QING SUN; WEI TANG; ALBERT CHAN; ADRIAN WU; NAN SHAN ZHONG

    2006-01-01

    The house dust mites ( Dermatophagoides farinae, Der f) are the major source of aeroallergens implicated in the expression of atopic disorders, including asthma, allergic rhinitis and atopic dermatitis. In particular, strong circumstantial evidence suggests that house dust mite antigens are important precipitating factors of asthma. Many house dust mite allergens are proteases that can elicit airway inflammation by stimulating the release of cytokines from bronchial epithelial cells. To investigate whether Derf allergen proteases induced cytokine production from the epithelial cell line BEAS-2B,BEAS-2B cells were cultured with 4 different concentrations of Derf (0.02, 0.2, 2, 20 μg/ml) for 24-96 h, after which supernatants were assayed for interleukin (IL)-6 and IL-8 with ELISA. Reverse transcription-PCR was also performed. The cell sheets were intact throughout the observation in control group without any exposure to Derf antigen. In the experimental groups cells treated with Der f allergen showed changes in the anchorage status of the monolayer. There was a significant increase in the level of cytokine production compared with the untreated sample. The release of IL-6 and IL-8 increased in a concentration-dependent manner ( P < 0.05, respectively) with the addition of increasing dosage of Der f to the cell sheets. Levels of IL-6 and IL-8 began to rise at 24 h and 48 h after allergen exposure, and they increased significantly in the supernatants at 72 h and 96 h. At the same time the concentration dependence of induction of IL-6 and IL-8 expression as well as an increase in the expression of IL-6 and IL-8 mRNA manifested evidently. HDM-induced airway inflammation may include Der f-mediated release of inflammatory mediators, and the proteolytic activity of an allergen may stimulate the release of proinflammatory cytokines from human bronchial epithelium. It is suggested that IL-6 and IL-8 production by bronchial epithelial cells may play a role in the

  3. Amelioration of ovalbumin-induced allergic airway disease following Der p 1 peptide immunotherapy is not associated with induction of IL-35.

    Science.gov (United States)

    Moldaver, D M; Bharhani, M S; Wattie, J N; Ellis, R; Neighbour, H; Lloyd, C M; Inman, M D; Larché, M

    2014-03-01

    In the present study, we show therapeutic amelioration of established ovalbumin (OVA)-induced allergic airway disease following house dust mite (HDM) peptide therapy. Mice were sensitized and challenged with OVA and HDM protein extract (Dermatophagoides species) to induce dual allergen sensitization and allergic airway disease. Treatment of allergic mice with peptides derived from the major allergen Der p 1 suppressed OVA-induced airway hyperresponsiveness, tissue eosinophilia, and goblet cell hyperplasia upon rechallenge with allergen. Peptide treatment also suppressed OVA-specific T-cell proliferation. Resolution of airway pathophysiology was associated with a reduction in recruitment, proliferation, and effector function of T(H)2 cells and decreased interleukin (IL)-17⁺ T cells. Furthermore, peptide immunotherapy induced the regulatory cytokine IL-10 and increased the proportion of Fox p3⁺ cells among those expressing IL-10. Tolerance to OVA was not associated with increased IL-35. In conclusion, our results provide in vivo evidence for the creation of a tolerogenic environment following HDM peptide immunotherapy, leading to the therapeutic amelioration of established OVA-induced allergic airway disease.

  4. Mathematical models of blast induced TBI: current status, challenges and prospects

    Directory of Open Access Journals (Sweden)

    Raj K Gupta

    2013-05-01

    Full Text Available Blast induced traumatic brain injury (TBI has become a signature wound of recent military activities and is the leading cause of death and long-term disability among U.S. soldiers. The current limited understanding of brain injury mechanisms impedes the development of protection, diagnostic and treatment strategies. We believe mathematical models of blast wave brain injury biomechanics and neurobiology, complemented with in vitro and in vivo experimental studies, will enable a better understanding of injury mechanisms and accelerate the development of both protective and treatment strategies. The goal of this paper is to review the current state of the art in mathematical and computational modeling of blast induced TBI, identify research gaps and recommend future developments. A brief overview of blast wave physics, injury biomechanics and the neurobiology of brain injury is used as a foundation for a more detailed discussion of multiscale mathematical models of primary biomechanics and secondary injury and repair mechanisms. The paper also presents a discussion of model development strategies, experimental approaches to generate benchmark data for model validation and potential applications of the model for prevention and protection against blast wave TBI.

  5. Identification of two distinct allergenic sites on ryegrass-pollen allergen, Lol p IV.

    Science.gov (United States)

    Jaggi, K S; Ekramoddoullah, A K; Kisil, F T; Dzuba-Fischer, J M; Rector, E S; Sehon, A H

    1989-04-01

    Lol p IV is an important allergen of ryegrass pollen. For the immunochemical identification of antigenic and/or allergenic site(s), murine monoclonal antibodies (MAbs) were prepared against Lol p IV. The hybridoma cell-culture supernatants were screened for anti-Lol p IV antibodies by a combination of ELISA and Western immunoblot analyses. The MAbs were finally purified from ascites on a Mono Q ion-exchange column. In a competitive radioimmunoassay with Lol p IV as the solid phase and 125I-labeled MAbs, it was established that MAbs 90, 91, 92, 93, and 94, although they differed in their relative affinities, recognized in common with one another an epitope designated as antigenic site A, whereas MAb 12 recognized a different epitope referred to as site B. Sites A and B were also demonstrated to constitute allergenic determinants of Lol p IV. Differences in the repertoire of specificities of the human IgE antibodies directed to Lol p IV were also demonstrated. Interestingly, it was found that sera from both allergic as well as from nonatopic individuals had IgG antibodies to sites A and/or B.

  6. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Science.gov (United States)

    Singh, Shailbala; Yang, Guojun; Schluns, Kimberly S; Anthony, Scott M; Sastry, K Jagannadha

    2014-01-01

    Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA) metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer) for harnessing the adjuvant potential of natural killer T (NKT) cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  7. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.

    Directory of Open Access Journals (Sweden)

    Shailbala Singh

    Full Text Available Sublingual route offers a safer and more practical approach for delivering vaccines relative to other systemic and mucosal immunization strategies. Here we present evidence demonstrating protection against ovalbumin expressing B16 (B16-OVA metastatic melanoma lung tumor formation by sublingual vaccination with the model tumor antigen OVA plus synthetic glycolipid alpha-galactosylceramide (aGalCer for harnessing the adjuvant potential of natural killer T (NKT cells, which effectively bridge innate and adaptive arms of the immune system. The protective efficacy of immunization with OVA plus aGalCer was antigen-specific as immunized mice challenged with parental B16 tumors lacking OVA expression were not protected. Multiple sublingual immunizations in the presence, but not in the absence of aGalCer, resulted in repeated activation of NKT cells in the draining lymph nodes, spleens, and lungs of immunized animals concurrent with progressively increasing OVA-specific CD8+ T cell responses as well as serum IgG and vaginal IgA levels. Furthermore, sublingual administration of the antigen only in the presence of the aGalCer adjuvant effectively boosted the OVA-specific immune responses. These results support potential clinical utility of sublingual route of vaccination with aGalCer-for prevention of pulmonary metastases.

  8. Agrochemical-induced stress in stingless bees: peculiarities, underlying basis, and challenges.

    Science.gov (United States)

    Lima, M A P; Martins, G F; Oliveira, E E; Guedes, R N C

    2016-10-01

    The toxicological stress induced by pesticides, particularly neonicotinoid insecticides, and its consequences in bees has been the focus of much recent attention, particularly for honey bees. However, the emphasis on honey bees and neonicotinoids has led to neglect of the relevance of stingless bees, the prevailing pollinators of natural and agricultural tropical ecosystems, and of other agrochemicals, including other pesticides and even leaf fertilizers. Consequently, studies focusing on agrochemical effects on stingless bees are sparse, usually limited to histopathological studies, and lack a holistic assessment of the effects of these compounds on physiology and behavior. Such effects have consequences for individual and colony fitness and are likely to affect both the stingless bee populations and the associated community, thereby producing a hierarchy of consequences thus far overlooked. Herein, we review the current literature on stingless bee-agrochemical interactions and discuss the underlying mechanisms involved in reported stress symptoms, as well as the potential consequences based on the peculiarities of these pollinators.

  9. Assessment of drug-induced hepatotoxicity in clinical practice: A challenge for gastroenterologists

    Institute of Scientific and Technical Information of China (English)

    Raúl J Andrade; Mercedes Robles; Alejandra Fernández-Casta(n)er; Susana López-Ortega; M Carmen López-Vega; M Isabel Lucena

    2007-01-01

    Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and postcommercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice.To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be finetuned as further information is collected.

  10. The laminin β1-competing peptide YIGSR induces a hypercontractile, hypoproliferative airway smooth muscle phenotype in an animal model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2010-12-01

    Full Text Available Abstract Background Fibroproliferative airway remodelling, including increased airway smooth muscle (ASM mass and contractility, contributes to airway hyperresponsiveness in asthma. In vitro studies have shown that maturation of ASM cells to a (hypercontractile phenotype is dependent on laminin, which can be inhibited by the laminin-competing peptide Tyr-Ile-Gly-Ser-Arg (YIGSR. The role of laminins in ASM remodelling in chronic asthma in vivo, however, has not yet been established. Methods Using an established guinea pig model of allergic asthma, we investigated the effects of topical treatment of the airways with YIGSR on features of airway remodelling induced by repeated allergen challenge, including ASM hyperplasia and hypercontractility, inflammation and fibrosis. Human ASM cells were used to investigate the direct effects of YIGSR on ASM proliferation in vitro. Results Topical administration of YIGSR attenuated allergen-induced ASM hyperplasia and pulmonary expression of the proliferative marker proliferating cell nuclear antigen (PCNA. Treatment with YIGSR also increased both the expression of sm-MHC and ASM contractility in saline- and allergen-challenged animals; this suggests that treatment with the laminin-competing peptide YIGSR mimics rather than inhibits laminin function in vivo. In addition, treatment with YIGSR increased allergen-induced fibrosis and submucosal eosinophilia. Immobilized YIGSR concentration-dependently reduced PDGF-induced proliferation of cultured ASM to a similar extent as laminin-coated culture plates. Notably, the effects of both immobilized YIGSR and laminin were antagonized by soluble YIGSR. Conclusion These results indicate that the laminin-competing peptide YIGSR promotes a contractile, hypoproliferative ASM phenotype in vivo, an effect that appears to be linked to the microenvironment in which the cells are exposed to the peptide.

  11. Allergenic sesquiterpene lactones from cushion bush (Leucophyta brownii Cass.)

    DEFF Research Database (Denmark)

    Paulsen, Evy; Gade Hyldgaard, Mette; Andersen, Klaus E.

    2017-01-01

    BACKGROUND: The Australian cushion bush (Leucophyta brownii) of the Compositae family of plants has become a popular pot and container plant. The plant produces the sesquiterpene lactone allergen calocephalin. OBJECTIVES: To assess the sensitizing potential of sesquiterpene lactones from cushion ...

  12. The effects of gastric digestion on codfish allergenicity

    DEFF Research Database (Denmark)

    Untersmayr, Eva; Poulsen, Lars K.; Platzer, Michael H;

    2005-01-01

    In a recent murine study, we showed that impaired gastric digestion supports the induction of fish allergy by protecting the digestion-sensitive major allergen parvalbumin and thus enhancing its sensitizing properties....

  13. Heat killed multi-serotype Shigella immunogens induced humoral immunity and protection against heterologous challenge in rabbit model.

    Science.gov (United States)

    Nag, Dhrubajyoti; Sinha, Ritam; Mitra, Soma; Barman, Soumik; Takeda, Yoshifumi; Shinoda, Sumio; Chakrabarti, M K; Koley, Hemanta

    2015-11-01

    Recently we have shown the homologous protective efficacy of heat killed multi-serotype Shigella (HKMS) immunogens in a guinea pig colitis model. In our present study, we have advanced our research by immunizing rabbits with a reduced number of oral doses and evaluating the host's adaptive immune responses. The duration of immunogenicity and subsequently protective efficacy was determined against wild type heterologous Shigella strains in a rabbit luminal model. After three successive oral immunizations with HKMS immunogens, serum and lymphocyte supernatant antibody titer against the heterologous shigellae were reciprocally increased and remained at an elevated level up to 180 days. Serogroup and serotype specific O-antigen of lipopolysaccharide and immunogenic proteins of heterologous challenge strains were detected by immunoblot assay. Up-regulation of IL-12p35, IFN-γ and IL-10 mRNA expression was detected in immunized rabbit peripheral blood mononuclear cells (PBMC) after stimulation with HKMS in vitro. HKMS-specific plasma cell response was confirmed by production of a relatively higher level of HKMS-specific IgG in immunized PBMC supernatant compared to control group. Furthermore, the immunized groups of rabbits exhibited complete protection against wild type heterologous shigellae challenge. Thus HKMS immunogens induced humoral and Th1-mediated adaptive immunity and provided complete protection in a rabbit model. These immunogens could be a broad spectrum non-living vaccine candidate for human use in the near future.

  14. FasL基因和屋尘螨过敏原基因共表达质粒DNA疫苗对屋尘螨致敏/激发小鼠气道炎症的作用%Effects of DNA vaccine encoding both FasL and house dust mite allergen Der p2 on the airway inflammations in mice sensitized/challenged with house dust mite

    Institute of Scientific and Technical Information of China (English)

    王彦; 林科雄; 王长征; 吴奎; 毕玉田

    2011-01-01

    目的:观察FasL基因和屋尘螨过敏原Der p2基因共表达质粒的DNA疫苗(DNA-FasL-Der p2)对屋尘螨致敏/激发小鼠气道炎症的作用.方法:DNA-FasL-Der p2肌注接种屋尘螨致敏/激发C57BL/6小鼠,再次激发后处死小鼠.观察肺组织病理变化,检测支气管肺泡灌洗液(BALF)细胞总数和分类计数,以及IL-5、IFN-γ水平.并与仅编码Der p2基因的DNA疫苗(DNA-Der p2)比较.结果:接种DNA-FasL-Der p2和DNA-Der p2均能显著减轻屋尘螨致敏/激发小鼠气道炎症.减少BALF中细胞总数和嗜酸粒细胞比例.降低BALF中IL-5水平,以DNA-FasL-Der p2更显著.结论:DNA-FasL-Derp2可有效抑制屋尘螨致敏/激发小鼠气道炎症,而且比DNA-Der p2更有效.%Objective To investigate the effects of DNA vaccine encoding both FasL and house dust mite (HDM) allergen Der p2 (DNA-FasL-Der p2) on the airway inflammation in mice challenged with HDM.Methods HDM sensitized and challenged C57BL/6 mice were immunized with DNA-FasL-Der p2 or DNA-Der p2 (without FasL)DNA vaccine,then they were re-challenged with HDM.Two days after the last challenge, bronchoalveolar lavage fluid (BALF) was collected and lung histology was examined.The levels of IL-5 and IFN-γ in BALF supematants were analyzed by ELISA, total cell count and differential cell count in BALF sediment were determined.Results Both DNA-FasL-Der p2 and DNA-Der p2 relieved airway inflammation and decreased the level of IL-5, total cell count and the percentage of eosinophils in BALF.The improvement of DNA-FasL-Der p2 was more significant than that of DNA-Der p2.Conclusion DNA-FasL-Der p2 could reduce airway allergic inflammation in HDM-challenged mice.And DNA-FasL-Der p2 was more effective than that of DNA-Der p2.

  15. Recent Advances in NSAIDs-Induced Enteropathy Therapeutics: New Options, New Challenges

    Directory of Open Access Journals (Sweden)

    Yun Jeong Lim