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C Andre - One of the best experts on this subject based on the ideXlab platform.
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immunotherapy with a calcium phosphate adsorbed five Grass Pollen Extract in seasonal rhinoconjunctivitis a double blind placebo controlled study
Clinical & Experimental Allergy, 2001Co-Authors: Francisque Leynadier, B Dollois, Patrice Terrier, M T Guinnepain, D Firon, C Traube, Rayyan Fadel, M. Epstein, L. Banoun, C AndreAbstract:Background Calcium phosphate-adsorbed allergen Extracts are used for subcutaneous immunotherapy to avoid the use of aluminium adjuvants. Objectives A double-blind, placebo-controlled study was performed in order to confirm the safety and assess the efficacy of a standardized five-Grass-Pollen Extract adsorbed onto calcium phosphate for specific immunotherapy (IT). Methods Twenty-nine patients with seasonal rhinoconjunctivitis were randomized to receive either the active preparation (16 patients) or placebo (13 patients), in a 1-year study. During the increasing dose phase, an Extract ranging from 0.1 IR per ml to 50 IR per ml was administered at a rate of one subcutaneous injection per week until a maintenance dose was reached. The patients were assessed by symptom diary and rescue medications during seasonal exposure and specific nasal and skin reactivity before and after IT. Immunological parameters (specific IgE and IgG 4 antibodies) were assessed before, during and after IT. Results The overall symptoms score (mean AUC) was not significantly different between the IT group and the placebo group during Grass-Pollen exposure (49.6 vs. 56, respectively). The total medication score (mean AUC) was significantly lower in the IT group than in the placebo group (11 vs. 41, P < 0.01, Mann-Whitney U-test). The cumulative symptom/medication score was significantly lower in the IT group than in the placebo group (64.5 VS. 102.3, P < 0.05, U-test). A significant increase in nasal reactivity threshold was observed after IT in the IT group (21. 4 IR/mL before IT vs. 63.4 IR/mL after IT, P < 0.01, Wilcoxon), whereas no significant changes were observed in the placebo group (31.0 IR/mL before IT vs. 37.7 IR/mL after IT). IT induced a significant reduction in Grass Pollen cutaneous reactivity in the actively treated group (P < 0.001). A significant increase in serum-specific IgG 4 antibody response was observed in the IT group (3.1% before IT VS. 10.1% after IT, P < 0.001). Nine patients in the IT group developed moderate immediate systemic reactions vs. two patients in the placebo group. Conclusion Specific immunotherapy with calcium phosphate-adsorbed standardized Grass Pollen Extract was safe and effective for the treatment of patients with seasonal allergic rhinoconjunctivitis.
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sublingual swallow immunotherapy slit with a standardized five Grass Pollen Extract drops and sublingual tablets versus placebo in seasonal rhinitis
Allergy, 1999Co-Authors: A Pradalier, D Basset, A Claudel, P Couturier, F Wessel, S Galvain, C AndreAbstract:Background: Recent studies have demonstrated the efficacy of sublingual-swallow immunotherapy (SLIT) in seasonal and perennial rhinitis. Sublingual administration of solutions is not convenient for all patients. The aim of the study was to evaluate the efficacy and safety of immunotherapy administered sublingually, initially as drops, and then as tablets during maintenance therapy. Methods: A total of 126 patients with Grass-Pollen seasonal rhinitis were included in this double-blind, randomized, placebo-controlled trial. During the progression of doses phase, the five-Grass Extract was given as sublingual drops from 1 to 100 IR/ml. Once the 100 IR dose was reached, the drops were replaced by a single 100-IR sublingual tablet per day. Results: Throughout the Grass-Pollen season, patients in the active treatment group had significantly lower (P<0.05) total conjunctivitis and ocular redness scores. Rhinitis symptoms were not significantly different between the two groups. Patients given the active treatment were significantly (P<0.02) less likely to have asthma symptoms. The global medication score showed no significant difference between the two groups. A highly significant difference in favor of the active treatment group was seen in inhaled salbutamol use (P<0.01). Conclusions: Clinical benefits achieved during the present study included significant improvements in conjunctivitis symptoms and prevention of asthma symptoms. The overall safety profile of the active treatment (drops or tablets) was good.
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clinical efficacy of sublingual swallow immunotherapy a double blind olacebo controlled trial of a standardized five Grass Pollen Extract in rhinitis
Allergy, 1998Co-Authors: Reymond Clavel, C AndreAbstract:Sublingual-swallow immunotherapy (SLIT) using high doses of standardized allergen Extracts has been found to be effective in reducing allergic symptoms and medication needs. A double-blind, placebo-controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT. Some 136 patients with Grass-Pollen rhinitis with or without mild asthma were studied. Patients received either placebo or SLIT with a standardized Grass-Pollen Extract administered daily with increasing doses up to 300 IR (index of reactivity) from January to the end of July 1994. During the Grass-Pollen season, patients were instructed to use medications as required and to visit their doctors in case of asthma. Symptom-medications scores were assessed during the Pollen season, and serum-specific IgG4 was measured before and at the end of SLIT. In the SLIT group, drug consumption dropped significantly throughout the Pollen season (P<0.02). Moreover, at the peak of the Pollen season, betamethasone consumption was significantly reduced in the SLIT group (P<0.02). Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group (P<0.02). IgG4 levels increased significantly in the SLIT group (P<0.001) but without correlation with symptoms. Side-effects were comparable in both groups. This study indicates that SLIT in Grass-Pollen rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug consumption and the need for oral corticosteroids.
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clinical efficacy of sublingual swallow immunotherapy a double blind placebo controlled trial of a standardized five Grass Pollen Extract in rhinitis
Allergy, 1998Co-Authors: Reymond Clavel, Jean Bousquet, C AndreAbstract:Sublingual-swallow immunotherapy (SLIT) using high doses of standardized allergen Extracts has been found to be effective in reducing allergic symptoms and medication needs. A double-blind, placebo-controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT. Some 136 patients with Grass-Pollen rhinitis with or without mild asthma were studied. Patients received either placebo or SLIT with a standardized Grass-Pollen Extract administered daily with increasing doses up to 300 IR (index of reactivity) from January to the end of July 1994. During the Grass-Pollen season, patients were instructed to use medications as required and to visit their doctors in case of asthma. Symptom-medications scores were assessed during the Pollen season, and serum-specific IgG4 was measured before and at the end of SLIT. In the SLIT group, drug consumption dropped significantly throughout the Pollen season (P < 0.02). Moreover, at the peak of the Pollen season, betamethasone consumption was significantly reduced in the SLIT group (P < 0.02). Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group (P < 0.02). IgG4 levels increased significantly in the SLIT group (P < 0.001) but without correlation with symptoms. Side-effects were comparable in both groups. This study indicates that SLIT in Grass-Pollen rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug consumption and the need for oral corticosteroids.
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a double blind placebo controlled trial by the sublingual route of immunotherapy with a standardized Grass Pollen Extract
Allergy, 1994Co-Authors: A. Sabbah, Suzanne Hassoun, Jenny Sellin, C Andre, H SicardAbstract:Fifty-eight patients with well-documented history of seasonal rhinoconjunctivitis caused by Grass Pollens were allocated randomly on a double-blind basis to receive either sublingual therapy with a solution of purified, standardized allergen preparation (Stallergenes) or a matched placebo for 17 weeks. The assessment of the effect of oral immunotherapy, done with drops of five-Grass allergen Extract, was on the clinical symptoms and on the medication score of the authorized rescue treatments. The actively treated patients had significantly (P<0.05 to P<0.01) fewer symptoms of rhinitis (sneezing and rhinorrhea) and of conjunctivitis (redness and tears) during the Pollen season than the placebo group. Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group (P<0.01). Side-effects were negligible. This study concludes that perlingual immunotherapy with Grass Pollen Extract in Grass-Pollen-sensitive seasonal hay fever and conjunctivitis patients is effective, easy to perform, inexpensive, and safe.
Oliver Pfaar - One of the best experts on this subject based on the ideXlab platform.
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a high polymerized Grass Pollen Extract is efficacious and safe in a randomized double blind placebo controlled study using a novel up dosing cluster protocol
Allergy, 2014Co-Authors: L Klimek, J Uhlig, R Mosges, K Rettig, Oliver PfaarAbstract:Background Cluster immunotherapy represents an interesting alternative to conventional up-dosing schedules because it allows achieving the maintenance dose within a shorter time interval. In this study, the efficacy and safety of cluster immunotherapy with a high polymerized allergen Extract of a Grass/rye Pollen mixture have been evaluated in a randomized, double-blind, placebo-controlled, multicenter study. Methods In total, 121 patients with allergic rhinoconjunctivitis due to Grass Pollen were randomized 1 : 1 to verum or placebo group. A short cluster up-dosing schedule of only 1 week was applied to achieve the maintenance dose which was administered monthly during the study period of 1 year. Total combined symptom and medication score (TCS) was defined as primary outcome parameter. Secondary outcome parameters were individual symptom and medication scores, ‘well days,’ global improvement as well as immunological effects and nasal allergen challenge. The safety profile was evaluated based on the European academy of allergy and clinical immunology grading system. Results Significant reduction in the verum compared to the placebo group (intention-to-treat, population, verum: n = 55; placebo: n = 47) was found regarding TCS (P = 0.005), rhinoconjunctivitis total symptom score (RTSS, P = 0.006), and total rescue medication score (TRMS, P = 0.002). Additionally, secondary outcomes such as ‘well days,’ nasal challenge results, and increase of specific IgG4 were in favor of the active treatment. All systemic adverse reactions (0.8% of all injections in the verum group) were of mild intensity. No severe reactions related to the study medication were observed. Conclusion Cluster immunotherapy with high polymerized Grass Pollen Extracts resulted in significant clinical efficacy and has been shown to be a safe treatment for Grass Pollen-allergic patients.
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depigmented polymerized mixed Grass birch Pollen Extract immunotherapy is effective in polysensitized patients
Allergy, 2013Co-Authors: Oliver Pfaar, ADAM SAGER, Ludger Klimek, Tilo Biedermann, David RobinsonAbstract:Background Although many patients with allergic rhinoconjunctivitis have symptoms due to sensitization with more than one Pollen allergen, and mixed Pollen Extracts are widely used for allergen immunotherapy in practice, there are few published trials. Methods We performed a 2-year multicentre, double-blind, placebo-controlled trial of subcutaneous immunotherapy with mixed depigmented–polymerized birch and Grass Pollen Extract in 285 patients with allergic rhinoconjunctivitis symptomatic during both birch and Grass Pollen seasons. Primary outcome was combined symptom and medication score (SMS) assessed by daily visual analogue scales (VAS). Analysis included a placebo-based analysis examining the effect of treatment only on days when placebo patients were symptomatic. Results There was a significant reduction in median SMS for actively treated patients (median 5.70 (interquartile range 2.62–10.02) compared with 7.07 (3.47–10.71) for placebo, P = 0.0385). Rhinitis quality-of-life scores were significantly better for active compared with placebo, and other secondary endpoints were not significantly different. Placebo-based analysis showed a 33.7% reduced SMS at year 2 for active treatment compared with placebo on days when placebo patients were symptomatic. Both birch Pollen- and Grass Pollen-specific IgG4 increased with active treatment. Conclusions This study shows efficacy of mixed Pollen Extracts for immunotherapy for patients symptomatic to both birch and Grass Pollen allergens. The relatively modest effect may reflect 50% dose reduction for each allergen in the mixture. It supports VAS for symptom assessment and placebo-based analysis as useful for the analysis of immunotherapy trials. The safety of modified Extracts may allow study of mixed Extracts without dose reduction to improve efficacy.
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specific subcutaneous immunotherapy with recombinant Grass Pollen allergens first randomized dose ranging safety study
Clinical & Experimental Allergy, 2012Co-Authors: Ludger Klimek, Philipp Schendzielorz, R Pinol, Oliver PfaarAbstract:SummaryBackground Allergen-specific immunotherapy (SIT) with native allergen Extracts and allergoids has been performed successfully for decades. Preliminary studies revealed the use of recombinant allergen-preparations as a promising option for SIT. Objective The present study was designed to investigate the dose-ranging safety in SCIT with a mixture of five recombinant Grass Pollen allergens containing equimolar amounts of rPhl p 1, rPhl p2, rPhl p 5a, rPhl p 5b and rPhl p 6, adsorbed to aluminium hydroxide. Methods A randomized, double blind, placebo-controlled, dose-ranging safety study (EudraCT number 2007-002808-18) was performed in 50 patients with allergic rhinoconjunctivitis, with or without asthma. Patients were randomized to groups of 10 to receive maximum doses of 20, 40, 80 or 120 μg of total Grass Pollen recombinant protein or placebo. The primary end-point of this trial was the number of patients with at least one systemic reaction with possible, probable or definite relationship to the study medication determined at the end of the up-dosing phase. Secondary end-points included titrated intracutaneous test with natural six-Grass Pollen Extract, allergen-specific conjunctival provocation test as well as IgG and IgE-levels throughout the study. Results Eight of the 50 patients revealed systemic reactions grade 1 or 2 corresponding to the primary end-point definition. No systemic reactions grade 3 or 4 occurred in any dosage group. The systemic reactions were well distributed among the active groups. Results of secondary end-points imply that the study medication is effective and provokes immunological effects. Conclusions and Clinical Relevance The first DBPC SCIT-DRF with a mixture of recombinant Phleum allergens (Phl p 1, 2, 5a, 5b, 6) in patients with rhinoconjunctivitis plus/minus asthma showed no major side effects in very high doses up to 120 μg.
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a randomized placebo controlled trial of rush preseasonal depigmented polymerized Grass Pollen immunotherapy
Allergy, 2012Co-Authors: Oliver Pfaar, Zoe Urry, Matthias Bräutigam, ADAM SAGER, D. Richards, David Robinson, Catherine M Hawrylowicz, Ludger KlimekAbstract:To cite this article: Pfaar O, Urry Z, Robinson DS, Sager A, Richards D, Hawrylowicz CM, Brautigam M, Klimek L. A randomized placebo-controlled trial of rush preseasonal depigmented polymerized Grass Pollen immunotherapy. Allergy 2012; 67: 272–279. Abstract: Background: Specific subcutaneous immunotherapy (SCIT) for seasonal rhinoconjunctivitis with unmodified allergen Extracts is effective, but limited by risk of side-effects and involves treatment over 3 years. We examined a depigmented polymerized Grass Pollen Extract for immunogenicity and for clinical efficacy in a rush preseasonal regimen. Methods: Depigmented polymerized Grass Pollen Extract was tested for proliferation and cytokine production by peripheral blood mononuclear cells. A prospective, double-blind, placebo-controlled trial of 195 Grass Pollen allergic patients treated with preseasonal rush immunotherapy using depigmented polymerized allergenic Extract of mixed Grass Pollen was performed over 2 years. Primary outcome was combined symptom and medication score (SMS) during the peak of the second Grass Pollen season. Secondary outcomes included combined score over the whole season, during the first Grass Pollen season, individual symptom and medication scores, quality of life, well days/hell days and responder analysis. Adverse events were classified using the EAACI scale. Grass Pollen-specific IgE and IgG4 were measured before and during treatment. Results: Depigmented polymerized Extract stimulated dose-dependent T-cell proliferation and cytokine production. Patients treated with preseasonal SCIT showed improved combined scores during peak season at year 2 (median 3.93, interquartile range 0.77–6.27 vs median 5.86 for placebo, 3.11–8.36, P < 0.01). Most secondary outcomes were significantly better for active treatment. Side-effects were minimal, with no grade 3 or 4 reactions. Conclusions: Depigmented polymerized Grass Pollen Extract is immunogenic and clinically effective in rush preseasonal SCIT. This form of immunotherapy may be an attractive option for some patients.
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Sustained clinical efficacy of sublingual immunotherapy with a high-dose Grass Pollen Extract
European annals of allergy and clinical immunology, 2011Co-Authors: Piotr Kuna, Bolesław Samoliński, Oliver Pfaar, Margitta Worm, Leszek KlimekAbstract:Background: Sublingual immunotherapy (SLIT) with a high-dose 6-Grass Pollen SingleDose preparation was shown to be effective and safe in a 2-year randomized, double-blind, placebo-controlled trial. Objective: We evaluated the effect of the third year of SLIT in comparison to the second year. Methods: 46 Grass Pollen-allergic patients who had received active treatment for 3 consecutive years were included in the safety set. Diary data from 39 subjects were evaluated to calculate symptom and medication scores as well as 'well days'. Results: Symptoms and medication intake further decreased in the third year of SLIT during the Grass Pollen season in comparison to the previous years and the number of 'well days' increased accordingly. No serious adverse events occurred during the three years of SLIT. Conclusion: The third year of SLIT with the high-dose 6-Grass Pollen preparation results in sustained and even further increased clinical efficacy.
Rudolf Valenta - One of the best experts on this subject based on the ideXlab platform.
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detection of genuine Grass Pollen sensitization in children by skin testing with a recombinant Grass Pollen hybrid
Applied Immunohistochemistry & Molecular Morphology, 2019Co-Authors: Nikolaos Douladiris, Rudolf Valenta, Victoria Garib, Margit Focketejkl, Nikolaos G Papadopoulos, Birgit LinhartAbstract:Background Skin testing represents a commonly used first diagnostic method in clinical practice, but allergen Extracts may vary in composition and often contain cross-reactive allergens and therefore do not always allow the precise identification of the sensitizing allergen source. Our aim was to investigate the suitability of a single recombinant hybrid molecule, consisting of the four major timothy Grass Pollen allergens (Phl p 1, Phl p 2, Phl p 5, and Phl p 6) for in vivo diagnosis of genuine Grass Pollen allergy in children suffering from pollinosis. Methods Sixty-four children aged from 6 to 17 years with a positive skin reaction and/or specific IgE to Grass Pollen Extract and respiratory symptoms of pollinosis as well as 9 control children with allergy to other allergen sources were studied. SPT was performed with the recombinant hybrid, the four recombinant timothy Grass Pollen allergens, and Grass Pollen Extract. Specific IgE reactivity to 176 micro-arrayed allergen molecules was determined using ImmunoCAP ISAC technology. IgE reactivity to the hybrid was detected by non-denaturing RAST-based dot blot assay. Results Genuine Grass Pollen sensitization was confirmed in 94% of the children with positive SPT to Grass Pollen Extract by SPT and IgE reactivity to the hybrid. The four hybrid-negative children showed IgE reactivity to cross-reactive allergens such as Phl p 4, Phl p 11, and Phl p 12 and had also sensitizations to Pollen allergens from unrelated plants. Conclusions The recombinant hybrid molecule represents a useful tool for in vivo diagnosis of genuine Grass Pollen sensitization.
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recombinant allergen based monitoring of antibody responses during injection Grass Pollen immunotherapy and after 5 years of discontinuation
Allergy, 2011Co-Authors: Elisabeth Gadermaier, Kerstin Westritschnig, Ines Swoboda, Sabine Flicker, J Staikuniene, Sandra Scheiblhofer, Josef Thalhamer, Michael Kundi, Rudolf ValentaAbstract:To cite this article: Gadermaier E, Staikuniene J, Scheiblhofer S, Thalhamer J, Kundi M, Westritschnig K, Swoboda I, Flicker S, Valenta R. Recombinant allergen–based monitoring of antibody responses during injection Grass Pollen immunotherapy and after 5 years of discontinuation. Allergy 2011; 66: 1174–1182. Abstract Background: Subcutaneous injection immunotherapy (SCIT) is considered as antigen-specific and disease-modifying treatment with long-lasting effect. Methods: We used a panel of recombinant Grass Pollen allergens for analyzing allergen-specific IgE, IgG1-IgG4, IgM, IgA, and light-chain (kappa, lambda) responses in Grass Pollen–allergic patients who had received one course of injection immunotherapy (SCIT) with an aluminum hydroxide-adsorbed Grass Pollen Extract or only anti-inflammatory treatment. Serum samples were analyzed before and after 5 months of treatment as well as after 5 years. Results: After 5 months of SCIT but not of anti-inflammatory treatment, IgG1 > IgG4 > IgG2 > IgA antibody responses using both kappa and lambda light chains specific for major Grass Pollen allergens (Phl p 1, Phl p 5, Phl p 6, Phl p 2) increased significantly, whereas specific IgM or IgG3 levels were unaltered. Allergen-dependent basophil degranulation was only inhibited with SCIT sera containing therapy-induced allergen-specific IgG antibodies. Likewise, decreases in Phl p 1- and Phl p 5-specific IgE levels and significant (P < 0.001) reduction in symptom and medication scores were found only in the SCIT group but not in the group of patients receiving anti-inflammatory treatment. After 5 years, allergen-specific IgG antibody levels in the SCIT group had returned to baseline levels and there was no significant difference regarding symptoms between the SCIT and non-SCIT groups. Conclusion: The results from our observational study demonstrate that only SCIT but not anti-inflammatory treatment induces allergen-specific IgG and reduces boosts of allergen-specific IgE production but that one SCIT course was not sufficient to achieve long-term immunological and clinical effects.
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Skin test diagnosis of Grass Pollen allergy with a recombinant hybrid molecule
The Journal of Allergy and Clinical Immunology, 2007Co-Authors: C. Metz-favre, Margarete Focke-tejkl, Ashok Purohit, Birgit Linhart, Rudolf Valenta, Frederic De Blay, Gabrielle PauliAbstract:Background A recombinant hybrid molecule (HM) consisting of 4 major allergens from timothy Grass (Phl p 1, 2, 5, and 6) was expressed in Escherichia coli , purified, and characterized regarding its immunologic properties. Objective We sought to determine whether the recombinant HM can be used for the diagnosis of Grass Pollen allergy by means of skin testing. Methods Skin prick testing was performed in 32 patients with Grass Pollen allergy and in 9 control individuals by using increasing concentrations (4, 12, 36, and 108 μg/mL) of the HM and using commercial Grass Pollen Extract. Specific IgE reactivities against the HM, Grass Pollen Extract, and a panel of purified Grass Pollen allergens (recombinant Phl p 1, 2, 5, 6, 7, 12, and 13 and natural Phl p 4) were measured by means of ELISA, and timothy Grass Pollen–specific IgE levels were determined by using ImmunoCAP. Results Grass Pollen allergy was diagnosed in all patients by means of skin testing with the HM. No false-positive skin test responses were obtained in the control individuals. There was an excellent correlation between IgE levels obtained with the HM and natural Grass Pollen Extract measured by means of ELISA ( r = 0.98, P r = 0.98, P Conclusions The recombinant HM permitted accurate and specific in vivo diagnosis of Grass Pollen allergy in all tested patients. It can be considered a well-defined tool for the diagnosis and perhaps for immunotherapy of Grass Pollen allergy. Clinical implications A recombinant HM can replace traditional allergen Extracts for skin test–based diagnosis of Grass Pollen allergy.
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mutual boosting effects of sensitization with timothy Grass Pollen and latex glove Extract on ige antibody responses in a mouse model
Journal of Investigative Dermatology, 2000Co-Authors: Oliver Kuβ, Tina Leakakos, W. Truscott, Thomas L. Diepgen, Vera Mahler, Rudolf Valenta, Gerold SchulerAbstract:Type I allergy to natural rubber latex can be an important health problem for latex-exposed individuals (e.g., health care workers, spina bifida children). Also beyond these risk groups, a high sensitization rate of varying and partly unknown clinical relevance has been reported. Atopy represents a risk factor for latex allergy and recent studies indicate that patients suffering from Pollen allergies may have Pollen allergen-specific IgE antibodies which cross-react with latex allergens. In order to investigate whether sensitization to Pollen allergens can have priming effects on the production of IgE antibodies against latex in vivo, a mouse model was established. Groups of 10 BALB/C mice were immunized with Al(OH)3-adsorbed Pollen Extracts from timothy Grass, ragweed, mugwort, or birch. For control purposes, one additional group received adjuvant only and another group was not immunized. Half of the mice of each group were subsequently immunized with Al(OH)3-adsorbed latex glove Extract, the other half with adjuvant only. Pollen and latex-specific IgE- and IgG1-antibody responses were analyzed by enzyme-linked immunosorbent assay and statistically evaluated by analysis of variance. Antibody responses to cross-reactive antigens were investigated by immunoblotting. We found significantly increased IgE reactivities to latex after Pollen sensitization and vice versa. Moreover, mice immunized with timothy Grass Pollen Extract alone – without subsequent latex immunization – displayed IgE reactivity to latex. Cross-reactive antibodies were directed against Pollen antigens of approximately 60 kDa molecular weight. Our results thus demonstrate a mutual boosting effect of Pollen and latex sensitization in vivo which may be also operative in polysensitized plant allergic patients.
Cornelis M. Van Drunen - One of the best experts on this subject based on the ideXlab platform.
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comparison of timothy Grass Pollen Extract and single major allergen induced gene expression and mediator release in airway epithelial cells a meta analysis
Clinical & Experimental Allergy, 2012Co-Authors: K I L Roschmann, Silvia Luiten, Martijs J Jonker, Timo M Breit, A Petersen, Wytske J. Fokkens, A M Van Kuijen, Cornelis M. Van DrunenAbstract:SummaryBackground Seasonal allergic rhinitis (AR) is a global health problem and its prevalence has increased considerably in the last decades. As the allergic response with its clinical manifestations is triggered by only a few proteins within natural Extracts, there is an increasing tendency for single-component-resolved diagnosis and immunotherapy. Objective As natural exposure is not to single proteins, but to complex mixtures of molecules, we were interested in comparing the activation of respiratory epithelial cells induced by the purified major allergen Phl p 1 with the induction caused by a complete Extract of Timothy Grass Pollen (GPE). Methods NCI-H292 cells were exposed to GPE or Ph1 p 1 for 24 h, isolated RNA and cell culture supernatants were used for microarray analysis, multiplex enzyme-linked immunosorbant assay (ELISA) and subsequent analysis. Results We found 262 genes that showed a GPE-induced change of at least 3-fold, whereas Ph1 p 1-stimulation resulted in 71 genes with a fold induction of more than 3-fold. Besides genes that were regulated by both stimuli, we also detected genes displaying an opposite response after stimulation, suggesting that GPE might be more than purified major allergens with regard to induced immune responses. Conclusions and Clinical Relevance Additional components within GPE and the resulting modulation of general processes affecting gene transcription and signalling pathways might be crucial to maintain/overcome the diseased phenotype and to induce the influx of cells contributing to late-phase allergic responses. When the initial process of sensitization is the matter of interest or late-phase allergic responses, one might miss important immune modulatory molecules and their interaction with allergens by applying single components only.
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timothy Grass Pollen Extract induced gene expression and signalling pathways in airway epithelial cells
Clinical & Experimental Allergy, 2011Co-Authors: K I L Roschmann, Silvia Luiten, Martijs J Jonker, Timo M Breit, A Petersen, Wytske J. Fokkens, Cornelis M. Van DrunenAbstract:Cite this as: K. I. L. Roschmann, S. Luiten, M. J. Jonker, T. M. Breit, W. J. Fokkens, A. Petersen and C. M. van Drunen, Clinical & Experimental Allergy, 2011 (41) 830–841. Summary Background Grass Pollen allergy is one of the most common allergies worldwide and airborne allergens are the major cause of allergic rhinitis. Airway epithelial cells (AECs) are the first to encounter and respond to aeroallergens and are therefore interesting targets for the development of new therapeutics. Our understanding of the epithelial contribution to immune responses is limited as most studies focus on only a few individual genes or proteins. Objective To describe in detail the Timothy Grass Pollen Extract (GPE)-induced gene expression in AECs. Methods NCI-H292 cells were exposed to GPE for 24 h, and isolated RNA and cell culture supernatants were used for microarray analysis and multiplex ELISA, respectively. Results Eleven thousand and seven hundred fifty-eight transcripts were affected after exposure to GPE, with 141 genes up-regulated and 121 genes down-regulated by more than threefold. The gene ontology group cell communication was among the most prominent categories. Network analysis revealed that a substantial part of regulated genes are related to the cytokines IL-6, IL-8, IL-1A, and the transcription factor FOS. After analysing significantly regulated signalling pathways, we found, among others, epidermal growth factor receptor 1, IL-1, Notch-, and Wnt-related signalling members. Unexpectedly, we found Jagged to be down-regulated and an increased release of IL-12, in line with a more Th1-biased response induced by GPE. Conclusion and Clinical Relevance Our data show that the stimulation of AECs with GPE results in the induction of a broad response on RNA and protein level by which they are able to affect the initiation and regulation of local immune responses. Detailed understanding of GPE-induced genes and signalling pathways will allow us to better define the pathogenesis of the allergic response and to identify new targets for treatment.
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diminished response to Grass Pollen allergen challenge in subjects with concurrent house dust mite allergy
Rhinology, 2009Co-Authors: Susanne M Reinartz, Cornelis M. Van Drunen, Serge A Versteeg, Laurian Zuidmeer, Wytske J. FokkensAbstract:Introduction: The clinical manifestation of allergic rhinitis is influenced by many factors; while different subpopulations are not well defined. Different combinations of allergic sensitization may lead to different clinical manifestations of allergic disease. Methods: In a nasal allergen challenge model we compared allergic rhinitis symptoms between subjects mono-sensitized to Grass Pollen or house dust mite, poly-sensitized subjects, and healthy controls. We measured visual analogue scales of symptoms and peak nasal inspiratory flow. We also compared serum total IgE, allergen-specific IgE and IgG4, and basophil hista- mine release. Results: Nasal challenge with Grass Pollen Extract led to a significantly larger increase in sub- jective (p = 0.031) and objective (p = 0.001) nasal symptoms in Grass Pollen mono-sensitized subjects than in poly-sensitized subjects. No differences were found in serum levels of allergen- specific IgE and IgG4 or in biological activity of IgE (basophil histamine release) between mono-sensitized and poly-sensitized subjects. We found a strong inverse correlation between serum allergen-specific IgE and basophil histamine release (-0.789, p = 0.001). Conclusions: Grass Pollen mono-sensitized subjects have a more severe clinical response to nasal challenge than poly-sensitized subjects. This cannot be explained by serum levels of IgE or its biological activity. The continuous allergen exposure in poly-sensitized subjects may alter local immuno-regulatory processes, leading to a reduced clinical response to allergen challenge. SUMMARY
Nicholas Moore - One of the best experts on this subject based on the ideXlab platform.
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an observational cohort study of the use of five Grass Pollen Extract sublingual immunotherapy during the 2015 Pollen season in france
Allergy Asthma & Clinical Immunology, 2018Co-Authors: Patrick Blin, S Lignotmaleyran, H Maizi, S Lorrain, C Drozperroteau, R Lassalle, Bruno Falissard, Martine Drouet, Pascal Demoly, Nicholas MooreAbstract:Allergic rhinitis affects around one quarter of the Western European population. Prophylactic allergen immunotherapy may be useful to reduce the risk of acute symptomatic attacks (hayfever). A five-Grass Pollen Extract sublingual immunotherapy (5GPE-SLIT) has been developed for the treatment of allergic rhinitis to Grass Pollen. The objective of this study was to describe real-world treatment patterns with 5GPE-SLIT in France with respect to the prescribing information. This prospective cohort study was conducted by 90 community and hospital allergists. Adults and children (> 5 years old) starting a first treatment with 5GPE-SLIT prior to the 2015 Pollen season were eligible. Data was collected at the inclusion visit and at the end of the Pollen season. The primary outcome variable was compatibility of 5GPE-SLIT prescription with the prescribing information. This was determined with respect to four variables: (1) interval between 5GPE-SLIT initiation and onset of the Pollen season ≥ 3 months, (2) age of patient ≥ 5 years, (3) intermittent symptoms or mild symptom severity (4) confirmatory diagnostic test. At study end, symptoms reported during the Pollen season and any modifications to treatment or adverse events were documented. 280 adults and 203 children were enrolled. The prescribing information was respected for 82.5% of adults and 86.7% of children. A skin test was performed for all patients. 5GPE-SLIT was started 3–5 months before the Pollen season for 85.3%. Treatment was discontinued before the start of the Pollen season in 11.0% of patients overall, generally because of an adverse event (78.8% of discontinuations). The mean duration of treatment was 5.2 months in adults and 5.6 months in children. At the end of follow-up, symptoms during the Pollen season were intermittent for 75.0% of adults and 85.7% of children, and severity was mild for 61.8 and 66.0% respectively. During 5GPE-SLIT, the following symptoms reported during the previous year were not reported again in > 50% of patients: nasal congestion, rhinorrhoea, repeated sneezing, conjunctivitis and nasal pruritus. 5GPE-SLIT use was generally consistent with prescribing recommendations and was associated with an improvement of AR severity, with resolution of the principal AR symptoms in around half the patients treated. Trial registration EUPAS9358. Registered 13 May 2015. Not prospectively registered. http://www.encepp.eu/encepp/viewResource.htm?id=16229
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An observational cohort study of the use of five-Grass-Pollen Extract sublingual immunotherapy during the 2015 Pollen season in France
Allergy Asthma and Clinical Immunology, 2018Co-Authors: Patrick Blin, H Maizi, S Lorrain, Séverine Lignot-maleyran, Cécile Droz-perroteau, R Lassalle, Bruno Falissard, Martine Drouet, Pascal Demoly, Nicholas MooreAbstract:Background: Allergic rhinitis affects around one quarter of the Western European population. Prophylactic allergen immunotherapy may be useful to reduce the risk of acute symptomatic attacks (hayfever). A five-Grass Pollen Extract sublingual immunotherapy (5GPE-SLIT) has been developed for the treatment of allergic rhinitis to Grass Pollen. The objective of this study was to describe real-world treatment patterns with 5GPE-SLIT in France with respect to the prescribing information. Methods: This prospective cohort study was conducted by 90 community and hospital allergists. Adults and children (> 5 years old) starting a first treatment with 5GPE-SLIT prior to the 2015 Pollen season were eligible. Data was collected at the inclusion visit and at the end of the Pollen season. The primary outcome variable was compatibility of 5GPE-SLIT prescription with the prescribing information. This was determined with respect to four variables: (1) interval between 5GPE-SLIT initiation and onset of the Pollen season ≥ 3 months, (2) age of patient ≥ 5 years, (3) intermittent symptoms or mild symptom severity (4) confirmatory diagnostic test. At study end, symptoms reported during the Pollen season and any modifications to treatment or adverse events were documented. Results: 280 adults and 203 children were enrolled. The prescribing information was respected for 82.5% of adults and 86.7% of children. A skin test was performed for all patients. 5GPE-SLIT was started 3-5 months before the Pollen season for 85.3%. Treatment was discontinued before the start of the Pollen season in 11.0% of patients overall, generally because of an adverse event (78.8% of discontinuations). The mean duration of treatment was 5.2 months in adults and 5.6 months in children. At the end of follow-up, symptoms during the Pollen season were intermittent for 75.0% of adults and 85.7% of children, and severity was mild for 61.8 and 66.0% respectively. During 5GPE-SLIT, the following symptoms reported during the previous year were not reported again in > 50% of patients: nasal congestion, rhinorrhoea, repeated sneezing, conjunctivitis and nasal pruritus. Conclusions: 5GPE-SLIT use was generally consistent with prescribing recommendations and was associated with an improvement of AR severity, with resolution of the principal AR symptoms in around half the patients treated.Trial registration EUPAS9358. Registered 13 May 2015. Not prospectively registered. http://www.encepp.eu/encepp/viewResource.htm?id=16229.
