[Practice patterns in Mexican allergologists about specific immunotherapy with allergens].

PubMed

Larenas Linnemann, Désirée; Guidos Fogelbach, Guillermo Arturo; Arias Cruz, Alfredo

2008-01-01

Immunotherapy has been practiced since over a hundred years. Since the first applications up today changes have occurred in the preparation, dose and duration of the treatment, as well as in the extracts used. Guidelines have been published in Mexico and other countries to try to unify these practice patterns of immunotherapy. By means of a questionnaire, sent in various occasions to all members of the Colegio Mexicano de Inmunología Clínica y Alergia (CMICA) and of the Colegio Mexicano de Pediatras, Especialistas en Inmunología y Alergia (CoMPedIA) we tried to get a picture of the daily practice patterns of immunotherapy in the allergist's office. Results will be presented in a descriptive manner. A response rate of 61 (17%) was obtained from the College members. For immunotherapy allergists use locally made and imported extracts, generally mixed in their office (20% over 10 allergens in one bottle). Eighty percent adds bacterial vaccine at some point and 60% uses sublingual immunotherapy. Most use Evans without albumin as diluent, don't routinely premedicate, reach maintenance treatment after more than six months and 46% recommends a maximum duration of immunotherapy of two years or less. We present a diagnosis on the current situation of practice patterns concerning allergen immunotherapy among the members of both Mexican colleges of allergists. The methods used by the allergists for indication, preparation and administration are quite diverse.

Mechanisms of allergen-specific immunotherapy and novel ways for vaccine development.

PubMed

Jutel, Marek; Van de Veen, Willem; Agache, Ioana; Azkur, Kürsat A; Akdis, Mübeccel; Akdis, Cezmi A

2013-12-01

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.

Modified Allergens for Immunotherapy.

PubMed

Satitsuksanoa, Pattraporn; Głobińska, Anna; Jansen, Kirstin; van de Veen, Willem; Akdis, Mübeccel

2018-02-16

During the past few decades, modified allergens have been developed for use in allergen-specific immunotherapy (AIT) with the aim to improve efficacy and reduce adverse effects. This review aims to provide an overview of the different types of modified allergens, their mechanism of action and their potential for improving AIT. In-depth research in the field of allergen modifications as well as the advance of recombinant DNA technology have paved the way for improved diagnosis and research on human allergic diseases. A wide range of structurally modified allergens has been generated including allergen peptides, chemically altered allergoids, adjuvant-coupled allergens, and nanoparticle-based allergy vaccines. These modified allergens show promise for the development of AIT regimens with improved safety and long-term efficacy. Certain modifications ensure reduced IgE reactivity and retained T cell reactivity, which facilities induction of immune tolerance to the allergen. To date, multiple clinical trials have been performed using modified allergens. Promising results were obtained for the modified cat, grass and birch pollen, and house dust mite allergens. The use of modified allergens holds promise for improving AIT efficacy and safety. There is however a need for larger clinical studies to reliably assess the added benefit for the patient of using modified allergens for AIT.

Allergen-specific sublingual immunotherapy in the treatment of migraines: a prospective study.

PubMed

Theodoropoulos, D S; Katzenberger, D R; Jones, W M; Morris, D L; Her, C; Cullen, N A M; Morrisa, D L

2011-10-01

Inflammation is a cardinal feature of migraines. A number of observations point to the possibility that an allergic component of a type I (IgE-mediated) nature may be involved in at least some migraineurs. Not only are migraines frequent among patients with allergic rhinitis but quite frequently the same medical approaches are beneficial in both diseases: anti-inflammatories, adrenergic tone modifiers, immune suppressants. The effect that immunotherapy for allergic rhinitis has upon migraines is studied. Patients were recruited who suffered from typical migraines but were not treated with regular migraine controllers (beta blockers, antiepileptics, tricyclics, etc.). They underwent allergen-specific, sublingual immunotherapy with physician-formulated, individually-prepared airborne allergen extracts. Response to treatment was assessed with serum C-reactive protein level changes and symptom scores. Serum C-reactive protein (CRP), an acute phase reactant, was chosen as a marker because its usefulness has already been assessed in interictal migraine activity. Interictal serum CRP levels decline was observed in the course of sublingual immunotherapy. Concurrent improvement in symptom scores for both rhinitis and migraines was also observed. In patients with allergic rhinitis, migraine development and course may have a significant allergic component. Assessment of migraineurs for the possibility of coexisting allergic rhinitis is justified. Treatment of allergic rhinitis by immune response modifiers, such as immunotherapy, may have a place in the management of migraines for these patients.

Grass-specific CD4(+) T-cells exhibit varying degrees of cross-reactivity, implications for allergen-specific immunotherapy.

PubMed

Archila, L D; DeLong, J H; Wambre, E; James, E A; Robinson, D M; Kwok, W W

2014-07-01

Conceptually, allergic responses may involve cross-reactivity by antibodies or T-cells. While IgE cross-reactivity among grass-pollen allergens has been observed, cross-reactivity at the allergen-specific T-cell level has been less documented. Identification of the patterns of cross-reactivity may improve our understanding, allowing optimization of better immunotherapy strategies. We use Phleum pratense as model for the studying of cross-reactivity at the allergen-specific CD4(+) T cell level among DR04:01 restricted Pooideae grass-pollen T-cell epitopes. After in vitro culture of blood mono-nucleated cells from grass-pollen-allergic subjects with specific Pooideae antigenic epitopes, dual tetramer staining with APC-labelled DR04:01/Phleum pratense tetramers and PE-labelled DR04:01/Pooideae grass homolog tetramers was assessed to identify cross-reactivity among allergen-specific DR04:01-restricted T-cells in six subjects. Direct ex vivo staining enabled the comparison of frequency and phenotype of different Pooideae grass-pollen reactive T-cells. Intracellular cytokine staining (ICS) assays were also used to examine phenotypes of these T-cells. T-cells with various degrees of cross-reactive profiles could be detected. Poa p 1 97-116 , Lol p 1 221-240 , Lol p 5a 199-218 , and Poa p 5a 199-218 were identified as minimally cross-reactive T-cell epitopes that do not show cross-reactivity to Phl p 1 and Phl p 5a epitopes. Ex vivo tetramer staining assays demonstrated T-cells that recognized these minimally cross-reactive T-cell epitopes are present in Grass-pollen-allergic subjects. Our results suggest that not all Pooideae grass epitopes with sequence homology are cross-reactive. Non-cross-reactive T-cells with comparable frequency, phenotype and functionality to Phl p-specific T-cells suggest that a multiple allergen system should be considered for immunotherapy instead of a mono-allergen system. © 2014 John Wiley & Sons Ltd.

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy.

PubMed

Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-06-01

Animal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases. Allergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment. In atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles.

Outstanding animal studies in allergy II. From atopic barrier and microbiome to allergen-specific immunotherapy

PubMed Central

Jensen-Jarolim, Erika; Pali-Schöll, Isabella; Roth-Walter, Franziska

2017-01-01

Purpose of review Animal studies published within the past 18 months were assessed, focusing on innate and specific immunomodulation, providing knowledge of high translational relevance for human atopic and allergic diseases. Recent findings Allergic companion animals represent alternative models, but most studies were done in mice. Atopic dermatitis mouse models were refined by the utilization of cytokines like IL-23 and relevant skin allergens or enzymes. A novel IL-6 reporter mouse allows biomonitoring of inflammation. Both skin pH and the (transferable) microflora have a pivotal role in modulating the skin barrier. The microflora of the gastrointestinal mucosa maintains tolerance to dietary compounds and can be disturbed by antiacid drugs. A key mouse study evidenced that dust from Amish households, but not from Hutterites protected mice against asthma. In studies on subcutaneous and sublingual allergen-specific immunotherapy, much focus was given on delivery and adjuvants, using poly-lacto-co-glycolic particles, CpGs, probiotics or Vitamin D3. The epicutaneous and intralymphatic routes showed promising results in mice and horses in terms of prophylactic and therapeutic allergy treatment. Summary In atopic dermatitis, food allergies and asthma, environmental factors, together with the resident microflora and barrier status, decide on sensitization versus tolerance. Also allergen-specific immunotherapy operates with immunomodulatory principles. PMID:28375932

Changes in skin reactivity and associated factors in patients sensitized to house dust mites after 1 year of allergen-specific immunotherapy.

PubMed

Son, Jeong-Yeop; Jung, Mann-Hong; Koh, Kwang-Wook; Park, Eun-Kee; Heo, Jeong-Hoon; Choi, Gil-Soon; Kim, Hee-Kyoo

2017-04-01

Allergen-specific immunotherapy (SIT) can significantly improve symptoms and reduce the need for symptomatic medication. The aim of this study was to investigate changes in skin reactivity to house dust mites (HDMs) as an immunologic response and associated factors after 1 year of immunotherapy. A total of 80 patients with allergic airway diseases who received subcutaneous SIT with HDMs from 2009 to 2014 were evaluated. The investigated parameters were basic demographic characteristics, skin reactivity and specific IgE for HDM, serum total IgE level, blood eosinophil counts, and medication score. The mean levels of skin reactivity to HDMs, blood eosinophil counts, and medication scores after 1 year were significantly reduced from baseline. In univariate comparison of the changes in skin reactivity to HDMs, age ≤30 years, HDMs only as target of immunotherapy, and high initial skin reactivity (≥2) to HDMs were significantly associated with the reduction in skin test reactivity. In multivariate analysis, high initial skin reactivity and HDMs only as target allergens were significantly associated with changes in skin reactivity to HDMs. In the receiver operating characteristic curve of the initial mean skin reactivity to HDMs for more than 50% reduction, the optimal cutoff value was 2.14. This study showed significant reductions in allergen skin reactivity to HDMs after 1 year of immunotherapy in patients sensitized to HDMs. The extent of initial allergen skin reactivity and only HDMs as target allergen were important predictive factors for changes in skin reactivity.

New developments in allergen immunotherapy.

PubMed

Vadlamudi, Anusha; Shaker, Marcus

2015-10-01

Allergic rhinitis, conjunctivitis, and asthma impact quality of life and cost billions of dollars in lost wages, productivity, and medical expenditures. Allergen immunotherapy is the only therapy that alters the allergen immune response, resulting in fewer symptoms upon natural exposure. This review summarizes recent immunotherapy developments. Subcutaneous immunotherapy (SCIT) remains a disease modifying treatment for allergic rhinoconjunctivitis and asthma with rare complications of therapy. Recent evidence suggests that SCIT may be effective in select cases of atopic dermatitis, particularly for patients with dust mite sensitivity. Sublingual immunotherapy (SLIT) tablets are now commercially available for grass and ragweed allergy and appear to have a superior safety profile to SCIT with similar long-term effectiveness, because as with SCIT, symptom improvement persists after the SLIT course is completed. SLIT tablets are administered daily at home (after initial supervised dosing) and may be used shortly before and during the target pollen seasons in a precoseasonal fashion (instead of perennial dosing). Research continues into experimental approaches using oral food allergen immunotherapy (OIT) to modify the natural history of food allergies. Although a proportion of patients in OIT trials experience sustained unresponsiveness, many do not and current recommendations limit the use of OIT to research protocols. Patients have new well tolerated and effective options for more convenient treatment of asthma and allergic rhinoconjunctivitis associated with grass and ragweed allergy. SCIT remains effective for polysensitized patients and may be an option for some patients with atopic dermatitis. Research continues into novel food allergy treatments.

[The use of Russian allergoids for the specific immunotherapy of pollinosis].

PubMed

Fradkin, V A; Roshal', N I; Goriachkina, L A; Nikonorova, M V; Astaf'eva, N G; Luss, L V; Raĭkis, V N

1993-01-01

For three years 128 pollinosis patients received specific immunotherapy with cereals, weed and tree pollen allergens manufactured by the Scientific and Industrial Amalgamation "Allergen" (Stavropol). For comparison, a group of 42 patients was treated with the corresponding allergens according to the commonly used treatment scheme. Patients who had earlier undergone treatment with water-saline extracts of allergens, that proved to be ineffective, formed a special group. In sensitive patients reaction to the skin test with allergoids was by half less pronounced than reaction to the skin test with allergens. In allergometric titration on the nasal mucosa, reaction to the introduction of allergoids could be registered when they were used at a 10- to 100-fold higher concentration than allergens. The course of specific immunotherapy with allergoids was found to lead to a decrease in the level of allergen-specific IgE antibodies (p > 0.05) and total IgE (p < 0.01). An increase in the level of IgG antibodies was noted (p < 0.01). Specific immunotherapy with allergoids was more effective than that with water-saline extracts of allergens. The use of allergoids made it possible to prescribe specific immunotherapy to a wider circle of patients.

Current insights in allergen immunotherapy.

PubMed

Passalacqua, Giovanni; Bagnasco, Diego; Ferrando, Matteo; Heffler, Enrico; Puggioni, Francesca; Canonica, Giorgio Walter

2018-02-01

Allergen-specific immunotherapy (AIT) in its subcutaneous and sublingual forms is currently a well-established and experimentally supported treatment for respiratory allergy and hymenoptera venom allergy. There have been advances in its use linked strictly to the advancement in the knowledge of the molecular mechanisms of allergy, the production of well-characterized extracts, and diagnostic techniques. The use of AIT in asthma and the application of new approaches are expanding. We briefly review the advances and concerns in the use of AIT. PubMed and Scopus. The most recent and clinically relevant literature was selected and reviewed. The introduction of high-quality products supported by large dose-finding trials has yielded better defined indications, contraindications, and modalities of use. Some specific products in tablet form have recently been approved in the United States. Sublingual immunotherapy has been found to be effective in asthma, which until recently had been a matter of debate. Another promising therapy is oral and sublingual desensitization for food allergy, for which encouraging results have recently been reported. In the near future, other options will be available, including new routes of administration (intralymphatic and epicutaneous), allergoids, engineered allergens, and peptides. The use of component-resolved diagnosis techniques will further refine and target AIT prescriptions. This condensed and updated review shows that AIT remains a viable treatment option, especially after the introduction of standardized tablets for some allergens. Food allergy and new administration routes represent a promising expansion. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Perspectives in allergen immunotherapy: 2017 and beyond.

PubMed

Pfaar, O; Bonini, S; Cardona, V; Demoly, P; Jakob, T; Jutel, M; Kleine-Tebbe, J; Klimek, L; Klysner, S; Kopp, M V; Kuna, P; Larché, M; Muraro, A; Schmidt-Weber, C B; Shamji, M H; Simonsen, K; Somoza, C; Valovirta, E; Zieglmayer, P; Zuberbier, T; Wahn, U

2018-01-01

The Future of the Allergists and Specific Immunotherapy (FASIT) workshop provides a regular platform for global experts from academia, allergy clinics, regulatory authorities and industry to review developments in the field of allergen immunotherapy (AIT). The most recent meeting, held in February 2017, had two main themes: advances in AIT and hot topics in AIT from the regulatory point of view. The first theme covered opportunities for personalized AIT, advances in adjuvants and delivery systems, and the development of new molecules and future vaccines for AIT. Key topics in the second part of the meeting were the effects of the enactment of European Directive 2001/83 on the availability of allergens for therapy and diagnosis across the EU, the challenges of conducting Phase 3 studies in the field, the future role of allergen exposure chambers in AIT studies and specific considerations in performing AIT studies in the paediatric population. Finally, the group highlighted the forthcoming EAACI guidelines and their particular importance for the standardization of practice in the treatment of allergies. This review presents a comprehensive insight into those panel discussions and highlights unmet needs and also possible solutions to them for the future. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Factors influencing the prescription of allergen immunotherapy: the allergen immunotherapy decision analysis (AIDA) study.

PubMed

Frati, F; Incorvaia, C; Cadario, G; Fiocchi, A; Senna, G E; Rossi, O; Romano, A; Scala, E; Romano, C; Ingrassia, A; Zambito, M; Dell'albani, I; Scurati, S; Passalacqua, G; Canonica, G W

2013-10-01

The evidence of efficacy of allergen immunotherapy (AIT) for respiratory allergy has been demonstrated by a number of meta-analyses. However, the daily practice of AIT is quite different from controlled trials, facing challenges in terms of selection of patients, practical performance, and, of particular importance, use of allergen extracts of inadequate quality. We here performed a survey, named the Allergen Immunotherapy Decision Analysis (AIDA), to evaluate which criteria are used by specialists to choose a product for sublingual immunotherapy (SLIT) in patients with respiratory allergy. A questionnaire composed of 14 items to be ranked by each participant according to the importance attributed when choosing SLIT products was submitted to 444 Italian specialists. The responses of the 169 (38.1%) physicians, who answered all questions, were analysed. Most of the respondents were allergists (79%), followed by pulmonologists (10.8%), both allergists and pulmonologists (4.8%), and otorhinolaryngologists (3%); 59.8% of the respondents were males and 40.2% were females. The age distribution showed that 89.9% of the respondents were aged between 35 and 64 years. All respondents usually prescribed AIT products in their clinical practice: 31.4% used only SLIT, whereas 69.2% used both subcutaneous and sublingual administration. The rankings, expressed as means, attributed by physicians for each of the 14 items were as follows: level of evidence-based medicine (EBM ) validation of efficacy (3.44), level of EBM validation of safety (4.30), standardization of the product (5.37), efficacy based on personal experience (5.82), defined content(s) of the major allergen(s) in micrograms (5.96), scientific evidence for each single allergen (6.17), safety based on personal experience (6.32), ease of administration protocol (8.08), cost and terms of payment (e.g. instalments) (9.17), dose personalization (9.24), patient preference (9.25), ease of product storage (9.93), reimbursement

Regulatory environment for allergen-specific immunotherapy.

PubMed

Kaul, S; May, S; Lüttkopf, D; Vieths, Stefan

2011-06-01

Products for specific immunotherapy (SIT) are medicinal products according to the European Regulations. To obtain a marketing authorization (MA) within the European Community, the quality, safety and efficacy have to be proven. During the development phase of a medicinal product, applicants have the opportunity to apply for scientific advice by national competent authorities or the European Medicines Agency (EMA) to compile a suitable development plan for the examination of quality and performance of nonclinical and clinical trials. Moreover, a paediatric investigation plan has to be submitted to the Paediatric Committee of the EMA and has to be approved before submission of an application for MA. Several regulatory procedures exist for obtaining a MA in the European Community. The national procedure leads only to marketability in one country whereas the Mutual Recognition, the Decentralized and Centralized Procedures (CP) are intended for MA in several or all member states of the European Union. The CP is mandatory for certain medicinal products, for example for drug substances derived by biotechnological processes such as recombinant allergens. Named Patient Products for SIT are a specialty because they are manufactured on the basis of an individual prescription and marketed without a MA. © 2011 John Wiley & Sons A/S.

Safety of allergen immunotherapy: a review of premedication and dose adjustment.

PubMed

Morris, A Erika; Marshall, Gailen D

2012-03-01

From the first allergen immunotherapy proposed in the early 1900s to the present day, numerous studies have proven the efficacy of allergen immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity. The major risk, however small, with allergen immunotherapy is anaphylaxis. There has been considerable interest and debate regarding risk factors for immunotherapy reactions (local and systemic) and interventions to reduce the occurrence of these reactions. One of these interventions that is especially debated regards dose adjustment for various reasons, but in particular for local reactions. In this review, we discuss the safety of immunotherapy and provide a comprehensive review of the literature regarding immunotherapy schedules and doses.

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

PubMed Central

Valenta, Rudolf; Campana, Raffaela; Focke-Tejkl, Margit; Niederberger, Verena

2016-01-01

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. PMID:26853127

[Influence of the difference in the pollen count on medical costs in an allergen-specific immunotherapy for Japanese cedar pollinosis].

PubMed

Yuta, Atsushi; Miyamoto, Yukiko; Hattori, Reiko; Ogihara, Hitomi; Takeuchi, Kazuhiko; Majima, Yuichi

2007-11-01

We studied medical economic efficacy and influence by the different number of pollen scattering in patients treated with allergen-specific immunotherapy for Japanese cedar pollinosis. We calculated medical treatment costs and the medicine expense from medical records in eighteen cedar pollinosis patients treated with allergen-specific immunotherapy (IT-G) and with medications (M-G). We examined with the same patients for three years of different pollen scattering, mass scattering year (2005), moderate scattering year (2003), a few scattering year (2004). Furthermore, satisfaction of treatment and symptom score measured by visual analog scale in both subjects was studied in a mass scattering year. Total medical costs at hospital was cheaper in IT-G than in M-G. The result was depended on prescribed medical costs. In addition, prescribed medicine agents and total medical costs did not increase by the mass scattering year of pollen. Satisfaction of treatment and symptom score in IT-G was better than that in M-G. Immunotherapy had a benefit on a medical economy.

Allergen immunotherapy in allergic rhinitis: current use and future trends.

PubMed

Klimek, Ludger; Pfaar, Oliver; Bousquet, Jean; Senti, Gabriela; Kündig, Thomas

2017-09-01

Type-1 allergies are among the most chronic common diseases of humans. Allergen immunotherapy (AIT) is the only causative and disease-modifying treatment option besides allergen avoidance. Severe systemic adverse allergic reactions may be induced by every AIT treatment. Different approaches have been used to provide safer AIT preparations to lower or even totally overcome this risk. Areas covered: A structured literature recherche in Medline and Pubmed under inclusion of national and international guidelines and Cochrane meta-analyses has been performed aiming at reviewing clinical use of such approaches in AIT. New allergen preparations may include allergoids, recombinant allergens (recA) and modified recombinant allergens (recA) in subcutaneous as well as in mucosal immunotherapies (application e.g. using bronchial, nasal, oral and sublingual application) with sublingual being the established mucosal application route and new ways of application like intralymphatic and epicutaneous immunotherapy. Expert commentary: Immune-modifying agents like Virus-like particles and CpG-motifs, adjuvants like MPL and aluminum hydroxide are evaluated and found to increase and direct the immunological response toward immunological tolerance. New forms of allergen extracts can improve safety and efficacy of AIT and may change our way of performing allergen immunotherapy in the future.

Specific immunotherapy in grass pollen allergy

PubMed Central

Mailhol, Claire; Didier, Alain

2012-01-01

Since its description by Noon in 1911, desensitization, or allergen specific immunotherapy (SIT), has been largely used in respiratory allergic diseases treatment. It remains the only etiologic treatment for allergic diseases. The development of the sublingual route and new forms of medication, as an alternative to subcutaneous injection, has led to large scale clinical trials. Many of them had been performed with allergen tablets, particularly in the field of pollen allergy. These studies have confirmed that SIT is efficient in reducing all respiratory allergic symptoms. Data on long-term benefits and sustained efficacy after stopping treatment have also been published. These show an impact on natural history of allergic disease, in particular, a reduction in the risk of asthma in desensitized rhinitic subjects and in the acquisition of new sensitivities. The basic mechanisms of immunotherapy are becoming better understood and allow us to envisage improvements in this therapeutic method in the future. The sublingual route appears to be safer with a better safety profile. This may lead to an extension of allergen specific immunotherapy indications in patients with respiratory allergic diseases. PMID:23095875

[The clinical efficacy of allergen-specific immunotherapy with water-salt extracts and adjuvant allergens for atopic asthma with household sensitization].

PubMed

Ushakova, D V; Nikonov, E L

To evaluate the clinical and economic efficiency of allergen-specific immunotherapy (ASIT); to comparatively analyze the efficiency of various therapy regimens for atopic asthma. The clinical and economic efficiency of asthma therapy using ASIT with water-salt allergen extracts or the adjuvant drug alustal 'mite allergen' and only with medicines were comparatively analyzed. The investigation enrolled 156 patients with mild and moderate atopic asthma, household allergy. In Group 1 (n = 57), ASIT was performed using the classical scheme by subcutaneous injection of house dust mite allergen (JSC 'I.I. Mechnikov Biomed', Russia). In Group 2 (n = 43), ASIT was conducted using the alustal 'mite allergen' (Stallergenes, France). Group 3 (n = 56) received only medical therapy. ASIT with both water-salt allergen extracts and the adjuvant allergen alustal is an effective treatment for mild and moderate atopic asthma. ASIT greatly reduces the need for anti-inflammatory treatment and the use of symptomatic drugs and improves the physical and psychoemotional indicators of quality of life in patients. The economic benefit of ASIT is delayed, but its use significantly reduces financing costs. ASIT is a reasonable, highly effective and ultimately cost-effective treatment in patients with atopic asthma. A variety of drugs for ASIT can choose schemes that are convenient and acceptable for each patient, which allows wider use of this treatment.

Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: results of a phase I trial.

PubMed

Fellrath, Jean-Marc; Kettner, Alexander; Dufour, Nathalie; Frigerio, Christian; Schneeberger, Dominique; Leimgruber, Annette; Corradin, Gampietro; Spertini, François

2003-04-01

There is a need to improve the safety and efficacy of allergen-specific immunotherapy. Long synthetic peptide-based immunotherapy was proven safe, immunogenic, and protective in preclinical trials. To evaluate the safety and immunogenicity of an allergen-derived long synthetic overlapping peptide (LSP) immunotherapy, we designed a double-blind, placebo-controlled phase I clinical trial in patients hypersensitive to bee venom. Patients from the active group were injected at day 0 with a mixture of 3 LSPs mapping the entire PLA2 molecule, a major bee venom allergen, in a dose-escalating protocol to a maintenance dose of 100 microg per peptide repeated at days 4, 7, 14, 42, and 70. The control group was injected with human albumin. Whereas specific T-cell proliferation in the peptide group increased up to day 14, a sharp decline was observed thereafter, ending in specific T-cell hyporesponsiveness at day 80. Serum-specific IgG4 response was enhanced, in contrast to anti-PLA2 IgE. Specific T-cell cytokine modulation was marked by increased IL-10 and IFN-gamma secretion. LSP injections were well tolerated in all patients except for mild, late allergic reactions in 2 patients at day 70. The results of this short-term study demonstrate that LSP-based allergen immunotherapy was safe and able to induce T(H)1-type immune deviation, allergen-specific IL-10 production, and T-cell hyporesponsiveness. LSPs, which offer the advantage of covering all possible T-cell epitopes for any HLA genotype, can be considered candidates for a novel and safe approach of specific immunotherapy.

Recombinant Allergens in Structural Biology, Diagnosis, and Immunotherapy

PubMed Central

Tscheppe, Angelika; Breiteneder, Heimo

2017-01-01

The years 1988–1995 witnessed the beginning of allergen cloning and the generation of recombinant allergens, which opened up new avenues for the diagnosis and research of human allergic diseases. Most crystal and solution structures of allergens have been obtained using recombinant allergens. Structural information on allergens allows insights into their evolutionary biology, illustrates clinically observed cross-reactivities, and makes the design of hypoallergenic derivatives for allergy vaccines possible. Recombinant allergens are widely used in molecule-based allergy diagnosis such as protein microarrays or suspension arrays. Recombinant technologies have been used to produce well-characterized, noncontaminated vaccine components with known biological activities including a variety of allergen derivatives with reduced IgE reactivity. Such recombinant hypoallergens as well as wild-type recombinant allergens have been used successfully in several immunotherapy trials for more than a decade to treat birch and grass pollen allergy. As a more recent application, the development of antibody repertoires directed against conformational epitopes during immunotherapy has been monitored by recombinant allergen chimeras. Although much progress has been made, the number and quality of recombinant allergens will undoubtedly increase and keep improving our knowledge in basic scientific investigations, diagnosis, and therapy of human allergic diseases. PMID:28467993

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

PubMed

Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P

2011-10-01

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.

Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers.

PubMed

Shamji, Mohamed H; Durham, Stephen R

2017-12-01

Allergen immunotherapy is effective in patients with IgE-dependent allergic rhinitis and asthma. When immunotherapy is given continuously for 3 years, there is persistent clinical benefit for several years after its discontinuation. This disease-modifying effect is both antigen-specific and antigen-driven. Clinical improvement is accompanied by decreases in numbers of effector cells in target organs, including mast cells, basophils, eosinophils, and type 2 innate lymphoid cells. Immunotherapy results in the production of blocking IgG/IgG 4 antibodies that can inhibit IgE-dependent activation mediated through both high-affinity IgE receptors (FcεRI) on mast cells and basophils and low-affinity IgE receptors (FcεRII) on B cells. Suppression of T H 2 immunity can occur as a consequence of either deletion or anergy of antigen-specific T cells; induction of antigen-specific regulatory T cells; or immune deviation in favor of T H 1 responses. It is not clear whether the altered long-term memory resides within the T-cell or the B-cell compartment. Recent data highlight the role of IL-10-producing regulatory B cells and "protective" antibodies that likely contribute to long-term tolerance. Understanding mechanisms underlying induction and persistence of tolerance should identify predictive biomarkers of clinical response and discover novel and more effective strategies for immunotherapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Molecular diagnosis and immunotherapy.

PubMed

Sastre, Joaquín; Sastre-Ibañez, Marina

2016-12-01

To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy. As specific allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy. Molecular diagnosis, when used with other tools and patients' clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice.

Specific immunotherapy and biological treatments for occupational allergy.

PubMed

Moscato, Gianna; Pala, Gianni; Sastre, Joaquin

2014-12-01

Occupational allergy represents a substantial health, social, and financial burden for the society. Its management is a complex task that, in selected cases, may also include allergen-specific immunotherapy. The purpose of this article is to review clinical data on allergen immunotherapy and biological treatments applied to occupational allergy in 2013. Immunotherapy in occupational allergic diseases has been scarcely used, and only for a few sensitizers, such as latex, flour, and Hymenoptera venom, partly due to the lack of standardized extracts. The recent use of the molecular diagnosis can improve the indication and selection of suitable allergens for preparing new standardized and powerful extracts for immunotherapy. Some recent reports suggest a beneficial role of treatment with omalizumab in workers with occupational asthma who continue to be exposed to the causal agent. Although scarce, available data suggest that immunotherapy and biological treatments may allow allergic workers to continue their work activity, but further studies are needed to standardize extracts and to evaluate the cost-effectiveness of these treatments, when exposure at the workplace cannot be avoided.

Allergen-Specific Immunotherapy with Monomeric Allergoid in a Mouse Model of Atopic Dermatitis

PubMed Central

Babakhin, Alexander; Andreev, Sergey; Nikonova, Alexandra; Shilovsky, Igor; Buzuk, Andrey; Elisyutina, Olga; Fedenko, Elena; Khaitov, Musa

2015-01-01

Atopic dermatitis (AD) is a widespread and difficult to treat allergic skin disease and is a tough challenge for healthcare. In this study, we investigated whether allergen-specific immunotherapy (ASIT) with a monomeric allergoid obtained by succinylation of ovalbumin (sOVA) is effective in a mouse model of atopic dermatitis. An experimental model of AD was reproduced by epicutaneous sensitization with ovalbumin (OVA). ASIT was performed with subcutaneous (SC) administration of increasing doses of OVA or sOVA. The levels of anti-OVA antibodies, as well as cytokines, were detected by ELISA. Skin samples from patch areas were taken for histologic examination. ASIT with either OVA or sOVA resulted in a reduction of both the anti-OVA IgE level and the IgG1/IgG2a ratio. Moreover, ASIT with sOVA increased the IFN-γ level in supernatants after splenocyte stimulation with OVA. Histologic analysis of skin samples from the sites of allergen application showed that ASIT improved the histologic picture by decreasing allergic inflammation in comparison with untreated mice. These data suggest that ASIT with a succinylated allergen represents promising approach for the treatment of AD. PMID:26275152

Comparison of allergenicity and immunogenicity of an intact allergen vaccine and commercially available allergoid products for birch pollen immunotherapy.

PubMed

Lund, L; Henmar, H; Würtzen, P A; Lund, G; Hjortskov, N; Larsen, J N

2007-04-01

Specific immunotherapy with intact allergen vaccine is a well-documented treatment for allergic diseases. Different vaccine formulations are currently commercially available, the active ingredient either being intact allergens or chemically modified allergoids. The rationale behind allergoids is to decrease allergenicity while maintaining immunogenicity. However, data from the German health authorities based on reporting of adverse events over a 10-year period did not indicate increased safety of allergoids over intact allergens. The objective of this study was to investigate the effect of chemical modification on allergenicity and immunogenicity comparing four commercial allergoid products for birch pollen immunotherapy with an intact allergen vaccine. Solid-phase IgE inhibition and histamine release assays were selected as model systems for allergenicity, and a combination of human T cell proliferation and IgG titres following mouse immunizations were used to address the immunogenicity of the intact allergen vaccine and the four allergoids. In all assays, the products were normalized with respect to the manufacturer's recommended maintenance dose. IgE inhibition experiments showed a change in epitope composition comparing intact allergen vaccine with allergoid. One allergoid product induced enhanced histamine release compared to the intact allergens, while the other three allergoids showed reduced release. Standard T cell stimulation assays using lines from allergic patients showed a reduced response for all allergoids compared with the intact allergen vaccine regardless of the cell type used for antigen presentation. All allergoids showed reduced capacity to induce allergen-specific IgG responses in mice. While some allergoids were associated with reduced allergenicity, a clear reduction in immunogenicity was observed for all allergoid products compared with the intact allergen vaccine, and the commercial allergoids tested therefore do not fulfil the allergoid

Does evidence support the use of cat allergen immunotherapy?

PubMed

Dhami, Sangeeta; Agarwal, Arnav

2018-06-04

Cat allergy can manifest as allergic rhinitis, conjunctivitis and/or asthma. With widespread cat ownership and exposure, cat allergy has emerged as a major cause of morbidity. Cat allergen immunotherapy is a potential disease modifying treatment for patients with cat allergy. We examine evidence on the effectiveness, cost-effectiveness and safety of cat allergen immunotherapy and consider the clinical contexts in which it should be prescribed. The European Association of Allergy and Clinical Immunology systematic reviews on allergic rhinitis and asthma along with the accompanying guidelines on allergic rhinitis were used as primary sources of evidence. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are most common routes of administration for allergen immunotherapy (AIT). A limited number of high-quality studies related to cat dander have shown mixed results in improvements in ocular and nasal symptoms, asthma symptoms, peak expiratory flow rate and medication use scores with subcutaneous immunotherapy. Two studies examining cat dander and cat-related allergy response with sublingual immunotherapy have shown mixed results in terms of symptomatic response. One randomized trial examining intralymphatic immunotherapy has shown a positive symptom response and a favourable safety profile. Although studies have reported mixed results regarding safety of SCIT, adverse events have been reported more commonly with SCIT than SLIT. There is a limited body of high-quality evidence on the effectiveness and safety of cat AIT and no high-quality data on its cost-effectiveness. The available evidence on effectiveness is mixed based on studying a limited array of immunological, physiological and patient-reported outcome measures. Based on this evidence and extrapolating on the wider evidence base in AIT, it is likely that some patients may benefit from this modality of treatment, particularly those with moderate-to-severe disease who are inadequately

Allergen-specific immunotherapy prescription patterns in veterinary practice: a US population-based cohort study.

PubMed

Tater, Kathy Chu; Cole, William Elliott; Pion, Paul David

2017-08-01

Poor adherence to continuing allergen-specific immunotherapy treatment (ASIT) may be an issue in veterinary medicine. No studies describe how allergen tests are used in general veterinary practice, including the percentage of patients that receive ASIT after allergen testing. Assess veterinary ASIT patterns in United States general practices. Dogs (n = 2,557) and 121 cats allergen-tested at 177 hospitals (173 general practice and four specialty practices) in 44 states. Invoiced service descriptions of allergen tests and ASIT orders were retrieved from an aggregated database of veterinary practices. In general practice, 42% (992 of 2,360) of patients did not begin ASIT after allergen testing. ASIT was not refilled for 29% (398 of 1,368) of patients after the initial order. ASIT was initiated and refilled more often in dogs (56.6%, 71.4%, respectively) than cats (38%, 67.4%). Specialty practice patients had the highest ASIT initiation (94.4%) and refill (92.7%) percentages in comparison to general practices (P < 0.001). Size, age, geographical region and type of practice were associated with whether dogs were started on ASIT. Geographical region was also associated with refilling a prescription for ASIT, which was considered to be evidence of adherence to continuing treatment. Almost one third of clients failed to continue ASIT beyond the initial order, which is a much shorter duration of therapy than the 12 months recommended for determining ASIT efficacy. A large number of general practice patients did not begin ASIT after allergen testing, likely due to differences in how clinicians in general and dermatology practices use allergen tests. © 2017 ESVD and ACVD.

Novel approaches and perspectives in allergen immunotherapy.

PubMed

Hoffmann, H J; Valovirta, E; Pfaar, O; Moingeon, P; Schmid, J M; Skaarup, S H; Cardell, L-O; Simonsen, K; Larché, M; Durham, S R; Sørensen, P

2017-07-01

In this review, we report on relevant current topics in allergen immunotherapy (AIT) which were broadly discussed during the first Aarhus Immunotherapy Symposium (Aarhus, Denmark) in December 2015 by leading clinicians, scientists and industry representatives in the field. The aim of this symposium was to highlight AIT-related aspects of public health, clinical efficacy evaluation, mechanisms, development of new biomarkers and an overview of novel therapeutic approaches. Allergy is a public health issue of high socioeconomic relevance, and development of evidence-based action plans to address allergy as a public health issue ought to be on national and regional agendas. The underlying mechanisms are in the focus of current research that lays the ground for innovative therapies. Standardization and harmonization of clinical endpoints in AIT trials as well as current knowledge about potential biomarkers have substantiated proof of effectiveness of this disease-modifying therapeutic option. Novel treatments such as 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 fraction of patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Allergen-specific oral immunotherapy for peanut allergy.

PubMed

Nurmatov, Ulugbek; Venderbosch, Iris; Devereux, Graham; Simons, F Estelle R; Sheikh, Aziz

2012-09-12

Peanut allergy is one of the most common forms of food allergy encountered in clinical practice.  In most cases, it does not spontaneously resolve; furthermore, it is frequently implicated in acute life-threatening reactions. The current management of peanut allergy centres on meticulous avoidance of peanuts and peanut-containing foods. Allergen-specific oral immunotherapy (OIT) for peanut allergy aims to induce desensitisation and then tolerance to peanut, and has the potential to revolutionise the management of peanut allergy. However, at present there is still considerable uncertainty about the effectiveness and safety of this approach. To establish the effectiveness and safety of OIT in people with IgE-mediated peanut allergy who develop symptoms after peanut ingestion. We searched in the following databases: AMED, BIOSIS, CAB, CINAHL, The Cochrane Library, EMBASE, Global Health, Google Scholar, IndMed, ISI Web of Science, LILACS, MEDLINE, PakMediNet and TRIP. We also searched registers of on-going and unpublished trials. The date of the most recent search was January 2012. Randomised controlled trials (RCTs), quasi-RCTs or controlled clinical trials involving children or adults with clinical features indicative of IgE-mediated peanut allergy treated with allergen-specific OIT, compared with control group receiving either placebo or no treatment, were eligible for inclusion. Two review authors independently checked and reviewed titles and abstracts of identified studies and assessed risk of bias. The full text of potentially relevant trials was assessed. Data extraction was independently performed by two reviewers with disagreements resolved through discussion. We found one small RCT, judged to be at low risk of bias, that enrolled 28 children aged 1 to 16 years with evidence of sensitisation to peanut and a clinical history of reaction to peanut within 60 minutes of exposure. The study did not include children who had moderate to severe asthma or who had a

The local and systemic side-effects of venom and inhaled-allergen subcutaneous immunotherapy.

PubMed

Adamic, Katja; Zidarn, Mihaela; Bajrovic, Nissera; Erzen, Renato; Kopac, Peter; Music, Ema

2009-01-01

Although immunotherapy is effective in allergic rhinitis, conjunctivitis, asthma and stinging insect hypersensitivity, it carries a risk of anaphylactic reactions. In a 4-year retrospective survey, we investigated 1257 adult patients who had received venom or inhaled-allergen subcutaneous immunotherapy. The dose-increase phase was performed as the 2-day rush protocol for venom immunotherapy and the 6-week protocol for inhaled-allergen immunotherapy. A total of 904 patients received venom immunotherapy and 353 patients inhaled-allergen immunotherapy. The prevalence of systemic reactions was 13.6%. The frequency of systemic reactions was higher during the maintenance phase than in the dose-increase phase (9.6% vs. 5.9%) and was highest in both phases of treatment with honeybee venom (P < 0.001). The majority of systemic reactions were mild. Five (0.4%) patients had reaction with a fall of blood pressure and were treated with adrenaline. There was no fatal outcome. The systemic side-effects during the dose-increase phase of venom immunotherapy occurred at a median dose of 46 microg (range 2-100 microg). Large local reactions occurred in 13.9% of patients without any significant difference between the allergens. We have shown that systemic reactions are not rare even during maintenance phase in patients with a well tolerated dose-increase phase of treatment. The most prominent risk factor for systemic reactions was immunotherapy with honeybee extract.

Rush allergen specific immunotherapy protocol in feline atopic dermatitis: a pilot study of four cats.

PubMed

Trimmer, Ann M; Griffin, Craig E; Boord, Mona J; Rosenkrantz, Wayne S

2005-10-01

Rush immunotherapy has been shown to be as safe as conventional immunotherapy in canine atopic patients. Rush immunotherapy has not been reported in the feline atopic patient. The purpose of this pilot study was to determine a safe protocol for rush immunotherapy in feline atopic patients. Four atopic cats diagnosed by history, physical examination and exclusion of appropriate differential diagnoses were included in the study. Allergens were identified via liquid phase immunoenzymatic testing (VARL: Veterinary Allergy Reference Labs, Pasadena, CA). Cats were premedicated with 1.5 mg triamcinolone orally 24 and 2 h prior to first injection and 10 mg hydroxyzine PO 24, 12 and 2 h prior to first injection. An intravenous catheter was placed prior to first injection. Allergen extracts (Greer Laboratories, Lenoir, North Carolina) were all administered subcutaneously at increasing protein nitrogen units (pnu) every 30 minutes for 5 h to maintenance dose of 15,000 pnus ml-1. Vital signs were assessed every 15 minutes. Two cats developed mild pruritus and the subsequent injection was delayed 30 minutes. No changes in either cat's vital signs were noted, nor was there any further pruritus. All four cats successfully completed rush immunotherapy. Two cats developed a dermal swelling on the dorsal neck one week later. In these four cats, this protocol appeared to be a safe regimen to reach maintenance therapy. A larger sample of feline patients is needed to determine the incidence of adverse reactions and to follow the success of ASIT based upon this method of induction.

Patient knowledge, perceptions, expectations and satisfaction on allergen-specific immunotherapy: a survey.

PubMed

Baiardini, Ilaria; Puggioni, Francesca; Menoni, Stefania; Boot, Johan Diderik; Diamant, Zuzana; Braido, Fulvio; Canonica, Giorgio Walter

2013-03-01

Assessing patient's perspective provides useful information enabling a customized approach which has been advocated by current guidelines. In this multicentre cross-sectional study we evaluated personal viewpoints on allergen-specific immunotherapy (SIT) in patients treated with subcutaneous (SCIT) or sublingual (SLIT) immunotherapy. A survey of 28 questions assessing patient's knowledge, perceptions, expectations and satisfaction was developed by an expert panel and was applied by physicians from allergology centres in patients with respiratory allergy treated with SIT. Treating physicians independently reported their satisfaction level regarding SIT for each patient. Fully completed surveys from 434 patients (55.3% male; 66.7% poly-sensitized, 74% SLIT) were analysed. Mean duration of SIT was 2.5 years with different allergens. Most patients acquired their SIT knowledge from their physician (95%) and consequently, their physicians' opinion in their choice to start with SIT was important. Most patients perceived SIT to be safe and easy to integrate into their daily routine. The main motivations for SIT were its supposed potential to alter the course of the disease (45.7%), less need of (28.2%), or dissatisfaction with current pharmacotherapy (19.3%). Both patients' and physicians' satisfaction was high (VAS-scores 74/100 and 78/100, respectively) and showed a significant correlation (SCIT: r=0.612; SLIT: r=0.608). No major difference was found in patients' answers based on the level of education. In this real life study evaluating different aspects of patient's perspective on SIT, the majority of patients had an adequate level of knowledge, perceptions, expectations and satisfaction about SIT, which corresponded well with the physician's perceptions and satisfaction. Our data warrant the use of patient's perspectives on chronic SIT treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Non-injection routes for allergen immunotherapy: focus on sublingual immunotherapy.

PubMed

Passalacqua, Giovanni; Guerra, Laura; Pasquali, Mercedes; Canonica, Giorgio Walter

2006-01-01

Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.

Allergen-specific immunotherapy in horses with insect bite hypersensitivity: a double-blind, randomized, placebo-controlled study.

PubMed

Ginel, Pedro J; Hernández, Eduardo; Lucena, Rosario; Blanco, Beatriz; Novales, Manuel; Mozos, Elena

2014-02-01

Insect bite hypersensitivity (IBH) is a common cause of pruritus in horses, but there are few controlled studies on the efficacy of allergen-specific immunotherapy (ASIT). Atopic dermatitis and IBH can present with overlapping clinical signs; multiple insect and environmental allergens could be indicated in these horses to achieve effective hyposensitization. Although the success of ASIT using Culicoides spp. whole-body extracts is controversial, there are no controlled studies published that clearly show benefit from this form of therapy. The objective was to evaluate the efficacy of ASIT in horses with IBH using commercially available extracts and tests. Twenty horses with seasonal pruritus and positive intradermal reactions to a whole Culicoides extract. An enzyme-linked immunosorbent assay test (Allercept(®) ) was used to detect concurrent allergen-specific IgE for other insects and environmental allergens. The ASIT was formulated by adding the relevant serologically positive allergens to the Culicoides extract. After randomization, 10 horses received ASIT and the rest a placebo solution. Clinical response was assessed every 4 months during 1 year using a clinical scoring system based on the severity of four clinical signs at 10 different body regions. Horses were not stabled and, to minimize dropouts, an insect repellent was used weekly in both groups. Differences in clinical scores between groups were nonsignificant at any re-evaluation, while both groups improved to a similar extent, probably due to the insecticide treatment. Using commercially available extracts and tests, we could not demonstrate a beneficial effect of 1 year multiple ASIT in nonstabled horses with IBH. © 2013 ESVD and ACVD.

EAACI Guidelines on allergen immunotherapy: IgE-mediated food allergy.

PubMed

Pajno, G B; Fernandez-Rivas, M; Arasi, S; Roberts, G; Akdis, C A; Alvaro-Lozano, M; Beyer, K; Bindslev-Jensen, C; Burks, W; Ebisawa, M; Eigenmann, P; Knol, E; Nadeau, K C; Poulsen, L K; van Ree, R; Santos, A F; du Toit, G; Dhami, S; Nurmatov, U; Boloh, Y; Makela, M; O'Mahony, L; Papadopoulos, N; Sackesen, C; Agache, I; Angier, E; Halken, S; Jutel, M; Lau, S; Pfaar, O; Ryan, D; Sturm, G; Varga, E-M; van Wijk, R G; Sheikh, A; Muraro, A

2018-04-01

Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food allergen immunotherapy (FA-AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE-mediated Food Allergy, aims to provide evidence-based recommendations for active treatment of IgE-mediated food allergy with FA-AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post-discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA-AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post-discontinuation is also suggested, but not confirmed. Adverse events during FA-AIT have been frequently reported, but few subjects discontinue FA-AIT as a result of these. Taking into account the current evidence, FA-AIT should only be performed in research centers or in clinical centers with an extensive experience in FA-AIT. Patients and their families should be provided with information about the use of FA-AIT for IgE-mediated food allergy to allow them to make an informed decision about the therapy. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy

PubMed Central

Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

2008-01-01

Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients. PMID:18647321

Allergenicity, immunogenicity and dose-relationship of three intact allergen vaccines and four allergoid vaccines for subcutaneous grass pollen immunotherapy.

PubMed

Henmar, H; Lund, G; Lund, L; Petersen, A; Würtzen, P A

2008-09-01

Different vaccines containing intact allergens or chemically modified allergoids as active ingredients are commercially available for specific immunotherapy. Allergoids are claimed to have decreased allergenicity without loss of immunogenicity and this is stated to allow administration of high allergoid doses. We compared the allergenicity and immunogenicity of four commercially available chemically modified grass pollen allergoid products with three commercially available intact grass pollen allergen vaccines. The allergenicity was investigated with immunoglobulin (Ig)E-inhibition and basophil activation assays. Human T cell proliferation and specific IgG-titres following mouse immunizations were used to address immunogenicity. Furthermore, intact allergen vaccines with different contents of active ingredients were selected to study the influence of the allergen dose. In general, a lower allergenicity for allergen vaccines was clearly linked to a reduced immunogenicity. Compared with the vaccine with the highest amount of intact allergen, the allergoids caused reduced basophil activation as well as diminished immunogenicity demonstrated by reduced T cell activation and/or reduced induction of murine grass-specific IgG antibodies. Interestingly, intact allergen vaccines with lower content of active ingredient exhibited similarly reduced allergenicity, while immunogenicity was still higher or equal to that of allergoids. The low allergenicity observed for some allergoids was inherently linked to a significantly lower immunogenic response questioning the rationale behind the chemical modification into allergoids. In addition, the linkage between allergenicity, immunogenicity and dose found for intact allergen vaccines and the immunogen as well as allergenic immune responses observed for allergoids suggest that the modified allergen vaccines do not contain high doses of immunologically active ingredients.

[Specific immunotherapy with depigmented allergoids].

PubMed

Klimek, L; Thorn, C; Pfaar, O

2010-01-01

Specific immunotherapy is the only available causative treatment for IgE-mediated allergic conditions. The state of the art is treatment via the subcutaneous route with crude extracts in a water solution, with physically linked (semidepot) extracts or chemically modified semidepot extracts (allergoids). A relatively new purification method combines depigmentation followed by polymerization with glutaraldehyde. This modification results in increased tolerance with a reduction in both local and systemic adverse effects. As controlled clinical trials have shown, the effectiveness is comparable to that of specific immunotherapy with crude allergen extracts. Recent data suggest that the modified polymerized allergoids allow a safe rush titration in a few days or even in 1 day (ultra-rush titration).

Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma

PubMed Central

Alessandrini, Francesca; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Russkamp, Dennis; Chaker, Adam; Ollert, Markus; Gutermuth, Jan; Schmidt-Weber, Carsten B.

2017-01-01

Background Allergen-specific immunotherapy (AIT) is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma. Objective Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways. Methods In C57BL/6J mice, a model of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro. Results AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells. Conclusions This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis. PMID:28570653

Improved efficacy of allergen-specific immunotherapy by JAK inhibition in a murine model of allergic asthma.

PubMed

Aguilar-Pimentel, Antonio; Graessel, Anke; Alessandrini, Francesca; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Russkamp, Dennis; Chaker, Adam; Ollert, Markus; Blank, Simon; Gutermuth, Jan; Schmidt-Weber, Carsten B

2017-01-01

Allergen-specific immunotherapy (AIT) is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma. Our aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways. In C57BL/6J mice, a model of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro. AIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells. This proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis.

Non-adherence to subcutaneous allergen immunotherapy: inadequate health insurance coverage is the leading cause.

PubMed

Vaswani, Ravi; Garg, Akshay; Parikh, Leena; Vaswani, Surender

2015-09-01

To sustain the long-lasting beneficial effects of subcutaneous allergen immunotherapy, the recommended duration of treatment is 3 to 5 years. Nevertheless, many patients discontinue allergy injections prematurely and therefore might not appreciate the full therapeutic benefit. To examine factors leading to premature discontinuation of subcutaneous allergen immunotherapy (cessation before completion of the recommended duration). Patients who discontinued immunotherapy before the completion of the prescribed duration and received their final injection from January 2008 through September 2013 were contacted to identify the reason for stopping the allergy injections. Phase of treatment (escalation or maintenance) was used to measure the duration of treatment at the time of cessation and patients were grouped accordingly. The study population consisted of 555 patients with allergic rhinitis and/or asthma who terminated immunotherapy prematurely. Two hundred thirteen (38%) were men and 342 (62%) were women. The following reasons were cited by patients for non-adherence to immunotherapy: requirement of copayment for allergy injections and/or payment for allergen extract by their health insurer (40%); inconvenience of travel (15%); change of residence (8%); concurrent health problems (5%); patient-perceived ineffectiveness (4%); patient-perceived lack of need to continue immunotherapy (2%); adverse effects from injection (local reaction 1%; systemic allergic reaction 0.5%); and trial of alternative medicine (0.1%). The remaining 24.4% did not provide a reason for discontinuation. Of the various factors, inadequate reimbursement for allergen extract and allergy injections by health insurers is the most common reason cited for non-adherence to subcutaneous allergen immunotherapy. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chinese Guideline on allergen immunotherapy for allergic rhinitis

PubMed Central

Bao, Yixiao; Chen, Jianjun; Cheng, Lei; Guo, Yinshi; Hong, Suling; Kong, Weijia; Lai, He; Li, Houyong; Li, Huabin; Li, Jing; Li, Tianying; Lin, Xiaoping; Liu, Shixi; Liu, Zheng; Lou, Hongfei; Meng, Juan; Qiu, Qianhui; Shen, Kunling; Tang, Wei; Tao, Zezhang; Wang, Chengshuo; Wang, Xiangdong; Wei, Qingyu; Xiang, Li; Xie, Hua; Xu, Yu; Zhang, Gehua; Zhang, Yuan; Zheng, Yiwu; Zhi, Yuxiang; Chen, Dehua; Hong, Haiyu; Li, Quansheng; Liu, Lin; Meng, Yifan; Wang, Nan; Wang, Yihui; Zhou, Yue

2017-01-01

The present document is based on a consensus reached by a panel of experts from Chinese Society of Allergy (CSA) and Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G). Allergen immunotherapy (AIT), has increasingly been used as a treatment for allergic rhinitis (AR) globally, as it has been shown to provide a long-term effect in improving nasal and ocular symptoms, reducing medication need, and improving quality of life. AIT is currently the only curative intervention that can potentially modify the immune system in individuals suffering from AR and prevent the development of new sensitization and the progression of disease from AR to asthma. Although the use of AIT is becoming more acceptable in China, to date no AR immunotherapy guideline from China is available for use by the international community. This document has thus been produced and covers the main aspects of AIT undertaken in China; including selection of patients for AIT, the allergen extracts available on the Chinese market, schedules and doses of allergen employed in different routes of AIT, assessment of effect and safety, patients’ administration and follow-up, and management of adverse reactions. The Chinese guideline for AR immunotherapy will thus serve as a reference point by doctors, healthcare professionals and organizations involved in the AIT of AR in China. Moreover, this guideline will serve as a source of information for the international community on AIT treatment strategies employed in China. PMID:29268533

Greater Real-Life Diagnostic Efficacy of Allergen Molecule-Based Diagnosis for Prescription of Immunotherapy in an Area with Multiple Pollen Exposure.

PubMed

Saltabayeva, Ulbosin; Garib, Victoria; Morenko, Marina; Rosenson, Rafail; Ispayeva, Zhanat; Gatauova, Madina; Zulus, Loreta; Karaulov, Alexander; Gastager, Felix; Valenta, Rudolf

2017-01-01

Allergen molecule-based diagnosis has been suggested to facilitate the identification of disease-causing allergen sources and the prescription of allergen-specific immunotherapy (AIT). The aim of the current study was to compare allergen molecule-based IgE serology with allergen extract-based skin testing for the identification of the disease-causing allergen sources. The study was conducted in an area where patients are exposed to pollen from multiple sources (trees, grasses, and weeds) at the same time to compare the diagnostic efficiency of the 2 forms of diagnosis. Patients from Astana, Kazakhstan, who suffered from pollen-induced allergy (n = 95) were subjected to skin prick testing (SPT) with a local panel of tree pollen, grass pollen, and weed pollen allergen extracts and IgE antibodies specific for marker allergen molecules (nArt v 1, nArt v 3, rAmb a 1, rPhl p 1, rPhl p 5, rBet v 1) were measured by ImmunoCAP. Direct and indirect costs for diagnosis based on SPT and marker allergen-based IgE serology as well as direct costs for immunotherapy depending on SPT and serological test results were calculated. The costs for SPT-based diagnosis per patient were lower than the costs for allergen molecule-based IgE serology. However, allergen molecule-based serology was more precise in detecting the disease-causing allergen sources. A lower number of immunotherapy treatments (n = 119) was needed according to molecular diagnosis as compared to extract-based diagnosis (n = 275), which considerably reduced the total costs for diagnosis and for a 3-year treatment from EUR 1,112.30 to 521.77 per patient. The results from this real-life study show that SPT is less expensive than allergen molecule-based diagnostic testing, but molecular diagnosis allowed more precise prescription of immunotherapy which substantially reduced treatment costs and combined costs for diagnosis and treatment. © 2017 The Author(s) Published by S. Karger AG, Basel.

Greater Real-Life Diagnostic Efficacy of Allergen Molecule-Based Diagnosis for Prescription of Immunotherapy in an Area with Multiple Pollen Exposure

PubMed Central

Saltabayeva, Ulbosin; Garib, Victoria; Morenko, Marina; Rosenson, Rafail; Ispayeva, Zhanat; Gatauova, Madina; Zulus, Loreta; Karaulov, Alexander; Gastager, Felix; Valenta, Rudolf

2017-01-01

Background Allergen molecule-based diagnosis has been suggested to facilitate the identification of disease-causing allergen sources and the prescription of allergen-specific immunotherapy (AIT). The aim of the current study was to compare allergen molecule-based IgE serology with allergen extract-based skin testing for the identification of the disease-causing allergen sources. The study was conducted in an area where patients are exposed to pollen from multiple sources (trees, grasses, and weeds) at the same time to compare the diagnostic efficiency of the 2 forms of diagnosis. Methods Patients from Astana, Kazakhstan, who suffered from pollen-induced allergy (n = 95) were subjected to skin prick testing (SPT) with a local panel of tree pollen, grass pollen, and weed pollen allergen extracts and IgE antibodies specific for marker allergen molecules (nArt v 1, nArt v 3, rAmb a 1, rPhl p 1, rPhl p 5, rBet v 1) were measured by ImmunoCAP. Direct and indirect costs for diagnosis based on SPT and marker allergen-based IgE serology as well as direct costs for immunotherapy depending on SPT and serological test results were calculated. Results The costs for SPT-based diagnosis per patient were lower than the costs for allergen molecule-based IgE serology. However, allergen molecule-based serology was more precise in detecting the disease-causing allergen sources. A lower number of immunotherapy treatments (n = 119) was needed according to molecular diagnosis as compared to extract-based diagnosis (n = 275), which considerably reduced the total costs for diagnosis and for a 3-year treatment from EUR 1,112.30 to 521.77 per patient. Conclusions The results from this real-life study show that SPT is less expensive than allergen molecule-based diagnostic testing, but molecular diagnosis allowed more precise prescription of immunotherapy which substantially reduced treatment costs and combined costs for diagnosis and treatment. PMID:28654920

[Comparative analysis of the effectiveness of different methods of allergen-specific immunotherapy of bronchial asthma].

PubMed

Besh, O M; Radchenko, O M

2014-01-01

The article presents a comparative analysis of the effectiveness of different methods of allergen- specific immunotherapy of light and medium- severe persistent asthma using a special questionnaire of quality of life of patients. It is noted that traditional survey methods involving physical, laboratory and instrumental studies do not give an opportunity to get a complete assessment of the patient, because it does not provide information about its psychological and social adjustment to illness. It is proved that a comprehensive description of the physical, psychological and social components of the patient's condition allows the assessment of its quality of life. Established that chronic asthma affects the quality of life of patients, making certain psychological, emotional and social problems. The disease limits the vitality of patients, their performance, leading to social exclusion and psychological discomfort. Studies have shown that holding the base of treatment with different ways ASIT it positively affects the quality of life for patients. However, treatment of sublingual allergen patients perceive better adherence to such treatment was higher.

Specific immunotherapy ameliorates ulcerative colitis.

PubMed

Cai, Min; Zeng, Lu; Li, Lin-Jing; Mo, Li-Hua; Xie, Rui-Di; Feng, Bai-Sui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

2016-01-01

Hypersensitivity reaction to certain allergens plays a role in the pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the effect of specific immunotherapy in a group of IBD patients. Patients with both ulcerative colitis (UC) and food allergy were recruited into this study. Food allergy was diagnosed by skin prick test and serum specific IgE. The patients were treated with specific immunotherapy (SIT) and Clostridium butyricum (CB) capsules. After treating with SIT and CB, the clinical symptoms of UC were markedly suppressed as shown by reduced truncated Mayo scores and medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor necrosis factor (TNF)-α were also suppressed. Treating with SIT alone or CB alone did not show appreciable improvement of the clinical symptoms of UC. UC with food allergy can be ameliorated by administration with SIT and butyrate-production probiotics.

The anti-vaccination movement and resistance to allergen-immunotherapy: a guide for clinical allergists.

PubMed

Behrmann, Jason

2010-09-15

Despite over a century of clinical use and a well-documented record of efficacy and safety, a growing minority in society questions the validity of vaccination and fear that this common public health intervention is the root-cause of severe health problems. This article questions whether growing public anti-vaccine sentiments might have the potential to spill-over into other therapies distinct from vaccination, namely allergen-immunotherapy. Allergen-immunotherapy shares certain medical vernacular with vaccination (e.g., allergy shots, allergy vaccines), and thus may become "guilty by association" due to these similarities. Indeed, this article demonstrates that anti-vaccine websites have begun unduly discrediting this allergy treatment regimen. Following an explanation of the anti-vaccine movement, the article aims to provide guidance on how clinicians can respond to patient fears towards allergen-immunotherapy in the clinical setting. This guide focuses on the provision of reliable information to patients in order to dispel misconceived associations between vaccination and allergen-immunotherapy, and the discussion of the risks and benefits of both therapies in order to assist patients in making autonomous decisions about their choice of allergy treatment.

The anti-vaccination movement and resistance to allergen-immunotherapy: a guide for clinical allergists

PubMed Central

2010-01-01

Despite over a century of clinical use and a well-documented record of efficacy and safety, a growing minority in society questions the validity of vaccination and fear that this common public health intervention is the root-cause of severe health problems. This article questions whether growing public anti-vaccine sentiments might have the potential to spill-over into other therapies distinct from vaccination, namely allergen-immunotherapy. Allergen-immunotherapy shares certain medical vernacular with vaccination (e.g., allergy shots, allergy vaccines), and thus may become "guilty by association" due to these similarities. Indeed, this article demonstrates that anti-vaccine websites have begun unduly discrediting this allergy treatment regimen. Following an explanation of the anti-vaccine movement, the article aims to provide guidance on how clinicians can respond to patient fears towards allergen-immunotherapy in the clinical setting. This guide focuses on the provision of reliable information to patients in order to dispel misconceived associations between vaccination and allergen-immunotherapy, and the discussion of the risks and benefits of both therapies in order to assist patients in making autonomous decisions about their choice of allergy treatment. PMID:20843332

Kinetics and dynamic evaluation of specific immunotherapy.

PubMed

Pereira, C; Botelho, F; Tavares, B; Lourenço, C; Baeta, C; Palma-Carlos, A G; Lima, J; Chieira, C

2004-12-01

Specific immunotherapy (SIT) is frequently used in the treatment of allergic diseases. However, the mechanisms by which SIT achieves clinical improvement remained unclear. We decided to study the in vivo kinetics of this therapy, using a nuclear medicine approach (leukocytes labelled with 99mTc-HMPAO) in patients on maintenance doses of specific immunotherapy with confirmed clinical efficacy. We studied 13 allergic patients grouped according to different treatment schedules: subcutaneous aqueous allergenic extract (3 latex and 2 hymenoptera venom), subcutaneous depot extract (2 house dust mite and 2 pollens), subcutaneous modified allergens (2 pollens), sublingual extract (2 house dust mites). The control group included two allergic patients submitted to subcutaneous injections of bacterial extract (1 patient--positive control), and aqueous solution (1 patient). At the same time that the therapeutic allergen was administered subcutaneously, the autologous labelled white cells were injected intravenously in a peripheral vein in the contralateral arm. A thoracic dynamic acquisition of 60 mins, 64x64 matrix, 2 frame/min, in anterior view was performed. Static acquisition for 256x256 matrix, during 5 mins each at 60, 90, 120, 180, 240, 300 and 360 mins after the administration of the radiolabelled leukocytes, in thoracic (anterior and posterior), and abdominal view were performed. During the examination, the local erythema was monitored. A similar procedure was undertaken for Sublingual administration of immunotherapy. The inflammatory activity at the site of SIT injection (aqueous depot extract) started in the first hour and the increase was time related. For modified allergen extract and sublingual SIT the activity was present since the beginning of the administration. The ascendant lymphatic drainage, which was directed to the homolateral axillary region, to the lymphoid tissue of the upper mediastinum and to the anterior region of the neck began earlier. Thoracic

[Serious systemic adverse events associated with allergen-specific immunotherapy in children with asthma].

PubMed

Dai, Li; Huang, Ying; Wang, Ying; Han, Huan-Li; Li, Qu-Bei; Jiang, Yong-Hui

2014-01-01

To retrospectively assess serious systemic adverse effects of standardized dust-mite vaccine in children with asthma. Medical records of 704 children (5-17 years in age) with asthma between January, 2005 and December, 2011 were reviewed. Serious systemic adverse events following treatment with a standardized dust-mite vaccine in these children were analyzed. A total of 336 systemic adverse reactions were observed in 17.0% (120/704) of the patients analyzed of these adverse reactions, 18 (5.4%) were serious (level 3), 318 (94.6%) were not serious (below level 3), and no single case of anaphylactic shock (level 4) was recorded. Systemic adverse events occurred most frequently in the 5 to 11-year age group and in the summer season (from June to August). In the 18 severe cases, the peak expiratory flow (PEF) dropped by 20% immediately after the vaccine injection, and other major clinical symptoms included cough, wheezing and urticaria. All children with serious systemic adverse effects were given inhaled hormone and atomized short-acting beta agonists, oral antihistamines, intravenous dexamethasone and/or intramuscular adrenaline. After these treatments, the clinical symptoms were significantly relieved. The rate of serious systemic adverse events following allergen-specific immunotherapy is relatively low in children with allergic asthma. Conventional medications are effective in managing these immunotherapy-associated adverse events.

Time course of serum inhibitory activity for facilitated allergen-IgE binding during bee venom immunotherapy in children.

PubMed

Varga, E-M; Francis, J N; Zach, M S; Klunker, S; Aberer, W; Durham, S R

2009-09-01

Immunotherapy for bee venom allergy is effective and provides long-term protection. Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. Following grass pollen immunotherapy, elevation of antigen-specific IgG4 is accompanied by increases in IgG-dependent serum inhibitory activity for IgE-facilitated binding of allergen-IgE complexes to B cells. As this 'functional' assay of inhibitory antibodies may be more predictive of clinical efficacy, we investigated the time course of serum inhibitory activity for IgE-facilitated antigen binding during venom immunotherapy (VIT) in children and following 2 years of VIT withdrawal. Ten bee venom-allergic children (mean age: 9.3 years; m/f, 7/3) with moderate to severe allergic reactions to bee stings received VIT. A separate group of seven children (mean age: 14 years; m/f, 5/2) were investigated 2 years after VIT withdrawal. Ten age- and gender-matched children served as non-allergic controls. Allergen-specific serum IgG4 and IgE levels were measured by ELISA at baseline, after 2 years of VIT and 2 years after VIT withdrawal. Serum inhibitory activity was assessed using the facilitated-allergen binding (FAB) assay. Sera obtained during VIT significantly inhibited allergen-IgE binding to B-cells (pre-treatment=104+/-23%; 2 years=46+/-15%; P<0.001) when compared with sera obtained after treatment withdrawal and sera from normal controls. In parallel to FAB inhibition during VIT, significantly higher IgG4 levels were noted after immunotherapy (pre-treatment=8.6+/-2.3 AU; 2 years=26.7+/-3.5 AU; P<0.001) compared with those observed after withdrawal and in the controls. In contrast, progressively lower IgE concentrations were observed compared with pre-treatment (44+/-7 AU) in sera obtained after 2 years of VIT (25+/-5 AU; P<0.01) and 2 years following the withdrawal of VIT (10+/-3 AU; P<0.05). In contrast to grass pollen immunotherapy, the persistent decline in venom-specific IgE levels

Allergen immunotherapy in people, dogs, cats and horses - differences, similarities and research needs.

PubMed

Mueller, R S; Jensen-Jarolim, E; Roth-Walter, F; Marti, E; Janda, J; Seida, A A; DeBoer, D

2018-04-19

In human patients with seasonal allergic rhinoconjunctivitis sensitized to grass pollen, the first successful allergen immunotherapy (AIT) was reported in 1911. Today, immunotherapy is an accepted treatment for allergic asthma, allergic rhinitis and hypersensitivities to insect venom. AIT is also used for atopic dermatitis and recently for food allergy. Subcutaneous, epicutaneous, intralymphatic, oral and sublingual protocols of AIT exist. In animals, most data are available in dogs where subcutaneous AIT is an accepted treatment for atopic dermatitis. Initiating a regulatory response and a production of "blocking" IgG antibodies with AIT are similar mechanisms in human beings and dogs with allergic diseases. Although subcutaneous immunotherapy is used for atopic dermatitis in cats, data for its efficacy is sparse. There is some evidence for successful treatment of feline asthma with AIT. In horses, most studies evaluate the effect of AIT on insect hypersensitivity with conflicting results though promising pilot studies have demonstrated the prophylaxis of insect hypersensitivity with recombinant antigens of biting midges (Culicoides spp.). Optimising AIT using allergoids, peptide immunotherapy, recombinant allergens and new adjuvants with the different administration types of allergen extracts hopefully will further improve compliance and efficacy of this proven treatment modality. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

PubMed

Kiel, Menno A; Röder, Esther; Gerth van Wijk, Roy; Al, Maiwenn J; Hop, Wim C J; Rutten-van Mölken, Maureen P M H

2013-08-01

Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent. Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

State of the art on food allergen immunotherapy: oral, sublingual, and epicutaneous.

PubMed

Jones, Stacie M; Burks, A Wesley; Dupont, Christophe

2014-02-01

IgE-mediated food allergy is a global health problem that affects millions of persons and affects every aspect of life for the patient. Developing effective treatment strategies to augment current practice standards of strict dietary avoidance of antigens and availability of self-injectable epinephrine has been a major focus of research teams, advocacy groups, funding agencies, and patients and their families. Significant progress has been made through the development of allergen-specific immunotherapy encompassing 3 major forms of treatment: oral, sublingual, and epicutaneous immunotherapy. These therapies are in various stages of clinical investigation, with some successes noted in clinical outcomes and modulation of immune mechanisms toward effective therapy. Here we review recent progress and areas of concern for the role of these forms of immunotherapy as an emerging treatment for food allergy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Patient initiation and persistence with allergen immunotherapy.

PubMed

Anolik, Robert; Schwartz, Ann Marie; Sajjan, Shiva; Allen-Ramey, Felicia

2014-07-01

Allergen immunotherapy (AIT) is advised for patients with allergic rhinitis who remain symptomatic despite the use of pharmacotherapy and allergen avoidance. Several factors influence the decision to initiate and complete the AIT regimen. To evaluate patient initiation and persistence with subcutaneous and sublingual immunotherapies (SCIT and SLIT) according to physician recommendation. A retrospective review of electronic health records of patients with allergic rhinitis for whom AIT was recommended was conducted in a large private allergy practice in Pennsylvania. Of 8,790 patients advised to consider AIT, 36.2% initiated AIT (57% adults, 43% children); 78% chose SCIT and 22% chose SLIT drops. Election of AIT was significantly associated with select comorbidities, specifically chronic sinusitis (8.1% for AIT vs 10% for no AIT), allergic conjunctivitis (12.5% for AIT vs 18.5% for no AIT), and asthma (33.8% for AIT vs 37.4% for no AIT; P < .05). Choice of SCIT vs SLIT drops was significantly associated with older age, female sex, select comorbidities, and more allergy medications at initiation (P < .05). Of adults, 30.2% completed at least 3 years of recommended treatment. Median time on treatment was longer for adults on SCIT vs SLIT drops (3 vs 1.6 years). Similarly, 35.4% of children completed treatment, with a longer median time on treatment for SCIT (4.7 years) vs SLIT drops (3.5 years). A minority of patients initiated AIT according to allergist recommendation and a subset of these patients completed therapy. AIT might be an underused option that could benefit patients unable to manage allergic rhinitis symptoms by other means. clinicaltrials.gov Identifier: NCT01549340. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia).

PubMed

Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante

2017-01-01

Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed ( Ambrosia artemisiifolia ) is on the rise throughout Europe, having a significant negative impact on the patients' and their family's quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success.

A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen (Ambrosia artemisiifolia)

PubMed Central

Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante

2017-01-01

Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed (Ambrosia artemisiifolia) is on the rise throughout Europe, having a significant negative impact on the patients’ and their family’s quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success. PMID:28243068

A review of allergoid immunotherapy: is cat allergy a suitable target?

PubMed

Nguyen, Nhung T; Raskopf, Esther; Shah-Hosseini, Kija; Zadoyan, Gregor; Mösges, Ralph

2016-01-01

To modify the course of allergy, different types of specific allergen immunotherapy have been developed such as sublingual immunotherapy and subcutaneous immunotherapy with native allergens or subcutaneous immunotherapy with polymerized allergoids. However, the optimal specific immunotherapy, especially for cat allergy, remains undetermined. Few studies investigating immunotherapy in cat allergy have been published, and the risk of serious adverse reactions and systemic reactions has often been an important issue. Monomeric allergoids have lower allergenic potential while their immunogenicity remains constant, resulting in excellent safety with notable efficacy. Specific immunotherapy with monomeric allergoids could, therefore, be of high value, especially in cat allergy as well as other types of allergy, and bring relief to a great community of patients.

Factors influencing the quality of Myrmecia pilosula (Jack Jumper) ant venom for use in in vitro and in vivo diagnoses of allergen sensitization and in allergen immunotherapy.

PubMed

Wanandy, T; Dwyer, H E; McLean, L; Davies, N W; Nichols, D; Gueven, N; Brown, S G A; Wiese, M D

2017-11-01

Allergen immunotherapy uses pharmaceutical preparations derived from naturally occurring source materials, which contain water-soluble allergenic components responsible for allergic reactions. The success of in vivo and in vitro diagnoses in allergen sensitization and allergen immunotherapy largely depends on the quality, composition and uniformity of allergenic materials used to produce the active ingredients, and the formulation employed to prepare finished products. We aimed to examine the factors influencing batch-to-batch consistency of Jack Jumper (Myrmecia pilosula) ant venom (JJAV) in the form of active pharmaceutical ingredient (AI) and informed whether factors such as temperature, artificial light and container materials influence the quality of JJAV AIs. We also aimed to establish handling and storage requirements of JJAV AIs to ensure preservation of allergenic activities during usage in the diagnosis of allergen sensitization and in allergen immunotherapy. The quality and consistency of JJAV AIs were analysed using a combination of bicinchoninic acid assay for total protein quantification, HPLC-UV for JJAV allergen peptides quantification, ELISA inhibition for total allergenic potency, SDS-PAGE, AU-PAGE and immunoblot for qualitative assessment of JJAV components, and Limulus Amebocyte Lysate assay for the quantification of endotoxin concentration. API-ZYM and Zymogram assays were used to probe the presence of enzymatic activities in JJAV. Pharmaceutical-grade JJAV for allergen immunotherapy has good batch-to-batch consistency. Temporary storage at 4°C and light exposure do not affect the quality of JJAV. Exposure to temperature above 40°C degrades high MW allergens in JJAV. Vials containing JJAV must be stored frozen and in upright position during long-term storage. We have identified factors, which can influence the quality and consistency of JJAV AIs, and provided a framework for appropriate handling, transporting and storage of JJAV to be used

Sialylated Fetuin-A as a candidate predictive biomarker for successful grass pollen allergen immunotherapy.

PubMed

Caillot, Noémie; Bouley, Julien; Jain, Karine; Mariano, Sandrine; Luce, Sonia; Horiot, Stéphane; Airouche, Sabi; Beuraud, Chloé; Beauvallet, Christian; Devillier, Philippe; Chollet-Martin, Sylvie; Kellenberger, Christine; Mascarell, Laurent; Chabre, Henri; Batard, Thierry; Nony, Emmanuel; Lombardi, Vincent; Baron-Bodo, Véronique; Moingeon, Philippe

2017-09-01

Eligibility to immunotherapy is based on the determination of IgE reactivity to a specific allergen by means of skin prick or in vitro testing. Biomarkers predicting the likelihood of clinical improvement during immunotherapy would significantly improve patient selection. Proteins were differentially assessed by using 2-dimensional differential gel electrophoresis and label-free mass spectrometry in pretreatment sera obtained from clinical responders and nonresponders within a cohort of 82 patients with grass pollen allergy receiving sublingual immunotherapy or placebo. Functional studies of Fetuin-A (FetA) were conducted by using gene silencing in a mouse asthma model, human dendritic cell in vitro stimulation assays, and surface plasmon resonance. Analysis by using quantitative proteomics of pretreatment sera from patients with grass pollen allergy reveals that high levels of O-glycosylated sialylated FetA isoforms are found in patients exhibiting a strong decrease in rhinoconjunctivitis symptoms after sublingual immunotherapy. Although FetA is involved in numerous inflammatory conditions, its potential role in allergy is unknown. In vivo silencing of the FETUA gene in BALB/c mice results in a dramatic upregulation of airway hyperresponsiveness, lung resistance, and T H 2 responses after allergic sensitization to ovalbumin. Both sialylated and nonsialytated FetA bind to LPS, but only the former synergizes with LPS and grass pollen or mite allergens to enhance the Toll-like receptor 4-mediated proallergic properties of human dendritic cells. As a reflection of the patient's inflammatory status, pretreatment levels of sialylated FetA in the blood are indicative of the likelihood of clinical responses during grass pollen immunotherapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Consolidated Standards of Reporting Trials (CONSORT) Statement applied to allergen-specific immunotherapy with inhalant allergens: a Global Allergy and Asthma European Network (GA(2)LEN) article.

PubMed

Bousquet, Philippe J; Calderón, Moisés A; Demoly, Pascal; Larenas, Désirée; Passalacqua, Giovanni; Bachert, Claus; Brozek, Jan; Canonica, G Walter; Casale, Thomas; Fonseca, Joao; Dahl, Ronald; Durham, Stephen R; Merk, Hans; Worm, Margitta; Wahn, Ulrich; Zuberbier, Torsten; Schünemann, Holger J; Bousquet, Jean

2011-01-01

Randomized trials provide evidence to inform treatment decisions. The Consolidated Standards of Reporting Trials (CONSORT) Statement is a set of recommendations for the reporting of trials. We sought to assess the quality of reporting allergen-specific immunotherapy trials according to CONSORT criteria. The reporting of the procedure, randomization, dropouts, strict conduct of intention-to-treat (ITT) analysis, and sample size calculation according to CONSORT were assessed in the 46 subcutaneous and 48 sublingual immunotherapy (SLIT) blind, placebo-controlled randomized trials published between 1996 and 2009 in English. One subcutaneous immunotherapy (2.2%) and 3 SLIT (6.6%) trials met CONSORT Statement criteria. These were used for the registration of sublingual tablets to the European Medicines Agency. In subcutaneous immunotherapy, 16 (35%) studies reported a CONSORT flow chart, and 12 (26%) provided a description of dropouts. Adequate randomization was reported in 9 (35%) studies, and incomplete randomization was reported in 15 (33%). Power analysis was reported in 15 (33%) studies. In SLIT, 20 (42%) studies reported a CONSORT flow chart, and 16 (32%) a description of dropouts. ITT analysis was carried out in 1 (2.2%) SLIT study, and a modified ITT analysis was used in 1 (2.2%) subcutaneous immunotherapy study and 2 (4.4%) SLIT studies. Adequate randomization was reported in 6 (12%) studies, and incomplete randomization was reported in 16 (32%). Power analysis was reported in 15 (27%) studies. As in other areas of medicine, the quality of reporting of most immunotherapy trials is low, and only 4.2% of SLIT randomized controlled trials met all of the criteria of the CONSORT Statement. Use of the CONSORT criteria should be encouraged. Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy.

PubMed

Sturm, G J; Varga, E-M; Roberts, G; Mosbech, H; Bilò, M B; Akdis, C A; Antolín-Amérigo, D; Cichocka-Jarosz, E; Gawlik, R; Jakob, T; Kosnik, M; Lange, J; Mingomataj, E; Mitsias, D I; Ollert, M; Oude Elberink, J N G; Pfaar, O; Pitsios, C; Pravettoni, V; Ruëff, F; Sin, B A; Agache, I; Angier, E; Arasi, S; Calderón, M A; Fernandez-Rivas, M; Halken, S; Jutel, M; Lau, S; Pajno, G B; van Ree, R; Ryan, D; Spranger, O; van Wijk, R G; Dhami, S; Zaman, H; Sheikh, A; Muraro, A

2018-04-01

Hymenoptera venom allergy is a potentially life-threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic-allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life-threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H 1 -antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence-based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta-analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom-allergic children and adults to prevent further moderate-to-severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence-based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Allergen immunotherapy with heat-killed Listeria monocytogenes alleviates peanut and food-induced anaphylaxis in dogs.

PubMed

Frick, O L; Teuber, S S; Buchanan, B B; Morigasaki, S; Umetsu, D T

2005-02-01

Heat-killed Listeria monocytogenes (HKL) potently stimulates interferon (IFN)-gamma production in CD4 T-lymphocytes, and when used as adjuvant for immunotherapy, reduces immunoglobulin (Ig)E production and reverses established allergen-induced airway hyperreactivity (AHR) in a murine model of asthma. We asked if such treatment could decrease established peanut-induced anaphylaxis or cow's milk-induced food allergy in highly food-allergic dogs. We therefore studied four 4-year-old atopic colony dogs extremely allergic to peanut (Group I), as well as five 7-year-old dogs very allergic to wheat, milk and other foods (Group II). All dogs experienced marked allergic symptoms, including vomiting and diarrhea on oral challenge with the relevant foods. The dogs were then vaccinated once subcutaneously with peanut or milk and wheat with HKL emulsified in incomplete Freund's adjuvant. Following vaccination of the allergic dogs with HKL and allergen, oral challenges with peanut (Group I) or milk (Group II) elicited only minor or no symptoms. In addition, skin test end-point titrations showed marked reductions for >10 weeks after treatment, and levels of Ara h 1-specific IgE in serum of peanut sensitive dogs, as demonstrated by immunoblotting, were greatly reduced by treatment with HKL plus peanut allergen. Thus, HKL plus allergen treatment markedly improved established food allergic responses in dogs, suggesting that such an immunotherapy strategy in humans might greatly improve individuals with food allergy and anaphylaxis.

Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project.

PubMed

Bonertz, A; Roberts, G; Slater, J E; Bridgewater, J; Rabin, R L; Hoefnagel, M; Timon, M; Pini, C; Pfaar, O; Sheikh, A; Ryan, D; Akdis, C; Goldstein, J; Poulsen, L K; van Ree, R; Rhyner, C; Barber, D; Palomares, O; Pawankar, R; Hamerlijnk, D; Klimek, L; Agache, I; Angier, E; Casale, T; Fernandez-Rivas, M; Halken, S; Jutel, M; Lau, S; Pajno, G; Sturm, G; Varga, E M; Gerth van Wijk, R; Bonini, S; Muraro, A; Vieths, S

2018-04-01

Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Specific allergen immunotherapy for the treatment of atopic eczema: a Cochrane systematic review.

PubMed

Tam, H H; Calderon, M A; Manikam, L; Nankervis, H; Núñez, I G; Williams, H C; Durham, S R; Boyle, R J

2016-09-01

Specific allergen immunotherapy (SIT) is an effective allergy treatment, but it is unclear whether SIT is effective for atopic eczema (AE). We undertook a systematic review to assess SIT efficacy and safety for treating AE. We searched databases, ongoing clinical trials registers, and conference proceedings up to July 2015. Randomized controlled trials (RCTs) of SIT using standardized allergen extracts, compared with placebo/control, for treating AE in patients with allergic sensitization were eligible. We identified 12 eligible trials with 733 participants. Interventions included subcutaneous (six trials), sublingual (four trials), oral or intradermal SIT in children/adults allergic to house dust mite (10 trials), grass pollen or other inhalants. Risk of bias was moderate, with high loss to follow-up and nonblinding as the main concerns. For our primary outcomes, three studies (208 participants) reported no significant difference - patient-reported global disease severity improvement RR 0.75 (95% CI 0.45, 1.26); and eczema symptoms mean difference -0.74 on a 20-point scale (95% CI -1.98, 0.50). Two studies (85 participants) reported a significant difference - SIT improved global disease severity RR 2.85 (95% CI 1.02, 7.96); and itch mean difference -4.20 on a 10-point scale (95% CI -3.69, -4.71). Meta-analysis was limited due to extreme statistical heterogeneity. For some secondary outcomes, meta-analyses showed benefits for SIT, for example investigator-rated improvement in eczema severity RR 1.48 (95% CI 1.16, 1.88; six trials, 262 participants). We found no evidence of adverse effects. The overall quality of evidence was low. We found no consistent evidence that SIT is effective for treating AE, but due to the low quality of evidence further research is needed to establish whether SIT has a role in AE treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recombinant allergens

PubMed Central

Jutel, Marek; Solarewicz-Madejek, Katarzyna; Smolinska, Sylwia

2012-01-01

Allergen specific immunotherapy (SIT) is the only known causative treatment of allergic diseases. Recombinant allergen-based vaccination strategies arose from a strong need to both to improve safety and enhance efficacy of SIT. In addition, new vaccines can be effective in allergies including food allergy or atopic dermatitis, which poorly respond to the current treatment with allergen extracts. A number of successful clinical studies with both wild-type and hypoallergenic derivatives of recombinant allergens vaccines have been reported for the last decade. They showed high efficacy and safety profile as well as very strong modulation of T and B cell responses to specific allergens. PMID:23095874

Anti-Interleukin-9 Antibody Increases the Effect of Allergen-Specific Immunotherapy in Murine Allergic Rhinitis.

PubMed

Shin, Ji Hyeon; Kim, Do Hyun; Kim, Boo Young; Kim, Sung Won; Hwang, Se Hwan; Lee, Joohyung; Kim, Soo Whan

2017-05-01

Interleukin (IL)-9 induces allergic responses; however, the roles of anti-IL-9 antibody in the induction of tolerance remain unclear. This study investigated the effects of anti-IL-9 antibody on oral tolerance (OT) in a mouse model of allergic rhinitis (AR). BALB/c mice were divided into 4 groups: the control, AR, OT, and OT with anti-IL-9 antibody (OT+IL9AB) groups. Ovalbumin (OVA) was used for sensitization and challenge. Mice in the OT and OT+IL9AB groups were fed OVA for immunotherapy. During immunotherapy, OT+IL9AB mice were injected with anti-IL-9 antibody. Allergic symptoms, tissue eosinophil counts, and serum OVA-specific immunoglobulin E (IgE) were measured. The mRNA expressions of cytokines and transcription factors of T cells of nasal mucosa were determined by real-time polymerase chain reaction (PCR). The protein levels of GATA3, ROR-γt, and Foxp3 in nasal mucosa were determined by Western blot. CD4⁺CD25⁺Foxp3⁺ T cells in the spleen were analyzed by flow cytometry. Administration of anti-IL-9 antibody decreased allergic symptoms, OVA-specific IgE levels, and eosinophil counts. In addition, it inhibited T-helper (Th) 2 responses, but had no effect on Th1 responses. Protein levels of ROR-γt and mRNA levels of PU.1 and ROR-γt were reduced by anti-IL-9 antibody. Anti-IL-9 antibody increased Foxp3 and IL-10 mRNA expression, Foxp3 protein, and induction of CD4⁺CD25⁺Foxp3⁺ T cells. Anti-IL-9 antibody decreased allergic inflammation through suppression of Th2 and Th17 cells. Anti-IL-9 antibody enhanced the tolerogenic effects of regulatory T cells. These results suggest that anti-IL-9 antibody might represent a potential therapeutic agent for allergen immunotherapy in patients with uncontrolled allergic airway disease. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

The efficacy of oral and subcutaneous antigen-specific immunotherapy in murine cow's milk- and peanut allergy models.

PubMed

Vonk, Marlotte M; Wagenaar, Laura; Pieters, Raymond H H; Knippels, Leon M J; Willemsen, Linette E M; Smit, Joost J; van Esch, Betty C A M; Garssen, Johan

2017-01-01

Antigen-specific immunotherapy (AIT) is a promising therapeutic approach for both cow's milk allergy (CMA) and peanut allergy (PNA), but needs optimization in terms of efficacy and safety. Compare oral immunotherapy (OIT) and subcutaneous immunotherapy (SCIT) in murine models for CMA and PNA and determine the dose of allergen needed to effectively modify parameters of allergy. Female C3H/HeOuJ mice were sensitized intragastrically (i.g.) to whey or peanut extract with cholera toxin. Mice were treated orally (5 times/week) or subcutaneously (3 times/week) for three consecutive weeks. Hereafter, the acute allergic skin response, anaphylactic shock symptoms and body temperature were measured upon intradermal (i.d.) and intraperitoneal (i.p.) challenge, and mast cell degranulation was measured upon i.g. challenge. Allergen-specific IgE, IgG1 and IgG2a were measured in serum at different time points. Single cell suspensions derived from lymph organs were stimulated with allergen to induce cytokine production and T cell phenotypes were assessed using flow cytometry. Both OIT and SCIT decreased clinically related signs upon challenge in the CMA and PNA model. Interestingly, a rise in allergen-specific IgE was observed during immunotherapy, hereafter, treated mice were protected against the increase in IgE caused by allergen challenge. Allergen-specific IgG1 and IgG2a increased due to both types of AIT. In the CMA model, SCIT and OIT reduced the percentage of activated Th2 cells and increased the percentage of activated Th1 cells in the spleen. OIT increased the percentage of regulatory T cells (Tregs) and activated Th2 cells in the MLN. Th2 cytokines IL-5, IL-13 and IL-10 were reduced after OIT, but not after SCIT. In the PNA model, no differences were observed in percentages of T cell subsets. SCIT induced Th2 cytokines IL-5 and IL-10, whereas OIT had no effect. We have shown clinical protection against allergic manifestations after OIT and SCIT in a CMA and PNA model

[An analysis of skin prick test reactivity to dust mite in overweight and normal weight children with allergic asthma before and after specific immunotherapy].

PubMed

Wang, Jian; Huang, Ying; Zhang, Xue-Li; Huang, Xia; Xu, Xiao-Wen; Liang, Fan-Mei

2016-04-01

To study the skin prick test (SPT) reactivity to house dust mite allergens in overweight and normal weight children with allergic asthma before and after standard subcutaneous specific immunotherapy. Two hundred and fifteen children with allergic asthma who had positive SPT responses to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF) were enrolled. According to the weight index, they were classified into overweight (n=63) and normal weight groups (n=152). Skin indices (SI) to DP and DF were compared between the two groups at 6 months and 1 year after standard subcutaneous specific immunotherapy. The overweight group had a significantly larger histamine wheal diameter than the normal weight group after controlling the variation in testing time (P<0.05). After controlling the variation in weights, there were significant differences in the SIs to DP and DF before specific immunotherapy and at 6 months and 1 year after specific immunotherapy. At 6 months and 1 year after specific immunotherapy, the SIs to DP and DF were significantly reduced in both groups (P<0.05), and the overweight group had greater decreases in the SIs to DP and DF than the normal weight group. The overweight children with allergic asthma have stronger responses to histamine than the normal weight patients. Specific immunotherapy can reduce the reactivity to dust mite allergens in children with allergic asthma. Within one year after specific immunotherapy, the overweight children with allergic asthma have a significantly greater decrease in the reactivity to dust mite allergens than the normal weight patients.

Recent development in recombinant food allergen production (abstract)

USDA-ARS?s Scientific Manuscript database

Whether for understanding the properties of food allergens or for manufacturing vaccines for allergen-specific immunotherapy, well characterized pure allergens are required. This often necessitate the use of recombinant technology in obtaining food allergens due to the very low amounts of their natu...

Orphan immunotherapies for allergic diseases.

PubMed

Ridolo, Erminia; Montagni, Marcello; Incorvaia, Cristoforo; Senna, Gianenrico; Passalacqua, Giovanni

2016-03-01

As confirmed by systematic reviews and meta-analyses, allergen immunotherapy is clinically effective in the treatment of allergic diseases. In particular, subcutaneous immunotherapy is a pivotal treatment in patients with severe reactions to Hymenoptera venom, whereas subcutaneous immunotherapy and sublingual immunotherapy are indicated in the treatment of allergic rhinitis and asthma by inhalant allergens. Other allergies related to animal dander (other than cat, which is the most studied), such as dog, molds, occupational allergens, and insects, have also been recognized. For these allergens, immunotherapy is poorly studied and often unavailable. Thus, use of the term orphan immunotherapies is appropriate. We used MEDLINE to search the medical literature for English-language articles. Randomized, controlled, masked studies for orphan immunotherapies were selected. In the remaining cases, the available reports were described. The literature on food desensitization is abundant, but for other orphan allergens, such as mosquito, Argas reflexus, dog, or occupational allergens, there are only a few studies, and most are small studies or case reports. Orphan immunotherapy is associated with insufficient evidence of efficacy from controlled trials, an erroneous belief of the limited importance of some allergen sources, and the unlikelihood for producers to have a profit in making commercially available extracts (with an expensive process for registration) to be used in few patients. It should be taken into consideration that adequate preparations should be available also for orphan allergens. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Safety of Accelerated Schedules of Subcutaneous Allergen Immunotherapy with House Dust Mite Extract in Patients with Atopic Dermatitis

PubMed Central

Kim, Myoung-Eun; Kim, Jeong-Eun; Sung, Joon-Mo; Lee, Jin-Woo; Choi, Gil-Soon

2011-01-01

The safety of accelerated schedules of allergen immunotherapy (ASAI) in patients with bronchial asthma (BA) has been reported but there are little data on the safety of ASAI for patients with atopic dermatitis (AD). In this study, we investigated the safety of ASAI in patients with AD. Sixty patients with AD and 18 patients with BA sensitized to house dust mites (HDM) were studied. A maximum maintenance dose of HDM extract, adsorbed to aluminum hydroxide, was administered to patients by subcutaneous injection with either a 3-day protocol (rush immunotherapy) or 1-day protocol (ultra-rush immunotherapy). Systemic reactions were observed 4 of 15 patients (26.7%) with AD during rush immunotherapy, 13 of 45 patients (28.9%) with AD during ultra-rush immunotherapy, and 4 of 18 patients (22.2%) with BA during rush immunotherapy (P > 0.05). No severe or near fatal systemic reactions occurred in 78 subjects of this study. Systemic reactions developed within 4 hr after administration of the maximum allergen dose in 20 of 21 patients (95.2%) with AD and BA who showed systemic reactions during rush or ultra-rush immunotherapy. In conclusion, ASAI was safe and well tolerated in patients with AD. ASAI can be a useful therapeutic option for AD. PMID:21935270

Increased Expression of miR-146a in Children With Allergic Rhinitis After Allergen-Specific Immunotherapy.

PubMed

Luo, Xi; Hong, Haiyu; Tang, Jun; Wu, Xingmei; Lin, Zhibin; Ma, Renqiang; Fan, Yunping; Xu, Geng; Liu, Dabo; Li, Huabin

2016-03-01

MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). Twenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA. After 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10⁺CD4⁺ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups. Our findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.

Cluster Subcutaneous Allergen Specific Immunotherapy for the Treatment of Allergic Rhinitis: A Systematic Review and Meta-Analysis

PubMed Central

Sun, Yueqi; Luo, Xi; Li, Huabin

2014-01-01

Background Although allergen specific immunotherapy (SIT) represents the only immune- modifying and curative option available for patients with allergic rhinitis (AR), the optimal schedule for specific subcutaneous immunotherapy (SCIT) is still unknown. The objective of this study is to systematically assess the efficacy and safety of cluster SCIT for patients with AR. Methods By searching PubMed, EMBASE and the Cochrane clinical trials database from 1980 through May 10th, 2013, we collected and analyzed the randomized controlled trials (RCTs) of cluster SCIT to assess its efficacy and safety. Results Eight trials involving 567 participants were included in this systematic review. Our meta-analysis showed that cluster SCIT have similar effect in reduction of both rhinitis symptoms and the requirement for anti-allergic medication compared with conventional SCIT, but when comparing cluster SCIT with placebo, no statistic significance were found in reduction of symptom scores or medication scores. Some caution is required in this interpretation as there was significant heterogeneity between studies. Data relating to Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) in 3 included studies were analyzed, which consistently point to the efficacy of cluster SCIT in improving quality of life compared to placebo. To assess the safety of cluster SCIT, meta-analysis showed that no differences existed in the incidence of either local adverse reaction or systemic adverse reaction between the cluster group and control group. Conclusion Based on the current limited evidence, we still could not conclude affirmatively that cluster SCIT was a safe and efficacious option for the treatment of AR patients. Further large-scale, well-designed RCTs on this topic are still needed. PMID:24489740

Long-term efficacy of allergen specific immunotherapy in atopic dermatitis patients in relation to quality of life.

PubMed

Wyrzykowska, N; Czarnecka-Operacz, M; Adamski, Z

2015-01-01

Atopic dermatitis (AD) is an inflammatory, chronically relapsing and highly pruritic skin disorder that considerably effects patients' life. Dermatology Life Quality Index (DLQI) is often applied in clinical research in order to evaluate the impact of AD on daily performance of patients. The aim of the study was to evaluate the long-term effect of allergen specific immunotherapy (ASIT) on the quality of life in AD patients. 15 patients suffering from AD, allergic to house dust mites or grass pollen allergens, who were previously treated with ASIT participated in the study. Our treatment with allergy vaccinations was performed during the time period between 1995 and 2001. DLQI questionnaires have been filled by the patients before the treatment, after termination of ASIT and after 2 - 12 years of the observational period. The statistical tests revealed a significant difference between the DLQI before ASIT was introduced and after termination of ASIT. Every answer except two (describing the influence of skin condition on preventing from working or studying and on sexual life) of these periods also disclosed statistically significant difference. As for the relation between the DLQI after ASIT and the actual one the tests revealed non significant difference, also regarding to every single answer of the questionnaire. In relation to improvement of quality of life in AD patients, this study confirms the effectiveness of ASIT and it discloses the persistence of its results in long-term aspect.

International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics.

PubMed

Jutel, Marek; Agache, Ioana; Bonini, Sergio; Burks, A Wesley; Calderon, Moises; Canonica, Walter; Cox, Linda; Demoly, Pascal; Frew, Antony J; O'Hehir, Robyn; Kleine-Tebbe, Jörg; Muraro, Antonella; Lack, Gideon; Larenas, Désirée; Levin, Michael; Martin, Bryan L; Nelson, Harald; Pawankar, Ruby; Pfaar, Oliver; van Ree, Ronald; Sampson, Hugh; Sublett, James L; Sugita, Kazunari; Du Toit, George; Werfel, Thomas; Gerth van Wijk, Roy; Zhang, Luo; Akdis, Mübeccel; Akdis, Cezmi A

2016-02-01

This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Indoleamine 2,3-dioxygenase-dependent tryptophan metabolites contribute to tolerance induction during allergen immunotherapy in a mouse model.

PubMed

Taher, Yousef A; Piavaux, Benoit J A; Gras, Reneé; van Esch, Betty C A M; Hofman, Gerard A; Bloksma, Nanne; Henricks, Paul A J; van Oosterhout, Antoon J M

2008-04-01

The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive effects on asthma manifestations and (2) whether tryptophan depletion or generation of its downstream metabolites is involved. Ovalbumin (OVA)-sensitized and OVA-challenged BALB/c mice that display increased airway responsiveness to methacholine, serum OVA-specific IgE levels, bronchoalveolar eosinophilia, and TH2 cytokine levels were used as a model of allergic asthma. Sensitized mice received subcutaneous optimal (1 mg) or suboptimal (100 microg) OVA immunotherapy. Inhibition of IDO by 1-methyl-DL-tryptophan during immunotherapy, but not during inhalation challenge, partially reversed the suppressive effects of immunotherapy on airway eosinophilia and TH2 cytokine levels, whereas airway hyperresponsiveness and serum OVA-specific IgE levels remained suppressed. Administration of tryptophan during immunotherapy failed to abrogate its beneficial effects toward allergic airway inflammation. Interestingly, administration of tryptophan or its metabolites, kynurenine, 3-hydroxykynurenine, and xanthurenic acid, but not 3-hydroxyanthranilinic acid, quinolinic acid, and kynurenic acid, during suboptimal immunotherapy potentiated the reduction of eosinophilia. These effects coincided with reduced TH2 cytokine levels in bronchoalveolar lavage fluid, but no effects on IgE levels were detected. During immunotherapy, the tryptophan metabolites kynurenine, 3-hydroxykynurenine, and xanthurenic acid generated through IDO contribute to tolerance induction regarding TH2-dependent allergic airway inflammation.

Biomarkers for Allergen Immunotherapy: A "Panoromic" View.

PubMed

Moingeon, Philippe

2016-02-01

Biomarkers (BMKs) are biological parameters that can be measured to predict or monitor disease severity or treatment efficacy. The induction of regulatory dendritic cells (DCs) concomitantly with a downregulation of proallergic DC2s (ie, DCs supporting the differentiation of T-helper lymphocyte type 2 cells) in the blood of patients allergic to grass pollen has been correlated with the early onset of allergen immunotherapy efficacy. The combined use of omics technologies to compare biological samples from clinical responders and nonresponders is being implemented in the context of nonhypothesis-driven approaches. Such comprehensive "panoromic" strategies help identify completely novel candidate BMKs, to be subsequently validated as companion diagnostics in large-scale clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel immunotherapy vaccine development.

PubMed

Jutel, Marek; Akdis, Cezmi A

2014-12-01

Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept - as well as large, multicenter clinical studies. The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

Follow-up of venom immunotherapy (VIT) based on conventional techniques and monitoring of immunoglobulin E to individual venom allergens.

PubMed

Carballada, F; Boquete, M; Núñez, R; Lombardero, M; de la Torre, F

2010-01-01

To assess the efficacy of venom immunotherapy (VIT) and monitor changes in in vivo and in vitro test results after 5 years of treatment and subsequent follow-up. To study the profile of immunoglobulin (Ig) E to individual allergens prior to treatment and 1 year afterwards. We studied 562 patients with hymenoptera venom allergy (438 to bee, 124 to wasp), all of whom underwent immunotherapy with Apis or Vespula extract. The patients were followed up using conventional in vivo and in vitro tests, and in 51 cases, specific IgE against the main hymenoptera allergens was measured before starting and after 1 year of treatment. Of the 387 patients who completed VLT, 130 sensitized to Apis and 68 to Vespula suffered spontaneous re-stings during treatment. Of these, 123 (94.6%) did not suffer any reaction and 64 (94.1%) suffered only a local reaction. Sixty-two patients sensitized to Apis and 14 sensitized to Vespula suffered spontaneous re-stings after stopping treatment. Only 3 patients suffered a systemic reaction (grade I Müller). At the end of treatment, the results of skin tests and specific IgE to whole extract improved significantly. Reductions in IgE to the main allergens were observed after 1 year of treatment (median differences in Ves v 5, -238.0, P = .0425; and in Api m 1, -183.0, P = .0024). The high rate of spontaneous re-stings shows that efficacy is maintained for years after completing treatment in a real-world setting. Determination of IgE to individual venom allergens may offer new perspectives in the diagnosis and follow-up of these patients.

Immunotherapy: what lies beyond.

PubMed

Casale, Thomas B; Stokes, Jeffrey R

2014-03-01

Allergen immunotherapy has been used to treat allergic diseases, such as asthma, allergic rhinitis, and venom allergy, since first described over a century ago. The current standard of care in the United States involves subcutaneous administration of clinically relevant allergens for several months, building up to eventual monthly injections for typically 3 to 5 years. Recent advances have improved the safety and efficacy of immunotherapy. The addition of omalizumab or Toll-like receptor agonists to standard subcutaneous immunotherapy has proved beneficial. Altering the extract itself, either through chemical manipulation producing allergoids or directly producing recombinant proteins or significant peptides, has been evaluated with promising results. The use of different administration techniques, such as sublingual immunotherapy, is common in Europe and is on the immediate horizon in the United States. Other methods of administering allergen immunotherapy have been studied, including epicutaneous, intralymphatic, intranasal, and oral immunotherapy. In this review we focus on new types and routes of immunotherapy, exploring recent human clinical trial data. The promise of better immunotherapies appears closer than ever before, but much work is still needed to develop novel immunotherapies that induce immunologic tolerance and enhanced clinical efficacy and safety over that noted for subcutaneous allergen immunotherapy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

IgE and allergen-specific immunotherapy-induced IgG4 recognize similar epitopes of Bet v 1, the major allergen of birch pollen.

PubMed

Groh, N; von Loetzen, C S; Subbarayal, B; Möbs, C; Vogel, L; Hoffmann, A; Fötisch, K; Koutsouridou, A; Randow, S; Völker, E; Seutter von Loetzen, A; Rösch, P; Vieths, S; Pfützner, W; Bohle, B; Schiller, D

2017-05-01

Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G 4 which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG 4 specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG 4 antibodies are developed is under debate. We sought to analyze the epitope specificities of IgE and IgG 4 antibodies from sera of patients who received AIT. 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG 4 were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a _11x , modified in five potential epitopes, were analyzed by circular dichroism and nuclear magnetic resonance spectroscopy. IgE binding to Bet v 1 was assessed by ELISA and mediator release assays. Competitive binding of monoclonal antibodies specific for Bet v 1a and serum IgE/IgG 4 to rBet v 1a and serum antibody binding to a non-allergenic Bet v 1-type model protein presenting an individual epitope for IgE was analyzed in ELISA and western blot. rBet v 1a _11x had a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a _11x was concentration and buffer-dependent. Up to 1500-fold increase in the EC 50 for IgE-mediated mediator release induced by rBet v 1a _11x was determined. The reduction of IgE and IgG 4 binding to rBet v 1a _11x was comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG 4 to 66.1% and 64.9%, respectively. Serum IgE and IgG 4 bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera. Patients receiving AIT develop Bet v 1a-specific IgG 4 which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG 4 might stimulate the development of epitope-specific diagnostics and therapeutics. © 2016 John Wiley & Sons Ltd.

The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) survey: patients' experience with allergen immunotherapy.

PubMed

Skoner, David P; Blaiss, Michael S; Dykewicz, Mark S; Smith, Nancy; Leatherman, Bryan; Bielory, Leonard; Walstein, Nicole; Craig, Timothy J; Allen-Ramey, Felicia

2014-01-01

Allergen immunotherapy (AIT) is used for the treatment of allergic rhinoconjunctivitis as a subcutaneous injection (subcutaneous immunotherapy [SCIT]). Extracts used for SCIT are also used off-label to formulate a liquid delivered as sublingual drops (sublingual immunotherapy [SLIT]). This study was designed to survey patients' experiences and beliefs regarding SCIT and SLIT. People who had ever been diagnosed with nasal and/or ocular allergies were identified in a 2012 telephone survey of U.S. households. Respondents were asked questions about their or their child's use of SCIT and SLIT and their beliefs about AIT. Of 2765 respondents, 46.5% had ever heard of AIT and 22.7% had ever initiated it: 20.9% with SCIT and 1.8% with SLIT (p < 0.0001). The most frequently cited reason for beginning AIT was that symptoms were unresolved with other medications (SCIT, 32.1%; SLIT, 14.0%). Some or full symptom relief was reported by 74.9% of respondents treated with SCIT and 66.0% of those treated with SLIT (p = 0.17 for SCIT versus SLIT). Approximately one-third of respondents who had ever heard of or had been treated with AIT said "don't know" when asked if immunotherapy controls allergy symptoms for years (33.6%), is a very safe treatment (29.3%), or can cure allergy symptoms (27.5%). Effective relief of allergy symptoms was cited most often as the primary benefit of SCIT (37.8%) and convenience was the primary benefit of SLIT (14%). Only one-fifth of respondents had ever been treated with AIT, largely with SCIT. More than one-half of respondents had never heard of AIT and respondents' beliefs indicated a need for educational efforts.

A comparison of nanoparticullate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

PubMed Central

Klier, John; Geis, Sabine; Steuer, Jeanette; Geh, Katharina; Reese, Sven; Fuchs, Sebastian; Mueller, Ralf S.; Winter, Gerhard

2017-01-01

Abstract Introduction New therapeutic strategies to modulate the immune response of human and equine allergic asthma are still under extensive investigation. Immunomodulating agents stimulating T‐regulatory cells offer new treatment options beyond conventional symptomatic treatment or specific immunotherapy for human and equine allergic airway diseases, with the goal of a homoeostatic T‐helper cell balance. The aim of this study was to evaluate the effects of a nebulized gelatin nanoparticle‐CpG formulation (CpG‐GNP) with and without specific allergens for the treatment of spontaneous allergic equine asthma as a model for human asthma. Methods Twenty equine asthma‐affected horses were treated either with CpG‐GNP alone or CpG‐GNP with allergens. Two specific allergens were selected for each horse based on history and an in‐vitro test. Each horse received seven administrations of the respective nebulized composition and was examined before treatment, immediately after and 6 weeks after the treatment course. Results Clinical parameters such as breathing rate, indirect interpleural measurement, arterial blood gases, amount of tracheal mucus and percentage of neutrophils and cytokines in tracheal washes and serum samples were evaluated. Treatment with CpG‐GNP alone as well as in combinations with relevant allergens resulted in clinical improvement of nasal discharge, breathing rate, amount of secretion and viscosity, neutrophil percentage and partial oxygen pressure directly after and 6 weeks after treatment. There were no significant differences between the two treatments in clinical parameters or local cytokine profiles in the tracheal wash fluid (IL‐10, IFN‐g, and IL‐17). IL‐4 concentrations decreased significantly in both groups. Conclusion Nonspecific CpG‐GNP‐based immunotherapy shows potential as a treatment for equine and possibly also human allergic asthma. PMID:29094511

Antigen-Specific Tolerance in Immunotherapy of Th2-Associated Allergic Diseases

PubMed Central

Smarr, Charles B.; Bryce, Paul J.; Miller, Stephen D.

2013-01-01

Allergic diseases are an increasing health concern, particularly in the developed world. The standard clinical approach to treatment of allergic disease focuses on allergen avoidance and symptom control but does little to address the underlying Th2 bias of disease. Specific immunotherapy (SIT) consisting of controlled administration of allergen, however, has been demonstrated to successfully induce desensitization and tolerance in an antigen-specific manner for a variety of Th2-mediated diseases. This review focuses on the mechanisms by which current SIT approaches induce tolerance as well as discussing attempts to modify the safety and efficacy of SIT. These refinements focus on three major aspects of SIT: the route of antigen administration, modification of the antigen to remove allergenic epitopes and reduce adverse events and choice of adjuvant used to induce tolerance and/or immune deviation from Th2 to Th1 and regulatory T cell (Treg) phenotypes. Synthesis of these recent developments in SIT provides considerable promise for more robust therapies with improved safety profiles to improve resolution of allergic disease and its associated costs. PMID:24099300

Allergy immunotherapy with a hypoallergenic recombinant birch pollen allergen rBet v 1-FV in a randomized controlled trial.

PubMed

Klimek, Ludger; Bachert, Claus; Lukat, Karl-Friedrich; Pfaar, Oliver; Meyer, Hanns; Narkus, Annemie

2015-01-01

Pollen extracts and chemically modified allergoids are used successfully in allergen immunotherapy (AIT). Recombinant extracts offer potential advantages with respect to pharmaceutical quality, standardization and dosing. A hypoallergenic recombinant folding variant of the major birch pollen allergen (rBet v 1-FV) was compared with an established native birch preparation. A pre-seasonal, randomized, actively controlled phase II study was performed in birch pollen allergic rhino-conjunctivitis with or without asthma, GINA I/ II. 51 patients (24 rBet v 1-FV, 27 native extract) started therapy with subcutaneous allergen immunotherapy (SCIT). Primary end-point was a combined symptom medication score (SMS), changes in nasal provocation test, visual rating score and specific antibody responses secondary end-points. After one pre-seasonal treatment course the combined SMS was 5.86 (median; IQR: 14.02) for the rBet v 1-FV group versus 12.40 (median; IQR: 9.32) for the comparator during the three weeks pollen season (p = 0.330). After treatment in the second year, scores were 3.00 (median; IQR: 6.50) and 2.93 (4.86) respectively. Allergen tolerance in a nasal provocation test improved to a comparable extent in both groups. Significant increases in birch pollen-specific IgG1 and IgG4 were observed in both treatment groups following the first treatment phase and remained significantly raised until the end of the study. In this first in man, proof of concept phase II trial no statistical difference between rBet v 1-FV and an established natural pollen extract could be observed. rBet v 1-FV could be administered in higher doses than the native protein with no increase in adverse effects. The study was registered in clinicalTrials.gov (NCT00266526).

A study on allergen sensitivity in patients with allergic rhinitis in Bangalore, India.

PubMed

Gowda, G; Lakshmi, S; Parasuramalu, B G; Nagaraj, C; Gowda, B V C; Somashekara, K G

2014-10-01

Allergic rhinitis is the most common form of non-infectious rhinitis, affecting 500 million people worldwide, with one-fifth of those affected living in the Indian subcontinent. The skin prick test is the most valuable test for detecting offending allergens, and can be helpful for patient education, allergen avoidance and immunotherapy planning. The skin prick test was performed with 49 allergens in 486 patients who presented with symptoms of allergic rhinitis, and the allergen profile was studied. Of the 486 allergic rhinitis patients, 335 (68.93 per cent) showed allergen positivity to the skin prick test. Dust mite was the most common allergen, with positive results in 44.65 per cent of cases. The most common offending allergen in our study was the dust mite. Identification of specific allergens for a particular geographical area aids patient education and enables allergen-specific immunotherapy.

Determination of allergen specificity by heavy chains in grass pollen allergen-specific IgE antibodies.

PubMed

Gadermaier, Elisabeth; Flicker, Sabine; Lupinek, Christian; Steinberger, Peter; Valenta, Rudolf

2013-04-01

Affinity and clonality of allergen-specific IgE antibodies are important determinants for the magnitude of IgE-mediated allergic inflammation. We sought to analyze the contribution of heavy and light chains of human allergen-specific IgE antibodies for allergen specificity and to test whether promiscuous pairing of heavy and light chains with different allergen specificity allows binding and might affect affinity. Ten IgE Fabs specific for 3 non-cross-reactive major timothy grass pollen allergens (Phl p 1, Phl p 2, and Phl p 5) obtained by means of combinatorial cloning from patients with grass pollen allergy were used to construct stable recombinant single chain variable fragments (ScFvs) representing the original Fabs and shuffled ScFvs in which heavy chains were recombined with light chains from IgE Fabs with specificity for other allergens by using the pCANTAB 5 E expression system. Possible ancestor genes for the heavy chain and light chain variable region-encoding genes were determined by using sequence comparison with the ImMunoGeneTics database, and their chromosomal locations were determined. Recombinant ScFvs were tested for allergen specificity and epitope recognition by means of direct and sandwich ELISA, and affinity by using surface plasmon resonance experiments. The shuffling experiments demonstrate that promiscuous pairing of heavy and light chains is possible and maintains allergen specificity, which is mainly determined by the heavy chains. ScFvs consisting of different heavy and light chains exhibited different affinities and even epitope specificity for the corresponding allergen. Our results indicate that allergen specificity of allergen-specific IgE is mainly determined by the heavy chains. Different heavy and light chain pairings in allergen-specific IgE antibodies affect affinity and epitope specificity and thus might influence clinical reactivity to allergens. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by

The efficiency of peptide immunotherapy for respiratory allergy.

PubMed

Incorvaia, Cristoforo; Montagni, Marcello; Ridolo, Erminia

2016-06-01

Allergen immunotherapy (AIT) was introduced more than a century ago and is yet the only disease-modifying treatment for allergy. AIT is currently conducted with whole allergen extracts and several studies clearly support its efficacy in the treatment of respiratory allergies, however the need for a long treatment - that affects costs and patients compliance - and possible IgE-mediated adverse events are still unresolved issues. Peptide immunotherapy is based on the use of short synthetic peptides which represent major T-cell epitopes of the allergen with markedly reduced ability to cross-link IgE and activate mast cells and basophils. Data from clinical trials confirmed the efficacy and tolerability of peptide immunotherapy in patients with cat allergy, with a sustained clinical effect after a short course treatment. Peptide therapy is a promising safe and effective new specific treatment for allergy to be developed for the most important allergens causing rhinitis or asthma.

Safety and immunogenicity of a cluster specific immunotherapy in children with bronchial asthma and mite allergy.

PubMed

Schubert, R; Eickmeier, O; Garn, H; Baer, P C; Mueller, T; Schulze, J; Rose, M A; Rosewich, M; Renz, H; Zielen, S

2009-01-01

Cluster specific immunotherapy (SIT) is a modern form of allergen immunotherapy allowing safe administration of high allergen doses in a short time interval compared to classic SIT. In the current study, we investigated the safety profile and immunological effect of cluster SIT in children with allergic asthma due to house dust mite allergy. A total of 34 children (6-18 years) with allergic asthma were assigned to cluster (n = 22) or classic SIT (n = 12). To achieve a maintenance dose of allergen extract, cluster patients received 14 injections of house dust mite allergen within 6 weeks, whereas the classic SIT group received 14 injections within 14 weeks. Safety was monitored by recording adverse events. Immunogenicity was measured by specific IgG(Mite) and IgG4(Mite), by antibody-blocking properties on basophil activation, and by the T cell subset transcription factors Foxp3, T-bet, and GATA-3. There were no significant differences in local and systemic side effects between the two groups. In the cluster group, serum levels of specific IgG(Mite) (p < 0.001) and specific IgG4(Mite) (p < 0.001) significantly increased after 8 weeks, while it took 12 weeks in the classic SIT group. These data were confirmed by blocking CD63 expression as well as release of cysteinyl leukotrienes after in vitro basophil stimulation. No differences in transcription factor expression were found in the two groups. Cluster SIT is safe in children. Additionally, our data demonstrated an even more rapid induction of specific immune tolerance. Cluster SIT is an attractive alternative to conventional up-dosing schedules with fewer consultations for the patients. (c) 2008 S. Karger AG, Basel.

Allergens in veterinary medicine.

PubMed

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. © 2015 The Authors Allergy Published by John Wiley & Sons Ltd.

1alpha,25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-beta.

PubMed

Taher, Yousef A; van Esch, Betty C A M; Hofman, Gerard A; Henricks, Paul A J; van Oosterhout, Antoon J M

2008-04-15

1alpha,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), a potent inhibitor of NF-kappaB expression, can prevent the maturation of dendritic cells in vitro leading to tolerogenic dendritic cells with increased potential to induce regulatory T cells. Herein, we investigated whether the combination of allergen immunotherapy with 1,25(OH)(2)D(3) potentiates the suppressive effects of immunotherapy and whether the immunoregulatory cytokines IL-10 and TGF-beta are involved in the effector phase. OVA-sensitized and challenged BALB/c mice displayed airway hyperresponsiveness (AHR) and increased serum OVA-specific IgE levels, bronchoalveolar lavage eosinophilia, and Th2 cytokine levels. In this model, the dose response of allergen immunotherapy 10 days before OVA inhalation challenge shows strong suppression of asthma manifestations at 1 mg of OVA, but partial suppression of bronchoalveolar lavage eosinophilia, IgE up-regulation, and no reduction of AHR at 100 microg. Interestingly, coadministration of 10 ng of 1,25(OH)(2)D(3) with 100 microg of OVA immunotherapy significantly inhibited AHR and potentiated the reduction of serum OVA-specific IgE levels, airway eosinophilia, and Th2-related cytokines concomitant with increased IL-10 levels in lung tissues and TGF-beta and OVA-specific IgA levels in serum. Similar effects on suboptimal immunotherapy were observed by inhibition of the NF-kappaB pathway using the selective IkappaB kinase 2 inhibitor PS-1145. The suppressive effects of this combined immunotherapy were partially reversed by treatment with mAb to either IL-10R or TGF-beta before OVA inhalation challenge but completely abrogated when both Abs were given. These data demonstrate that 1,25(OH)(2)D(3) potentiates the efficacy of immunotherapy and that the regulatory cytokines IL-10 and TGF-beta play a crucial role in the effector phase of this mouse model.

Medication persistence with long-term, specific grass pollen immunotherapy measured by prescription renewal rates.

PubMed

Sieber, J; De Geest, S; Shah-Hosseini, K; Mösges, R

2011-04-01

We assessed medication persistence using prescription renewal rates for grass pollen specific immunotherapy (SIT) in a representative population of patients in Germany to evaluate whether the perception of superior persistence for the subcutaneous route compared to the sublingual route could be confirmed in clinical practice. Individual prescriptions for allergen immunotherapy were extracted from a national prescription database (INSIGHT Health) and followed over 3 years on a per-patient basis. However, patients' medical history and treatment schedules were not available for analysis. Products were identified by the national drug code (PZN number) and grouped to either subcutaneous immunotherapy (SCIT) with natural extract injections, SCIT with modified allergens (allergoids) or sublingual immunotherapy (SLIT) with natural pollen extract solutions. Persistence was defined as at least one prescription of the individual drug in the respective years. A total of 1409 patients started SIT in 2005 (112, 695, and 602 for natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively). In 2006, 71%, 55%, and 59% of those patients had at least one renewal prescription of natural extract SLIT, natural extract SCIT, and allergoid SCIT, respectively, as well as 51%, 34%, and 39% in 2007. In both years, persistence with natural extract SLIT was significantly higher than with natural extract SCIT (p = 0.0015 for 2006, p = 0.0003 for 2007) and allergoid SCIT (p = 0.0152 for 2006, p = 0.0111 for 2007). There were no significant differences between the two SCIT groups. Medication persistence with grass pollen SIT in a representative sample of patients in Germany was similar to published medication persistence in asthma and COPD patients. The sublingual application route shows significantly better persistency than the subcutaneous route with native allergens or allergoids.

Comparison of serum concentrations of environmental allergen-specific IgE in atopic and healthy (nonatopic) horses.

PubMed

Wilkołek, P; Sitkowski, W; Szczepanik, M; Adamek, Ł; Pluta, M; Taszkun, I; Gołyński, M; Malinowska, A

2017-12-01

Allergic responses in humans, horses and other species are mediated by immunoglobulin E (IgE) antibodies. Serum testing to detect allergen-specific IgE antibodies has been developed for dogs, cats and horses; this allows for the identification of allergens and determination of appropriate allergen- specific immunotherapies. This study compared serum allergen-specific IgE concentrations in atopic and healthy horses. The study was performed on Malopolski breed atopic (n=21) and nonatopic (n=21) clinically healthy horses. Allergen-specific IgE serum concentrations were measured in summer seasons of 2008-2015 using a monoclonal anti-IgE antibody. A Northern and Central European allergen panel containing mite, insect, mould and plant pollen allergens, including 15 tests of individual allergens and 5 tests of allergen mixtures was used. The mean allergen-specific IgE concentrations in the atopic and normal horse populations were compared. Among the atopic horses, the strongest positive reactions occurred against the storage mites Tyrophagus putrescentiae and the domestic mite Dermatophagoides farinae. The atopic horses also demonstrated high IgE concentrations against insects, particularly Tabanus sp., the plant pollens colza, cultivated rye and the mould pollen mixture Aspergillus/Penicillium. No horses in the atopic group were IgE-negative. Among all mite, insect, mould and some plant allergen groups the differences in mean specific IgE concentrations between allergic and healthy horses were significant. The mean IgE concentrations for most allergen groups were significantly higher in the atopic horses than in the healthy animals. However, a high incidence of positive reactions was observed in both healthy and allergic horses. Our results showed a high frequency of polysensitization in atopic horses. Copyright© by the Polish Academy of Sciences.

Selection of patients for sublingual versus subcutaneous immunotherapy.

PubMed

Larenas Linnemann, Désirée E S; Blaiss, Michael S

2014-01-01

Allergen immunotherapy is the sole treatment for IgE-mediated allergic diseases directed at the underlying mechanism. The two widely accepted administration routes are sublingual (SLIT) and subcutaneous (SCIT). We reviewed how patients should best be selected for immunotherapy and how the optimal administration route can be defined. Before deciding SCIT or SLIT, appropriate selection of patients for allergen immunotherapy (AIT) is mandatory. To be eligible for AIT, subjects must have a clear medical history of allergic disease, with exacerbation of symptoms on exposure to one or more allergens and a corresponding positive skin or in vitro test. Then the route of administration should be based on: published evidence of clinical and immunologic efficacy (which varies per allergic disease and per allergen); mono- or multi-allergen immunotherapy, for SLIT multi-allergen immunotherapy was not effective; safety: adverse events with SLIT are more frequent, but less severe; and, costs and patient preferences, closely related to adherence issues. All these are discussed in the article.

Molecular features of grass allergens and development of biotechnological approaches for allergy prevention.

PubMed

Devis, Deborah L; Davies, Janet M; Zhang, Dabing

2017-09-01

Allergic diseases are characterized by elevated allergen-specific IgE and excessive inflammatory cell responses. Among the reported plant allergens, grass pollen and grain allergens, derived from agriculturally important members of the Poaceae family such as rice, wheat and barley, are the most dominant and difficult to prevent. Although many allergen homologs have been predicted from species such as wheat and timothy grass, fundamental aspects such as the evolution and function of plant pollen allergens remain largely unclear. With the development of genetic engineering and genomics, more primary sequences, functions and structures of plant allergens have been uncovered, and molecular component-based allergen-specific immunotherapies are being developed. In this review, we aim to provide an update on (i) the distribution and importance of pollen and grain allergens of the Poaceae family, (ii) the origin and evolution, and functional aspects of plant pollen allergens, (iii) developments of allergen-specific immunotherapy for pollen allergy using biotechnology and (iv) development of less allergenic plants using gene engineering techniques. We also discuss future trends in revealing fundamental aspects of grass pollen allergens and possible biotechnological approaches to reduce the amount of pollen allergens in grasses. Copyright © 2017. Published by Elsevier Inc.

Pollinex Quattro: an innovative four injections immunotherapy in allergic rhinitis.

PubMed

Rosewich, Martin; Lee, Denise; Zielen, Stefan

2013-07-01

The prevalence of seasonal allergic rhinitis in the western world is high and increasing. Besides considerably affecting physical and psychosocial aspects of patients' lives, allergic rhinitis is often associated with allergic asthma and may aggravate this condition over time. Specific immunotherapy is currently the only approved therapy that can modify the underlying disease process and induce long-term tolerance to allergens. Pollinex Quattro is a subcutaneous four injections immunotherapy consisting of tyrosine-absorbed specific allergoids and enhanced with the adjuvant monophosphoryl lipid A (MPL(®)). MPL(®) induces a significant Th 1-type immune response, characterized by an increase of allergen-specific IgG antibody levels and dampening of the IgE response during allergen exposure. Due to this dual action of stimulating the immune system, Pollinex Quattro is clinically effective after only four injections given pre-seasonally. A large clinical program has demonstrated efficacy and tolerability of Pollinex Quattro in children, adolescents and adults with grass and tree pollen allergy. A health economics study concluded that an immunotherapy with only 4 injections might be more cost-beneficial than other application forms of immunotherapy.

In vitro evidence of efficacy and safety of a polymerized cat dander extract for allergen immunotherapy.

PubMed

Morales, María; Gallego, Mayte; Iraola, Victor; Taulés, Marta; de Oliveira, Eliandre; Moya, Raquel; Carnés, Jerónimo

2017-02-24

Allergy to cat epithelia is highly prevalent, being the major recommendation for allergy sufferers its avoidance. However, this is not always feasible. Allergen specific immunotherapy is therefore recommended for these patients. The use of polymerized allergen extracts, allergoids, would allow to achieve the high allergen doses suggested to be effective while maintaining safety. Cat native extract and its depigmented allergoid were manufactured and biochemically and immunochemically characterized. Protein and chromatographic profiles showed significant modification of the depigmented allergoid with respect to its corresponding native extract. However, the presence of different allergens (Fel d 1, Fel d 2, Fel d 3, Fel d 4 and Fel d 7) was confirmed in the allergoid. Differences in IgE-binding capacity were observed as loss of biological potency and lower stability of the IgE-allergen complex on surface plasmon resonance. The allergoid induced production of IgG antibodies able to block IgE-binding to native extract. Finally, studies carried out with peripheral-blood mononuclear cells from cat allergic patients showed that the allergoid induced IFN-γ and IL-10 production similar to that induced by native extract. Cat depigmented allergoid induced production of cytokines involved in a Th1 and Treg response, was able to induce production of IgG-antibodies that blocks IgE-binding to cat native extract, and showed reduced interaction with IgE, suggesting greater safety than native extract while maintaining in vitro efficacy.

Next generation immunotherapy for tree pollen allergies.

PubMed

Su, Yan; Romeu-Bonilla, Eliezer; Heiland, Teri

2017-10-03

Tree pollen induced allergies are one of the major medical and public health burdens in the industrialized world. Allergen-Specific Immunotherapy (AIT) through subcutaneous injection or sublingual delivery is the only approved therapy with curative potential to pollen induced allergies. AIT often is associated with severe side effects and requires long-term treatment. Safer, more effective and convenient allergen specific immunotherapies remain an unmet need. In this review article, we discuss the current progress in applying protein and peptide-based approaches and DNA vaccines to the clinical challenges posed by tree pollen allergies through the lens of preclinical animal models and clinical trials, with an emphasis on the birch and Japanese red cedar pollen induced allergies.

Specificity in cancer immunotherapy.

PubMed

Schietinger, Andrea; Philip, Mary; Schreiber, Hans

2008-10-01

From the earliest days in the field of tumor immunology three questions have been asked: do cancer cells express tumor-specific antigens, does the immune system recognize these antigens and if so, what is their biochemical nature? We now know that truly tumor-specific antigens exist, that they are caused by somatic mutations, and that these antigens can induce both humoral and cell-mediated immune responses. Because tumor-specific antigens are exclusively expressed by the cancer cell and are often crucial for tumorigenicity, they are ideal targets for anti-cancer immunotherapy. Nevertheless, the antigens that are targeted today by anti-tumor immunotherapy are not tumor-specific antigens, but antigens that are normal molecules also expressed by normal tissues (so-called "tumor-associated" antigens). If tumor-specific antigens exist and are ideal targets for immunotherapy, why are they not being targeted? In this review, we summarize current knowledge of tumor-specific antigens: their identification, immunological relevance and clinical use. We discuss novel tumor-specific epitopes and propose new approaches that could improve the success of cancer immunotherapy, especially for the treatment of solid tumors.

Local immunological mechanisms of sublingual immunotherapy.

PubMed

Allam, Jean-Pierre; Novak, Natalija

2011-12-01

To summarize novel insights into the immunological mechanisms of sublingual immunotherapy (SLIT). Within the recent decades, several alternative noninvasive allergen application strategies have been investigated in allergen-specific immunotherapy (AIT), of which intra-oral allergen application to sublingual mucosa has been proven to be well tolerated and effective. To date, SLIT is widely accepted by most allergists as an alternative option to conventional subcutaneous immunotherapy (SCIT). Although detailed immunological mechanisms remain to be elucidated, much scientific effort has been made to shed some light on local and systemic immunological responses to SLIT in mice as well as humans. Only a few studies focused on the detailed mechanisms following allergen application to the oral mucosa as part of the sophisticated mucosal immunological network. Within this network, the pro-tolerogenic properties of local antigen-presenting cells (APCs) such as dendritic cells - which are able to enforce tolerogenic mechanisms and to induce T-cell immune responses - play a central role. Further on, basic research focused not only on the immune response in nasal and bronchial mucosa but also on the systemic T-cell immune response. Thus, much exiting data have been published providing a better understanding of immunological features of SLIT but far more investigations are necessary to uncover further exciting details on the key mechanisms of SLIT.

Specific immunotherapy with allergoids in atopic subjects, hyporeactive to other vaccines.

PubMed

Vargiu, G; Valcurone, G; Agostoni, A; Sacchi, G; Tassi, G C

1986-01-01

Allergoids comply with the therapeutic requirement to reach high doses of the injected allergen, since the modifications of the allergens cause a loss of allergenicity, though the immunogenicity is being retained. Considering that it is possible to use a starting dose 40 times higher in comparison with retard vaccines, we thought it very expedient to treat with allergoids 18 patients allergic to parietaria, and 12 patients allergic to grass pollen, who had shown no clinical improvement after immunotherapy, lasting for at least three years with retard vaccines. The therapeutic results obtained are the following: improvement in 66% of the parietaria allergic patients after the first year, and of the 72% in the second year, of the 75% of the grass pollen allergic patients after the first year and of the 83% in the second year. They can be interpreted as due to the fact that such patients are always poorly reactive to the doses of allergens commonly present in retard vaccines. On the contrary, they do react to allergoids, both due to the high amount of allergen administered, and to the fact that polymerization brings about a stronger epitopic expression matched by a higher immunogenic activity. Moreover, the data are also indicative for a good relationship between the antibody titer of antigen-specific blocking IgG and the clinical effectiveness valued by means of symptom and medication scores.

House-dust mite allergy: mapping of Dermatophagoides pteronyssinus allergens for dogs by two-dimensional immunoblotting.

PubMed

Martins, Luís Miguel Lourenço; Marques, Andreia Grilo; Pereira, Luísa Maria Dotti Silva; Goicoa, Ana; Semião-Santos, Saul José; Bento, Ofélia Pereira

2015-04-01

Specific immunotherapy has shown to be very useful for allergy control in dogs, with a common success rate ranging from 65% to 70%. However, this efficacy could probably be improved and the identification of individual allergomes, with the choice of more adequate molecular allergen pools for specific immunotherapy, being the strategy. To map Dermatophagoides pteronyssinus (Der p) allergens for mite-sensitized atopic dogs, for better understanding how individual allergograms may influence the response to house-dust mite immunotherapy. To identify the Der p mite allergome for dogs, 20 individuals allergic to dust-mites and sensitized to Der p, were selected. The extract from Der p was submitted to isoelectric focusing (IEF), one-dimensional (1-D) and two-dimensional (2-D) sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Separated proteins were blotted onto polyvinylidene difluoride (PVDF) membranes and immunoblottings were performed with patient sera. Allergen-bound specific IgE was detected. Eleven allergens were identified from isoelectric focusing (IEF), as well as from 1-D SDS PAGE. From 2-D SDS-PAGE, 24 spots were identified. Several similarities were found between dog and human allergograms and no absolute correlation between sensitization and allergy was observed either. As in humans, different individual allergograms do not seem to implicate different clinical patterns, but may influence the response to specific immunotherapy. The molecular epidemiology approach in veterinary allergy management, by the characterization of individual patients' allergoms and by choosing the best molecular allergen pool for each patient could also improve the efficacy of allergy immunotherapy.

Ultrarush schedule of subcutaneous immunotherapy with modified allergen extracts is safe in paediatric age.

PubMed

Morais-Almeida, Mário; Arêde, Cristina; Sampaio, Graça; Borrego, Luis Miguel

2016-01-01

Traditional subcutaneous immunotherapy up dosing with allergenic extracts has been shown to be associated with frequent adverse reactions. In recent studies it has been demonstrated that using modified extracts, namely allergoids, it is a safe and effective procedure particularly on accelerated schedules. However data assessing its safety in paediatric age is scarce. To evaluate the safety profile in paediatric population of using modified allergen extracts, in an ultrarush schedule, to reach the maintenance dose in the first day. We included children undergoing treatment with subcutaneous immunotherapy during a five-year period, using modified aeroallergen extracts, depigmented, polymerized with glutaraldehyde and adsorbed on aluminium hydroxide using an ultrarush induction phase. The type of adverse reactions during the ultrarush protocol was recorded. We studied 100 paediatric patients (57 males) with a mean age of 11.6 years (5 to 18 years; standard deviation, 3.3), all with moderate to severe persistent rhinitis, with or without allergic conjunctivitis, asthma and atopic eczema, sensitized to mites and/or pollens. All reached the maintenance dose of 0.5 mL in the first day, except 1 child. During the ultrarush protocol the total number of injections was 199. There were 21 local adverse reactions in 11 patients, 11 immediate and 10 delayed; from those, had clinical relevance 1 immediate and 4 delayed. Systemic reactions were recorded in 2 cases, both immediate and mild. The ultrarush protocol, without premedication, was a safe alternative to be used in paediatric age during the induction phase of subcutaneous immunotherapy using allergoid depigmented extracts.

Ultrarush schedule of subcutaneous immunotherapy with modified allergen extracts is safe in paediatric age

PubMed Central

Arêde, Cristina; Sampaio, Graça; Borrego, Luis Miguel

2016-01-01

Background Traditional subcutaneous immunotherapy up dosing with allergenic extracts has been shown to be associated with frequent adverse reactions. In recent studies it has been demonstrated that using modified extracts, namely allergoids, it is a safe and effective procedure particularly on accelerated schedules. However data assessing its safety in paediatric age is scarce. Objective To evaluate the safety profile in paediatric population of using modified allergen extracts, in an ultrarush schedule, to reach the maintenance dose in the first day. Methods We included children undergoing treatment with subcutaneous immunotherapy during a five-year period, using modified aeroallergen extracts, depigmented, polymerized with glutaraldehyde and adsorbed on aluminium hydroxide using an ultrarush induction phase. The type of adverse reactions during the ultrarush protocol was recorded. Results We studied 100 paediatric patients (57 males) with a mean age of 11.6 years (5 to 18 years; standard deviation, 3.3), all with moderate to severe persistent rhinitis, with or without allergic conjunctivitis, asthma and atopic eczema, sensitized to mites and/or pollens. All reached the maintenance dose of 0.5 mL in the first day, except 1 child. During the ultrarush protocol the total number of injections was 199. There were 21 local adverse reactions in 11 patients, 11 immediate and 10 delayed; from those, had clinical relevance 1 immediate and 4 delayed. Systemic reactions were recorded in 2 cases, both immediate and mild. Conclusion The ultrarush protocol, without premedication, was a safe alternative to be used in paediatric age during the induction phase of subcutaneous immunotherapy using allergoid depigmented extracts. PMID:26844218

[The impact of subcutaneous immunotherapy with Dermatophagoides farinae and Dermatophagoides pteronyssinus on the quality of life of patients with allergic rhinitis and asthma].

PubMed

Yepes-Núñez, Juan José; Gómez, Carolina; Espinoza, Yeinis; Cardona, Ricardo

2014-01-01

The prevalence of asthma and allergic rhinitis in Colombia is increasing at the same rate as it is in other parts of the world. It has been determined that allergen-specific subcutaneous immunotherapy is effective in subjects with allergic rhinitis and asthma that are sensitized to house dust mites: Dermatophagoides farinae and Dermatophagoides pteronyssinus . To provide evidence on changes in the quality of life of subjects induced by allergen-specific subcutaneous immunotherapy with Dermatophagoides farinae and Dermatophagoides pteronyssinus . We selected 76 subjects with a diagnosis of respiratory allergy with sensitization to Dermatophagoides farinae and Dermatophagoides pteronyssinus . The instruments used for evaluating the quality of life were Kidscreen-27 and SF-36. These instruments were applied twice for each subject: once during the first visit, and during the twelfth visit corresponding to the one-year follow-up. Twenty-two subjects completed this study. After one year of treatment with allergen-specific subcutaneous immunotherapy, we found positive changes in terms of the quality of life. In children, the main change was in the School Environment domain while in adults it was in the Physical Function domain. We evaluated, for the first time in Colombia, benefits induced by allergen-specific subcutaneous immunotherapy for dust mites in terms of quality of life in subjects with allergic rhinitis and asthma. These results demonstrated that allergen-specific subcutaneous immunotherapy produces a positive influence on subjects sensitized to dust mites that received allergen-specific subcutaneous immunotherapy to Dermatophagoides farinae and Dermatophagoides pteronyssinus after one year.

Allergen content of grass pollen preparations for skin prick testing and sublingual immunotherapy.

PubMed

Sander, I; Fleischer, C; Meurer, U; Brüning, T; Raulf-Heimsoth, M

2009-10-01

The allergen content of diagnostics and immunotherapeutics is crucial for effective diagnosis and treatment. The aim of this study was to quantify and compare the allergen content of different grass pollen preparations for skin prick testing and sublingual immunotherapy (SLIT). Five skin prick test (SPT) solutions and 10 sublingual immunotherapeutics were analysed for protein and allergen concentration by Bradford assay, inhibition of IgE-binding to Phleum pratense ImmunoCAPs and content of the main allergen Phl p 5 by two-site enzyme immunoassay. In addition, the grass pollen preparations were compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analyses. Protein concentrations of SPT solutions ranged from 15 to 427 microg/ml, and Phl p 5 concentrations ranged from 0.15 to 18.3 microg/ml. The ranking of SPT solutions concerning Phl p 5 content and IgE inhibition capacity was the same, and the ranking of protein and allergen content was closely correlated (r = 0.9). Protein content of the maintenance doses of the immunotheurapeutics ranged from 5 to 153 microg, Phl p 5 content ranged from 0.2 to 21.6 microg. IgE inhibition capacity of the maintenance doses was closely correlated to their Phl p 5 and protein content. SDS-PAGE and immunoblots confirmed the differences in protein and allergen content. Grass pollen preparations for SPT and SLIT varied greatly concerning protein and allergen content. Whereas this result corresponds to previous analyses results of SPT solutions, it was the first comparison of grass pollen immunotherapeutics. For diagnosis and therapy, these differences should be taken into account.

484 Allergen Standardisation in Allergens and Allergoids—Challenges and Considerations

PubMed Central

Skinner, Murray; Bullimore, Alan; Hewings, Simon; Swan, Nicola

2012-01-01

Background The range of therapeutics and dosing schedules for allergen preparations and allergoids produced and used clinically are considerable. Standardisation of allergy immunotherapies is considered a positive step; however there are difficulties in identifying universal metrics for standardisation. Many advocate the use of major allergen content whilst others advocate total allergenicity. Additionally as a compounding argument, where major allergen is used, many disagree on what the major allergen is for certain species. Methods Major allergen content measurement allows a consistent recognised measure, and IgE responses of a serum pool are often dominated by IgE against major allergens. However issues such as specificity of different assays toward isoforms and other variants of single allergens often results in diverging allergen contents that can cause unexpected and misleading disparity. Other aspects that increase complication are the relevance to modified allergens, use of adjuvants and differing dosing regimes. Results The major allergen content of key products in different therapeutic formats has been measured. Conclusions This has been performed in conjunction with techniques such as total allergenicity, as allergy treatments and therapeutics require careful characterisation to allow supply of consistent, safe and efficacious products.

Hypoallergenic molecules for subcutaneous immunotherapy.

PubMed

Jongejan, Laurian; van Ree, Ronald; Poulsen, Lars K

2016-01-01

Although a large part of the population suffers from allergies, a cure is not yet available. Allergen-specific immunotherapy (AIT) offers promise for these patients. AIT has proven successful in insect and venom allergies; however, for food allergy this is still unclear. In this editorial we focus on the recent advances in a proof of concept study in food allergy, FAST (Food allergy specific immunotherapy), which may increase interest within the biomolecular and pharmaceutical industry to embark on similar projects of immunology driven precision medicine within the allergy field.

Immunosuppression in Early Postnatal Days Induces Persistent and Allergen-Specific Immune Tolerance to Asthma in Adult Mice

PubMed Central

Chen, Yan; Zhang, Jin; Lu, Yong; Wang, Libo

2015-01-01

Bronchial asthma is a chronic airway inflammatory condition with high morbidity, and effective treatments for asthma are limited. Allergen-specific immunotherapy can only induce peripheral immune tolerance and is not sustainable. Exploring new therapeutic strategies is of great clinical importance. Recombinant adenovirus (rAdV) was used as a vector to make cells expressing cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4Ig) a soluble CTLA4 immunoglobulin fusion protein. Dendritic cells (DCs) were modified using the rAdVs together with allergens. Then these modified DCs were transplanted to mice before allergen sensitization. The persistence and specificity of immune tolerance were evaluated in mice challenged with asthma allergens at 3 and 7 months. DCs modified by CTLA4Ig showed increased IL-10 secretion, decreased IL-12 secretion, and T cell stimulation in vitro. Mice treated with these DCs in the early neonatal period developed tolerance against the allergens that were used to induce asthma in the adult stage. Asthma symptoms, lung damage, airway reactivity, and inflammatory response all improved. Humoral immunity indices showed that this therapeutic strategy strongly suppressed mice immune responses and was maintained for as long as 7 months. Furthermore, allergen cross-sensitization and challenge experiments demonstrated that this immune tolerance was allergen-specific. Treatment with CTLA4Ig modified DCs in the early neonatal period, inducing persistent and allergen-specific immune tolerance to asthma in adult mice. Our results suggest that it may be possible to develop a vaccine for asthma. PMID:25860995

Adherence to allergen immunotherapy improves when patients choose the route of administration: Subcutaneous or sublingual.

PubMed

Sánchez, J

2015-01-01

Immunotherapy has shown to be an effective treatment for the management of some IgE-mediated allergies. However, due to its long duration, a high number of patients withdraw from it before completion. Explore if allowing patients to select the route of immunotherapy, educational sessions and strict follow-up could improve treatment compliance. Patients consulting allergy service were divided into two groups; if they chose the route of administration of immunotherapy, they were selected for the active group; if their physician decided, they were selected for the control group. All patients had to attend the allergy service monthly for control. Before the first application of immunotherapy, all patients received an educative session about the benefits and risks of the treatment. Patients in the active group received an additional session about subcutaneous and sublingual routes and they chose the most appropriate according to their personal characteristics. A total of 204 patients were in the active group and 103 were included in the control group. At six months, a total of 46 patients withdrew from immunotherapy during follow-up, 24 (11%) in the active group and 22 (21%) in the control group (p=0.02). In the active group we observed no statistically significant difference in adherence between those who preferred subcutaneous or sublingual immunotherapy; however in the control group, the drop out of sublingual immunotherapy was significantly higher than those who received subcutaneous (p=0.05). Educational sessions, strict follow-up and considering personal preferences of patients could improve adherence to allergen immunotherapy. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

Clinical and Immunological Changes of Immunotherapy in Patients with Atopic Dermatitis: Randomized Controlled Trial

PubMed Central

Sánchez Caraballo, Jorge Mario; Cardona Villa, Ricardo

2012-01-01

Background. Immunotherapy has proven to be an useful tool in the management of allergic respiratory diseases; however, little has been studied in atopic dermatitis. Objective. To evaluate the clinical and immunological impact of immunotherapy with mites allergen extracts in atopic dermatitis. Methods. Patients with atopic dermatitis were assigned with computer-generated randomization to either of the following groups: (a) controls received only topical treatment with steroids and/or tacrolimus and (b) actively treated patients received topical treatment plus immunotherapy. Levels of serum total IgE, mites-specific IgE and IgG4 were assessed at study start and after one year of immunotherapy. Results. 31 patients in the active group and 29 in the control group completed the study. Symptoms and medication scores were significantly reduced in the active group after six months. Three patients in the control group showed new sensitizations to mites, while 3 patients in the active group showed neosensitization to shrimp with negative oral food challenge. We observed significant increase of mites-specific IgG4 levels in active group. Conclusion. Specific allergen immunotherapy induced a tolerogenic IgG4 response to mite allergens associated with favorable clinical effects in atopic dermatitis patients. PMID:23724240

Conference Scene: novelties in immunotherapy.

PubMed

Mitsias, Dimitris I; Kalogiros, Lampros A; Papadopoulos, Nikolaos G

2013-10-01

The only method aiming to permanently cure allergic disorders is allergen immunotherapy. Over the last 20 years there has been great progress in understanding the mechanisms that govern allergen immunotherapy in order to meet three basic prerequisites: safety, effectiveness and compliance. In the present summary report from the European Academy of Allergology and Clinical Immunology-World Allergy Organization Congress held last June in Milan, we review key points concerning the main axes as diagnosis, novel modalities, routes and protocols, as well as two important immunotherapy fields: food and insect venom allergy.

Quality of life outcomes with sublingual immunotherapy.

PubMed

Wise, Sarah K; Woody, Jamie; Koepp, Sarah; Schlosser, Rodney J

2009-01-01

Immunotherapy is the titrated exposure of allergens to induce immunologic tolerance and offers long-term immune modification. Traditional subcutaneous immunotherapy (SCIT) has resulted in several deaths and raised safety concerns. Sublingual immunotherapy (SLIT) is an alternative administration route for allergen-specific immunotherapy. Compared to SCIT, SLIT has a shorter escalation phase, equal or greater efficacy for rhinitis, and an improved safety profile. The purpose of this study was to evaluate quality of life measures in a preliminary patient sample initiating SLIT at our institution. Patients with appropriate allergen reactivity were given the option to pursue immunotherapy by traditional SCIT or by SLIT techniques. Patients choosing SLIT completed the mini-Rhinoconjunctivitis Quality of Life Questionnaire (m-RQLQ), a 14-item Likert-type questionnaire, at baseline and during maintenance therapy. Patients typically reached maintenance dosing in less than 5 weeks. Paired m-RQLQ data were available for 15 patients after antigen titration. Initial m-RQLQ results indicate statistically significant (P < .05) improvement on 12 of 14 domains, including impact on regular and recreational activities, sleep, nose rubbing and nose blowing, stuffy nose and runny nose, itchy eyes, sore eyes, watery eyes, thirst, and tiredness. In addition, total m-RQLQ score showed statistically significant improvement (P = .001). No serious adverse events occurred with the initiation of SLIT. These results indicate that SLIT is effective in controlling allergic symptoms and is safe in an introductory patient sample. Double-blind placebo-controlled trials are needed to confirm our preliminary results.

Immunization with Hypoallergens of Shrimp Allergen Tropomyosin Inhibits Shrimp Tropomyosin Specific IgE Reactivity

PubMed Central

Wai, Christine Y. Y.; Leung, Nicki Y. H.; Ho, Marco H. K.; Gershwin, Laurel J.; Shu, Shang An; Leung, Patrick S. C.; Chu, Ka Hou

2014-01-01

Designer proteins deprived of its IgE-binding reactivity are being sought as a regimen for allergen-specific immunotherapy. Although shrimp tropomyosin (Met e 1) has long been identified as the major shellfish allergen, no immunotherapy is currently available. In this study, we aim at identifying the Met e 1 IgE epitopes for construction of hypoallergens and to determine the IgE inhibitory capacity of the hypoallergens. IgE-binding epitopes were defined by three online computational models, ELISA and dot-blot using sera from shrimp allergy patients. Based on the epitope data, two hypoallergenic derivatives were constructed by site-directed mutagenesis (MEM49) and epitope deletion (MED171). Nine regions on Met e 1 were defined as the major IgE-binding epitopes. Both hypoallergens MEM49 and MED171 showed marked reduction in their in vitro reactivity towards IgE from shrimp allergy patients and Met e 1-sensitized mice, as well as considerable decrease in induction of mast cell degranulation as demonstrated in passive cutaneous anaphylaxis assay. Both hypoallergens were able to induce Met e 1-recognizing IgG antibodies in mice, specifically IgG2a antibodies, that strongly inhibited IgE from shrimp allergy subjects and Met e 1-sensitized mice from binding to Met e 1. These results indicate that the two designer hypoallergenic molecules MEM49 and MED171 exhibit desirable preclinical characteristics, including marked reduction in IgE reactivity and allergenicity, as well as ability to induce blocking IgG antibodies. This approach therefore offers promises for development of immunotherapeutic regimen for shrimp tropomyosin allergy. PMID:25365343

Immunization with Hypoallergens of shrimp allergen tropomyosin inhibits shrimp tropomyosin specific IgE reactivity.

PubMed

Wai, Christine Y Y; Leung, Nicki Y H; Ho, Marco H K; Gershwin, Laurel J; Shu, Shang An; Leung, Patrick S C; Chu, Ka Hou

2014-01-01

Designer proteins deprived of its IgE-binding reactivity are being sought as a regimen for allergen-specific immunotherapy. Although shrimp tropomyosin (Met e 1) has long been identified as the major shellfish allergen, no immunotherapy is currently available. In this study, we aim at identifying the Met e 1 IgE epitopes for construction of hypoallergens and to determine the IgE inhibitory capacity of the hypoallergens. IgE-binding epitopes were defined by three online computational models, ELISA and dot-blot using sera from shrimp allergy patients. Based on the epitope data, two hypoallergenic derivatives were constructed by site-directed mutagenesis (MEM49) and epitope deletion (MED171). Nine regions on Met e 1 were defined as the major IgE-binding epitopes. Both hypoallergens MEM49 and MED171 showed marked reduction in their in vitro reactivity towards IgE from shrimp allergy patients and Met e 1-sensitized mice, as well as considerable decrease in induction of mast cell degranulation as demonstrated in passive cutaneous anaphylaxis assay. Both hypoallergens were able to induce Met e 1-recognizing IgG antibodies in mice, specifically IgG2a antibodies, that strongly inhibited IgE from shrimp allergy subjects and Met e 1-sensitized mice from binding to Met e 1. These results indicate that the two designer hypoallergenic molecules MEM49 and MED171 exhibit desirable preclinical characteristics, including marked reduction in IgE reactivity and allergenicity, as well as ability to induce blocking IgG antibodies. This approach therefore offers promises for development of immunotherapeutic regimen for shrimp tropomyosin allergy.

Issues in stinging insect allergy immunotherapy: a review.

PubMed

Finegold, Ira

2008-08-01

The treatment of insect allergy by desensitization still continues to present with some unanswered questions. This review will focus mainly on articles that have dealt with these issues in the past 2 years. With the publication in 2007 of Allergen Immunotherapy: a practice parameter second update, many of the key issues were reviewed and summarized. Other recent studies deal with omalizumab pretreatment of patients with systemic mastocytosis and very severe allergic reactions to immunotherapy. It would appear that venom immunotherapy is somewhat unique compared to inhalant allergen immunotherapy in that premedication prior to rush protocols may not be necessary and that intervals of therapy may be longer than with allergen immunotherapy. The use of concomitant medications such as beta-blockers may be indicated in special situations. Angiotensin-converting enzyme inhibitors can be stopped temporarily before venom injections to prevent reactions. The issue of when to discontinue immunotherapy remains unsettled and should be individualized to patient requirements. The newest revision of the Immunotherapy Parameters provides much needed information concerning successful treatment with immunotherapy of Hymenoptera-sensitive patients.

An assay that may predict the development of IgG enhancing allergen-specific IgE binding during birch immunotherapy

PubMed Central

Selb, R.; Eckl-Dorna, J.; Vrtala, S.; Valenta, R.; Niederberger, V.

2017-01-01

Background It has been shown that birch pollen immunotherapy can induce IgG antibodies which enhance IgE binding to Bet v 1. We aimed to develop a serological assay to predict the development of antibodies which enhance IgE binding to Bet v 1 during immunotherapy. Methods In 18 patients treated by Bet v 1-fragment-specific immunotherapy, the effects of IgG antibodies specific for the fragments on the binding of IgE antibodies to Bet v 1 were measured by ELISA. Blocking and possible enhancing effects on IgE binding were compared with skin sensitivity to Bet v 1 after treatment. Results We found that fragment-specific IgG enhanced IgE binding to Bet v 1 in two patients who also showed an increase of skin sensitivity to Bet v 1. Conclusion Our results indicate that it may be possible to develop serological tests which predict the induction of unfavourable IgG antibodies enhancing the binding of IgE to Bet v 1 during immunotherapy. PMID:23998344

Allergen concentration in natural rubber latex.

PubMed

Yeang, H-Y; Hamilton, R G; Bernstein, D I; Arif, S A M; Chow, K-S; Loke, Y-H; Raulf-Heimsoth, M; Wagner, S; Breiteneder, H; Biagini, R E

2006-08-01

Hevea brasiliensis latex serum is commonly used as the in vivo and in vitro reference antigen for latex allergy diagnosis as it contains the full complement of latex allergens. This study quantifies the concentrations of the significant allergens in latex serum and examines its suitability as an antigen source in latex allergy diagnosis and immunotherapy. The serum phase was extracted from centrifuged latex that was repeatedly freeze-thawed or glycerinated. Quantitation of latex allergens was performed by two-site immunoenzymetric assays. The abundance of RNA transcripts of the latex allergens was estimated from the number of their clones in an Expressed Sequence Tags library. The latex allergens, Hev b 1, 2, 3, 4, 5, 6, 7 and 13, were detected in freeze-thawed and glycerinated latex serum at levels ranging from 75 (Hev b 6) to 0.06 nmol/mg total proteins (Hev b 4). Hev b 6 content in the latex was up to a thousand times higher than the other seven latex allergens, depending on source and/or preparation procedure. Allergen concentration was reflected in the abundance of mRNA transcripts. When used as the antigen, latex serum may bias the outcome of latex allergy diagnostic tests towards sensitization to Hev b 6. Tests that make use of latex serum may fail to detect latex-specific IgE reactivity in subjects who are sensitized only to allergens that are present at low concentrations. Latex allergy diagnostics and immunotherapy that use whole latex serum as the antigen source may not be optimal because of the marked imbalance of its constituent allergens.

Intrauterine sensitization of allergen-specific IgE analyzed by a highly sensitive new allergen microarray.

PubMed

Kamemura, Norio; Tada, Hitomi; Shimojo, Naoki; Morita, Yoshinori; Kohno, Yoichi; Ichioka, Takao; Suzuki, Koichi; Kubota, Kenji; Hiyoshi, Mineyoshi; Kido, Hiroshi

2012-07-01

To design a rational allergy prevention program, it is important to determine whether allergic sensitization starts in utero under the maternal immune system. To investigate the origin of allergen-specific IgE antibodies in cord blood (CB) and maternofetal transfer of immunoglobulins. The levels of food and inhalant allergen-specific IgE, IgA, IgG, and IgG(4) antibodies in CB and maternal blood (MB) from 92 paired neonates and mothers were measured by using a novel allergen microarray of diamond-like-carbon-coated chip, with high-sensitivity detection of allergen-specific antibodies and allergen profiles. The levels of allergen-specific IgE antibodies against food and inhalant allergens and allergen profiles were identical in CB and newborn blood, but the levels and profiles, specifically against inhalant allergens, were different from those in MB. The level of allergen-specific IgA antibodies was below the detection levels in CB despite clear detection in MB. Therefore, contamination with MB in CB was excluded on the basis of extremely low levels of IgA antibodies in CB and the obvious mismatch of the allergen-specific IgE and IgA profiles between CB and MB. However, the levels of allergen-specific IgG and IgG(4) antibodies and their allergen profiles were almost identical in both MB and CB. Allergen-specific levels of IgE and IgA antibodies and their allergen profiles analyzed by the diamond-like-carbon allergen chip indicate that IgE antibodies in CB are of fetal origin. Food-allergen specific IgE antibodies were detected more often than inhalant-allergen specific IgE antibodies in CB, the reason of which remains unclarified. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

PubMed

Dhami, Sangeeta; Nurmatov, Ulugbek; Varga, Eva-Maria; Sturm, Gunter; Muraro, Antonella; Akdis, Cezmi A; Antolín-Amérigo, Darío; Bilò, M Beatrice; Bokanovic, Danijela; Calderon, Moises A; Cichocka-Jarosz, Ewa; Elberink, Joanna N G Oude; Gawlik, Radoslaw; Jakob, Thilo; Kosnik, Mitja; Lange, Joanna; Mingomataj, Ervin; Mitsias, Dimitris I; Mosbech, Holger; Pfaar, Oliver; Pitsios, Constantinos; Pravettoni, Valerio; Roberts, Graham; Ruëff, Franziska; Sin, Betül Ayşe; Sheikh, Aziz

2015-01-01

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 Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. 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. The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT.

Nanoparticle based-immunotherapy against allergy.

PubMed

Gamazo, Carlos; Gastaminza, Gabriel; Ferrer, Marta; Sanz, María L; Irache, Juan M

2014-01-01

Allergic diseases are one of the most prevalent diseases, reaching epidemic proportions in developed countries. An allergic reaction occurs after contact with an environmental protein, such as inhalants allergens (pollen, animal dander, house dust mites), or food proteins. This response is known as part of the type 2 immunity that is counterbalanced by Type 1 immunity and Tregs. Widely used allergen-specific immunotherapy (IT) is a long term treatment to induce such switch from Th2 to Th1 response. However, conventional IT requires multiple allergen injections over a long period of time and is not free of risk of producing allergic reactions. As a consequence, new safer and faster immunotherapeutic methods are required. This review deals with allergen IT using nanoparticles as allergen delivery system that will allow a different way of administration, reduce dose and diminish allergen exposure to IgE bound to mast cells or basophils.

Chemical modification of birch allergen extract leads to a reduction in allergenicity as well as immunogenicity.

PubMed

Würtzen, Peter Adler; Lund, Lise; Lund, Gitte; Holm, Jens; Millner, Anders; Henmar, Helene

2007-01-01

In Europe, specific immunotherapy is currently conducted with vaccines containing allergen preparations based on intact extracts. In addition to this, chemically modified allergen extracts (allergoids) are used for specific allergy treatment. Reduced allergenicity and thereby reduced risk of side effects in combination with retained ability to activate T cells and induce protective allergen-specific antibody responses has been claimed for allergoids. In the current study, we compared intact allergen extracts and allergoids with respect to allergenicity and immunogenicity. The immunological response to birch allergen extract, alum-adsorbed extract, birch allergoid and alum-adsorbed allergoid was investigated in vitro in human basophil histamine release assay and by stimulation of human allergen-specific T cell lines. In vivo, Bet v 1-specific IgG titers in mice were determined after repetitive immunizations. In all patients tested (n = 8), allergoid stimulations led to reduced histamine release compared to the intact allergen extract. However, the allergoid preparations were not recognized by Bet v 1-specific T cell lines (n = 7), which responded strongly to the intact allergen extract. Mouse immunizations showed a clearly reduced IgG induction by allergoids and a strongly potentiating effect of the alum adjuvant. Optimal IgG titers were obtained after 3 immunizations with intact allergen extracts, while 5 immunizations were needed to obtain maximal response to the allergoid. The reduced histamine release observed for allergoid preparations may be at the expense of immunological efficacy because the chemical modifications lead to a clear reduction in T cell activation and the ability to induce allergen-specific IgG antibody responses. Copyright 2007 S. Karger AG, Basel.

Agreement between allergen-specific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA

PubMed Central

Plant, Jon D; Neradelik, Moni B; Polissar, Nayak L; Fadok, Valerie A; Scott, Brian A

2014-01-01

Background Canine allergen-specific IgE assays in the USA are not subjected to an independent laboratory reliability monitoring programme. Hypothesis/Objectives The aim of this study was to evaluate the agreement of diagnostic results and treatment recommendations of four serum IgE assays commercially available in the USA. Methods Replicate serum samples from 10 atopic dogs were submitted to each of four laboratories for allergen-specific IgE assays (ACTT®, VARL Liquid Gold, ALLERCEPT® and Greer® Aller-g-complete®). The interlaboratory agreement of standard, regional panels and ensuing treatment recommendations were analysed with the kappa statistic (κ) to account for agreement that might occur merely by chance. Six comparisons of pairs of laboratories and overall agreement among laboratories were analysed for ungrouped allergens (as tested) and also with allergens grouped according to reported cross-reactivity and taxonomy. Results The overall chance-corrected agreement of the positive/negative test results for ungrouped and grouped allergens was slight (κ = 0.14 and 0.13, respectively). Subset analysis of the laboratory pair with the highest level of diagnostic agreement (κ = 0.36) found slight agreement (κ = 0.13) for ungrouped plants and fungi, but substantial agreement (κ = 0.71) for ungrouped mites. The overall agreement of the treatment recommendations was slight (κ = 0.11). Altogether, 85.1% of ungrouped allergen treatment recommendations were unique to one laboratory or another. Conclusions and clinical importance Our study indicated that the choice of IgE assay may have a major influence on the positive/negative results and ensuing treatment recommendations. PMID:24461034

Pepsinized cashew proteins are hypoallergenic and immunogenic and provide effective immunotherapy in mice with cashew allergy.

PubMed

Kulis, Mike; Macqueen, Ian; Li, Yifan; Guo, Rishu; Zhong, Xiao-Ping; Burks, A Wesley

2012-09-01

IgE-mediated allergic reactions to cashews and other nuts can trigger life-threatening anaphylaxis. Proactive therapies to decrease reaction severity do not exist. We aimed to determine the efficacy of pepsin-digested cashew proteins used as immunotherapy in a murine model of cashew allergy. Mice were sensitized to cashew and then underwent challenges with digested or native cashew allergens to assess the allergenicity of the protein preparations. Using native or pepsinized cashew proteins, mice underwent oral or intraperitoneal sensitization protocols to determine the immunogenic properties of the protein preparations. Finally, cashew-sensitized mice underwent an immunotherapy protocol with native or pepsinized cashew proteins and subsequent provocation challenges. Pepsinized cashew proteins elicited weaker allergic reactions than native cashew proteins but importantly retained the ability to stimulate cellular proliferation and cytokine production. Mice sensitized with pepsinized proteins reacted on challenge with native allergens, demonstrating that pepsinized allergens retain immunogenicity in vivo. Immunotherapy with pepsinized cashew allergens significantly decreased allergic symptoms and body temperature decrease relative to placebo after challenge with native and pepsinized proteins. Immunologic changes were comparable after immunotherapy with native or pepsinized allergens: T(H)2-type cytokine secretion from splenocytes was decreased, whereas specific IgG(1) and IgG(2a) levels were increased. Pepsinized cashew proteins are effective in treating cashew allergy in mice and appear to work through the same mechanisms as native protein immunotherapy. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Agreement between allergen-specific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA.

PubMed

Plant, Jon D; Neradelik, Moni B; Polissar, Nayak L; Fadok, Valerie A; Scott, Brian A

2014-02-01

Canine allergen-specific IgE assays in the USA are not subjected to an independent laboratory reliability monitoring programme. The aim of this study was to evaluate the agreement of diagnostic results and treatment recommendations of four serum IgE assays commercially available in the USA. Replicate serum samples from 10 atopic dogs were submitted to each of four laboratories for allergen-specific IgE assays (ACTT(®) , VARL Liquid Gold, ALLERCEPT(®) and Greer(®) Aller-g-complete(®) ). The interlaboratory agreement of standard, regional panels and ensuing treatment recommendations were analysed with the kappa statistic (κ) to account for agreement that might occur merely by chance. Six comparisons of pairs of laboratories and overall agreement among laboratories were analysed for ungrouped allergens (as tested) and also with allergens grouped according to reported cross-reactivity and taxonomy. The overall chance-corrected agreement of the positive/negative test results for ungrouped and grouped allergens was slight (κ = 0.14 and 0.13, respectively). Subset analysis of the laboratory pair with the highest level of diagnostic agreement (κ = 0.36) found slight agreement (κ = 0.13) for ungrouped plants and fungi, but substantial agreement (κ = 0.71) for ungrouped mites. The overall agreement of the treatment recommendations was slight (κ = 0.11). Altogether, 85.1% of ungrouped allergen treatment recommendations were unique to one laboratory or another. Our study indicated that the choice of IgE assay may have a major influence on the positive/negative results and ensuing treatment recommendations. © 2014 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and the ACVD.

Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis.

PubMed

Dhami, S; Zaman, H; Varga, E-M; Sturm, G J; Muraro, A; Akdis, C A; Antolín-Amérigo, D; Bilò, M B; Bokanovic, D; Calderon, M A; Cichocka-Jarosz, E; Oude Elberink, J N G; Gawlik, R; Jakob, T; Kosnik, M; Lange, J; Mingomataj, E; Mitsias, D I; Mosbech, H; Ollert, M; Pfaar, O; Pitsios, C; Pravettoni, V; Roberts, G; Ruëff, F; Sin, B A; Asaria, M; Netuveli, G; Sheikh, A

2017-03-01

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. 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 descriptively summarized and, where possible, meta-analysed. Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy.

PubMed

Li, Lisha; Guan, Kai

2016-07-01

Although many patients with allergic rhinitis have symptoms due to sensitization to more than one kind of allergens, and mixed allergen extracts are widely used for immunotherapy, there are few published trials. Our study aimed to evaluate the effect of multiple-allergen immunotherapy on improving the symptoms and quality of life of allergic rhinitis patients. We performed a 1-year single-center observation study of subcutaneous immunotherapy using house dust mite extract (n = 12), weed pollen extract (n = 21), or mixed house dust mite/weed pollen extract (n = 11) in 44 allergic rhinitis patients. All the allergens responsible for the symptom of each patient were included in his immunotherapy. Symptom score, medication score, and quality of life of the patients were evaluated before and after 1-year immunotherapy. Quality of life was evaluated with the Rhinoconjunctivitis Quality of Life Questionnaire. In all 3 groups receiving subcutaneous immunotherapy, significant improvement of symptom score, medication score, and quality of life was found vs. baseline at 1 year, irrespective of the allergen used. In the weed pollen season, the changes of quality of life questionnaire score after 1-year treatment were not significantly different between the weed pollen group (1.55 ± 1.24) and the mixed house dust mite/weed pollen group (1.14 ± 1.01). The same happened in the nonpollen seasons, during which dust mite immunotherapy (1.23 ± 1.63) and mixed immunotherapy (0.60 ± 0.47) did not show significantly different effect on the quality of life. The multiple-allergen immunotherapy might be effective in polysensitized allergic rhinitis patients, and could improve their quality of life. Our result did not show significant difference between the effects of multiple-allergen immunotherapy and mono-allergen immunotherapy.

Identification and characterization of major cat allergen Fel d 1 mimotopes on filamentous phage carriers.

PubMed

Luzar, Jernej; Molek, Peter; Šilar, Mira; Korošec, Peter; Košnik, Mitja; Štrukelj, Borut; Lunder, Mojca

2016-03-01

Cat allergy is one of the most prevalent allergies worldwide and can lead to the development of rhinitis and asthma. Thus far, only allergen extracts from natural sources have been used for allergen-specific immunotherapy. However, extracts and whole allergens in immunotherapy present an anaphylaxis risk. Identification of allergen epitopes or mimotopes has an important role in development of safe and effective allergen-specific immunotherapy. Moreover, with a suitable immunogenic carrier, the absence of sufficient immune response elicited by short peptides could be surmounted. In this study, we identified five structural mimotopes of the major cat allergen Fel d 1 by immunoscreening with random peptide phage libraries. The mimotopes were computationally mapped to the allergen surface, and their IgE reactivity was confirmed using sera from cat-allergic patients. Importantly, the mimotopes showed no basophil activation of the corresponding cat-allergic patients, which makes them good candidates for the development of hypoallergenic vaccine. As bacteriophage particles are becoming increasingly recognized as immunogenic carriers, we constructed bacteriophage particles displaying multiple copies of each selected mimotope on major phage coat protein. These constructed phages elicited T cell-mediated immune response, which was predominated by the type 1 T cell response. Mimotopes alone contributed to the type 1 T cell response by promoting IL-2 production. Fel d 1 mimotopes, as well as their filamentous phage immunogenic carriers, represent promising candidates in the development of hypoallergenic vaccine against cat allergy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pediatric investigation plans for specific immunotherapy: Questionable contributions to childhood health.

PubMed

Rose, Klaus; Kopp, Matthias Volkmar

2015-12-01

Allergen-specific immunotherapy (SIT) is the only disease-modifying treatment for children, adolescents, and adults with allergic diseases. The EU has a combined system of national and EU-wide marketing authorization for all medicines. Germany introduced a new therapy allergen ordinance in 2008. Allergen products manufacturers had to apply for marketing authorization application for the major allergen groups (grass group, birch group, mites group, bee/wasp venom). Due to the EU pediatric regulation, in force since 2007, manufacturers had also to submit a pediatric investigation plan (PIP) for each allergen product. We investigated the allergic rhinoconjunctivitis (ARC) standard PIP, developed jointly by the European Medicines Agency (EMA) and the German Paul Ehrlich Institut (PEI). We analyzed the 118 EMA PIP decisions, looked for SIT trials in children in www.clinicaltrials.gov, and further analyzed EMA/EU justifications. The PIPs request a 1-year dose-finding study in adults, a 5-year placebo-controlled (PC) efficacy & safety (E&S) study in adults, and a 5-year PC E&S study in children. Fifty-eight PIP development programs will have to be performed until 2031. But children benefit even more from SIT for ARC than adults. There is no convincing medical/scientific justification for PC E&S studies in children in the relevant EMA documents. The PIP requirement to withhold effective treatment to thousands of children in the placebo group over a 5-year period raises profound concerns. The EMA justifications are formalistic and lack scientific foundation. A critical academic review of the ARC PIPs and the entire PIP system is urgently needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides lacking allergen-specific T cell epitopes reduces Bet v 1-specific T cell responses via blocking antibodies in a murine model for birch pollen allergy.

PubMed

Linhart, B; Narayanan, M; Focke-Tejkl, M; Wrba, F; Vrtala, S; Valenta, R

2014-02-01

Vaccines consisting of allergen-derived peptides lacking IgE reactivity and allergen-specific T cell epitopes bound to allergen-unrelated carrier molecules have been suggested as candidates for allergen-specific immunotherapy. To study whether prophylactic and therapeutic vaccination with carrier-bound peptides from the major birch pollen allergen Bet v 1 lacking allergen-specific T cell epitopes has influence on Bet v 1-specific T cell responses. Three Bet v 1-derived peptides, devoid of Bet v 1-specific T cell epitopes, were coupled to KLH and adsorbed to aluminium hydroxide to obtain a Bet v 1-specific allergy vaccine. Groups of BALB/c mice were immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet v 1- and peptide-specific antibody responses were analysed by ELISA. T cell and cytokine responses to Bet v 1, KLH, and the peptides were studied in proliferation assays. The effects of peptide-specific and allergen-specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies. Prophylactic and therapeutic vaccination with carrier-bound Bet v 1 peptides induced a Bet v 1-specific IgG antibody response without priming/boosting of Bet v 1-specific T cells. Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1-specific antibodies which suppressed Bet v 1-specific T cell responses and allergic lung inflammation. Vaccination with carrier-bound allergen-derived peptides lacking allergen-specific T cell epitopes induces allergen-specific IgG antibodies which suppress allergen-specific T cell responses and allergic lung inflammation. © 2013 John Wiley & Sons Ltd.

Induction of Bronchial Tolerance After 1 Cycle of Monophosphoryl-A-Adjuvanted Specific Immunotherapy in Children With Grass Pollen Allergies

PubMed Central

Girod, Katharina; Zielen, Stefan; Schubert, Ralf; Schulze, Johannes

2016-01-01

Purpose Subcutaneous allergen-specific immunotherapy (SCIT) is a well-established and clinically effective method to treat allergic diseases, such as rhinitis and asthma. It remains unclear how soon after initiation of an ultra-short course of grass pollen immunotherapy adjuvanted with monophosphoryl lipid A (MPL)-specific bronchial tolerance can be induced. Methods In a prospective study of 69 children double-sensitized to birch and grass pollens (51 males, average age 11.1 years), development of bronchial tolerance after 1 cycle of SCIT for grass was evaluated. In all the patients, the bronchial allergen provocation test (BAP) was performed before and after treatment. According to the results of the first BAP, the patients were divided into 2 groups: those showing a negative BAP with a decrease in FEV1 of <20% (seasonal allergic rhinitis [SAR] group, n=47); and those showing a positive BAP with a decrease in FEV1 of ≥20% (SAR with allergic asthma [SAR and Asthma] group, n=22). All the patients received MPL-adjuvanted, ultra-short course immunotherapy for birch, but only those with a positive BAP to grass received MPL-SCIT for grass. Results After the pollen season, the BAP in the SAR group remained unchanged, while it was improved in the SAR and Asthma group (decrease in FEV1 of 28.8% vs 12.5%, P<0.01). The IgG4 levels increased after SCIT (median before SCIT 0.34 to 11.4 after SCIT), whereas the total and specific IgE levels remained unchanged. Conclusions After 1 cycle of MPL-SCIT, specific bronchial tolerance may be significantly induced, whereas in patients without SCIT, bronchial hyperactivity may remain unchanged. PMID:26922936

Maintenance dosing for sublingual immunotherapy by prominent European allergen manufacturers expressed in bioequivalent allergy units.

PubMed

Larenas-Linnemann, Désirée; Esch, Robert; Plunkett, Greg; Brown, Shannon; Maddox, Daniel; Barnes, Charles; Constable, Derek

2011-11-01

Sublingual immunotherapy (SLIT) has become established in Europe, and its efficacy is being evaluated in the United States. The doses used for SLIT in Europe today are difficult to evaluate, because each manufacturer expresses the potency of its extracts differently. To compare in vitro European SLIT maintenance solutions against US licensed standardized allergenic extract concentrates and to determine the monthly SLIT doses delivered expressed in bioequivalent allergy units ([B]AU). We studied Dermatophagoides pteronyssinus, timothy grass pollen, cat (hair) and short ragweed pollen allergen extracts. The SLIT maintenance solutions of 4 leading European manufacturers and standardized concentrate extracts of 3 US manufacturers were analyzed with the following assays: protein content, relative potency (immunoglobulin E [IgE]-binding enzyme-linked immunosorbent assay [ELISA] inhibition) and major allergen content. The relative monthly allergen dose in (B)AU was calculated for each recommended SLIT schedule. Relative potency was approximately 10 times higher for US concentrate standardized extracts-which are meant to be diluted-than for European SLIT maintenance solutions of D pteronyssinus and timothy grass pollen. For cat (hair) and short ragweed pollen, the difference was less. Measurements of relative potency and major allergen content correlated well. In our assays, European mite extracts contain a very low quantity of Der p 2 compared with US mites. Recommended SLIT doses in Europe vary widely among the manufacturers, but are consistently lower (Eur1) or higher (Eur4) over all four allergens tested. SLIT efficacy probably depends on additional factors apart from the exact dose. SLIT dose finding studies should be done for each product. Copyright © 2011 American College of Allergy. Published by Elsevier Inc. All rights reserved.

Rational design of hypoallergens applied to the major cat allergen Fel d 1.

PubMed

Saarne, T; Kaiser, L; Grönlund, H; Rasool, O; Gafvelin, G; van Hage-Hamsten, M

2005-05-01

Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.

Effect of Two Years of Treatment with Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at Three Years among Patients with Moderate to Severe Seasonal Allergic Rhinitis: A Randomized Clinical Trial

PubMed Central

Scadding, Guy W.; Calderon, Moises A.; Shamji, Mohamed H.; Eifan, Aarif O.; Penagos, Martin; Dumitru, Florentina; Sever, Michelle L.; Bahnson, Henry T; Lawson, Kaitie; Harris, Kristina M.; Plough, Audrey G.; Panza, Joy Laurienzo; Qin, Tielin; Lim, Noha; Tchao, Nadia K.; Togias, Alkis; Durham, Stephen R.

2017-01-01

Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least two years following discontinuation of treatment. Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy compared with placebo provides improved nasal response to allergen challenge at 3 year follow-up. Design, Setting, Participants A randomized double-blind, placebo-controlled, 3-parallel group study performed in a single academic centre, Imperial College London, including adult patients with moderate-to-severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrolment was March 2011, last follow-up February 2015. Intervention Thirty-six participants received 2 years sublingual immunotherapy (daily tablets containing 15 microgram of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 micrograms of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years and at 3 years (1 year after treatment discontinuation). Main outcomes and measures Total nasal symptom scores (TNSS, range 0 (best) to 12 (worst) were recorded during 0–10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy to placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Results Among 106 participants who were randomized (mean age 33.5 years, 32.1% female), 92 completed the study at 3 years. Imputed TNSS scores [mean (95% confidence intervals)] pre-treatment and

Safety considerations in providing allergen immunotherapy in the office.

PubMed

Mattos, Jose L; Lee, Stella

2016-06-01

This review highlights the risks of allergy immunotherapy, methods to improve the quality and safety of allergy treatment, the current status of allergy quality metrics, and the future of quality measurement. In the current healthcare environment, the emphasis on outcomes measurement is increasing, and providers must be better equipped in the development, measurement, and reporting of safety and quality measures. Immunotherapy offers the only potential cure for allergic disease and asthma. Although well tolerated and effective, immunotherapy can be associated with serious consequence, including anaphylaxis and death. Many predisposing factors and errors that lead to serious systemic reactions are preventable, and the evaluation and implementation of quality measures are crucial to developing a safe immunotherapy practice. Although quality metrics for immunotherapy are in their infancy, they will become increasingly sophisticated, and providers will face increased pressure to deliver safe, high-quality, patient-centered, evidence-based, and efficient allergy care. The establishment of safety in the allergy office involves recognition of potential risk factors for anaphylaxis, the development and measurement of quality metrics, and changing systems-wide practices if needed. Quality improvement is a continuous process, and although national allergy-specific quality metrics do not yet exist, they are in development.

Letter to the Editor: Can dog allergen immunotherapy reduce concomitant allergic sensitization to other furry animals? A preliminary experience.

PubMed

Liccardi, G; Calzetta, L; Salzillo, A; Billeri, L; Lucà, G; Rogliani, P

2017-03-01

It has been shown that allergen immunotherapy (AIT) is effective in reducing symptoms of allergic asthma and rhinitis. Data on the efficacy are less convincing with regard to AIT for allergens of common pets (cats/dogs). We describe a case of dog allergy in which we explored if dog AIT (DAI) could reduce a concomitant allergic sensitization to other allergens of furry animals. Our case demonstrates the efficacy of sublingual DAI on SPTs, symptom score, and spirometric responses despite persistent exposure to dog allergens at home in a patient sensitized, but not exposed, to several other furry animals. Moreover, this is the first report suggesting that DAI is able to reduce SPTs responses not only to dog, but also to other furry animals such as rabbit, horse, mouse, rat, hamster, cow. We recommend an accurate anamnesis and diagnosis of dog allergy before prescribing DAI. In particular, the use of ImmunoCAP ISAC is essential to verify the presence of IgE to lipocalins / albumins belonging to other furry animals. Obviously further studies carried out by using different DAI schedules, allergen amount and time of re-evaluation, laboratory procedure should be performed to confirm our findings.

The future of immunotherapy for canine atopic dermatitis: a review.

PubMed

DeBoer, Douglas J

2017-02-01

Allergen specific immunotherapy (ASIT) is a foundation treatment for canine atopic dermatitis (CAD), though few critical studies have documented its effectiveness as a disease-modifying treatment in dogs. The mechanisms by which ASIT works in dogs have not been elucidated, although they are likely to parallel those known for humans. Current ASIT approaches in CAD focus on either subcutaneous or sublingual administration. Greater knowledge of major allergens in dogs, ideal dosage regimes and details of allergen admixture are likely to lead to better efficacy in CAD. Evaluation of biomarkers for successful therapy may also be of benefit. Potentially important advances in human medicine, that have yet to be explored in dogs, include use of modified allergen preparations such as allergoids, recombinant major allergens or allergen peptides; modification with adjuvants; or packaging of the above in virus-like particles. Co-administration of immunomodulators such as CpG oligodeoxynucleotides or specific monoclonal antibodies might direct the immune response in the desired direction while calming the "cytokine storm" of active disease. Initial trials of alternative routes of administration such as intralymphatic immunotherapy have yielded exciting results in humans, and continuing study in dogs is underway. Progress in ASIT of human food allergy may provide clues that will assist with improved diagnosis and patient management of CAD. Importantly, further study must be undertaken to clarify the conditions under which ASIT is a valuable treatment modality for dogs. © 2017 ESVD and ACVD.

Allergy to grass pollen: mapping of Dactylis glomerata and Phleum pratense allergens for dogs by two-dimensional immunoblotting

PubMed Central

Marques, Andreia Grilo; Pereira, Luísa Maria Dotti Silva; Semião-Santos, Saul José; Bento, Ofélia Pereira

2017-01-01

Introduction Much less is known about grass-pollen allergens to dogs, when compared with humans. Genetic-based patterns might play an important role in sensitization profiles, conditioning the success of allergen-specific immunotherapy. Aim Mapping of Dactylis glomerata (D. glomerata) and Phleum pratense (P. pratense) allergens for grass pollen-sensitized atopic dogs, for better understanding how individual allergograms may influence the response to grass-pollen immunotherapy. Material and methods To identify D. glomerata and P. pratense allergoms for dogs, 15 individuals allergic to grass pollen and sensitized to D. glomerata and P. pratense were selected. D. glomerata and P. pratense proteomes were separated by isoelectric focusing (IEF), one-dimensional (1-D) and two-dimensional (2-D) sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Separated proteins were blotted onto Polyvinylidene difluoride (PVDF) membranes and allergens were identified by patient sera IgE in Western Blotting (WB). Results In D. glomerata, 17 allergens were identified from IEF and 11 from 1-D SDS-PAGE, while from P. pratense, 18 and 6 allergens were identified, respectively. From 2-D SDS-PAGE 13 spots were identified from D. glomerata and 27 from P. pratense. Conclusions Several similarities were found between dog and human D. glomerata and P. pratense sensitization profiles but no relationship between clinical signs and a specific pattern of allergen recognition was observed. Similarities were found in each patient pattern of sensitization between D. glomerata and P. pratense, also suggesting cross-reactive phenomena. Further molecular epidemiology approach is needed to understand the role of the sensitization pattern in allergen-specific immunotherapy effectiveness in grass-pollen allergic dogs. PMID:28261033

Subtropical grass pollen allergens are important for allergic respiratory diseases in subtropical regions

PubMed Central

2012-01-01

Background Grass pollen allergens are a major cause of allergic respiratory disease but traditionally prescribing practice for grass pollen allergen-specific immunotherapy has favoured pollen extracts of temperate grasses. Here we aim to compare allergy to subtropical and temperate grass pollens in patients with allergic rhinitis from a subtropical region of Australia. Methods Sensitization to pollen extracts of the subtropical Bahia grass (Paspalum notatum), Johnson grass (Sorghum halepense) and Bermuda grass (Cynodon dactylon) as well as the temperate Ryegrass (Lolium perenne) were measured by skin prick in 233 subjects from Brisbane. Grass pollen-specific IgE reactivity was tested by ELISA and cross-inhibition ELISA. Results Patients with grass pollen allergy from a subtropical region showed higher skin prick diameters with subtropical Bahia grass and Bermuda grass pollens than with Johnson grass and Ryegrass pollens. IgE reactivity was higher with pollen of Bahia grass than Bermuda grass, Johnson grass and Ryegrass. Patients showed asymmetric cross-inhibition of IgE reactivity with subtropical grass pollens that was not blocked by temperate grass pollen allergens indicating the presence of species-specific IgE binding sites of subtropical grass pollen allergens that are not represented in temperate grass pollens. Conclusions Subtropical grass pollens are more important allergen sources than temperate grass pollens for patients from a subtropical region. Targeting allergen-specific immunotherapy to subtropical grass pollen allergens in patients with allergic rhinitis in subtropical regions could improve treatment efficacy thereby reducing the burden of allergic rhinitis and asthma. PMID:22409901

Development of cockroach immunotherapy by the Inner-City Asthma Consortium

PubMed Central

Wood, Robert A.; Togias, Alkis; Wildfire, Jeremy; Visness, Cynthia M.; Matsui, Elizabeth C.; Gruchalla, Rebecca; Hershey, Gurjit; Liu, Andrew H.; O’Connor, George T.; Pongracic, Jacqueline A.; Zoratti, Edward; Little, Frederic; Granada, Mark; Kennedy, Suzanne; Durham, Stephen R.; Shamji, Mohamed H.; Busse, William W.

2014-01-01

Background Cockroach allergy is a key contributor to asthma morbidity in children living in urban environments. Objective We sought to document immune responses to cockroach allergen and provide direction for the development of immunotherapy for cockroach allergy. Methods Four pilot studies were conducted: (1) an open-label study to assess the safety of cockroach sublingual immunotherapy (SLIT) in adults and children; (2) a randomized, double-blind biomarker study of cockroach SLIT versus placebo in adults; (3) a randomized, double-blind biomarker study of 2 doses of cockroach SLIT versus placebo in children; and (4) an open-label safety and biomarker study of cockroach subcutaneous immunotherapy (SCIT) in adults. Results The adult SLIT trial (n = 54; age, 18–54 years) found a significantly greater increase in cockroach-specific IgE levels between the active and placebo groups (geometric mean ratio, 1.92; P < .0001) and a trend toward increased cockroach-specific IgG4 levels in actively treated subjects (P = .09) but no evidence of functional blocking antibody response. The pediatric SLIT trial (n = 99; age, 5–17 years) found significant differences in IgE, IgG, and IgG4 responses between both active groups and the placebo group but no consistent differences between the high- and low-dose groups. In the SCIT study the treatment resulted in significant changes from baseline in cockroach IgE, IgG4, and blocking antibody levels. The safety profile of cockroach immunotherapy was reassuring in all studies. Conclusions The administration of cockroach allergen by means of SCIT is immunologically more active than SLIT, especially with regard to IgG4 levels and blocking antibody responses. No safety concerns were raised in any age group. These pilot studies suggest that immunotherapy with cockroach allergen is more likely to be effective with SCIT. PMID:24184147

Allergen immunotherapy: clinical and practical education of Italian trainees in allergy and clinical immunology schools.

PubMed

Ridolo, E; Incorvaia, C; Senna, G E; Montagni, M; Olivieri, E; Canonica, G W

2013-10-01

We performed a survey, based on a questionnaire including 20 items, submitted anonymously to Italian trainees in Allergology and Clinical Immunology, in order to obtain information about their specific allergen immunotherapy (AIT) practices. The questionnaire was sent to 40 trainees, who had attended the last two years of the training course. Thirty-four subjects (mean age: 27 years, 65% females) adequately completed the survey. The answers to the questionnaire showed that only 60% of the training programs included lectures on AIT. Among the trainees using AIT, only 40% declared being able to prescribe it independently, while 60% were guided by a tutor. Of the trainees who were able to prescribe AIT autonomously, 60% were familiar with both routes of administration, i.e. subcutaneous (SCIT) and sublingual immunotherapy (SLIT), while 25% of these used only SLIT. In 80% of the training institutions involved, the trainees could attend a dedicated AIT outpatient ward for SCIT administration; only 40% administered AIT personally, and in half of these cases, they were guided by a tutor. Only 70% of trainees had experience in the follow-up of patients still under treatment and of patients who had completed treatment. Analysis of the answers obtained for questions on venom immunotherapy (VIT) showed that, in 90% of cases, the trainees attended a dedicated outpatients ward where VIT is administered, but with a role limited to observation/cooperation. Only 30% were involved in the follow-up of patients who were under treatment or who had completed VIT. Only 20% of the trainees felt confident enough about VIT to prescribe this treatment independently, 80% knew there were several administration protocols, and the majority prescribed products from three different manufacturers. These findings suggest that there is significant room for improving the instructions provided regarding allergology and clinical immunology to trainees in Italy with respect to AIT.

Specific immunotherapy in ovarian cancer: a systematic review.

PubMed

Alipour, Soroush; Zoghi, Samaneh; Khalili, Nastaran; Hirbod-Mobarakeh, Armin; Emens, Leisha A; Rezaei, Nima

2016-10-01

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several approaches of active and passive immunotherapy for EOC have been studied. The aim of this systematic review was to assess the clinical efficacy of specific immunotherapy in patients with EOC. We found 4524 references in seven databases and we included ten controlled clinical trials with 2285 patients with EOC reporting five active immunotherapeutic agents and three passive immunotherapies. Meta-analysis of six studies showed that overall there was not any significant difference in overall survival and recurrence-free survival between patients undergoing specific immunotherapy and those in control group. Most of the studies we evaluated reported a positive outcome from treatment with specific immunotherapy, although this was not significant.

A double blind, randomized, placebo controlled trial of the efficacy, quality of life and safety of food allergen-specific sublingual immunotherapy in client owned dogs with adverse food reactions: a small pilot study.

PubMed

Maina, Elisa; Cox, Eric

2016-10-01

Food allergen-specific sublingual immunotherapy (FA-SLIT) has emerged as a novel and successful approach for desensitizing human patients to specific food allergens. It has not been tested in dogs. To investigate the efficacy, quality of life (QoL), tolerability and safety of FA-SLIT in dogs with adverse food reactions (AFR). Dogs with proven AFR were randomized to treatment (T group; n = 7) or placebo (P group; n = 6) to receive either FA-SLIT (based on the results of a food elimination trial) or glycerinated saline, respectively. The treatment was continued daily for 6 months with fortnightly dosage escalations. To evaluate the treatment, pruritus Visual Analog Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index (CADESI-04), QoL, faecal consistency scores, owner assessment, overall tolerability scores and blood analyses were assessed. Eleven dogs completed the study, two dogs in the T group were withdrawn by the owner after FA-SLIT exacerbated clinical signs of AFR. Statistical tests showed significant protection against food challenge induced clinical signs following FA-SLIT therapy, as indicated by reduced pVAS and CADESI scores (P < 0.05). The QoL did not differ between groups. The treatment was rated as effective or quite effective by 80% of the owners, whereas placebo was rated as ineffective by all owners. FA-SLIT was effective, well tolerated and safe. No severe adverse events were recorded; erythema and pruritus were reported in association with only 0.7% of the dispensed doses. Larger clinical trials with more extended maintenance immunotherapy periods will be needed to provide more precise estimates of efficacy and frequency of adverse events. © 2016 ESVD and ACVD.

Personalized Medicine in Allergic Asthma: At the Crossroads of Allergen Immunotherapy and "Biologicals".

PubMed

Fritzsching, Benedikt

2017-01-01

Major allergic disease can be viewed as clinical syndromes rather than discrete disease entities. Emerging evidence indicates that allergic asthma includes several disease phenotypes. Immunological deviation toward high T helper cell type 2 cytokine levels has been demonstrated for a subgroup of pediatric asthma patients, and now, several novel monoclonal antibodies have been approved for treatment of this subgroup as a stratified approach of "personalized" medicine in allergy. Introduction of component-based IgE testing before allergen immunotherapy (AIT), i.e., testing for IgE cross-reactivity before initiation of AIT, has also brought stratified medicine into allergy therapy. Improved responder criteria, which identify treatment-responders previous to therapy, might foster this stratification and even individualized AIT might have an impact for tailor-made therapy in the future. Furthermore, combining antibody-based treatment with AIT could help to establish more rapid AIT protocols even for allergens with a high risk of anaphylactic reactions. Efforts to advance such "personalized" medicine in pediatric allergy might be challenged by several issues including high costs for the health-care system, increasing complexity of allergy therapy, the need for physician allergy expertise, and furthermore ethical considerations and data safety issues.

Health economic comparison of SLIT allergen and SCIT allergoid immunotherapy in patients with seasonal grass-allergic rhinoconjunctivitis in Germany.

PubMed

Verheggen, Bram G; Westerhout, Kirsten Y; Schreder, Carl H; Augustin, Matthias

2015-01-01

Allergoids are chemically modified allergen extracts administered to reduce allergenicity and to maintain immunogenicity. Oralair® (the 5-grass tablet) is a sublingual native grass allergen tablet for pre- and co-seasonal treatment. Based on a literature review, meta-analysis, and cost-effectiveness analysis the relative effects and costs of the 5-grass tablet versus a mix of subcutaneous allergoid compounds for grass pollen allergic rhinoconjunctivitis were assessed. A Markov model with a time horizon of nine years was used to assess the costs and effects of three-year immunotherapy treatment. Relative efficacy expressed as standardized mean differences was estimated using an indirect comparison on symptom scores extracted from available clinical trials. The Rhinitis Symptom Utility Index (RSUI) was applied as a proxy to estimate utility values for symptom scores. Drug acquisition and other medical costs were derived from published sources as well as estimates for resource use, immunotherapy persistence, and occurrence of asthma. The analysis was executed from the German payer's perspective, which includes payments of the Statutory Health Insurance (SHI) and additional payments by insurants. Comprehensive deterministic and probabilistic sensitivity analyses and different scenarios were performed to test the uncertainty concerning the incremental model outcomes. The applied model predicted a cost-utility ratio of the 5-grass tablet versus a market mix of injectable allergoid products of € 12,593 per QALY in the base case analysis. Predicted incremental costs and QALYs were € 458 (95% confidence interval, CI: € 220; € 739) and 0.036 (95% CI: 0.002; 0.078), respectively. Compared to the allergoid mix the probability of the 5-grass tablet being the most cost-effective treatment option was predicted to be 76% at a willingness-to-pay threshold of € 20,000. The results were most sensitive to changes in efficacy estimates, duration of the pollen season, and

Fusion proteins of flagellin and the major birch pollen allergen Bet v 1 show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity.

PubMed

Kitzmüller, Claudia; Kalser, Julia; Mutschlechner, Sonja; Hauser, Michael; Zlabinger, Gerhard J; Ferreira, Fatima; Bohle, Barbara

2018-01-01

Recombinant fusion proteins of flagellin and antigens have been demonstrated to induce strong innate and adaptive immune responses. Such fusion proteins can enhance the efficacy of allergen-specific immunotherapy. We sought to characterize different fusion proteins of flagellin and the major birch pollen allergen Bet v 1 for suitability as allergy vaccines. A truncated version of flagellin (NtCFlg) was genetically fused to the N- or C-terminus of Bet v 1. Toll-like receptor (TLR) 5 binding was assessed with HEK293 cells expressing TLR5. Upregulation of CD40, CD80, CD83, and CD86 on monocyte-derived dendritic cells from allergic patients was analyzed by using flow cytometry. The T cell-stimulatory capacity of the fusion proteins was assessed with naive and Bet v 1-specific T cells. IgE binding was tested in inhibition ELISAs and basophil activation tests. Mice were immunized with the fusion proteins in the absence and presence of aluminum hydroxide. Cellular and antibody responses were monitored. Murine antibodies were tested for blocking capacity in basophil activation tests. Both fusion proteins matured monocyte-derived dendritic cells through TLR5. Compared with Bet v 1, the fusion proteins showed stronger T cell-stimulatory and reduced IgE-binding capacity and induced murine Bet v 1-specific antibodies in the absence of aluminum hydroxide. However, only antibodies induced by means of immunization with NtCFlg fused to the C-terminus of Bet v 1 inhibited binding of patients' IgE antibodies to Bet v 1. Bet v 1-flagellin fusion proteins show enhanced immunogenicity, reduced allergenicity, and intrinsic adjuvanticity and thus represent promising vaccines for birch pollen allergen-specific immunotherapy. However, the sequential order of allergen and adjuvant within a fusion protein determines its immunologic characteristics. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of grass allergen tablet (GRAZAX) for the prevention of seasonal grass pollen induced rhinoconjunctivitis - a Northern European perspective.

PubMed

Bachert, C; Vestenbaek, U; Christensen, J; Griffiths, U K; Poulsen, P B

2007-05-01

The prevalence of allergic rhinoconjunctivitis has increased dramatically. Seventeen million people in the United Kingdom, Germany, the Netherlands, Sweden, Denmark, Norway and Finland suffer from grass pollen induced allergic rhinitis. Symptomatic therapy with antihistamines and topical steroids is partially effective but allergen-specific immunotherapy by injection or sublingual routes is superior. The grass allergen tablet (GRAZAX) is a new allergen-specific immunotherapy for home administration. To assess the cost-effectiveness of the grass allergen tablet compared with symptomatic medication in seven Northern European countries. A prospective pharmacoeconomic analysis was carried out alongside a multinational clinical trial. Pooled data on resource use and health outcomes were collected. A societal perspective was adopted, and the analysis had a 9-year time horizon. The outcome measure was Quality Adjusted Life Years (QALYs). The grass allergen tablet was clinically superior to symptomatic treatment, producing statistically significant differences for all efficacy end-points, including the number of QALYs gained - 0.976 vs. 0.947 QALYs gained. There was a significantly higher usage of the rescue medications loratadine and budesonide, and more hours missed from work (production loss), in the symptomatic treatment group. The cost per QALY gained in the grass allergen tablet group was similar in the seven countries (euro 12,930 to euro 18,263 for an annual cost of the grass allergen tablet of euro 1500). The analysis showed that the grass allergen tablet was cost-effective for all countries for an annual treatment cost below euro 2200. The pharmacoeconomic analysis illustrated that allergen-specific immunotherapy with the grass allergen tablet is a cost-effective intervention for the prevention of grass pollen induced rhinoconjunctivitis in Northern European countries, for a tablet price below euro 6. In Germany for example the price of the tablet is euro 2

Sublingual immunotherapy: World Allergy Organization position paper 2013 update.

PubMed

Canonica, Giorgio Walter; Cox, Linda; Pawankar, Ruby; Baena-Cagnani, Carlos E; Blaiss, Michael; Bonini, Sergio; Bousquet, Jean; Calderón, Moises; Compalati, Enrico; Durham, Stephen R; van Wijk, Roy Gerth; Larenas-Linnemann, Désirée; Nelson, Harold; Passalacqua, Giovanni; Pfaar, Oliver; Rosário, Nelson; Ryan, Dermot; Rosenwasser, Lanny; Schmid-Grendelmeier, Peter; Senna, Gianenrico; Valovirta, Erkka; Van Bever, Hugo; Vichyanond, Pakit; Wahn, Ulrich; Yusuf, Osman

2014-03-28

We have prepared this document, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update", according to the evidence-based criteria, revising and updating chapters of the originally published paper, "Sublingual Immunotherapy: World Allergy Organization Position Paper 2009", available at http://www.waojournal.org. Namely, these comprise: "Mechanisms of sublingual immunotherapy;" "Clinical efficacy of sublingual immunotherapy" - reporting all the data of all controlled trials published after 2009; "Safety of sublingual immunotherapy" - with the recently published Grading System for adverse reactions; "Impact of sublingual immunotherapy on the natural history of respiratory allergy" - with the relevant evidences published since 2009; "Efficacy of SLIT in children" - with detailed analysis of all the studies; "Definition of SLIT patient selection" - reporting the criteria for eligibility to sublingual immunotherapy; "The future of immunotherapy in the community care setting"; "Methodology of clinical trials according to the current scientific and regulatory standards"; and "Guideline development: from evidence-based medicine to patients' views" - including the evolution of the methods to make clinical recommendations.Additionally, we have added new chapters to cover a few emerging crucial topics: "Practical aspects of schedules and dosages and counseling for adherence" - which is crucial in clinical practice for all treatments; "Perspectives and new approaches" - including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, "Raising public awareness about sublingual immunotherapy", as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail.

Molecular aspects of allergens in atopic dermatitis

PubMed Central

Campana, Raffaela; Dzoro, Sheron; Mittermann, Irene; Fedenko, Elena; Elisyutina, Olga; Khaitov, Musa; Karaulov, Alexander; Valenta, Rudolf

2017-01-01

Purpose of review Molecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens. Here we review recent work showing the usefulness of molecular allergology to study mechanisms of atopic dermatitis, for diagnosis and eventually for treatment and prevention of atopic dermatitis. Recent findings IgE sensitization to airborne, food-derived, microbial allergens, and autoallergens has been found to be associated with atopic dermatitis. Using defined allergen molecules and non-IgE-reactive allergen derivatives, evidence could be provided for the existence of IgE- and non-IgE-mediated mechanisms of inflammation in atopic dermatitis. Furthermore, effects of epicutaneous allergen administration on systemic allergen-specific immune responses have been studied. Multi-allergen tests containing micro-arrayed allergen molecules have been shown to be useful for the identification of culprit allergens in atopic dermatitis and may improve the management of atopic dermatitis by allergen-specific immunotherapy, allergen avoidance, and IgE-targeting therapies in a personalized medicine approach. Summary Molecular allergology allows for dissection of the pathomechanisms of atopic dermatitis, provides new forms of allergy diagnosis for identification of disease-causing allergens, and opens the door to new forms of management by allergen-specific and T cells-targeting or IgE-targeting interventions in a personalized medicine approach. PMID:28622169

Allergy multivaccines created by DNA shuffling of tree pollen allergens.

PubMed

Wallner, Michael; Stöcklinger, Angelika; Thalhamer, Theresa; Bohle, Barbara; Vogel, Lothar; Briza, Peter; Breiteneder, Heimo; Vieths, Stefan; Hartl, Arnulf; Mari, Adriano; Ebner, Christof; Lackner, Peter; Hammerl, Peter; Thalhamer, Josef; Ferreira, Fatima

2007-08-01

The major allergens of trees belonging to the Fagales order are collectively known as the Bet v 1 family. Members of the Fagales order have distinct geographic distribution, and it is expected that depending on the exposure pattern of the individual, inclusion of other Bet v 1 family members might increase the efficacy of the treatment. We aimed to generate molecules that are suitable for specific immunotherapy not only against birch pollen allergy but also against allergies caused by other cross-reactive tree pollens. Fourteen genes of the Bet v 1 family were randomly recombined in vitro by means of DNA shuffling. This library of chimeric proteins was screened for molecules displaying low capacity to induce release of inflammatory mediators but with T-cell immunogenicity higher than that of the parental allergens. Two chimeric proteins were selected from the library of shuffled clones displaying low allergenicity and high immunogenicity, as determined in in vitro assays using human and animal cells and antibodies, as well as in vivo in animal models of allergy. Our results show that it is possible to randomly recombine in vitro T- and B-cell epitopes of a family of related allergens and to select chimeric proteins that perfectly match the criteria presently thought to be relevant for improving allergen-specific immunotherapy. The hypoallergenic chimeras described here recombine epitopes of the major Fagales pollen allergens and thus can efficiently substitute a mixture of extracts used for treating patients with tree pollen-induced spring pollinosis worldwide.

A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge.

PubMed

Bolhaar, S T H P; Zuidmeer, L; Ma, Y; Ferreira, F; Bruijnzeel-Koomen, C A F M; Hoffmann-Sommergruber, K; van Ree, R; Knulst, A C

2005-12-01

Allergen-specific immunotherapy for food allergy has been hindered by severe side-effects in the past. Well-characterized hypo-allergenic recombinant food allergens potentially offer a safe solution. To demonstrate hypo-allergenicity of a mutated major food allergen from apple, Mal d 1, in vitro and in vivo. A mutant of the major apple allergen, Mal d 1, was obtained by site-directed mutagenesis exchanging five amino acid residues. Fourteen patients with combined birch pollen-related apple allergy were included in the study. Hypo-allergenicity of the mutant rMal d 1 (rMal d 1mut) compared with rMal d 1 was assessed by in vitro methods, i.e. RAST (inhibition), immunoblotting and basophil histamine release (BHR) and in vivo by skin prick test and double-blind placebo-controlled food challenge (DBPCFC). RAST analysis (n = 14) revealed that IgE reactivity to rMal d 1mut was twofold lower than that of the wild-type molecule (95% confidence interval (CI): 1.7-2.4). RAST inhibition (n = 6) showed a 7.8-fold decrease in IgE-binding potency (95% CI: 3.0-12.6). In contrast to this moderate decrease in IgE-binding potency, the biological activity of rMal d 1mut assessed by SPT and BHR decreased 10-200-fold. Hypo-allergenicity was confirmed by DBPCFC (n = 2) with both recombinant molecules. A moderate decrease in IgE-binding potency translates into a potent inhibition of biological activity. This is the first study that confirms by DBPCFC that a mutated recombinant major food allergen is clinically hypo-allergenic. This paves the way towards safer immunotherapy for the treatment of food-allergic patients.

[The role of the basophil activation test (BAT) in qualification for specific immunotherapy with inhalant allergens].

PubMed

Bulanda, Małgorzata; Dyga, Wojciech; Rusinek, Barbara; Czarnobilska, Ewa

Qualification for specific immunotherapy (SIT) according to the guidelines of the European Academy of Allergy and Clinical Immunology (EAACI) includes medical history, skin prik tests (SPT) and/or measuring the concentration of sIgE. It is necessary to perform additional diagnostic tests in case of discrepancies between the history and the results of SPT/sIgE or differences between SPT and sIgE. Basophil activation test (BAT) assesses the expression of activation markers of these cells, eg. CD63 and CD203c after stimulation. The aim of our study was to evaluate the usefulness of BAT in the qualification for the SIT in comparison to the SPT and sIgE and in case of discrepancies between the results of SPT and sIgE. The study included 30 patients with allergic rhinitis (AR) caused by allergy to house dust mite (Dermatophagoides pteronyssinus, Dp) or birch pollen qualified for SIT. All patients had SPT, sIgE and BAT determination. The group of patients with allergy to birch was a control group for Dp allergic and vice versa. BAT with CD63 antigen expression was performed using a Flow2CAST test. Basophils were stimulated with allergen preparation (50, 500, and 5000 SBU/ml concentrations). BAT results were expressed as a stimulation index (SI). For optimal concentrations of 50 and 500 SBU/ml parameters comparing BAT to SPT and sIgE as the gold standards were consecutively: sensitivity 82-100% and 93-100%, specificity 50-94% and 47-89%, positive predictive value 65- 94% and 61-87%, negative predictive value 86-100% and 93-100%. Correlation BAT - SPT and BAT - sIgE ranged within 0.59 to 0.84 and 0.51 to 0.72. BAT was helpful in 2 of 30 patients with incompatible results of SPT and sIgE. Optimal concentrations for basophil stimulation are 50 and 500 SBU/ ml. BAT may be useful diagnostic tool in the qualification for the SIT in case of discrepancies between the results of SPT and sIgE.

Immunotherapy in allergy and cellular tests

PubMed Central

Chirumbolo, Salvatore

2014-01-01

The basophil activation test (BAT) is an in vitro assay where the activation of basophils upon exposure to various IgE-challenging molecules is measured by flow cytometry. It is a cellular test able to investigate basophil behavior during allergy and allergy immunotherapy. A panoply of critical issues and suggestive advances have rendered this assay a promising yet puzzling tool to endeavor a full comprehension of innate immunity of allergy desensitization and manage allergen or monoclonal anti-IgE therapy. In this review a brief state of art of BAT in immunotherapy is described focusing onto the analytical issue pertaining BAT performance in allergy specific therapy. PMID:24717453

Detection of cross-reactivity for atopic immunoglobulin E against multiple allergens.

PubMed

Chiou, Yee-Hsuan; Yuo, Chung-Yee; Wang, Lin-Yu; Huang, Shiao-ping

2003-03-01

The existence of specific immunoglobulin E (IgE) allows us to determine the allergens that cause the allergic disease. For the purposes of allergen avoidance and immunotherapy, the measurement of specific IgE is widely applied in clinical laboratories. However, if IgE from the serum of an allergic patient exhibits reactivity to multiple allergens, it would cause a problem. The present study analyzes whether the serum IgE with multiple reactivity is due to the presence of unique IgE against the common epitope shared by different allergens or the presence of multiple IgEs against different epitopes on different allergens. The quantitative-competitive inhibition tests and the immunoblotting were applied to analyze the immunosimilarity among examined allergens. The result shows that the competitive inhibition of IgE binding between shrimp and crab allergens is higher than those between either shrimp and cockroach or between crab and cockroach. Furthermore, the results of immunoblotting are consistent with those of quantitative-competitive inhibition tests. These results allow us to detect the cross-reactivity for atopic IgE against multiple allergens.

Allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens: an in vitro study.

PubMed

Siman, Isabella Lima; de Aquino, Lais Martins; Ynoue, Leandro Hideki; Miranda, Juliana Silva; Pajuaba, Ana Claudia Arantes Marquez; Cunha-Júnior, Jair Pereira; Silva, Deise Aparecida Oliveira; Taketomi, Ernesto Akio

2013-01-01

One of the purposes of specific immunotherapy (SIT) is to modulate humoral immune response against allergens with significant increases in allergen-specific IgG levels, commonly associated with blocking activity. The present study investigated in vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to Dermatophagoides pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were purified by ammonium sulfate precipitation followed by protein-G affinity chromatography. Purity was checked by SDS-PAGE and immunoreactivity by slot-blot and immunoblot assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretic profile of the ammonium sulfate precipitated fraction showed strongly stained bands in ligand fraction after chromatography, compatible with molecular weight of human whole IgG molecule. The purity degree was confirmed by detecting strong immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific IgG fraction was capable of significantly reducing levels of IgE anti-Dpt, resulting in 35%-51% inhibition of IgE reactivity to Dpt in atopic patients sera. This study showed that allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens. This approach reinforces that intermittent measurement of serum allergen-specific IgG antibodies will be an important objective laboratorial parameter that will help specialists to follow their patients under SIT.

Non-fragrance allergens in specific cosmetic products.

PubMed

Travassos, Ana Rita; Claes, Lieve; Boey, Lies; Drieghe, Jacques; Goossens, An

2011-11-01

Reports about the nature of the ingredients responsible for allergic contact dermatitis caused by specific cosmetic products are scarce. Between January 2000 and December 2010, the specific cosmetic products having caused allergic contact dermatitis, as well as the individual allergenic cosmetic ingredients present in them, were recorded by use of a standardized form. Among 11 different categories of cosmetic product, skin care products, followed by hair care and body-cleansing products, were most often involved. The presence of the allergenic ingredient(s) in a specific cosmetic product was confirmed according to the ingredient label in 959 of 1448 records. Six hundred and twenty-one of 959 concerned non-fragrance components, preservatives being responsible for 58% of them. Reactions to formaldehyde and formaldehyde-releasers were most often correlated with body-cleansing products, particularly 2-bromo-2-nitropropane-1,3-diol and skin care products. They were followed by the methylchloroisothiazolinone/methylisothiazolinone mixture, most frequently found as allergens in hair care and intimate hygiene products, and facial cleansers (in the last category together with diazolidinyl urea). Octocrylene was by far the most frequent (photo)allergen in sun care products. This study provides information on the presence and frequency of allergens in specific causal cosmetic products. © 2011 John Wiley & Sons A/S.

National clinical practice guidelines for allergen immunotherapy: An international assessment applying AGREE-II.

PubMed

Larenas-Linnemann, D E S; Antolín-Amérigo, D; Parisi, C; Nakonechna, A; Luna-Pech, J A; Wedi, B; Davila, I; Gómez, M; Levin, M; Ortega Martell, J A; Klimek, L; Rosario, N; Muraro, A M; Agache, I; Bousquet, J; Sheikh, A; Pfaar, O

2018-03-01

Since 1988, numerous allergen immunotherapy guidelines (AIT-GLs) have been developed by national and international organizations to guide physicians in AIT. Even so, AIT is still severely underused. To evaluate AIT-GLs with AGREE-II, developed in 2010 by McMaster University methodologists to comprehensively evaluate GL quality. Allergist, from different continents, knowledgeable in AIT and AGREE-II trained were selected into the project team. The project received methodologists' guidance. AIT-GLs in any language were sought from 1980 to 2016; AIT-GLs were AGREE II-evaluated by at least 2 team members, independently; discrepancies were resolved in a second round, by team discussion or methodologists' consulting. We found 31 AIT-GLs (15 post-2010), ranging from local consensus reports to international position papers (EAACI, AAAAI-ACAAI, WAO). Pre-2010 GLs scored 1.6-4.6 (23%-67%) and post-2010 GLs scored 2.1-6 (30%-86%), on a 7-point Likert scale. The highest scores went to: German-Austrian-Swiss (6.0), Mexican (5.1), and the AAAAI/ACAAI AIT-GL (4.7). These were also the only 3 GLs that received "yes" of both evaluators to the item: "I would recommend this GL for use." The domains of "Stakeholder involvement" and "Rigor of Development" only scored 3/7, and "Applicability" scored the lowest. Strikingly, newer GLs only scored clearly better in "Editorial independence" and "Global evaluation." In AIT-GLs, there is still a lot of room for improvement, especially in domains crucial for the dissemination. For some GLs, the "Scientific rigor" domain flawed. When resources are limited, transculturizing a high-quality GL might be preferable over developing a GL from zero. Our study and AGREE-II could help to select the best candidate. We here evaluate allergen immunotherapy guideline (AIT-GL) quality. Only high-quality AIT-GLs should be consulted for AIT management decisions. In low-resource settings, transculturization of these is preferred over developing low

Epicutaneous immunotherapy on intact skin using a new delivery system in a murine model of allergy.

PubMed

Mondoulet, L; Dioszeghy, V; Ligouis, M; Dhelft, V; Dupont, C; Benhamou, P-H

2010-04-01

Allergen-specific immunotherapy, subcutaneous immunotherapy (SCIT) or oral, has been used for almost a century to redirect inappropriate immune responses in atopic patients. A new mode of administration through the intact skin [epicutaneous immunotherapy (EPIT)], using an original epicutaneous delivery system, may represent an alternative to these classical methods. Proof of concept of efficacy of EPIT on intact skin in mice sensitized to aeroallergens or food allergens. Mice were sensitized to pollen (n=18), house dust mite (HDM, n=24), ovalbumin (OVA, n=18) or peanut (n=18), and allocated to four groups: EPIT, SCIT, not treated (NT) and control. Specific Ig (sIg)E, sIgG1 and sIgG2a were monitored. After 8 weeks of treatment, plethysmography was performed after aerosol provocation with appropriate allergens. At the highest doses of methacholine, pause enhancement (Penh) values were significantly decreased in the EPIT group vs. the sensitized NT groups (7.5 vs. 12.3 - pollen, 7.6 vs. 8.9 - HDM, 11.5 vs. 14.5 - OVA, 7.6 vs. 12.8 - peanut, respectively) (P<0.05). With all the allergens tested, Penh values were similar in SCIT, EPIT and control. IgG2a for pollen, HDM, OVA and peanuts were significantly increased in the EPIT group vs. NT: 0.97 vs. 0.42 microg/mL, 2.5 vs. 0.46 microg/mL, 0.39 vs. 0.05 microg/mL and 15.0 vs. 5.5 microg/mL, respectively (P<0.05). There were no significant differences between EPIT and SCIT groups. The IgE/IgG2a ratio decreased significantly in the EPIT group for the four allergens from 70 to 58 (pollen), 175 to 26 (HDM), 5433 to 120 (OVA) and 49 to 6 (peanut), respectively (P<0.05). In mice sensitized to the four allergens tested, EPIT was as efficacious as SCIT, considered as the reference immunotherapy. These first results have to be confirmed by clinical studies.

Preservation of allergic contact dermatitis to poison ivy (urushiol) in late HIV disease. The implications and relevance to immunotherapy with contact allergens.

PubMed

Smith, K J; Skelton, H G; Nelson, A; Wagner, K F; Hackley, B E

1997-01-01

Delayed hypersensitivity reactions (DTH) are lost with progression of HIV disease. This loss of DTH commonly occurs before the onset of opportunistic infections and is an independent predictor of disease progression. We wanted to determine whether patients in late HIV disease with a history of allergic contact dermatitis (ACD) to poison ivy continue to react to poison ivy. Twelve HIV+ patients with a past history of ACD to poison ivy were tested with an extract prepared from poison ivy leaves. All but 1 patient had CD4+ T cell counts < 200/microliters, and 5 patients had had an opportunistic infection. All 12 patients showed positive reactions ranging from mild erythema and infiltration to marked erythema with bulla formation. ACD is considered a variant of DTH, and as DTH results in a T helper 1 cytokine pattern. However, the antigen-specific effector cells in ACD may be more diverse than in DTH. This diversity could explain the continued reaction to some contact allergens in late disease and may be important in the use of contact allergens for immunotherapy.

Factors affecting allergen-specific IgE serum levels in cats

PubMed Central

Belova, S.; Wilhelm, S.; Linek, M.; Beco, L.; Fontaine, J.; Bergvall, K.; Favrot, C.

2012-01-01

Pruritic skin diseases are common in cats and demand rigorous diagnostic workup for finding an underlying etiology. Measurement of a serum allergen-specific IgE in a pruritic cat is often used to make or confirm the diagnosis of a skin hypersensitivity disease, although current evidence suggests that elevated allergen-specific IgE do not always correlate with a clinical disease and vice versa. The aim of the study was to to assess the possible influence of age, deworming status, lifestyle, flea treatment, and gender on allergen-specific IgE levels and to evaluate the reliability of IgE testing in predicting the final diagnosis of a pruritic cat. For this purpose sera of 179 cats with pruritus of different causes and 20 healthy cats were evaluated for allergen-specific IgE against environmental, food and flea allergens using the Fc-epsilon receptor based enzyme-linked immunosorbent assay (ELISA) test. The results of the study showed positive correlation between age, outdoor life style, absence of deworming, absence of flea control measures and levels of allergen-specific IgE. Gender and living area (urban versus rural) did not seem to affect the formation of allergen-specific IgE. According to these findings, evaluating allergen-specific IgE levels, is not a reliable test to diagnose hypersensitivity to food or environmental allergens in cats. On the contrary, this test can be successfully used for diagnosing feline flea bite hypersensitivity. PMID:22754094

Immunotherapy with the storage mite lepidoglyphus destructor.

PubMed

Armentia-Medina, A; Tapias, J A; Martín, J F; Ventas, P; Fernández, A

1995-01-01

We carried out a double-blind clinical trial of immunotherapy on 35 patients sensitized to the storage mite Lepidoglyphus destructor (Ld). Before and after 12 months of specific hyposensitization (Abelló Lab., Spain) we performed in vivo (skin tests with Ld, methacholine and challenge tests), and in vitro tests (specific IgE, IgG, IgG1 and IgG4 to Ld and specific IgE, IgG, IgG1 and IgG4 to their major allergen Lep dI). We also monitored the efficacy and safety of the immunotherapy with clinical and analytical controls (symptoms and medication score, detection of immune complexes). After therapy we found a significant decrease in specific skin reactivity, dose of positive challenge tests, and hyperresponsiveness to methacholine. Sputum eosinophilia decreased. Specific IgE to Ld was increased and we also observed an increase in specific IgG1 and IgG4 to Ld and Lep DI. The placebo group showed no changes in these variables. There were no severe secondary reactions after treatment with the extract. Patients-self-evaluation was favourable and their labour absence decreased. No development of circulating immune complexes was associated with this immunotherapy.

Cur l 3, a major allergen of Curvularia lunata-derived short synthetic peptides, shows promise for successful immunotherapy.

PubMed

Sharma, Vidhu; Singh, Bhanu Pratap; Arora, Naveen

2011-12-01

Allergens with reduced IgE binding and intact T cell reactivity are required for safety and efficacy of immunotherapy (IT). Curvularia lunata is an important fungus for respiratory allergic disorders having cross-reactive and specific allergens. Previously, we have identified major allergens-namely, Cur l 1 (31 kD, serine protease), Cur l 2 (48 kD, enolase), and Cur l 3 (12 kD, cytochrome c)-from this fungus. Furthermore, Cur l 3 epitope-peptide, P6, showed immunogenicity and higher IgE binding, where cysteine and histidine were observed to be vital for IgE binding. Thus, this peptide and three derivatives with reduced IgE binding were selected for analysis in mice. In the present study, the effect of IT was assessed with Cur l 3, P6, its derivatives (P6.1-6.3), and P10 in a mouse model of allergy. IT with P6.2 and P10 reduced IgE and IgG1 levels significantly (P < 0.05), with increase in IgG2a levels as compared to other antigens. There was a significant reduction of IL-4 level associated with increased IFN-γ after IT. Airway inflammation was reduced significantly in terms of eosinophil counts in lung tissue and bronchoalveolar lavage fluid. IT with P6 and P6.2 induced significantly higher IL-10 secretion than baseline after 40 days of treatment. Generally, the effect of IT was more pronounced after 40 days than after 10 days of treatment. In summary, the modified peptide, P6.2, with reduced IgE binding, but intact immunogenicity, showed promise for successful IT.

New strategies for allergen T cell epitope identification: going beyond IgE

PubMed Central

Schulten, Véronique; Peters, Bjoern; Sette, Alessandro

2014-01-01

Background Type I allergy and allergic asthma are common diseases in the developed world associated with IgE antibodies and Th2 cell reactivity. To date, the only causative treatment for allergic disease is specific immunotherapy (SIT). Method Here, we review recent works from our laboratory focused on identifying human T cell epitopes associated with allergic disease and their potential use as biomarkers or therapeutic targets for SIT. In previous studies, we have mapped T cell epitopes associated with the major ten Timothy grass (Tg) allergens, defined on the basis of human IgE reactivity by ELISPOT. Results Interestingly, in about 33% of allergic donors no T cell epitopes from overlapping peptides spanning the entire sequences of these allergens were identified, despite vigorous T cell responses to the Tg extract. Using a bioinformatics-proteomic approach, we identified a set of 93 novel Tg proteins, many of which were found to elicit IL-5 production in T cells from allergic donors despite lacking IgE reactivity. Next, we assessed T cell responses to the novel Tg proteins in donors who had been treated with subcutaneous specific immunotherapy (SCIT). A subset of these proteins showed a strong reduction of IL-5 responses in donors who had received SCIT compared to allergic donors, which correlated with patient's self-reported improvement of allergic symptoms. Conclusion A bioinformatics-proteomic approach has successfully identified additional Tg-derived T cell targets independent of IgE reactivity. This method can be applied to other allergies potentially leading to the discovery of promising therapeutic targets for allergen-specific immunotherapy. PMID:25402674

Mold Allergens in Respiratory Allergy: From Structure to Therapy

PubMed Central

Twaroch, Teresa E; Curin, Mirela; Swoboda, Ines

2015-01-01

Allergic reactions to fungi were described 300 years ago, but the importance of allergy to fungi has been underestimated for a long time. Allergens from fungi mainly cause respiratory and skin symptoms in sensitized patients. In this review, we will focus on fungi and fungal allergens involved in respiratory forms of allergy, such as allergic rhinitis and asthma. Fungi can act as indoor and outdoor respiratory allergen sources, and depending on climate conditions, the rates of sensitization in individuals attending allergy clinics range from 5% to 20%. Due to the poor quality of natural fungal allergen extracts, diagnosis of fungal allergy is hampered, and allergen-specific immunotherapy is rarely given. Several factors are responsible for the poor quality of natural fungal extracts, among which the influence of culture conditions on allergen contents. However, molecular cloning techniques have allowed us to isolate DNAs coding for fungal allergens and to produce a continuously growing panel of recombinant allergens for the diagnosis of fungal allergy. Moreover, technologies are now available for the preparation of recombinant and synthetic fungal allergen derivatives which can be used to develop safe vaccines for the treatment of fungal allergy. PMID:25840710

Sensitization rates of causative allergens for dogs with atopic dermatitis: detection of canine allergen-specific IgE

PubMed Central

Kang, Min-Hee; Kim, Ha-Jung; Jang, Hye-Jin

2014-01-01

Allergen-specific IgE serology tests became commercially available in the 1980s. Since then these tests have been widely used to diagnose and treat allergic skin diseases. However, the relationship between a positive reaction and disease occurrence has been controversial. The purpose of this study was to evaluate allergens using a serologic allergy test in dogs with atopic dermatitis (AD). Dogs clinically diagnosed with AD (n=101) were tested using an allergen-specific IgE immunoassay. Among the total 92 environmental and food allergens, house dust and house dust mites were the most common. Several allergens including airborne pollens and molds produced positive reactions, and which was considered increasing allergens relating to the climate changes. The presence of antibodies against staphylococci and Malassezia in cases of canine AD was warranted in this study. Additionally, strong (chicken, turkey, brown rice, brewer's yeast, and soybean) and weakly (rabbit, vension, duck, and tuna) positive reactions to food allergens could be used for avoidance and limited-allergen trials. PMID:24962408

Sensitization rates of causative allergens for dogs with atopic dermatitis: detection of canine allergen-specific IgE.

PubMed

Kang, Min-Hee; Kim, Ha-Jung; Jang, Hye-Jin; Park, Hee-Myung

2014-12-01

Allergen-specific IgE serology tests became commercially available in the 1980s. Since then these tests have been widely used to diagnose and treat allergic skin diseases. However, the relationship between a positive reaction and disease occurrence has been controversial. The purpose of this study was to evaluate allergens using a serologic allergy test in dogs with atopic dermatitis (AD). Dogs clinically diagnosed with AD (n = 101) were tested using an allergen-specific IgE immunoassay. Among the total 92 environmental and food allergens, house dust and house dust mites were the most common. Several allergens including airborne pollens and molds produced positive reactions, and which was considered increasing allergens relating to the climate changes. The presence of antibodies against staphylococci and Malassezia in cases of canine AD was warranted in this study. Additionally, strong (chicken, turkey, brown rice, brewer's yeast, and soybean) and weakly (rabbit, vension, duck, and tuna) positive reactions to food allergens could be used for avoidance and limited-allergen trials.

Allergen immunotherapy for IgE-mediated food allergy: a systematic review and meta-analysis.

PubMed

Nurmatov, U; Dhami, S; Arasi, S; Pajno, G B; Fernandez-Rivas, M; Muraro, A; Roberts, G; Akdis, C; Alvaro-Lozano, M; Beyer, K; Bindslev-Jensen, C; Burks, W; du Toit, G; Ebisawa, M; Eigenmann, P; Knol, E; Makela, M; Nadeau, K C; O'Mahony, L; Papadopoulos, N; Poulsen, L K; Sackesen, C; Sampson, H; Santos, A F; van Ree, R; Timmermans, F; Sheikh, A

2017-08-01

The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated Food Allergy. To inform the development of clinical recommendations, we sought to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT in the management of food allergy. We undertook a systematic review and meta-analysis that involved searching nine international electronic databases for randomized controlled trials (RCTs) and nonrandomized studies (NRS). Eligible studies were independently assessed by two reviewers against predefined eligibility criteria. The quality of studies was assessed using the Cochrane Risk of Bias tool for RCTs and the Cochrane ACROBAT-NRS tool for quasi-RCTs. Random-effects meta-analyses were undertaken, with planned subgroup and sensitivity analyses. We identified 1814 potentially relevant papers from which we selected 31 eligible studies, comprising of 25 RCTs and six NRS, studying a total of 1259 patients. Twenty-five trials evaluated oral immunotherapy (OIT), five studies investigated sublingual immunotherapy, and one study evaluated epicutaneous immunotherapy. The majority of these studies were in children. Twenty-seven studies assessed desensitization, and eight studies investigated sustained unresponsiveness postdiscontinuation of AIT. Meta-analyses demonstrated a substantial benefit in terms of desensitization (risk ratio (RR) = 0.16, 95% CI 0.10, 0.26) and suggested, but did not confirm sustained unresponsiveness (RR = 0.29, 95% CI 0.08, 1.13). Only one study reported on disease-specific quality of life (QoL), which reported no comparative results between OIT and control group. Meta-analyses revealed that the risk of experiencing a systemic adverse reaction was higher in those receiving AIT, with a more marked increase in the risk of local adverse reactions. Sensitivity analysis excluding those studies judged to be at high risk of bias demonstrated the

Kissing selectively decreases allergen-specific IgE production in atopic patients.

PubMed

Kimata, H

2006-05-01

Stress enhanced allergic skin wheal responses and allergen-specific IgE production. In contrast, mothers' kissing caused relaxation in infants, and kissing by lovers or spouses to atopic patients reduced allergic skin wheal responses. I studied the effect of kissing on production of allergen-specific IgE and cytokines in atopic patients. Twenty-four patients with mild atopic eczema and 24 patients with mild allergic rhinitis kissed with lovers or spouses freely for 30 min while listening to soft music. Just before and immediately after kissing, blood mononuclear cells were separated cultured for allergen, and production of allergen-specific immunoglobulin and cytokine was measured. Kissing selectively decreased allergen-specific IgE production with skewing cytokine pattern toward Th1 type. Kissing may alleviate allergic symptoms by decrease in allergen-specific IgE production.

Sublingual immunotherapy: World Allergy Organization position paper 2013 update

PubMed Central

2014-01-01

We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations. Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail. PMID:24679069

Sublingual immunotherapy for allergic rhinitis: where are we now?

PubMed

Incorvaia, Cristoforo; Mauro, Marina; Ridolo, Erminia

2015-01-01

Sublingual immunotherapy (SLIT) was introduced in the 1980s as a safer option to subcutaneous immunotherapy and in the latest decade achieved significant advances. Its efficacy in allergic rhinitis is supported by a number of meta-analyses. The development of SLIT preparations in tablets to fulfill the requirements of regulatory agencies for quality of allergen extracts made available optimal products for grass-pollen-induced allergic rhinitis. Preparations of other allergens based on the same production methods are currently in progress. A notable outcome of SLIT, that is shared with subcutaneous immunotherapy, is the evident cost-effectiveness, showing significant cost savings as early as 3 months from starting the treatment, that become as high as 80% compared with drug treatment in the ensuing years.

Lactobacillus buchneri S-layer as carrier for an Ara h 2-derived peptide for peanut allergen-specific immunotherapy.

PubMed

Anzengruber, Julia; Bublin, Merima; Bönisch, Eva; Janesch, Bettina; Tscheppe, Angelika; Braun, Matthias L; Varga, Eva-Maria; Hafner, Christine; Breiteneder, Heimo; Schäffer, Christina

2017-05-01

Peanut allergy is an IgE-mediated severe hypersensitivity disorder. The lack of a treatment of this potentially fatal allergy has led to intensive research on vaccine development. Here, we describe the design and initial characterization of a carrier-bound peptide derived from the most potent peanut allergen, Ara h 2, as a candidate vaccine. Based on the adjuvant capability of bacterial surface (S-) layers, a fusion protein of the S-layer protein SlpB from Lactobacillus buchneri CD034 and the Ara h 2-derived peptide AH3a42 was produced. This peptide comprised immunodominant B-cell epitopes as well as one T cell epitope. The fusion protein SlpB-AH3a42 was expressed in E. coli, purified, and tested for its IgE binding capacity as well as for its ability to activate sensitized rat basophil leukemia (RBL) cells. The capacity of Ara h 2-specific IgG rabbit-antibodies raised against SlpB-AH3a42 or Ara h 2 to inhibit IgE-binding was determined by ELISA inhibition assays using sera of peanut allergic patients sensitized to Ara h 2. IgE specific to the SlpB-AH3a42 fusion protein was detected in 69% (25 of 36) of the sera. Despite the recognition by IgE, the SlpB-AH3a42 fusion protein was unable to induce β-hexosaminidase release from sensitized RBL cells at concentrations up to 100ng per ml. The inhibition of IgE-binding to the natural allergen observed after pre-incubation of the 20 sera with rabbit anti-SlpB-AH3a42 IgG was more than 30% for four sera, more than 20% for eight sera, and below 10% for eight sera. In comparison, anti-Ara h 2 rabbit IgG antibodies inhibited binding to Ara h 2 by 48% ±13.5%. Our data provide evidence for the feasibility of this novel approach towards the development of a peanut allergen peptide-based carrier-bound vaccine. Our experiments further indicate that more than one allergen-peptide will be needed to induce a broader protection of patients allergic to Ara h 2. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights

Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: an EAACI Position Paper.

PubMed

Shamji, M H; Kappen, J H; Akdis, M; Jensen-Jarolim, E; Knol, E F; Kleine-Tebbe, J; Bohle, B; Chaker, A M; Till, S J; Valenta, R; Poulsen, L K; Calderon, M A; Demoly, P; Pfaar, O; Jacobsen, L; Durham, S R; Schmidt-Weber, C B

2017-08-01

Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mimotopes identify conformational epitopes on parvalbumin, the major fish allergen.

PubMed

Untersmayr, Eva; Szalai, Krisztina; Riemer, Angelika B; Hemmer, Wolfgang; Swoboda, Ines; Hantusch, Brigitte; Schöll, Isabella; Spitzauer, Susanne; Scheiner, Otto; Jarisch, Reinhart; Boltz-Nitulescu, George; Jensen-Jarolim, Erika

2006-03-01

Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate mimotopes, which mimic epitopes on parvalbumin. Parvalbumin-specific IgE was purified from sera of fish-allergic patients and used for screening of a constrained decamer phage library. After four rounds of biopanning using parvalbumin-specific IgE, five phage clones were selected which were specifically recognized by parvalbumin-specific IgE as well as IgG. DNA sequencing and peptide alignment revealed a high degree of sequence similarities between the mimotopes. Interestingly, on the surface of natural parvalbumin three regions could be defined by computational mimotope matching. In accordance, previously defined allergenic peptides of cod parvalbumin highlighted areas in close proximity or overlapping with the mimotope matching sites. From the presented data we conclude that our approach identified conformational epitopes of parvalbumin relevant for IgE and IgG binding. We suggest that these mimotopes are suitable candidates for an epitope-specific immunotherapy of fish-allergic patients.

Specific immunotherapy in renal cancer: a systematic review.

PubMed

Hirbod-Mobarakeh, Armin; Gordan, Hesam Addin; Zahiri, Zahra; Mirshahvalad, Mohammad; Hosseinverdi, Sima; Rini, Brian I; Rezaei, Nima

2017-02-01

Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration). We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58-0.89, p = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients undergoing specific immunotherapy

Recombinant allergy vaccines based on allergen-derived B cell epitopes.

PubMed

Valenta, Rudolf; Campana, Raffaela; Niederberger, Verena

2017-09-01

Immunoglobulin E (IgE)-associated allergy is the most common immunologically-mediated hypersensitivity disease. It affects more than 25% of the population. In IgE-sensitized subjects, allergen encounter can causes a variety of symptoms ranging from hayfever (allergic rhinoconjunctivitis) to asthma, skin inflammation, food allergy and severe life-threatening anaphylactic shock. Allergen-specific immunotherapy (AIT) is based on vaccination with the disease-causing allergens. AIT is an extremely effective, causative and disease-modifying treatment. However, administration of natural allergens can cause severe side effects and the quality of natural allergen extracts limits its application. Research in the field of molecular allergen characterization has allowed deciphering the molecular structures of the disease-causing allergens and it has become possible to engineer novel molecular allergy vaccines which precisely target the mechanisms of the allergic immune response and even appear suitable for prophylactic allergy vaccination. Here we discuss recombinant allergy vaccines which are based on allergen-derived B cell epitopes regarding their molecular and immunological properties and review the results obtained in clinical studies with this new type of allergy vaccines. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Specific immunotherapy in hepatocellular cancer: A systematic review.

PubMed

Baradaran Noveiry, Behnoud; Hirbod-Mobarakeh, Armin; Khalili, Nastaran; Hourshad, Niloufar; Greten, Tim F; Abou-Alfa, Ghassan K; Rezaei, Nima

2017-02-01

In recent years, several novel immunotherapeutic approaches were developed and investigated in patients with hepatocellular carcinoma (HCC). We designed this systematic review, to evaluate clinical efficacy of specific immunotherapy in patients with HCC, according to the guidelines of Border of Immune Tolerance Education and Research Network (BITERN) and Cochrane collaboration. We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey, and ProQuest through the 9th of December 2015. One author reviewed and retrieved citations from these seven databases for irrelevant and duplicate studies, and two other authors independently extracted data from the studies and rated their quality. We collated study findings and calculated a weighted treatment effect across studies using Review Manager. We found 12144 references in seven databases of which 21 controlled studies with 1885 HCC patients in different stages were included in this systematic review after the primary and secondary screenings. Overall, patients undergoing specific immunotherapy had significantly higher overall survival than those in control group (HR = 0.59; 95% CI = 0.47-0.76, P < 0.0001). There was a significant difference in recurrence-free survival between patients undergoing specific immunotherapy and patients in control groups and patients in immunotherapy groups overall had less recurrence than control group (HR = 0.54; 95% CI = 0.46-0.63, P < 0.00001). Results of this systematic review based on the available literature suggest that overall specific immunotherapeutic approaches could be beneficiary for the treatment of patients with HCC. This further supports the current and ongoing evaluations of specific immunotherapies in the field. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Responses of human birch pollen allergen-reactive T cells to chemically modified allergens (allergoids).

PubMed

Dormann, D; Ebner, C; Jarman, E R; Montermann, E; Kraft, D; Reske-Kunz, A B

1998-11-01

Allergoids are widely used in specific immunotherapy for the treatment of IgE-mediated allergic diseases. The aim of this study was to analyse whether a modification of birch pollen allergens with formaldehyde affects the availability of T-cell epitopes. Efficient modification of the allergens was verified by determining IgE and IgG binding activity using ELISA inhibition tests. T-cell responses to birch pollen allergoids were analysed in polyclonal systems, using peripheral blood mononuclear cells (PBMC) of five birch pollen-allergic individuals, as well as birch pollen extract-reactive T-cell lines (TCL), established from the peripheral blood of 14 birch pollen-allergic donors. To determine whether the modification of natural (n)Bet v 1 with formaldehyde or maleic anhydride results in epitope-specific changes in T-cell reactivities, 22 Bet v 1-specific T-cell clones (TCC), established from nine additional birch pollen-allergic individuals, were tested for their reactivity with these products. The majority of PBMC and TCL showed a reduced response to the birch pollen extract allergoid. Bet v 1-specific TCC could be divided into allergoid-reactive and -non-reactive TCC. No simple correlation between possible modification sites of formaldehyde in the respective T-cell epitopes and the stimulatory potential of the allergoid was observed. Mechanisms of suppression or of anergy induction were excluded as an explanation for the non-reactivity of representative TCC. All TCC could be stimulated by maleylated and unmodified nBet v 1 to a similar extent. These results demonstrate differences in the availability of T-cell epitopes between allergoids and unmodified allergens, which are most likely due to structural changes within the allergen molecule.

Current Status of Standardization of Inhalant Allergen Extracts in Korea

PubMed Central

Jeong, Kyoung Yong; Lee, Jae-Hyun; Kim, Eun-Jin; Lee, Joo-Shil; Cho, Sang-Heon; Hong, Soo-Jong

2014-01-01

Allergy diagnosis and immunotherapy in Korea rely mostly on imported allergen extracts. However, some allergens that are not important in Western countries are not commercially available, and even the same species of allergen source often displays differences in allergenicity due to amino acid sequence polymorphisms. Therefore, it is essential to prepare allergen extracts that reflect regional characteristics. Allergen standardization has been performed since 2009 with the support of the Korea Center for Disease Control and Prevention. Here, we summarize the current status of allergen standardization, focusing on the house dust mite and cockroach. Pollen allergens that are under investigation are also briefly described. PMID:24843793

Effects of venom immunotherapy on serum level of CCL5/RANTES in patients with Hymenoptera venom allergy.

PubMed

Gawlik, Radoslaw; Glück, Joanna; Jawor, Barbara; Rogala, Barbara

2015-01-01

Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Venom immunotherapy is a recommended treatment of insect allergy with still the mechanism not being completely understood. We decided to assess the serum CCL5/RANTES level in patients who experienced severe anaphylactic reaction to Hymenoptera venom and to find out changes in the course of immunotherapy. Twenty patients (9 men, 11 women, mean age: 31.91 ± 7.63 years) with history of anaphylactic reaction after insect sting were included into the study. Diagnosis was made according to sIgE and skin tests. All of them were enrolled into rush venom immunotherapy with bee or wasp venom extracts (Pharmalgen, ALK-Abello, Horsholm, Denmark). Serum levels of CCL5/RANTES were measured using a commercially available ELISA kit (R&D Systems, Minneapolis, MN). CCL5/RANTES serum concentration are higher in insect venom allergic patients than in healthy controls (887.5 ± 322.77 versus 387.27 ± 85.11 pg/ml). Serum concentration of CCL5/RANTES in insect venom allergic patient was significantly reduced in the course of allergen immunotherapy already after 6 days of vaccination (887.5 ± 322.77 versus 567.32 ± 92.16 pg/ml). CCL5/RANTES serum doesn't correlate with specific IgE. Chemokine CCL5/RANTES participates in allergic inflammation induced by Hymenoptera venom allergens. Specific immunotherapy reduces chemokine CCL5/RANTES serum level already after initial days of venom immunotherapy.

[Adherence in specific immunotherapy].

PubMed

Lemberg, M-L; Joisten, M-J; Mösges, R

2017-04-01

Allergies are steadily gaining in importance in the Western world. For over one hundred years, immunology has been the only causal treatment. Specific immunotherapy (SIT) aims at the cure of allergy or at least freedom from allergy symptoms. In association with this, adherence poses a complex problem. Both treatment applications commonly used in Germany-sublingual and subcutaneous immunotherapy-show poor persistence on the part of the patients. In most cases, SIT is not carried out to the end of the recommended duration and instead is discontinued prematurely. Corresponding figures from 3‑year studies in the literature range from 41- 93% for uncompleted SLIT and from 40-77% for uncompleted SCIT. Patient adherence is subject to influencing factors of various dimensions that are interdependent in complex relationships. The physician-patient relationship is just as decisive a factor for treatment success as the patient's understanding of allergy, treatment, and the importance of adherence.

Molecular biomarkers for grass pollen immunotherapy

PubMed Central

Popescu, Florin-Dan

2014-01-01

Grass pollen allergy represents a significant cause of allergic morbidity worldwide. Component-resolved diagnosis biomarkers are increasingly used in allergy practice in order to evaluate the sensitization to grass pollen allergens, allowing the clinician to confirm genuine sensitization to the corresponding allergen plant sources and supporting an accurate prescription of allergy immunotherapy (AIT), an important approach in many regions of the world with great plant biodiversity and/or where pollen seasons may overlap. The search for candidate predictive biomarkers for grass pollen immunotherapy (tolerogenic dendritic cells and regulatory T cells biomarkers, serum blocking antibodies biomarkers, especially functional ones, immune activation and immune tolerance soluble biomarkers and apoptosis biomarkers) opens new opportunities for the early detection of clinical responders for AIT, for the follow-up of these patients and for the development of new allergy vaccines. PMID:25237628

Immunotherapy (oral and sublingual) for food allergy to fruits.

PubMed

Yepes-Nuñez, Juan Jose; Zhang, Yuan; Roqué i Figuls, Marta; Bartra Tomas, Joan; Reyes, Juan Manuel; Pineda de la Losa, Fernando; Enrique, Ernesto

2015-11-09

Food allergy is an abnormal immunological response following exposure (usually ingestion) to a food. Elimination of the allergen is the principle treatment for food allergy, including allergy to fruit. Accidental ingestion of allergenic foods can result in severe anaphylactic reactions. Allergen-specific immunotherapy (SIT) is a specific treatment, when the avoidance of allergenic foods is problematic. Recently, studies have been conducted on different types of immunotherapy for the treatment of food allergy, including oral (OIT) and sublingual immunotherapy (SLIT). To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits, when compared with placebo or an elimination strategy. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and AMED were searched for published results along with trial registries and the Journal of Negative Results in BioMedicine for grey literature. The date of the most recent search was July 2015. Randomised controlled trials (RCTs) comparing OIT or SLIT with placebo or an elimination diet were included. Participants were children or adults diagnosed with food allergy who presented immediate fruit reactions. We used standard methodological procedures expected by the Cochrane Collaboration. We assessed treatment effect through risk ratios (RRs) for dichotomous outcomes. We identified two RCTs (N=89) eligible for inclusion. These RCTs addressed oral or sublingual immunotherapy, both in adults, with an allergy to apple or peach respectively. Both studies enrolled a small number of participants and used different methods to provide these differing types of immunotherapy. Both studies were judged to be at high risk of bias in at least one domain. Overall, the quality of evidence was judged to be very low due to the small number of studies and participants and possible bias. The studies were clinically heterogeneous and hence we did not pool the

Specific IgE and IgG measured by the MeDALL allergen-chip depend on allergen and route of exposure: The EGEA study.

PubMed

Siroux, Valérie; Lupinek, Christian; Resch, Yvonne; Curin, Mirela; Just, Jocelyne; Keil, Thomas; Kiss, Renata; Lødrup Carlsen, Karin; Melén, Erik; Nadif, Rachel; Pin, Isabelle; Skrindo, Ingebjørg; Vrtala, Susanne; Wickman, Magnus; Anto, Josep Maria; Valenta, Rudolf; Bousquet, Jean

2017-02-01

The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses. We sought to investigate the natural IgE and IgG responses toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads. A cross-sectional analysis was conducted in 340 adults of the EGEA (Epidemiological study of the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) (170 with and 170 without asthma) cohort. IgE and IgG responses to 47 inhalant and food allergen components were analyzed in sera using allergen microarray and compared between 5 French regions according to the route of allergen exposure (inhaled vs food allergens). Overall 48.8% of the population had allergen-specific IgE levels of 0.3 ISAC standardized units (ISU) or more to at least 1 of the 47 allergens with no significant differences across the regions. For ubiquitous respiratory allergens (ie, grass, olive/ash pollen, house dust mites), specific IgE did not show marked differences between regions and specific IgG (≥0.5 ISU) was present in most subjects everywhere. For regionally occurring pollen allergens (ragweed, birch, cypress), IgE sensitization was significantly associated with regional pollen exposure. For airborne allergens cross-reacting with food allergens, frequent IgG recognition was observed even in regions with low allergen prevalence (Bet v 1) or for allergens less frequently recognized by IgE (profilins). The variability in allergen-specific IgE and IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergen. Allergen contact by the oral route might preferentially induce IgG responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Oral and sublingual immunotherapy for egg allergy.

PubMed

Romantsik, Olga; Tosca, Maria Angela; Zappettini, Simona; Calevo, Maria Grazia

2018-04-20

Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy might be an optional treatment, through desensitization to egg allergen. To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy. We searched 13 databases for journal articles, conference proceedings, theses and trials registers using a combination of subject headings and text words (last search 31 March 2017). We included randomized controlled trials (RCTs) comparing oral immunotherapy or sublingual immunotherapy administered by any protocol with placebo or an elimination diet. Participants were children or adults with clinical egg allergy. We retrieved 97 studies from the electronic searches. We selected studies, extracted data and assessed the methodological quality. We attempted to contact the study investigators to obtain the unpublished data, wherever possible. We used the I² statistic to assess statistical heterogeneity. We estimated a pooled risk ratio (RR) with 95% confidence interval (CI) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low (I² value less than 50%). We rated the quality of evidence for all outcomes using GRADE. We included 10 RCTs that met our inclusion criteria, that involved a total of 439 children (oral immunotherapy 249; control intervention 190), aged 1 year to 18 years. Each study used a different oral immunotherapy protocol; none used sublingual immunotherapy. Three studies used placebo and seven used an egg avoidance diet as the control. Primary outcomes were: an increased amount of egg that can be ingested and tolerated without adverse events while receiving allergen-specific oral immunotherapy or sublingual immunotherapy, compared to control; and a complete recovery from egg allergy after completion of oral

Ragweed sublingual tablet immunotherapy: part I - evidence-based clinical efficacy and safety.

PubMed

Creticos, Peter Socrates; Pfaar, Oliver

2018-06-01

Sublingual tablet immunotherapy provides an attractive alternative approach to allergen immunotherapy, as the allergen is administered as a rapidly dissolving sublingual tablet. Part I of this two-part series on the ragweed sublingual tablet describes the dose-ranging clinical work, the safety studies and the clinical outcomes from the pivotal trials which provide clear evidence for statistically significant and clinically meaningful benefit in the treatment of patients suffering from ragweed-induced seasonal allergic rhinitis-conjunctivitis with or without milder asthma. The robust results observed in the clinical trials performed with the ragweed sublingual tablet are defined by the quality of their study design, their use of a standardized allergen extract, their consistent reproducibility in demonstrating therapeutic efficacy and their properly quantified and graded safety data.

Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report.

PubMed

Burks, A Wesley; Calderon, Moises A; Casale, Thomas; Cox, Linda; Demoly, Pascal; Jutel, Marek; Nelson, Harold; Akdis, Cezmi A

2013-05-01

Allergy immunotherapy (AIT) is an effective treatment for allergic asthma and rhinitis, as well as venom-induced anaphylaxis. In addition to reducing symptoms, AIT can change the course of allergic disease and induce allergen-specific immune tolerance. In current clinical practice immunotherapy is delivered either subcutaneously or sublingually; some allergens, such as grass pollen, can be delivered through either route, whereas others, such as venoms, are only delivered subcutaneously. Both subcutaneous and sublingual immunotherapy appear to have a duration of efficacy of up to 12 years, and both can prevent the development of asthma and new allergen sensitivities. In spite of the advances with AIT, safer and more effective AIT strategies are needed, especially for patients with asthma, atopic dermatitis, or food allergy. Novel approaches to improve AIT include use of adjuvants or recombinant allergens and alternate routes of administration. As part of the PRACTALL initiatives, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology nominated an expert team to develop a comprehensive consensus report on the mechanisms of AIT and its use in clinical practice, as well as unmet needs and ongoing developments in AIT. This resulting report is endorsed by both academies. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Indoor Allergens and Allergic Respiratory Disease

PubMed Central

Chapman, Martin D.; Wünschmann, Sabina

2016-01-01

Purpose of review The purpose of this review is to evaluate the most recent findings on indoor allergens and their impact on allergic diseases. Recent findings Indoor allergens are present inside buildings (home, work environment, school), and given the chronic nature of the exposures, indoor allergies tend to be associated with the development of asthma. The most common indoor allergens are derived from dust mites, cockroaches, mammals (including wild rodents and pets), and fungi. The advent of molecular biology and proteomics has led to the identification, cloning, and expression of new indoor allergens, which have facilitated research to elucidate their role in allergic diseases. This review is an update on new allergens and their molecular features, together with the most recent reports on their avoidance for allergy prevention and their use for diagnosis and treatment. Summary Research progress on indoor allergens will result in the development of new diagnostic tools and design of coherent strategies for immunotherapy. PMID:27184001

Component resolution reveals additional major allergens in patients with honeybee venom allergy.

PubMed

Köhler, Julian; Blank, Simon; Müller, Sabine; Bantleon, Frank; Frick, Marcel; Huss-Marp, Johannes; Lidholm, Jonas; Spillner, Edzard; Jakob, Thilo

2014-05-01

Detection of IgE to recombinant Hymenoptera venom allergens has been suggested to improve the diagnostic precision in Hymenoptera venom allergy. However, the frequency of sensitization to the only available recombinant honeybee venom (HBV) allergen, rApi m 1, in patients with HBV allergy is limited, suggesting that additional HBV allergens might be of relevance. We performed an analysis of sensitization profiles of patients with HBV allergy to a panel of HBV allergens. Diagnosis of HBV allergy (n = 144) was based on history, skin test results, and allergen-specific IgE levels to HBV. IgE reactivity to 6 HBV allergens devoid of cross-reactive carbohydrate determinants (CCD) was analyzed by ImmunoCAP. IgE reactivity to rApi m 1, rApi m 2, rApi m 3, nApi m 4, rApi m 5, and rApi m 10 was detected in 72.2%, 47.9%, 50.0%, 22.9%, 58.3%, and 61.8% of the patients with HBV allergy, respectively. Positive results to at least 1 HBV allergen were detected in 94.4%. IgE reactivity to Api m 3, Api m 10, or both was detected in 68.0% and represented the only HBV allergen-specific IgE in 5% of the patients. Limited inhibition of IgE binding by therapeutic HBV and limited induction of Api m 3- and Api m 10-specific IgG4 in patients obtaining immunotherapy supports recent reports on the underrepresentation of these allergens in therapeutic HBV preparations. Analysis of a panel of CCD-free HBV allergens improved diagnostic sensitivity compared with use of rApi m 1 alone, identified additional major allergens, and revealed sensitizations to allergens that have been reported to be absent or underrepresented in therapeutic HBV preparations. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Fragrance allergens in 'specific' cosmetic products.

PubMed

Nardelli, Andrea; Drieghe, Jacques; Claes, Lieve; Boey, Lies; Goossens, An

2011-04-01

Together with preservative agents, fragrance components are the most important sensitizing culprits in cosmetic products. To identify the nature of the fragrance ingredients responsible for allergic contact dermatitis (ACD) from specific cosmetic products. Between 2000 and 2009, positive patch test reactions or positive usage tests with the patients' own cosmetic products, were recorded using a standardised form. Of the 806 cosmetic records, corresponding to 485 patient files, 344 concerned reactions to fragrance ingredients that according to the label were present ('Presence Confirmed' [PC n = 301]) or suspected to be present ('Presence Not Confirmed' [PNC n = 376]) in the causal cosmetic products used, which belonged to 15 different categories, toilet waters/fine perfumes being the most frequent. Geraniol in fragrance mix I (FM I) and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) in FM II were the most frequent PC, and together with hydroxycitronellal and Evernia prunastri (oak moss) the most frequent PNC ingredients in the causal cosmetic products. Limonene was the most frequent PC confirmed fragrance allergen. This study not only underlines the usefulness of fragrance-ingredient labelling in order to identify the causal allergen(s) present in specific cosmetic products, but may also provide information on trends in the actual use of sensitizing fragrance ingredients in them. © 2011 John Wiley & Sons A/S.

Immunotherapy for food allergy.

PubMed

Wild, L G; Lehrer, S B

2001-01-01

Food allergy is an important cause of life-threatening hypersensitivity reactions. Avoidance of allergenic foods is the only method of prevention that currently is available for sensitized patients. This method of prevention is difficult and often impossible. With better characterization of allergens and better understanding of the immunologic mechanism, investigators have developed several therapeutic modalities that potentially are applicable to the treatment and prevention of food allergy. Therapeutic options currently under investigation include peptide immunotherapy, DNA immunization, immunization with immunostimulatory sequences, anti-IgE therapy, and genetic modification of foods. These exciting developments hold promise for the safe and effective treatment and prevention of food allergy in the next several years.

Safety and efficacy of epicutaneous immunotherapy for food allergy.

PubMed

Wang, Julie; Sampson, Hugh A

2018-06-01

Food allergy is increasingly common in children, affecting about 4%-8%. The mainstays of management remain allergen avoidance and emergency preparedness to treat allergic reactions with emergency medications. Unfortunately, these approaches are unsatisfactory for many patients and their families as the restrictions, constant vigilance, and unpredictable severity of allergic reactions negatively impact quality of life. In recent decades, there has been significant interest in developing treatments for food allergy that lead to desensitization to increase thresholds for triggering allergic reactions and decrease the risk of reacting to allergen-contaminated food products. Epicutaneous immunotherapy (EPIT) is a novel therapy that is currently under investigation, delivering allergen via repeated applications to the skin and targeting antigen-presenting cells in the superficial skin layers. Murine models have demonstrated that allergen uptake is an active process by skin dendritic cells with subsequent migration to draining lymph nodes. Allergen exposure to the non-vascularized epidermis limits systemic absorption, contributing to the high-safety profile. Results from murine experiments showed that EPIT has comparable efficacy as subcutaneous immunotherapy in terms of challenge outcomes, airway hyper-responsiveness, and immunologic parameters. Several clinical trials of EPIT have recently been completed or are ongoing. Results support the high safety and tolerability of this approach. Efficacy data suggest that the change in threshold eliciting dose following 1 year of therapy is less than that seen compared to high-dose (2-4 g peanut protein) oral immunotherapy, but more prolonged treatment with EPIT appears to lead to increasing desensitization. Additional data from larger-scale studies should provide a more robust assessment of safety and efficacy of EPIT. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

PubMed Central

Qi, Xing-Shun

2017-01-01

Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients. PMID:28265583

Characterization of epitope specificities of reference antibodies used for the quantification of the birch pollen allergen Bet v 1.

PubMed

Brier, S; Le Mignon, M; Jain, K; Lebrun, C; Peurois, F; Kellenberger, C; Bordas-Le Floch, V; Mascarell, L; Nony, E; Moingeon, P

2018-05-01

Accurate allergen quantification is needed to document the consistency of allergen extracts used for immunotherapy. Herein, we characterize the epitope specificities of two monoclonal antibodies used in an ELISA for the quantification of the major birch pollen allergen Bet v 1, established as a reference by the BSP090 European project. The ability of mAbs 5B4 and 6H4 to recognize Bet v 1 isoforms was addressed by immunochromatography. The capacity of each mAb to compete with patients' IgE for binding to Bet v 1 was measured by ELISA inhibition. Epitope mapping was performed by pepscan analysis, site-directed mutagenesis, and hydrogen/deuterium exchange-mass spectrometry. The 5B4 epitope corresponds to a peptide sequence (I56-K68) overlapping with the binding sites of patients' serum IgEs. Mutation of residues P59, E60, and K65 abolishes 5B4 binding to Bet v 1 and reduces the level of IgE recognition. In contrast, 6H4 recognizes a conformational epitope lying opposite to the 5B4 binding site, involving residues located in segments I44-K55 and R70-F79. Substitution of E45 reduces the binding capacity of 6H4, confirming that it is critical for the interaction. Both mAbs interact with >90% of Bet v 1 content present in the birch pollen extract, while displaying a weak cross-reactivity with other allergens of the PR-10 family. MAbs 5B4 and 6H4 recognize structurally distinct epitopes present in the vast majority of Bet v 1 isoforms. These results support the relevance as a reference method of the Bet v 1-specific quantitative ELISA adopted by the European Pharmacopoeia. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Effects of local nasal immunotherapy in allergic airway inflammation: Using urea denatured Dermatophagoides pteronyssinus

PubMed Central

Yu, Sheng-Jie; Liao, En-Chih; Tsai, Jaw-Ji

2015-01-01

Despite improvements in anti-allergy medication, the prevalence of allergic airway inflammation remains high, affecting up to 40% of the population worldwide. Allergen immunotherapy is effective for inducing tolerance but has the adverse effect of severe allergic reaction. This can be avoided by denaturing with urea. In this study, we demonstrated that the serum level of allergen-specific IgE in mice sensitized with native Dermatophagoides pteronyssinus (Der p) crude extract after receiving local nasal immunotherapy (LNIT) with urea-denatured Der p crude extract (DN-Dp) significantly decreased compared to that in the normal saline (NS) treatment group. Expressions of IL-4 were significantly reduced in lung tissues after treatment. Inflammation around the bronchial epithelium improved and airway hypersensitivity was down-regulated. LNIT with DN-Dp can down-regulate IL-1b, IL-6 and TNF-a expression and then decrease Der p-induced allergic airway inflammation. This therapeutic modality may be used as an alternative treatment for airway allergic diseases. PMID:25933184

Allergen-Specific Cytokine Polarization Protects Shetland Ponies against Culicoides obsoletus-Induced Insect Bite Hypersensitivity

PubMed Central

Meulenbroeks, Chantal; van der Lugt, Jaco J.; van der Meide, Nathalie M. A.; Willemse, Ton; Rutten, Victor P. M. G.; Zaiss, Dietmar M. W.

2015-01-01

The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus). We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected and healthy ponies and cytokine expression was determined by RT-PCR. In addition, allergen-specific antibody titers were measured and cytokine expression of in vitro stimulated, allergen-specific CD4 T-cells was determined. 24 hrs after allergen injection, a significant increase in mRNA expression of the type-2 cytokine IL-4 was observed in the skin of IBH-affected Shetland ponies. In the skin of healthy ponies, however, an increase in IFNγ mRNA expression was found. Analysis of allergen-specific antibody titers revealed that all animals produced allergen-specific antibodies, and allergen-specific stimulation of CD4 T-cells revealed a significant higher percentage of IFNγ-expressing CD4 T-cells in healthy ponies compared to IBH-affected ponies. These data indicate that horses not affected by IBH, in contrast to the so far established dogma, are not immunologically ignorant but have a Th1-skewed allergen-specific immune response that appears to protect against IBH-associated symptoms. To our knowledge this is the first demonstration of a natural situation, in which an allergen-specific immune skewing is protective in an allergic disorder. PMID:25901733

Comparing Proteolytic Fingerprints of Antigen-Presenting Cells during Allergen Processing.

PubMed

Hofer, Heidi; Weidinger, Tamara; Briza, Peter; Asam, Claudia; Wolf, Martin; Twaroch, Teresa E; Stolz, Frank; Neubauer, Angela; Dall, Elfriede; Hammerl, Peter; Jacquet, Alain; Wallner, Michael

2017-06-08

Endolysosomal processing has a critical influence on immunogenicity as well as immune polarization of protein antigens. In industrialized countries, allergies affect around 25% of the population. For the rational design of protein-based allergy therapeutics for immunotherapy, a good knowledge of T cell-reactive regions on allergens is required. Thus, we sought to analyze endolysosomal degradation patterns of inhalant allergens. Four major allergens from ragweed, birch, as well as house dust mites were produced as recombinant proteins. Endolysosomal proteases were purified by differential centrifugation from dendritic cells, macrophages, and B cells, and combined with allergens for proteolytic processing. Thereafter, endolysosomal proteolysis was monitored by protein gel electrophoresis and mass spectrometry. We found that the overall proteolytic activity of specific endolysosomal fractions differed substantially, whereas the degradation patterns of the four model allergens obtained with the different proteases were extremely similar. Moreover, previously identified T cell epitopes were assigned to endolysosomal peptides and indeed showed a good overlap with known T cell epitopes for all four candidate allergens. Thus, we propose that the degradome assay can be used as a predictor to determine antigenic peptides as potential T cell epitopes, which will help in the rational design of protein-based allergy vaccine candidates.

Comparing Proteolytic Fingerprints of Antigen-Presenting Cells during Allergen Processing

PubMed Central

Hofer, Heidi; Weidinger, Tamara; Briza, Peter; Asam, Claudia; Wolf, Martin; Twaroch, Teresa E.; Stolz, Frank; Neubauer, Angela; Dall, Elfriede; Hammerl, Peter; Jacquet, Alain; Wallner, Michael

2017-01-01

Endolysosomal processing has a critical influence on immunogenicity as well as immune polarization of protein antigens. In industrialized countries, allergies affect around 25% of the population. For the rational design of protein-based allergy therapeutics for immunotherapy, a good knowledge of T cell-reactive regions on allergens is required. Thus, we sought to analyze endolysosomal degradation patterns of inhalant allergens. Four major allergens from ragweed, birch, as well as house dust mites were produced as recombinant proteins. Endolysosomal proteases were purified by differential centrifugation from dendritic cells, macrophages, and B cells, and combined with allergens for proteolytic processing. Thereafter, endolysosomal proteolysis was monitored by protein gel electrophoresis and mass spectrometry. We found that the overall proteolytic activity of specific endolysosomal fractions differed substantially, whereas the degradation patterns of the four model allergens obtained with the different proteases were extremely similar. Moreover, previously identified T cell epitopes were assigned to endolysosomal peptides and indeed showed a good overlap with known T cell epitopes for all four candidate allergens. Thus, we propose that the degradome assay can be used as a predictor to determine antigenic peptides as potential T cell epitopes, which will help in the rational design of protein-based allergy vaccine candidates. PMID:28594355

The influence of sublingual immunotherapy on several parameters of immunological response in children suffering from atopic asthma and allergic rhinitis depending on asthma features.

PubMed

Ciepiela, Olga; Zawadzka-Krajewska, Anna; Kotuła, Iwona; Demkow, Urszula

2014-01-01

The clinical efficacy of sublingual immunotherapy (SLIT) has already been proven and is known to be high. Its influence on the immunological system of patients suffering from bronchial asthma was also examined. However, it is still unclear how the polysensitisation, coexistence of other atopic disease and asthma treatment step influence the response to treatment with specific immunotherapy. Herein we evaluate the impact of one-year SLIT on selected markers of immunological response depending on different individual and clinical factors of children suffering from atopic asthma and allergic rhinitis. Twenty-five patients aged 8.1 ± 3.1 years (range 5-15 years), 21 boys and 4 girls, suffering from asthma and allergic rhinitis with polysensitisation to seasonal and non-seasonal allergens, shortlisted for SLIT, were included in the study. Th1 cell and Th2 cell percentages, Bcl-2 expression in T cells, and basophil activation after allergen challenge (house dust mite and/or grass pollen antigen in solution used for skin prick tests) in peripheral blood were measured using flow cytometry. The association between clinical features of asthma and the influence of SLIT on immunological parameters was evaluated with exact Fisher test. No association between the influence of one-year sublingual immunotherapy on immunological system and patients' age, polysensitisation, asthma treatment step, or coexistence of any other atopic diseases was observed. However, an increase of the Th1 percentage in children sensitised against more than three allergens was found more often (at the limit of statistical significance) than in the group of children sensitised against three or less allergens. Based on our results, we cannot point to any subgroup isolated in the study, in which the response of the immunological system to sublingual immunotherapy is more satisfactory than any other. Nevertheless, the increase of Th1 cells may be more specific for polysensitised children.

Defining pollen exposure times for clinical trials of allergen immunotherapy for pollen-induced rhinoconjunctivitis - an EAACI position paper.

PubMed

Pfaar, O; Bastl, K; Berger, U; Buters, J; Calderon, M A; Clot, B; Darsow, U; Demoly, P; Durham, S R; Galán, C; Gehrig, R; Gerth van Wijk, R; Jacobsen, L; Klimek, L; Sofiev, M; Thibaudon, M; Bergmann, K C

2017-05-01

Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus. A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus. The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for 'pollen season', 'high pollen season' (or 'peak pollen period') and 'high pollen days'. This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of immunoglobulin E measurements on IMMULITE and ImmunoCAP in samples consisting of allergen-specific mouse-human chimeric monoclonal antibodies towards allergen extracts and four recombinant allergens.

PubMed

Szecsi, Pal B; Stender, Steen

2013-01-01

Specific immunoglobulin E (IgE) antibody in vitro tests are performed on enzyme immunoassay systems. Poor agreement among systems has been reported and comparisons have been made exclusively with allergen extracts - not with recombinant allergens. Here we compare the ImmunoCAP and the IMMULITE systems. Ten patient samples with positive IgE toward egg white, birch pollen or cat or dog dander were compared using allergen extracts or the recombinant allergens Gal d 1, Bet v 1, Fel d 1 and Can f 1 with the two assay systems. Comparisons were also performed using four monoclonal mouse-human chimeric IgE antibodies specific for the same allergenic components. IMMULITE estimated a higher allergen-specific IgE concentration in sera than ImmunoCAP when testing with allergen extracts as well as recombinant allergens. The chimeric antibodies gave an equivalent response in the total IgE and specific IgE (sIgE) with an average ratio of 1.08 (range 0.9-1.3) on ImmunoCAP. In contrast, IMMULITE exhibited sIgE signals that were substantially higher than the summed level of IgE for all four chimeric antibodies (average ratio 2.96 and range 1.7-4.3). Comparison using chimeric antibodies allowed the evaluation of the true performance of the systems. ImmunoCAP measured total IgE and sIgE equally, whereas IMMULITE displayed higher sIgE signals when compared to the summed level of total IgE for all four chimeric antibodies. Results obtained with the two assay systems are not interchangeable by means of mathematical conversion. Copyright © 2013 S. Karger AG, Basel.

Regulatory changes that affect coding for immunotherapy.

PubMed

Atwater, J Spencer

2006-02-01

During the past decade, a variety of federal regulations have had a significant impact on the way allergen immunotherapy is reimbursed and how Current Procedural Terminology (CPT) codes are used for this purpose. As mandated by the US Congress, the Centers for Medicare and Medicaid Services (CMS) through the Office of the Inspector General (OIG) targeted immunotherapy codes for scrutiny, because they are some of the most frequently used codes. To examine how federal regulations have affected reimbursement for allergy immunotherapy and other allergy services. A review was performed of the OIG survey of allergy immunotherapy and the OIG recommendations on CPT coding compliance guidelines. A preliminary survey found problems with medical appropriateness of allergen immunotherapy. For this reason, the OIG performed a more comprehensive study of 301 physicians using code 95165 to analyze by medical record and billing data whether the new billing rules were being correctly used and found that only 44% of physicians were following the new definition of a billable dose. In the early 1990s, the federal government served notice of its intent to more aggressively identify and prosecute health care providers who improperly billed and collected for medical services. Through the adoption of the 1991 US Sentencing Commission Guidelines, the government sought to enhance compliance by mandating lesser criminal penalties for violating organizations that nevertheless maintained and operated "effective compliance plans." In 2002, the OIG audited health care providers and recouped dollar 14.4 billion in improper payments by Medicare. Between January and June 2003, Medicare excluded 1,241 individual providers and health care entities due to fraudulent billing practices. Federal regulations have significantly affected reimbursement for allergy immunotherapy and other allergy services. Allergists need to be aware of these changes and implement the new recommendations into their practices.

American Academy of Allergy, Asthma & Immunology membership experience with allergen immunotherapy safety in patients with specific medical conditions.

PubMed

Larenas-Linnemann, Désirée E S; Hauswirth, David W; Calabria, Christopher W; Sher, Lawrence D; Rank, Matthew A

2016-09-01

Little data in the literature exist concerning patients with certain underlying medical conditions who receive allergen subcutaneous immunotherapy (SCIT). To survey allergists' experience with SCIT in patients with medical conditions considered to impose an elevated risk for untoward outcomes. A Web-based survey was conducted among members of the American Academy of Allergy, Asthma & Immunology to query about their experience with SCIT in patients with certain medical conditions. There were 1085 replies (21% response), of whom, 86% were U.S. based, 51% were suburban, 31% were academic, 42% were medium-sized practices, and 54% had >15 years' experience. In responders' opinion, SCIT was "contraindicated" in patients with the following: acquired immune deficiency syndrome (AIDS) (48%), cancer (and still receiving active treatment) (33%), severe asthma (32%), and a history of transplantation (30%). Even so, survey responders collectively gave SCIT to >2400 patients for each of these conditions: severe asthma, coronary artery disease, cancer in remission, and autoimmune disorders; and to ≥5400 patients with hypertension and ≥4100 women who became pregnant. The experience of colleagues with these patients rarely resulted in major problems (i.e., activation of underlying disease, systemic reactions to SCIT, or SCIT discontinuation), with the exception of severe asthma (12.5%), initiation of SCIT during pregnancy (5.4%), and AIDS (4.2%). For most other conditions, it was ≤1.5% (e.g., continue during pregnancy, cancer in remission, history of transplantation, positive human immunodeficiency virus and no AIDS). According to the experience of a large group of practicing allergists, the American Academy of Allergy, Asthma & Immunology members, few medical conditions seemed to pose an elevated risk for untoward outcomes from SCIT. Because these are survey results, prospective research might yield even more solid data.

Advances and highlights in allergen immunotherapy: On the way to sustained clinical and immunologic tolerance.

PubMed

Berings, Margot; Karaaslan, Cagatay; Altunbulakli, Can; Gevaert, Philippe; Akdis, Mübeccel; Bachert, Claus; Akdis, Cezmi A

2017-11-01

Allergen immunotherapy (AIT) is an effective treatment strategy for allergic diseases and has been used for more than 100 years. In recent years, however, the expectations on concepts, conduct, statistical evaluation, and reporting have developed significantly. Products have undergone dose-response and confirmative studies in adults and children to provide evidence for the optimal dosage, safety, and efficacy of AIT vaccines using subcutaneous and sublingual delivery pathways in large patient cohorts, ensuring solid conclusions to be drawn from them for the advantage of patients and societies alike. Those standards should be followed today, and products answering to them should be preferred over others lacking optimization and proof of efficacy and safety. Molecular and cellular mechanisms of AIT include early mast cell and basophil desensitization effects, regulation of T- and B-cell responses, regulation of IgE and IgG 4 production, and inhibition of responses from eosinophils, mast cells, and basophils in the affected tissues. There were many developments to improve vaccination strategies, demonstration of new molecules involved in molecular mechanisms, and demonstration of new biomarkers for AIT during the last few years. The combination of probiotics, vitamins, and biological agents with AIT is highlighting current advances. Development of allergoids and recombinant and hypoallergenic vaccines to skew the immune response from IgE to IgG 4 and regulation of dendritic cell, mast cell, basophil, innate lymphoid cell, T-cell, and B-cell responses to allergens are also discussed in detail. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Orthologous Allergens and Diagnostic Utility of Major Allergen Alt a 1

PubMed Central

Moreno, Antonio; Alcover, Javier; Rodríguez, David; Palacios, Ricardo; Martínez-Naves, Eduardo

2016-01-01

Purpose Hypersensitivity to fungi is associated with rhinoconjunctivitis and asthma. For some fungi, such as Alternaria alternata (A. alternata), the symptoms of asthma are persistent, increasing disease severity and the risk of fatal outcomes. There are a large number of species of fungi but knowledge of them remains limited. This, together with the difficulties in obtaining adequate standardized extracts, means that there remain significant challenges in the diagnosis and immunotherapy of allergy associated with fungi. The type of indoor fungi related to asthma/allergy varies according to geographic, climatic, and seasonal factors, making their study difficult. The aim of this study was to determine hypersensitivity to indoor fungi in a population from Cuenca, Spain. Methods Thirty-five patients with symptoms compatible with rhinitis or asthma who showed clear worsening of their symptoms in their homes or workplace were included. In vivo and in vitro tests were made with a battery of fungal allergens, including the species isolated in the home or workplace. Results Ulocladium botrytis (U. botrytis) and A. alternata were the most representative species as a source of home sensitization. These species showed very high concordance in skin tests, specific IgE, and histamine release. The allergen Alt a 1, which was recognized in all patients, was detected in A. alternata, U. botrytis, and Stemphylium botryosum (S. botryosum). Conclusions U. botrytis and A. alternata were the most representative species as a source of home sensitization. Alt a 1 was recognized in all patients and may be considered a non-species-specific allergen that could be used as a diagnostic source of sensitization to some species of the Pleosporaceae family. PMID:27334781

[Cross reactions between pollens and vegetable food allergens].

PubMed

Pauli, G; Metz-Favre, C

2013-04-01

The association of food allergies and pollinosis are numerous, implicating tree, grass and weed pollens on one hand and on the other, several plant foods which after ingestion can induce an oral syndrome or more severe reactions such as urticaria, Quincke's edema, asthma and even anaphylactic shock. The molecular basis of cross reactions between pollens and vegetable food allergens is increasingly understood. The principal allergens involved are those of the Bet v 1 family, and profilins found in all pollens as well as in many fruits and vegetables; these two groups of allergens are denatured by high temperatures and by gastric enzymes, in contrast to LTP, which is only found in weeds and some tree pollens. Other molecules can be involved in cross reactions such as Bet v 6 (an isoflavone reductase), 1 beta glucanases and thaumatine-like proteins. Inhibition experiments confirmed that the epitopes responsible for primary sensitization come mainly from pollen allergens; the cross-reactive molecular allergen is related to the geographic environment of the patients. The practical aspects of managing these patients are underlined: explanations of co-sensitization, explanations for the lack of efficacy of some extracts, usefulness of a molecular diagnosis obtained either by CAP or microarray, prediction of severe clinical reactions induced by specific molecular allergens and the effectiveness of pollen immunotherapy on the cross-related food allergy. Copyright © 2013 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Novel strategies in immunotherapy for allergic diseases.

PubMed

Rajakulendran, Mohana; Tham, Elizabeth Huiwen; Soh, Jian Yi; Van Bever, H P

2018-04-01

Conventional immunotherapy (IT) for optimal control of respiratory and food allergies has been fraught with concerns of efficacy, safety, and tolerability. The development of adjuvants to conventional IT has potentially increased the effectiveness and safety of allergen IT, which may translate into improved clinical outcomes and sustained unresponsiveness even after cessation of therapy. Novel strategies incorporating the successful use of adjuvants such as allergoids, immunostimulatory DNA sequences, monoclonal antibodies, carriers, recombinant proteins, and probiotics have now been described in clinical and murine studies. Future approaches may include fungal compounds, parasitic molecules, vitamin D, and traditional Chinese herbs. More robust comparative clinical trials are needed to evaluate the safety, clinical efficacy, and cost effectiveness of various adjuvants in order to determine ideal candidates in disease-specific and allergen-specific models. Other suggested approaches to further optimize outcomes of IT include early introduction of IT during an optimal window period. Alternative routes of administration of IT to optimize delivery and yet minimize potential side effects require further evaluation for safety and efficacy before they can be recommended.

Novel strategies in immunotherapy for allergic diseases

PubMed Central

Tham, Elizabeth Huiwen; Soh, Jian Yi; Van Bever, HP

2018-01-01

Conventional immunotherapy (IT) for optimal control of respiratory and food allergies has been fraught with concerns of efficacy, safety, and tolerability. The development of adjuvants to conventional IT has potentially increased the effectiveness and safety of allergen IT, which may translate into improved clinical outcomes and sustained unresponsiveness even after cessation of therapy. Novel strategies incorporating the successful use of adjuvants such as allergoids, immunostimulatory DNA sequences, monoclonal antibodies, carriers, recombinant proteins, and probiotics have now been described in clinical and murine studies. Future approaches may include fungal compounds, parasitic molecules, vitamin D, and traditional Chinese herbs. More robust comparative clinical trials are needed to evaluate the safety, clinical efficacy, and cost effectiveness of various adjuvants in order to determine ideal candidates in disease-specific and allergen-specific models. Other suggested approaches to further optimize outcomes of IT include early introduction of IT during an optimal window period. Alternative routes of administration of IT to optimize delivery and yet minimize potential side effects require further evaluation for safety and efficacy before they can be recommended. PMID:29732290

Measurement of basophil-activating capacity of grass pollen allergens, allergoids and hypoallergenic recombinant derivatives by flow cytometry using anti-CD203c.

PubMed

Kahlert, H; Cromwell, O; Fiebig, H

2003-09-01

The assessment of the basophil-activating potential is an important aspect in the development of improved preparations for specific immunotherapy. The aim of the study was to evaluate the suitability of CD203c expression as a measure of basophil activation to compare allergoids with original allergen extracts, and recombinant hypoallergenic allergen derivatives with recombinant wild-type and natural allergens. Heparinized whole blood samples from grass pollen allergic subjects were stimulated with grass pollen allergens and allergen derivatives followed by labelling of the basophils with PE-conjugated anti-CD203c. After lysis of the erythrocytes and fixation, the basophils were detected by flow cytometry. In some experiments, histamine release was determined simultaneously. Grass pollen allergoids revealed a 10-10 000-fold reduction of basophil-activating capacity measured by CD203c expression. The deletion mutant DM4 of rPhl p 5b showed stronger hypoallergenic characteristics in a range of 50-10 000-fold reduction, whereas a combination mutant of rPhl p 5b and Phl p 6 revealed less hypoallergenic features. Histamine release experiments led to a similar outcome as CD203c measurement. The measurement of CD203c expression on basophils by flow cytometry provides a rapid and sensitive method for the estimation of the allergic or hypoallergenic features of allergen preparations. The results demonstrated the hypoallergenicity of grass pollen allergoids and of the rPhl p 5b variant DM4, which may be a candidate in future preparations for specific immunotherapy.

Glove-derived foreign proteins induce allergen-specific IgE in a mouse model.

PubMed

Busch, Marion; Schröder, Claudia; Baron, Jens-Malte; Ott, Hagen; Bruckner, Thomas; Diepgen, Thomas L; Mahler, Vera

2008-04-01

Currently, most medical gloves are produced with a low content of natural rubber latex (NRL) protein. However, they may be substituted by proteins of foreign origin to maintain specific properties of the material. The aim of this study was to investigate the allergenicity and immunogenicity of unexpected proteins (i.e., soy and casein) compared with NRL proteins in a murine model in BALB/c mice. All respective allergen sources (extracts from three brands of NRL gloves, soy, and casein) were able to induce significant allergen-specific IgE and IgG(1) responses. On average, the highest IgE induction occurred after immunization with NRL, followed by soy and casein. Certain individuals from each treatment group exhibited levels of specific IgE as high as due to NRL. To analyze further specific IgE responses on a single allergen level, we established a microarray based on recombinant allergens for allergen-specific murine IgE detection. Besides specific IgE against rHev b 3, -6, -7, -8, and -11, specific IgE against kappa-casein could be detected in mice immunized with NRL glove extract, indicating a sensitization potential of the contained foreign protein. The substitution of genuine latex proteins by proteins of foreign origin may lead to a shift and de novo increase in sensitization to the finished products.

Sequence conservation predicts T cell reactivity against ragweed allergens.

PubMed

Pham, J; Oseroff, C; Hinz, D; Sidney, J; Paul, S; Greenbaum, J; Vita, R; Phillips, E; Mallal, S; Peters, B; Sette, A

2016-09-01

Ragweed is a major cause of seasonal allergy, affecting millions of people worldwide. Several allergens have been defined based on IgE reactivity, but their relative immunogenicity in terms of T cell responses has not been studied. We comprehensively characterized T cell responses from atopic, ragweed-allergic subjects to Amb a 1, Amb a 3, Amb a 4, Amb a 5, Amb a 6, Amb a 8, Amb a 9, Amb a 10, Amb a 11, and Amb p 5 and examined their correlation with serological reactivity and sequence conservation in other allergens. Peripheral blood mononuclear cells (PBMCs) from donors positive for IgE towards ragweed extracts after in vitro expansion for secretion of IL-5 (a representative Th2 cytokine) and IFN-γ (Th1) in response to a panel of overlapping peptides spanning the above-listed allergens were assessed. Three previously identified dominant T cell epitopes (Amb a 1 176-191, 200-215, and 344-359) were confirmed, and three novel dominant epitopes (Amb a 1 280-295, 304-319, and 320-335) were identified. Amb a 1, the dominant IgE allergen, was also the dominant T cell allergen, but dominance patterns for T cell and IgE responses for the other ragweed allergens did not correlate. Dominance for T cell responses correlated with conservation of ragweed epitopes with sequences of other well-known allergens. These results provide the first assessment of the hierarchy of T cell reactivity in ragweed allergens, which is distinct from that observed for IgE reactivity and influenced by T cell epitope sequence conservation. The results suggest that ragweed allergens associated with lesser IgE reactivity and significant T cell reactivity may be targeted for T cell immunotherapy, and further support the development of immunotherapies against epitopes conserved across species to generate broad reactivity against many common allergens. © 2016 John Wiley & Sons Ltd.

Phage display peptide libraries in molecular allergology: from epitope mapping to mimotope-based immunotherapy.

PubMed

Luzar, J; Štrukelj, B; Lunder, M

2016-11-01

Identification of allergen epitopes is a key component in proper understanding of the pathogenesis of type I allergies, for understanding cross-reactivity and for the development of mimotope immunotherapeutics. Phage particles have garnered recognition in the field of molecular allergology due to their value not only in competitive immunoscreening of peptide libraries but also as immunogenic carriers of allergen mimotopes. They integrate epitope discovery technology and immunization functions into a single platform. This article provides an overview of allergen mimotopes identified through the phage display technique. We discuss the contribution of phage display peptide libraries in determining dominant B-cell epitopes of allergens, in developing mimotope immunotherapy, in understanding cross-reactivity, and in determining IgE epitope profiles of individual patients to improve diagnostics and individualize immunotherapy. We also discuss the advantages and pitfalls of the methodology used to identify and validate the mimotopes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression of an endotoxin-free S-layer/allergen fusion protein in gram-positive Bacillus subtilis 1012 for the potential application as vaccines for immunotherapy of atopic allergy

PubMed Central

2011-01-01

immunoblotting experiments with Bet v1 specific IgE containing serum samples from patients suffering birch pollen allergy. Conclusions The impact of this study can be seen in the usage of a gram-positive organism for the production of pyrogen-free self-assembling recombinant S-layer/allergen fusion protein with great relevance for the development of vaccines for immunotherapy of atopic allergy. PMID:21310062

Allergist-reported trends in the practice of food allergen oral immunotherapy.

PubMed

Greenhawt, Matthew J; Vickery, Brian P

2015-01-01

Food allergen oral immunotherapy (OIT) is an experimental, immune-modifying therapy that may induce clinical desensitization in some patients. OIT is still in early phase clinical research, but some providers may offer OIT as a clinical service. To understand the current practices of allergists who perform OIT, an online survey was sent by e-mail to members of the American Academy of Allergy Asthma & Immunology. Among 442 respondents, 61 reported participating in using OIT (13.8%), including 28 in nonacademic settings. Informed consent for OIT was obtained by 91.3%, institutional review board approval by 47.7% and Investigational New Drug approval by 38.1%. Compared with nonacademic participants, more academic participants used peanut OIT, obtained institutional review board and Investigational New Drug (P < .0001 respectively), and challenged patients before entry (P = .008). More nonacademic providers billed the patient or insurance for reimbursement (P < .0001). Low reported regard for the importance for US Food and Drug Administration approval or a standardized product (increased odds), and a high regard for better safety data (decreased odds) were associated with considering offering OIT as a service. Significant differences exist with OITs that occur in academic versus nonacademic settings. Further assessment is needed regarding the different motivations and practice styles among providers who offer OIT and those who are considering doing so. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI): A paediatric assessment.

PubMed

Rodríguez Del Río, Pablo; Vidal, Carmen; Just, Jocelyne; Tabar, Ana I; Sanchez-Machin, Inmaculada; Eberle, Peter; Borja, Jesus; Bubel, Petra; Pfaar, Oliver; Demoly, Pascal; Calderón, Moises A

2017-02-01

Safety data on 'real-life' allergen immunotherapy (AIT) in children and adolescents is usually extrapolated from studies in adults. Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospective European survey. Patient profiles and systemic reactions (SRs) were recorded. Descriptive, univariate and multivariate analyses were used to identify risk factors for SRs. A total of 1563 patients (mean ± SD age: 11.7 ± 3.9 years; rhinitis: 93.7%; asthma: 61.5%; polysensitization: 62.5%) and 1578 courses of AIT were assessed. Single-allergen AIT was administered in 89.5% of cases (n = 1412; mites: 49%; grass pollen: 25.8%; tree pollen: 8.7%; Alternaria: 4.6%; dander: 0.8%; weed pollen: 0.6%). Subcutaneous AIT (SCIT) was used in 71.4% (n = 1127) of the treatments, including 574 (50.9%) with natural extracts. Sublingual AIT (SLIT) was used for the remaining 451 treatments (drops: 73.8%; tablets: 26.2%). The mean ± SD follow-up period was 12.9 ± 3.3 months. The estimated total number of doses was 19,669 for SCIT and 131,550 for SLIT. Twenty-four patients (1.53%) experienced 29 SRs. Respiratory (55.7%) and skin symptoms (37.9%) were most frequent. Anaphylaxis was diagnosed in 3 SRs (10.3%), and adrenaline was administered in 2 of these cases. In a univariate analysis, the risk of SRs was lower in mite-sensitized patients and higher in cases of pollen polysensitization (>3), grass pollen extracts and the use of natural extracts (vs. allergoids). In a real-life paediatric setting, AIT is safe. SRs are infrequent and generally not severe. Pollen polysensitization, grass pollen extracts and natural extracts (vs. allergoids) were risk factors for AIT-associated SRs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

International consensus on allergy immunotherapy.

PubMed

Jutel, Marek; Agache, Ioana; Bonini, Sergio; Burks, A Wesley; Calderon, Moises; Canonica, Walter; Cox, Linda; Demoly, Pascal; Frew, Antony J; O'Hehir, Robin; Kleine-Tebbe, Jörg; Muraro, Antonella; Lack, Gideon; Larenas, Désirée; Levin, Michael; Nelson, Harald; Pawankar, Ruby; Pfaar, Oliver; van Ree, Ronald; Sampson, Hugh; Santos, Alexandra F; Du Toit, George; Werfel, Thomas; Gerth van Wijk, Roy; Zhang, Luo; Akdis, Cezmi A

2015-09-01

Allergen immunotherapy (AIT) has been used to treat allergic disease since the early 1900s. Despite numerous clinical trials and meta-analyses proving AIT efficacious, it remains underused and is estimated to be used in less than 10% of patients with allergic rhinitis or asthma worldwide. In addition, there are large differences between regions, which are not only due to socioeconomic status. There is practically no controversy about the use of AIT in the treatment of allergic rhinitis and allergic asthma, but for atopic dermatitis or food allergy, the indications for AIT are not well defined. The elaboration of a wider consensus is of utmost importance because AIT is the only treatment that can change the course of allergic disease by preventing the development of asthma and new allergen sensitizations and by inducing allergen-specific immune tolerance. Safer and more effective AIT strategies are being continuously developed both through elaboration of new allergen preparations and adjuvants and alternate routes of administration. A number of guidelines, consensus documents, or both are available on both the international and national levels. The international community of allergy specialists recognizes the need to develop a comprehensive consensus report to harmonize, disseminate, and implement the best AIT practice. Consequently, the International Collaboration in Asthma, Allergy and Immunology, formed by the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma & Immunology; and the World Allergy Organization, has decided to issue an international consensus on AIT. Copyright © 2015. Published by Elsevier Inc.

Simple methods to reduce major allergen Ara h 1 and Ana o 1/2 in peanut and cashew extracts

USDA-ARS?s Scientific Manuscript database

Whole peanut extracts are usually used in immunotherapy but may have side effects. Reducing major peanut allergen(s) in the extracts may reduce the side effects. Three simple methods were evaluated to reduce major allergen Ara h 1 from a peanut extract: (1) treatment with p-aminobenzamidine (pABA); ...

Charting novel allergens from date palm pollen (Phoenix sylvestris) using homology driven proteomics.

PubMed

Saha, Bodhisattwa; Bhattacharya, Swati Gupta

2017-08-08

E-reactive proteins have been identified using a stratified proteomic workflow incorporating manual de novo sequencing and homology-based proteomics. This study also gives an insight into the presence of glycan nature of the IgE binding epitopes. Five proteins have been found to be common with coconut pollen allergens and presumably responsible for cross-reactivity. These can be used in diagnostics to differentiate patient cohorts allergic to both coconut and date palm pollen from true date palm pollen allergic subjects. This would also determine better specific immunotherapy regimes between the two cohorts. The allergens identified herein have potential towards vaccine development in date palm pollen allergy as well as in enriching the existing catalogue of allergenic proteins. Copyright © 2017. Published by Elsevier B.V.

CD23 surface density on B cells is associated with IgE levels and determines IgE-facilitated allergen uptake, as well as activation of allergen-specific T cells.

PubMed

Selb, Regina; Eckl-Dorna, Julia; Neunkirchner, Alina; Schmetterer, Klaus; Marth, Katharina; Gamper, Jutta; Jahn-Schmid, Beatrice; Pickl, Winfried F; Valenta, Rudolf; Niederberger, Verena

2017-01-01

Increasing evidence suggests that the low-affinity receptor for IgE, CD23, plays an important role in controlling the activity of allergen-specific T cells through IgE-facilitated allergen presentation. We sought to determine the number of CD23 molecules on immune cells in allergic patients and to investigate whether the number of CD23 molecules on antigen-presenting cells is associated with IgE levels and influences allergen uptake and allergen-specific T-cell activation. Numbers of CD23 molecules on immune cells of allergic patients were quantified by using flow cytometry with QuantiBRITE beads and compared with total and allergen-specific IgE levels, as well as with allergen-induced immediate skin reactivity. Allergen uptake and allergen-specific T-cell activation in relation to CD23 surface density were determined by using flow cytometry in combination with confocal microscopy and T cells transfected with the T-cell receptor specific for the birch pollen allergen Bet v 1, respectively. Defined IgE-allergen immune complexes were formed with human monoclonal allergen-specific IgE and Bet v 1. In allergic patients the vast majority of CD23 molecules were expressed on naive IgD + B cells. The density of CD23 molecules on B cells but not the number of CD23 + cells correlated with total IgE levels (R S  = 0.53, P = .03) and allergen-induced skin reactions (R S  = 0.63, P = .008). Uptake of allergen-IgE complexes into B cells and activation of allergen-specific T cells depended on IgE binding to CD23 and were associated with CD23 surface density. Addition of monoclonal IgE to cultured PBMCs significantly (P = .04) increased CD23 expression on B cells. CD23 surface density on B cells of allergic patients is correlated with allergen-specific IgE levels and determines allergen uptake and subsequent activation of T cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Depigmented and polymerised house dust mite allergoid: allergen content, induction of IgG4 and clinical response.

PubMed

Gallego, M T; Iraola, V; Himly, M; Robinson, D S; Badiola, C; García-Robaina, J C; Briza, P; Carnés, J

2010-01-01

Polymerised allergenic extracts (allergoids) are commonly used in allergen immunotherapy. Clinical efficacy and safety of these extracts have been demonstrated. Recently, allergen sequences have been identified by mass spectrometry in depigmented and polymerised (Dpg-Pol) extracts. The objectives of this study were to investigate the presence of allergens in Dpg-Pol extracts of house dust mite and to analyze the immunological changes induced by these extracts in asthmatic patients enrolled in a double-blind, placebo-controlled study. Dpg-Pol extracts were manufactured and vaccines with a composition of 50% Dermatophagoides pteronyssinus and 50% D. farinae (100 HEPL/ml) were prepared. Allergen composition was analyzed by mass spectrometry. Patients with asthma and rhinoconjunctivitis were treated in a 1-year, double-blind, placebo-controlled, parallel-group study with 6 up-dosing and monthly maintenance injections. Specific IgE and IgG4 titres to D. pteronyssinus, Der p 1 and Der p 2 were measured in patients' sera using the CAP system and direct ELISA experiments. Sequences from the major allergens Der p 1 and Der p 2 and from other allergens were identified in native and Dpg-Pol extracts. There was a statistically significant increase in specific IgG4, a decrease in the ratio of IgE/IgG4 to D. pteronyssinus and a significant increase in specific IgG4 to Der p 1 and Der p 2 in the patients allotted to active treatment. The detection of allergen sequences suggests preservation of major and minor allergens in Dpg-Pol allergoids from house dust mites. Efficacy in asthma treatment and the increase in specific IgG4 seem to be associated with the presence of major allergens in Dpg-Pol allergen extracts. Copyright (c) 2010 S. Karger AG, Basel.

An update on molecular cat allergens: Fel d 1 and what else? Chapter 1: Fel d 1, the major cat allergen.

PubMed

Bonnet, B; Messaoudi, K; Jacomet, F; Michaud, E; Fauquert, J L; Caillaud, D; Evrard, B

2018-01-01

Cats are the major source of indoor inhalant allergens after house dust mites. The global incidence of cat allergies is rising sharply, posing a major public health problem. Ten cat allergens have been identified. The major allergen responsible for symptoms is Fel d 1, a secretoglobin and not a lipocalin, making the cat a special case among mammals. Given its clinical predominance, it is essential to have a good knowledge of this allergenic fraction, including its basic structure, to understand the new exciting diagnostic and therapeutic applications currently in development. The recent arrival of the component-resolved diagnosis, which uses molecular allergens, represents a unique opportunity to improve our understanding of the disease. Recombinant Fel d 1 is now available for in vitro diagnosis by the anti-Fel d 1 specific IgE assay. The first part of the review will seek to describe the recent advances related to Fel d 1 in terms of positive diagnosis and assessment of disease severity. In daily practice, anti-Fel d 1 IgE tend to replace those directed against the overall extract but is this attitude justified? We will look at the most recent arguments to try to answer this question. In parallel, a second revolution is taking place thanks to molecular engineering, which has allowed the development of various forms of recombinant Fel d 1 and which seeks to modify the immunomodulatory properties of the molecule and thus the clinical history of the disease via various modalities of anti-Fel d 1-specific immunotherapy. We will endeavor to give a clear and practical overview of all these trends.

Immunotherapy throughout the decades: from Noon to now.

PubMed

Finegold, Ira; Dockhorn, Robert J; Ein, Daniel; Dolen, William K; Oppenheimer, John; Potter, Lawrence H

2010-11-01

To review major milestones in the development of subcutaneous allergen immunotherapy in 20-year segments. Review of the literature available in textbooks and journals. Articles and books addressing major achievements in the development of subcutaneous allergy immunotherapy were selected for inclusion in this review. Immunotherapy administration has improved the lives of possibly millions of patients with hay fever. Asthmatic symptoms have been relieved if not ablated in millions as well. Insect venom hypersensitivity became treatable and highly effective. In the beginning years of immunotherapy, it was clear that immunotherapy worked; in the later years, the mechanisms for this efficacy were discovered. In this case, the therapy preceded its validation. Methods, materials, and safety have vastly improved. Postulated mechanisms explain much but not everything. There is still research to be accomplished, improvements to be made, and, of course, patients to be made well. Copyright © 2010 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Specific Immunotherapy in Hymenoptera Venom Allergy and Concomitant Malignancy: A Retrospective Follow-up Focusing on Effectiveness and Safety.

PubMed

Aeberhard, J; Haeberli, G; Müller, U R; Helbling, A

2017-01-01

Malignancies are often considered a contraindication for allergen-specific immunotherapy. Consequently, patients with severe Hymenoptera venom allergy and cancer require specific care. The aim of this retrospective study was to assess patients with Hymenoptera venom allergy and cancer undergoing venom immunotherapy (VIT). The study population comprised all patients referred for evaluation of Hymenoptera venom allergy or for a routine check-up during VIT from January 1, 2004 to December 31, 2008. Of the patients assessed, 2% (51 of 2594) had a documented Hymenoptera venom allergy and cancer (25 female, 26 male; mean age 58 years). Of these, 42 patients received VIT (82%): 25 patients had a previously diagnosed malignancy, 16 were diagnosed with malignancy during VIT, and 1 patient was diagnosed with cancer after completion of VIT. The most frequent type of tumor was breast cancer in female patients (60%) and prostate cancer in male patients (39%). Systemic allergic reactions during VIT were recorded in 7% of patients. A total of 19 patients experienced a field sting or underwent a sting challenge test during VIT: 95% tolerated the sting well. VIT was halted definitively in 9 patients (new diagnosis of cancer in 7 patients, reactivation of cancer in 1, and progressive polyneuropathy in 1). The effectiveness and adverse effects of VIT in patients with Hymenoptera venom allergy and cancer in remission are comparable to those of patients without malignancy. Our findings show that patients with Hymenoptera venom allergy and cancer are eligible for VIT.

Staphylococcal enterotoxin A-activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation.

PubMed

Zeng, Wei-Ping; McFarland, Margaret M; Zhou, Baohua; Holtfreter, Silva; Flesher, Susan; Cheung, Ambrose; Mallick, Avishek

2017-02-01

T H 2 responses are implicated in asthma pathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins. We used a mouse model of asthma to determine whether staphylococcal enterotoxins promote T H 2 differentiation of allergen-specific CD4 conventional T (Tcon) cells and asthma by activating allergen-nonspecific regulatory T (Treg) cells to create a T H 2-polarizing cytokine milieu. Ovalbumin (OVA)-specific, staphylococcal enterotoxin A (SEA)-nonreactive naive CD4 Tcon cells were cocultured with SEA-reactive allergen-nonspecific Treg or CD4 Tcon cells in the presence of OVA and SEA. The OVA-specific CD4 T cells were then analyzed for IL-13 and IFN-γ expression. SEA-activated Treg cells were analyzed for the expression of the T H 2-polarizing cytokine IL-4 and the T-cell activation markers CD69 and CD62L. For asthma induction, mice were intratracheally sensitized with OVA or cat dander extract (CDE) alone or together with SEA and then challenged with OVA or CDE. Mice were also subject to transient Treg cell depletion before sensitization with OVA plus SEA. Asthma features and T H 2 differentiation in these mice were analyzed. SEA-activated Treg cells induced IL-13 but suppressed IFN-γ expression in OVA-specific CD4 Tcon cells. SEA-activated Treg cells expressed IL-4, upregulated CD69, and downregulated CD62L. Sensitization with OVA plus SEA but not OVA alone induced asthma, and SEA exacerbated asthma induced by CDE. Depletion of Treg cells abolished these effects of SEA and IL-13 expression in OVA-specific T cells. SEA promoted T H 2 responses of allergen-specific T cells and asthma pathogenesis by activating Treg cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

[Allergens used in skin tests in Mexico].

PubMed

Larenas Linnemann, Désirée; Arias Cruz, Alfredo; Guidos Fogelbach, Guillermo Arturo; Cid del Prado, Mari Lou

2009-01-01

Immunotherapy is the only recognized causal treatment for allergies. It is prepared on an individual basis, based on the patient's clinical history and the result of the skin prick test (SPT). An adequate composition of the allergens with which to test the patient is crucial for an optimal diagnosis. To know allergens used in tests in allergy practices in Mexico. A national survey among all members of the Colegio Mexicano de Inmunología Clínica y Alergia (CMICA) and of the Colegio Mexicano de Pediatras Especialistas en Inmunología Clínica y Alergia (COMPEDIA) was carried out. In a second phase respondents were asked to send in the composition of a routine SPT in their clinic. The results are presented descriptively and the frequency is calculated by which certain allergen is tested in the interviewed practices. A survey response rate of 61 (17%) was obtained and 54% showed their SPT content. Weeds' representation in the SPT seems adequate; Atriplex is tested in all allergy practices. Some trees that show cross-reactivity might be eliminated from the SPT, but 20% doesn't test for Cynodon nor Holcus, and 25% doesn't for important allergens as cat, dog and cockroach. House dust and tobacco are still tested with certain frequency. The selection of which allergens to test in a SPT is based on multiple data, that change continuously with new investigations and discoveries. Our specialty is the most indicated--and obligated--to adjust constantly to these changes to have the best diagnostic tool to detect specific allergies.

Alternative products to treat allergic rhinitis and alternative routes for allergy immunotherapy.

PubMed

Ipci, Kagan; Oktemer, Tugba; Muluk, Nuray Bayar; Şahin, Ethem; Altıntoprak, Niyazi; Bafaqeeh, Sameer Ali; Kurt, Yasemin; Mladina, Ranko; Šubarić, Marin; Cingi, Cemal

2016-09-01

Some alternative products instead of immunotherapy are used in patients with allergic rhinitis (AR). In this paper, alternative products to treat allergic rhinitis and alternative routes for allergy immunotherapy are reviewed. Alternative products and methods used instead of immunotherapy are tea therapy, acupuncture, Nigella sativa, cinnamon bark, Spanish needle, acerola, capsaicin (Capsicum annum), allergen-absorbing ointment, and cellulose powder. N. sativa has been used in AR treatment due to its anti-inflammatory effects. N. sativa oil also inhibits the cyclooxygenase and 5-lipoxygenase pathways of arachidonic acid metabolism. The beneficial effects of N. sativa seed supplementation on the symptoms of AR may be due to its antihistaminic properties. To improve the efficacy of immunotherapy, some measures are taken regarding known immunotherapy applications and alternative routes of intralymphatic immunotherapy and epicutaneous immunotherapy are used. There are alternative routes and products to improve the efficacy of immunotherapy.

Food aversion: a critical balance between allergen-specific IgE levels and taste preference.

PubMed

Mirotti, Luciana; Mucida, Daniel; de Sá-Rocha, Luis Carlos; Costa-Pinto, Frederico Azevedo; Russo, Momtchilo

2010-03-01

Animals sensitized to allergens change their feeding behavior and avoid drinking the otherwise preferred sweetened solutions containing the allergens. This phenomenon, known as food aversion, appears to be mediated by allergen-specific IgE antibodies. Here we investigated food aversion in BALB/c and C57BL/6 mice, which differ in their allergic responses to the allergen ovalbumin as well as in their preference for sweet taste. BALB/c mice present higher levels of IgE and a natural lower preference for sweet flavors when compared to C57BL/6 mice. Specifically, we studied a conflicting situation in which animals simultaneously experienced the aversive contact with the allergen and the attractive sweet taste of increasing concentrations of sucrose. We found that BALB/c mice were more prone to develop food aversion than C57BL/6 mice and that this aversive behavior could be abolished in both strains by increasing the palatability of the solution containing the allergen. In both strains food aversion was positively correlated with the levels of allergen-specific IgE antibodies and inversely correlated with their preference for sucrose sweetened solutions. 2009 Elsevier Inc. All rights reserved.

Specific Immunoglobulin (Ig) G Reference Intervals for Common Food, Insect, and Mold Allergens.

PubMed

Martins, Thomas B; Bandhauer, Michael E; Wilcock, Diane M; Hill, Harry R; Slev, Patricia R

2016-12-01

The clinical utility of serum IgG measurement in the diagnosis of allergy and food-induced hypersensitivity has been largely discredited. Recent studies, however, have shown that specific IgG can inhibit IgE mediated allergies, and may play a role in allergen specific desensitization. Accurate reference intervals for IgG specific allergens have not been widely established and are needed for better interpretation of serum antibody concentrations. In this study we established 64 IgG reference intervals for 48 common food allergens, 5 venoms, and 11 molds. Specific IgG concentrations were determined employing an automated fluorescent enzyme immunoassay on serum samples from 130 normal adults (65 males and 65 females), age range 18-69 y, mean 37.3 y. The lower reference interval limit for all allergens tested (n=64) was <2 mcg/mL. The median upper reference interval value for all 64 allergens was 12.9 mcg/mL, with Tuna (f40) having the lowest upper interval limit at 3.8 mcg/mL, and the mold Setomelanomma rostrate (m8) demonstrating the highest upper interval limit at 131 mcg/L. The considerable variation observed among the upper reference interval limits emphasizes the need for the establishment of allergen specific ranges for IgG. These newly established ranges should be a useful aid for clinicians in the interpretation of laboratory serum IgG results. © 2016 by the Association of Clinical Scientists, Inc.

TLR9-based immunotherapy for the treatment of allergic diseases.

PubMed

Farrokhi, Shokrollah; Abbasirad, Narjes; Movahed, Ali; Khazaei, Hossein Ali; Pishjoo, Masoud; Rezaei, Nima

2017-03-01

Toll-like receptors (TLRs), a family of pattern recognition receptors expressed on many cell types of innate immunity, recognize the pathogen-associated molecular patterns of microbes. The hygiene hypothesis suggests that a reduced microbial exposure in early childhood increases the susceptibility to allergic diseases due to deviation in development of the immune system. TLRs are key roles in the right and healthy direction of adaptive immunity with the induction of T-helper 2 toward Th1 immune responses and regulatory T cells. TLR ligand CpG-ODN-based immunomodulation is independent of allergen and it mainly affects innate immune system. While, CpG-oligodeoxynucleotide-based vaccination is allergen specific and induces adaptive immune system. The use of agonists of TLR9 in two distinct strategies of immunotherapy, immunomodulation and vaccination, could be presented as the curative method for the treatment of allergic diseases.

Identification of novel allergens of Aspergillus fumigatus using immunoproteomics approach.

PubMed

Gautam, P; Sundaram, C S; Madan, T; Gade, W N; Shah, A; Sirdeshmukh, R; Sarma, P U

2007-08-01

Approximately 20% of the world's asthmatics are suffering from Aspergillus fumigatus (Afu)-induced allergies. The characterization of specific IgE-inducing allergens in allergic aspergillosis patients is fundamental for clinical diagnosis and for immunotherapy. Immunoproteomics combined with mass spectrometric analysis was used to identify proteins of third-week culture filtrate (3wcf) potentially responsible for Afu-specific IgE immunoreactivity, using pooled sera from Afu-sensitized asthmatics. Their allergenic potential was also tested against patients with allergic bronchopulmonary aspergillosis (ABPA), by two-dimensional (2-D) gel electrophoresis immunoblotting of 3wcf proteins with individual sera from such patients. This helped us to establish a set of candidate allergens, which could be explored further for diagnostic application in allergic aspergillosis asthmatics including ABPA. Peptide mass fingerprint using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and/or de novo sequencing by MS/MS analysis of the protein spots from 2-D gels led to the identification of a total of 16 allergens of Afu. Eleven of them are being reported as allergens for the first time and five had been reported earlier. Putative isoforms of the proteins Asp f 13 and chitosanase have been observed for the first time. When studied for reactivity of these proteins among patients with ABPA using their individual sera, these patients exhibited sensitization although the pattern was varying. Taken together, these proteins could thus be considered as potential allergens even among patients with ABPA. Three of these proteins viz. the hypothetical protein (# spot no. 5), extracellular arabinase (# spot no. 6) and chitosanase (# spot no. 11) could be major allergens with specific IgE immunoreactivity with six out of eight patients' sera. The immunoproteomic approach applied to the analysis of culture filtrate proteins resulted in the

Peptide immunotherapy in allergic asthma generates IL-10–dependent immunological tolerance associated with linked epitope suppression

PubMed Central

Campbell, John D.; Buckland, Karen F.; McMillan, Sarah J.; Kearley, Jennifer; Oldfield, William L.G.; Stern, Lawrence J.; Grönlund, Hans; van Hage, Marianne; Reynolds, Catherine J.; Boyton, Rosemary J.; Cobbold, Stephen P.; Kay, A. Barry; Altmann, Daniel M.; Larché, Mark

2009-01-01

Treatment of patients with allergic asthma using low doses of peptides containing T cell epitopes from Fel d 1, the major cat allergen, reduces allergic sensitization and improves surrogate markers of disease. Here, we demonstrate a key immunological mechanism, linked epitope suppression, associated with this therapeutic effect. Treatment with selected epitopes from a single allergen resulted in suppression of responses to other (“linked”) epitopes within the same molecule. This phenomenon was induced after peptide immunotherapy in human asthmatic subjects and in a novel HLA-DR1 transgenic mouse model of asthma. Tracking of allergen-specific T cells using DR1 tetramers determined that suppression was associated with the induction of interleukin (IL)-10+ T cells that were more abundant than T cells specific for the single-treatment peptide and was reversed by anti–IL-10 receptor administration. Resolution of airway pathophysiology in this model was associated with reduced recruitment, proliferation, and effector function of allergen-specific Th2 cells. Our results provide, for the first time, in vivo evidence of linked epitope suppression and IL-10 induction in both human allergic disease and a mouse model designed to closely mimic peptide therapy in humans. PMID:19528258

Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization.

PubMed

Renand, Amedee; Archila, Luis D; McGinty, John; Wambre, Erik; Robinson, David; Hales, Belinda J; Thomas, Wayne R; Kwok, William W

2015-12-01

In human subjects, allergen tolerance has been observed after high-dose allergen exposure or after completed allergen immunotherapy, which is related to the accumulation of anti-inflammatory IgG4. However, the specific T-cell response that leads to IgG4 induction during chronic allergen exposure remains poorly understood. We sought to evaluate the relationship between cat allergen-specific T-cell frequency, cat allergen-specific IgE and IgG4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG4 is produced. Fel d 1-, Fel d 4-, Fel d 7-, and Fel d 8-specific T-cell responses were characterized by CD154 expression after antigen stimulation. In allergic subjects without cat ownership, the frequency of cat allergen (Fel d 1 and Fel d 4)-specific TH2 (sTH2) cells correlates with higher IgE levels and is linked to asthma. Paradoxically, we observed that subjects with cat allergy and chronic cat exposure maintain a high frequency of sTH2 cells, which correlates with higher IgG4 levels and low sensitization. B cells from allergic, but not nonallergic subjects, are able to produce IgG4 after cognate interactions with sTH2 clones and Fel d 1 peptide or the Fel d 1 recombinant protein. These experiments suggest that (1) allergen-experienced B cells with the capacity to produce IgG4 are present in allergic subjects and (2) cat allergen exposure induces an IgG4 response in a TH2 cell-dependent manner. Thus IgG4 accumulation could be mediated by chronic activation of the TH2 response, which in turn drives desensitization. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Microarray evaluation of specific IgE to allergen components in elite athletes.

PubMed

Bonini, M; Marcomini, L; Gramiccioni, C; Tranquilli, C; Melioli, G; Canonica, G W; Bonini, S

2012-12-01

Allergic sensitization and diseases have been reported to have a very high and increasing prevalence in elite athletes. Over 80% of allergic athletes are poly-sensitized. This study aims at evaluating the potential diagnostic added value of a microarray technology (ImmunoCAP ISAC, Phadia AB [at present Thermo Fisher Scientific] Uppsala, Sweden which detects IgE antibodies to specific or cross-reacting allergen components. Seventy-two poly-sensitized athletes according to skin prick test (SPT) with different allergic phenotypes (asthma n = 19; rhino-conjunctivitis n = 20; food allergy and/or oral allergy syndrome n = 13; no clinical symptoms n = 20) and two different control populations (20 poly-sensitized sedentary subjects with respiratory allergy and 20 healthy athletes with negative SPT) were studied for detecting specific IgE (sIgE) both to allergen extracts (ImmunoCAPsIgE) and to allergen components (ImmunoCAP ISAC). ImmunoCAP ISAC detected the presence of sIgE in 90% of poly-sensitized athletes--in 96% with symptoms and in 75% without symptoms--and in 100% of allergic controls. The pattern of positivity towards the 103 components tested differed from subject to subject, even in those with the same sensitization to allergen extract SPT or sIgE. Based on the ISAC results, poly-sensitized athletes were classified into the following prototypical patterns, differently represented in the clinical phenotypes studied (P = 0.03): (1) One single predominant specific allergen positivity; (2) sIgE to two or more non-cross-reacting allergens; (3) sIgE to cross-reacting allergens; and (4) sIgE to components potentially responsible for severe allergic reactions. The ImmunoCAP ISAC represents a useful additional tool for diagnosis and management of poly-sensitized athletes. © 2012 John Wiley & Sons A/S.

[Clinical symptoms of the allergic rhinitis and coexisting cross reactions in patients treated with the birch and/or grasses allergens against a background of the pollen exposure].

PubMed

Myszkowska, Dorota; Mazur, Marcel; Ziemianin, Monika; Wach-Pizoń, Małgorzata; Czarnobilska, Ewa

During specific immunotherapy (SIT) it is recommended to monitor the patient symptoms in relation to the exposure of allergen which the patient is treated. The aim of the study was to analyze the clinical symptoms of allergic rhinitis (AR) and cross reactivity in patients undergoing specific immunotherapy using pollen allergens (SIT) (birch and/or grasses) against the pollen exposure in 2014-2016. The study group, consisted of patients with pollen allergy, treated by SIT with birch and grasses allergens, who showed oral allergy symptoms. Patients of the control group were sensitive to birch and/or grasses allergens and they were not treated with SIT. The analyses were based on the results of questionnaires and patient symptom diaries. Timing of the pollen seasons of birch and grasses were similar, however the significantly higher concentration of birch pollen was found in 2014 and 2016, comparing to 2015. The strongest relationship between the pollen concentration and symptoms severity was revealed in the study group in patients desensitized by combined vaccine (birch/grasses), while in the control group, in patients sensitive to both taxa. In 35.3% of patients in the study group, a significant decrease in symptoms after foods was found, especially in patients desensitized with mixed vaccine (birch, grasses) after consumption of vegetables and in patients desensitized with grasses allergens after the fruits and nuts. SIT has a significant impact on the symptoms score reduction, which could be modified by the changeable seasonal pollen exposure.

Allergenic proteins of natural rubber latex.

PubMed

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. Copyright 2002 Elsevier Science (USA).

Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome.

PubMed

Kim, Tae Beom; Shim, Young Sup; Lee, Sang Min; Son, Eun Suk; Shim, Jung Woo; Lee, Sang Pyo

2018-06-01

Post-orgasmic illness syndrome (POIS) is a very rare disease characterized by local allergic symptoms and transient flu-like illness that nearly always occur after masturbation, coitus, or spontaneous ejaculation and last for 2 to 7 days. In a previous case report, 2 patients with POIS received hyposensitization therapy composed of multiple subcutaneous injections of autologous semen that resulted in a gradual decrease of symptoms. However, this procedure requires patients to endure pain and discomfort during frequent subcutaneous injections and preceding masturbations to obtain the autologous semen used for therapy. Recent studies have suggested that intralymphatic immunotherapy is a promising new method of allergen-specific immunotherapy against allergic diseases, showing a faster onset and longer duration of therapeutic effects after only several intralymphatic injections. We report on a case of a Korean man with POIS who received intralymphatic immunotherapy that alleviated POIS-related symptoms and in whom the existence of semen-specific immunoglobulin E was confirmed using immunoglobulin E immunoblotting and enzyme-linked immunosorbent assay. Kim TB, Shim YS, Lee, SM, et al. Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome. Sex Med 2018;6:174-179. Copyright © 2018. Published by Elsevier Inc.

Efficacy of oral immunotherapy with a rice-based edible vaccine containing hypoallergenic Japanese cedar pollen allergens for treatment of established allergic conjunctivitis in mice.

PubMed

Fukuda, Ken; Ishida, Waka; Harada, Yosuke; Wakasa, Yuhya; Takagi, Hidenori; Takaiwa, Fumio; Fukushima, Atsuki

2018-01-01

We have previously shown that prophylactic oral administration of transgenic rice seeds expressing hypoallergenic modified antigens suppressed the development of allergic conjunctivitis induced by Japanese cedar pollen. We have now investigated the efficacy of oral immunotherapy with such transgenic rice for established allergic conjunctivitis in mice. BALB/c mice were sensitized with two intraperitoneal injections of Japanese cedar pollen in alum, challenged with pollen in eyedrops, and then fed for 16 days with transgenic rice seeds expressing modified Japanese cedar pollen allergens Cry j 1 and Cry j 2 or with nontransgenic rice seeds as a control. They were then challenged twice with pollen in eyedrops, with clinical signs being evaluated at 15 min after the first challenge and the eyes, blood, spleen, and lymph nodes being isolated at 24 h after the second challenge. The number of eosinophils in the conjunctiva and the clinical score for conjunctivitis were both significantly lower in mice fed the transgenic rice than in those fed nontransgenic rice. Oral vaccination with transgenic rice seeds also resulted in a significant increase in the production of IFN-γ by splenocytes, whereas it had no effect on the number of CD4 + CD25 + Foxp3 + regulatory T cells in the spleen or submandibular or mesenteric lymph nodes. Oral administration of transgenic rice seeds expressing hypoallergenic allergens ameliorated allergic conjunctivitis in the established setting. Such a rice-based edible vaccine is potentially both safe and effective for oral immunotherapy in individuals with allergic conjunctivitis. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Immunotherapeutic efficacy of liposome-encapsulated refined allergen vaccines against Dermatophagoides pteronyssinus allergy.

PubMed

Chaisri, Urai; Tungtrongchitr, Anchalee; Indrawattana, Nitaya; Meechan, Panisara; Phurttikul, Watchara; Tasaniyananda, Natt; Saelim, Nawannaporn; Chaicumpa, Wanpen; Sookrung, Nitat

2017-01-01

Allergen specific immunotherapy (AIT) can modulate the allergic response causing a long-term symptom subsidence/abolishment which leads to reduced drug use and prevention of new sensitization. AIT of house dust mite allergy (HDM) using the mite crude extract (CE) as the therapeutic agent is not only less effective than the AIT for many other allergens, but also frequently causes adverse effects during the treatment course. In this study, mouse model of Dermatophagoides pteronyssinus (Dp) allergy was invented for testing therapeutic efficacies of intranasally administered liposome (L) encapsulated vaccines made of single Dp major allergens (L-Der p 1, L-Der p 2), combined allergens (L-Der p 1 and Der p 2), and crude Dp extract (L-CE). The allergen sparing intranasal route was chosen as it is known that the effective cells induced at the nasal-associated lymphoid tissue can exert their activities at the lower respiratory tissue due to the common mucosal traffic. Liposome was chosen as the vaccine delivery vehicle and adjuvant as the micelles could reduce toxicity of the entrapped cargo. The Dp-CE allergic mice received eight doses of individual vaccines/placebo on alternate days. All vaccine formulations caused reduction of the Th2 response of the Dp allergic mice. However, only the vaccines made of single refined allergens induced expressions of immunosuppressive cytokines (TGF-β, IL-35 and/or IL-10) which are the imperative signatures of successful AIT. The data emphasize the superior therapeutic efficacy of single refined major allergen vaccines than the crude allergenic extract vaccine.

Specific oral tolerance induction in childhood.

PubMed

Peters, Rachel L; Dang, Thanh D; Allen, Katrina J

2016-12-01

Food allergy continues to be a significant public health concern for which there are no approved treatments and management strategies primarily include allergen avoidance and pharmacological measures for accidental exposures. Food allergy is thought to result from either a failure to establish oral tolerance or the breakdown of existing oral tolerance, and therefore, experimental preventative and treatment strategies are now aimed at inducing specific oral tolerance. This may occur in infancy prior to the development of food allergy through the optimal timing of dietary exposure (primary oral tolerance induction) or as a treatment for established food allergy through oral immunotherapy (secondary oral tolerance induction). Trials examining the effectiveness of early dietary allergen exposure to prevent food allergy have yielded promising results for peanut allergy but not so for other allergens, although the results of several trials are yet to be published. Although infant feeding guidelines no longer advise to avoid allergenic foods and exposure to food allergens orally is an important step in inducing food tolerance by the immune system, evidence regarding the optimal timing, dose and form of these foods into the infant's diet is lacking. Likewise, oral immunotherapy trials appear promising for inducing desensitization; however, the long-term efficacy in achieving sustained desensitization and optimal protocols to achieve this is unknown. More research is needed in this emerging field. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case-control study on 171 patients. The EFESO-children multicenter trial.

PubMed

Acquistapace, Franca; Agostinis, Fabio; Castella, Vincenzo; Kantar, Ahmad; Novembre, Elio; Perrone, Maria Rosaria; Pietrasanta, Michele; Sambugaro, Renato; Milani, Massimo

2009-11-01

Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in 'real life' in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case-control study to evaluate the effect of SLIT in children (age 6-18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case-control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone ALK-Abellò). Controls (n = 81) were defined as sex-age- and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean +/- SD) was 4.5 +/- 2.5 in cases and 9.0 +/- 3.0 in controls (-50%) (p = 0.0001). MS (mean +/- SD) was 2.5 +/- 1.9 and 3.6 +/- 2.1 in the case and control groups, respectively (-31%) (p = 0.0001). At the end of

Recombinant proteins and peptides as diagnostic and therapeutic reagents for arthropod allergies.

PubMed

Ramos, John Donnie A; Valmonte, Gardette R; de Guia, Roldan M

2007-01-01

Domestic arthropods are chief sources of potent allergens that trigger sensitization and stimulate IgE-mediated allergies. Diagnosis and immunotherapy of arthropod allergies rely on the use of natural allergen extracts which are associated with low specificity and efficacy, the risk of anaphylactic reactions, and the extended period of treatment. Most of the problems associated with natural allergen extracts for allergy diagnosis and immunotherapy can be circumvented with the use of recombinant allergens and peptides. Recombinant allergens are recently developed for microarray-based multi-allergen tests which provide component-resolved diagnosis (CRD) of the patient's sensitization profile. Moreover, recombinant protein technology and peptide chemistry have been used to construct isoallergens, allergen mutants, allergoids, T and B cell peptides, hypoallergens, and mimotopes with reduced allergenicity but enhanced immunogenicity for allergen-specific immunotherapy (SIT) and vaccination. The basics of recombinant arthropod allergen technology are in place providing a lucid future for the advancement of diagnosis and immunotherapy of arthropod allergies.

Mixing compatibilities of Aspergillus and American cockroach allergens with other high-protease fungal and insect extracts.

PubMed

Grier, Thomas J; Hall, Dawn M; Duncan, Elizabeth A; Coyne, Terrance C

2015-03-01

Recent studies have shown that Alternaria and German cockroach allergens can be degraded by endogenous proteases from other insect and fungal extracts when combined for immunotherapy, but data supporting the compatibilities of other high-protease products in comparable mixtures have not been reported. To assess the stabilities and compatibilities of Aspergillus fumigatus and American cockroach allergens after mixing with protease-rich extracts from other insects or fungi at concentrations similar to those recommended for subcutaneous immunotherapy. Mixtures containing A fumigatus, American cockroach, and other fungal or insect extracts were evaluated by quantitative (enzyme-linked immunosorbent assays) and qualitative (immunoblotting) methods. Test mixtures and control samples at 10% to 50% glycerin concentrations were analyzed after storage for up to 12 months at 2°C to 8°C. Moderate to high recoveries of Aspergillus extract activities were retained in control samples and extract mixtures under all conditions examined. American cockroach extract controls were partly degraded at 10% to 25% glycerin, and cockroach allergen compatibilities were decreased significantly in mixtures with several fungal extracts at 25% glycerin. Mixing with other insects did not compromise the stability of American cockroach allergens at 25% to 50% glycerin. Aspergillus extracts exhibited favorable stabilities after mixing with other high-protease products. American cockroach extract potencies were unstable in less than 50% glycerin, even in the absence of other protease-containing allergens, and were destabilized in mixtures with several fungal extracts. Addition of fungal and insect extracts to separate treatment vials or preparation of fungal-insect mixtures at elevated glycerin concentrations might be necessary to produce compatible patient formulations for allergen immunotherapy injections. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier

Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

PubMed

Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

2008-01-01

The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK.

PubMed

Witting Christensen, S K; Kortekaas Krohn, I; Thuraiaiyah, J; Skjold, T; Schmid, J M; Hoffmann, H J H

2014-10-01

Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity. We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10). Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05). Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Molecular determinants of T cell epitope recognition to the common Timothy grass allergen.

PubMed

Oseroff, Carla; Sidney, John; Kotturi, Maya F; Kolla, Ravi; Alam, Rafeul; Broide, David H; Wasserman, Stephen I; Weiskopf, Daniela; McKinney, Denise M; Chung, Jo L; Petersen, Arnd; Grey, Howard; Peters, Bjoern; Sette, Alessandro

2010-07-15

We investigated the molecular determinants of allergen-derived T cell epitopes in humans utilizing the Phleum pratense (Timothy grass) allergens (Phl p). PBMCs from allergic individuals were tested in ELISPOT assays with overlapping peptides spanning known Phl p allergens. A total of 43 distinct antigenic regions were recognized, illustrating the large breadth of grass-specific T cell epitopes. Th2 cytokines (as represented by IL-5) were predominant, whereas IFN-gamma, IL-10, and IL-17 were detected less frequently. Responses from specific immunotherapy treatment individuals were weaker and less consistent, yet similar in epitope specificity and cytokine pattern to allergic donors, whereas nonallergic individuals were essentially nonreactive. Despite the large breadth of recognition, nine dominant antigenic regions were defined, each recognized by multiple donors, accounting for 51% of the total response. Multiple HLA molecules and loci restricted the dominant regions, and the immunodominant epitopes could be predicted using bioinformatic algorithms specific for 23 common HLA-DR, DP, and DQ molecules. Immunodominance was also apparent at the Phl p Ag level. It was found that 52, 19, and 14% of the total response was directed to Phl p 5, 1, and 3, respectively. Interestingly, little or no correlation between Phl p-specific IgE levels and T cell responses was found. Thus, certain intrinsic features of the allergen protein might influence immunogenicity at the level of T cell reactivity. Consistent with this notion, different Phl p Ags were associated with distinct patterns of IL-5, IFN-gamma, IL-10, and IL-17 production.

The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC): verification of nasal allergen challenge procedures in a study utilizing an investigational immunotherapy for cat allergy.

PubMed

Neighbour, Helen; Soliman, Mena; Steacy, Lisa M; Hickey, Pascal; Forbes, Beth; Larché, Mark; Ellis, Anne K

2018-01-01

The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC) is a network of experienced Allergic Rhinitis (AR) researchers developing better research tools based on the nasal allergen challenge (NAC). A key objective of such is the ability to detect efficacy in a small population. AR-CIC sought to test its NAC protocol as a secondary objective in two small mechanistic research trials of a novel form of immunotherapy [Cat Peptide Antigen Desensitisation (Cat-PAD)] for which efficacy had previously been demonstrated. The primary objective (not presented here) was to identify potential biomarkers of efficacy for peptide immunotherapy, and this provided an ideal opportunity to corroborate the NAC protocol. We aim to clinically validate the AR-CIC NAC methodology in a pooled analysis of secondary endpoints measured in two open label mechanistic studies of cat allergic participants treated with Cat-PAD. Cat allergic AR sufferers with ongoing cat exposure were included. Participants had to demonstrate a total nasal symptom score (TNSS) of at least 8 (max 12) and/or achieve a reduction in peak nasal inspiratory flow (PNIF) of ≥ 50% during a screening titrated NAC. Eligible participants then underwent a baseline NAC visit with the allergen dose that produced a positive challenge at screening, followed by four monthly injections of 6 nmol Cat-PAD. A follow up NAC visit documented changes in nasal response 1 month following the completion of treatment. Nineteen subjects completed the study protocol in the two studies combined. Four injections of Cat-PAD resulted in a significant reduction in TNSS responses generated via NAC following allergen challenge (15 min p  < 0.05, 30 min p  < 0.05, 1 h p  < 0.01, 2 h p  < 0.05). There was modest correlation between symptom scores and PNIF measurements. This study supports the validity of the AR-CIC's optimised NAC protocol for conducting research of the potential efficacy of novel therapeutics in multi

Identification of Aspergillus (A. flavus and A. niger) Allergens and Heterogeneity of Allergic Patients' IgE Response.

PubMed

Vermani, Maansi; Vijayan, Vannan Kandi; Agarwal, Mahendra Kumar

2015-08-01

Aspergillus species (A. flavus and A. niger) are important sources of inhalant allergens. Current diagnostic modalities employ crude Aspergillus extracts which only indicate the source to which the patient has been sensitized, without identifying the number and type of allergens in crude extracts. We report a study on the identification of major and minor allergens of the two common airborne Aspergillus species and heterogeneity of patients' IgE response to them. Skin prick tests were performed on 300 patients of bronchial asthma and/or allergic rhinitis and 20 healthy volunteers. Allergen specific IgE in patients' sera was estimated by enzyme allergosorbent test (EAST). Immunoblots were performed to identify major/minor allergens of Aspergillus extracts and to study heterogeneity of patients'IgE response to them. Positive cutaneous responses were observed in 17% and 14.7% of patients with A. flavus and A. niger extracts, respectively. Corresponding EAST positivity was 69.2% and 68.7%. In immunoblots, 5 allergenic proteins were identified in A. niger extract, major allergens being 49, 55.4 and 81.5 kDa. Twelve proteins bound patients' IgE in A. flavus extract, three being major allergens (13.3, 34 and 37 kDa). The position and slopes of EAST binding and inhibition curves obtained with individual sera varied from patient to patient. The number and molecular weight of IgE-binding proteins in both the Aspergillus extracts varied among patients. These results gave evidence of heterogeneity of patients' IgE response to major/minor Aspergillus allergens. This approach will be helpful to identify disease eliciting molecules in the individual patients (component resolved diagnosis) and may improve allergen-specific immunotherapy.

Concentrated Protein Body Product Derived from Rice Endosperm as an Oral Tolerogen for Allergen-Specific Immunotherapy—A New Mucosal Vaccine Formulation against Japanese Cedar Pollen Allergy

PubMed Central

Wakasa, Yuhya; Takagi, Hidenori; Watanabe, Nobumasa; Kitamura, Noriko; Fujiwara, Yoshihiro; Ogo, Yuko; Hayashi, Shimpei; Yang, Lijun; Ohta, Masaru; Thet Tin, Wai Wai; Sekikawa, Kenji; Takano, Makoto; Ozawa, Kenjirou; Hiroi, Takachika; Takaiwa, Fumio

2015-01-01

The endoplasmic reticulum-derived type-I protein body (PB-I) from rice endosperm cells is an ideal candidate formulation for the oral delivery of bioencapsulated peptides as tolerogens for allergen-specific immunotherapy. In the present study, PBs containing the deconstructed Japanese cedar pollen allergens Cryptomeria japonica 1 (Cry j 1) and Cry j 2 were concentrated by treatment with thermostable α-amylase at 90°C to remove the starch from milled rice powder, which resulted in a 12.5-fold reduction of dry weight compared to the starting material. The modified Cry j 1 and Cry j 2 antigens in this concentrated PB product were more resistant to enzymatic digestion than those in the milled seed powder despite the absence of intact cell wall and starch, and remained stable for at least 10 months at room temperature without detectable loss or degradation. The high resistance of these allergens could be attributed to changes in protein physicochemical properties induced by the high temperature concentration process, as suggested by the decreased solubility of the antigens and seed proteins in PBs in step-wise-extraction experiments. Confocal microscopy showed that the morphology of antigen-containing PB-Is was preserved in the concentrated PB product. The concentrated PB product induced specific immune tolerance against Cry j 1 and Cry j 2 in mice when orally administered, supporting its potential use as a novel oral tolerogen formulation. PMID:25774686

Clinical allergy to hazelnut and peanut: identification of T cell cross-reactive allergens.

PubMed

Glaspole, Ian N; de Leon, Maria P; Prickett, Sara R; O'Hehir, Robyn E; Rolland, Jennifer M

2011-01-01

Peanut and tree nut allergies are life-threatening conditions for many affected individuals worldwide. Currently there is no cure. While co-allergy to peanut and tree nuts is a common clinical observation, and IgE cross-reactivity between peanut and tree nuts is reported, T cell cross-reactivity is poorly defined. Hazelnut-specific T cell lines were established using peripheral blood mononuclear cells from 5 subjects with co-allergy to hazelnut and peanut. These lines were stimulated with hazelnut and peanut extracts and purified major peanut allergens, Ara h 1 and Ara h 2. Proliferation was determined by (3)H-thymidine incorporation and secretion of key Th1 (IFN-γ) and Th2 (IL-5) cytokines analysed by ELISA. Hazelnut-specific T cell lines from all 5 subjects proliferated upon stimulation with both hazelnut and peanut extracts and for 4 subjects, to Ara h 1 and/or Ara h 2. Proliferating cells were mainly CD4+ T cells and produced both IL-5 and IFN-γ in response to hazelnut and peanut stimulation. Mitogenicity of extracts and allergens was excluded by their lack of stimulation of house dust mite-specific T cells. Our finding that hazelnut and peanut co-allergy is associated with cross-reactive T cell responses, driven partly by cross-reactivity to the major peanut allergens Ara h 1 and Ara h 2, points to future development of allergen immunotherapy by targeting cross-reactive T cells. Copyright © 2011 S. Karger AG, Basel.

[Sublingual immunotherapy in children. Immunotherapy Committee of the Spanish Society for Clinical Immunology and Pediatric Allergology].

PubMed

Lleonart, R; Muñoz, F; Eseverri, J L; Martínez-Cañabate, A; Tabar, A I; Pedemonte, C

2003-01-01

Sublingual immunotherapy is currently attracting growing interest because of its ease of administration and, according to previous studies, its infrequent and mild adverse effects. However, at least in children, the efficacy of this therapy has not been completely demonstrated. In addition, the mechanisms of action remain to be elucidated since few studies have been published and the results have been contradictory and sometimes inconclusive. For this reason, we performed a literature review through the MEDLINE database, selecting double-blind studies carried out in children. Only 10 studies meeting these requirements were retrieved. All the studies were performed by European researchers and nine were published in European journals. Efficacy was evaluated by clinical parameters and by reduction in medication use. The results on efficacy are not homogeneous, although most support the utility of this route of administration. Moreover, reports of allergens other than those used in these studies dust mites and grass pollens are lacking. In conclusion, further studies evaluating the efficacy of this therapy in children are required. Among the general population, if the efficacy of sublingual immunotherapy in the treatment of sensitization to hymenoptera venoms were demonstrated, as has been the case with subcutaneous immunotherapy, the utility of this route of administration would be definitively confirmed. Finally, sublingual immunotherapy could be used in children who have shown systemic reactions to subcutaneous immunotherapy or who refuse to undergo injections.

Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens.

PubMed

Werfel, T; Asero, R; Ballmer-Weber, B K; Beyer, K; Enrique, E; Knulst, A C; Mari, A; Muraro, A; Ollert, M; Poulsen, L K; Vieths, S; Worm, M; Hoffmann-Sommergruber, K

2015-09-01

In older children, adolescents, and adults, a substantial part of all IgE-mediated food allergies is caused by cross-reacting allergenic structures shared by inhalants and foods. IgE stimulated by a cross-reactive inhalant allergen can result in diverse patterns of allergic reactions to various foods. Local, mild, or severe systemic reactions may occur already after the first consumption of a food containing a cross-reactive allergen. In clinical practice, clinically relevant sensitizations are elucidated by skin prick testing or by the determination of specific IgE in vitro. Component-resolved diagnosis may help to reach a diagnosis and may predict the risk of a systemic reaction. Allergy needs to be confirmed in cases of unclear history by oral challenge tests. The therapeutic potential of allergen immunotherapy with inhalant allergens in pollen-related food allergy is not clear, and more placebo-controlled studies are needed. As we are facing an increasing incidence of pollen allergies, a shift in sensitization patterns and changes in nutritional habits, and the occurrence of new, so far unknown allergies due to cross-reactions are expected. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Application of phage peptide display technology for the study of food allergen epitopes.

PubMed

Chen, Xueni; Dreskin, Stephen C

2017-06-01

Phage peptide display technology has been used to identify IgE-binding mimotopes (mimics of natural epitopes) that mimic conformational epitopes. This approach is effective in the characterization of those epitopes that are important for eliciting IgE-mediated allergic responses by food allergens and those that are responsible for cross-reactivity among allergenic food proteins. Application of this technology will increase our understanding of the mechanisms whereby food allergens elicit allergic reactions, will facilitate the discovery of diagnostic reagents and may lead to mimotope-based immunotherapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

T cell epitope immunotherapy ameliorates allergic responses in a murine model of shrimp allergy.

PubMed

Wai, C Y Y; Leung, N Y H; Leung, P S C; Chu, K H

2016-03-01

Shellfish allergy is one of the most common food hypersensitivities worldwide but allergen-specific immunotherapy for shellfish allergy is not yet available. We believe that T cell peptide-based immunotherapy holds the potential for modulating allergic responses without IgE cross-linking. We sought to identify the immunodominant T cell epitopes of tropomyosin, the major shrimp allergen of Metapenaeus ensis (Met e 1), and to evaluate their therapeutic effects in a Balb/c mouse model of Met e 1 hypersensitivity. T cell epitopes of Met e 1 were first identified based on the proliferation and cytokine responses of splenocytes isolated from Met e 1-sensitized Balb/c mice upon stimulation by 18 synthetic peptides that span the full-length Met e 1. The immunodominant T cell peptides identified were then fed orally to Met e 1-sensitized Balb/c mice twice a week for four weeks. Allergic responses, serological antibody levels, intestinal histology and systemic and local cytokine profiles were compared between the treated and the untreated groups. Six major Met e 1 T cell epitopes were identified. Mice treated with the T cell epitope peptide mixture demonstrated an amelioration of systemic allergic symptoms and a significant reduction in Th2-associated antibody and cytokine responses. These benefits were accompanied by a shift to a balanced Th1/Th2 response, induction of IgG2a antibodies possessing in vitro and in vivo blocking activities and the induction of regulatory T cell responses. T cell epitope-based oral immunotherapy is effective in reducing allergic responses towards shrimp tropomyosin. This is a novel strategy for clinical management of shellfish allergy and is a model for mechanistic studies of oral immunotherapy. © 2015 John Wiley & Sons Ltd.

Reduced work/academic performance and quality of life in patients with allergic rhinitis and impact of allergen immunotherapy.

PubMed

Roger, A; Arcalá Campillo, E; Torres, M C; Millan, C; Jáuregui, I; Mohedano, E; Liñan, S; Verdu, P; Rubira, N; Santaolalla, M; González, P; Orovitg, A; Villarrubia, E

2016-01-01

Allergic rhinitis (AR) is characterised by burdensome nasal and/or ocular symptoms. This inflammatory disease can be debilitating and thus result in considerable health-related and economic consequences. In a cross-sectional study, adult subjects with AR (N = 683) completed three allergy-specific questionnaires that assessed the impact of AR on the work/academic performance, daily activities, health-related quality of life (HRQOL), and satisfaction with allergen immunotherapy (AIT). Regression analyses were used to examine the associations between several clinical variables and the patient-reported outcomes. Total loss of productivity was 21.0 and 21.2 % for employed and student patients, respectively, whereas the impairment of daily activities was 22.0 %. The mean overall HRQOL score was 1.94 ± 1.29 (on the scale of 0-6 points). Global score for satisfaction with AIT was 65.5 ± 24.8 (on a 0-100 scale). Simple regression analysis found statistically significant associations between loss of work and academic productivity, impairment of daily activities and the type and severity of AR. AIT was a protective factor. The persistent and more severe types of AR and lack of AIT contributed to the worsening of HRQOL. AR (the persistent and more severe form of the disease) has an impact on functional characteristics of adult patients in Spain. AIT might reduce the effect of this disease on the work/academic performance and HRQOL. Trial registration Retrospectively registered.

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

PubMed

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of oral immune cells in birch pollen-allergic patients: impact of the oral allergy syndrome and sublingual allergen immunotherapy on antigen-presenting cells.

PubMed

Mascarell, L; Rak, S; Worm, M; Melac, M; Soulie, S; Lescaille, G; Lemoine, F; Jospin, F; Paul, S; Caplier, L; Hasséus, B; Björhn, C; Zeldin, R K; Baron-Bodo, V; Moingeon, P

2015-04-01

A detailed characterization of human oral immune cells is needed to better understand local mechanisms associated with allergen capture following oral exposure. Oral immune cells were characterized by immunohistology and immunofluorescence in biopsies obtained from three healthy individuals and 23 birch pollen-allergic patients with/without oral allergy syndrome (OAS), at baseline and after 5 months of sublingual allergen immunotherapy (AIT). Similar cell subsets (i.e., dendritic cells, mast cells, and T lymphocytes) were detected in oral tissues from healthy and birch pollen-allergic individuals. CD207+ Langerhans cells (LCs) and CD11c+ myeloid dendritic cells (DCs) were found in both the epithelium and the papillary layer of the Lamina propria (LP), whereas CD68+ macrophages, CD117+ mast cells, and CD4+ /CD8+ T cells were rather located in both the papillary and reticular layers of the LP. Patterns of oral immune cells were identical in patients with/without OAS, except lower numbers of CD207+ LCs found in oral tissues from patients with OAS, when compared to OAS- patients (P < 0.05). A 5-month sublingual AIT had a limited impact on oral immune cells, with only a significant increase in IgE+ cells in patients from the active group. Colocalization experiments confirmed that such IgE-expressing cells mostly encompass CD68+ macrophages located in the LP, and to a lesser extent CD207+ LCs in the epithelium. Two cell subsets contribute to antigen/allergen uptake in human oral tissues, including (i) CD207+ LCs possibly involved in the physiopathology of OAS and (ii) CD68+ macrophages likely critical in allergen capture via IgE-facilitated mechanisms during sublingual AIT. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reactivity of IgE to the allergen hyaluronidase from Polybia paulista (Hymenoptera, Vespidae) venom.

PubMed

Justo Jacomini, Débora Laís; Gomes Moreira, Susana Margarida; Campos Pereira, Franco Dani; Zollner, Ricardo de Lima; Brochetto Braga, Márcia Regina

2014-05-01

To date, there are no allergenic extracts or components available in Brazil to diagnosis and treatment of patients with venom allergy from social wasp (Vespidae Family; Polistinae Subfamily) despite of the great number of existing species. We evaluated the immunogenic potential of the Hyal recombinant protein (Pp-Hyal-rec) which was expressed in an insoluble form in comparison with the allergenic native protein (Pp-Hyal-nat) for recognition of immunoglobulin E (IgE) in the serum of allergic patients to venom of the endemic social wasp Polybia paulista from São Paulo State, Brazil. Hyal cDNA from the venom of the social wasp P. paulista (Pp-Hyal) (GI: 302201582) was cloned into the expression vector pET-28a in Escherichia coli DE3 (BL21) cells. Solubilization and purification of Pp-Hyal-rec from inclusion bodies were performed using Ni(2+) affinity chromatography (Ni-NTA-Agarose) under denaturing conditions. Both the native (Pp-Hyal-nat) and the recombinant (Pp-Hyal-rec) purified allergens were used for Western blotting to assess the levels of Pp-Hyal-IgE specific in the serum of 10 patients exclusively reactive to the venom of the social wasp P. paulista. The immune sera specifically recognized the band corresponding to the Pp-Hyal-rec protein (40 kDa) at a higher intensity than the native allergen (39 kDa). The sera recognized other proteins in P. paulista crude venom extract to a lesser extent, likely corresponding to other venom allergens such as phospholipase (34 kDa), Antigen 5 (25 kDa), and proteases. The recognition pattern of the immune sera to the Pp-Hyal-rec allergen strongly suggests that this recombinant antigen could be used for developing a diagnostic allergy test as well as for specific immunotherapy (IT). Copyright © 2014 Elsevier Ltd. All rights reserved.

Evolutionary distance from human homologs reflects allergenicity of animal food proteins.

PubMed

Jenkins, John A; Breiteneder, Heimo; Mills, E N Clare

2007-12-01

In silico analysis of allergens can identify putative relationships among protein sequence, structure, and allergenic properties. Such systematic analysis reveals that most plant food allergens belong to a restricted number of protein superfamilies, with pollen allergens behaving similarly. We have investigated the structural relationships of animal food allergens and their evolutionary relatedness to human homologs to define how closely a protein must resemble a human counterpart to lose its allergenic potential. Profile-based sequence homology methods were used to classify animal food allergens into Pfam families, and in silico analyses of their evolutionary and structural relationships were performed. Animal food allergens could be classified into 3 main families--tropomyosins, EF-hand proteins, and caseins--along with 14 minor families each composed of 1 to 3 allergens. The evolutionary relationships of each of these allergen superfamilies showed that in general, proteins with a sequence identity to a human homolog above approximately 62% were rarely allergenic. Single substitutions in otherwise highly conserved regions containing IgE epitopes in EF-hand parvalbumins may modulate allergenicity. These data support the premise that certain protein structures are more allergenic than others. Contrasting with plant food allergens, animal allergens, such as the highly conserved tropomyosins, challenge the capability of the human immune system to discriminate between foreign and self-proteins. Such immune responses run close to becoming autoimmune responses. Exploiting the closeness between animal allergens and their human homologs in the development of recombinant allergens for immunotherapy will need to consider the potential for developing unanticipated autoimmune responses.

High serum levels of allergen specific IgG-4 (asIgG-4) for common food allergens in healthy blood donors.

PubMed

Kruszewski, J; Raczka, A; Kłos, M; Wiktor-Jedrzejczak, W

1994-01-01

High serum levels of asIgG-4 against common food allergens are found in many patients with symptoms suggesting food allergy. The same patients are frequently negative for allergen specific IgE (asIgE) against the same allergens. These data were frequently interpreted as suggestive of a role of asIgG-4 in food allergy. In order to evaluate this hypothesis we tested serum levels of asIgG-4 against food allergens in young blood donors without any signs or history of food allergy. Fifty young healthy male donors were evaluated. The serum levels of IgE, and asIgE and IgG-4 against 14 common food allergens were determined. The studies were carried out using commercially available 3M Diagnostics Systems kits. AsIgG-4 against food allergens were found in sera of 92% blood donors, and in 62% of these healthy persons the levels of asIgG-4 were higher than 10.0 micrograms/ml. In a small proportion of patients, high serum levels of IgE and asIgE against the same food and/or inhalant allergens were found. Common occurrence of asIgG-4 against food allergens in healthy persons (without any symptoms which could suggest allergy or food intolerance) argues against the possible participation of these antibodies in the pathogenesis of food allergy. It is possible that their occurrence is the result of immunization against food antigens (allergens). It remains to be resolved whether the presence of these antibodies represents an epiphenomenon or may have some other biological role.

Allergenicity of Peanut Proteins is Retained Following Enzymatic Hydrolysis

USDA-ARS?s Scientific Manuscript database

Rationale: Hydrolysis of peanut proteins by food-grade enzymes may reduce allergenicity and could lead to safer forms of immunotherapy. Methods: Light roasted peanut flour extracts were digested with pepsin (37°C, pH 2), Alcalase (60°C pH 8), or Flavourzyme (50°C, pH 7) up to 1 hr, or sequentially w...

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

PubMed Central

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. PMID:24795722

Applications and mechanisms of immunotherapy in allergic rhinitis and asthma.

PubMed

Kappen, Jasper H; Durham, Stephen R; Veen, Hans In 't; Shamji, Mohamed H

2017-01-01

Clinical and immunologic tolerance are hallmarks of successful allergen immunotherapy (AIT). Clinical benefits such as reduced symptoms, pharmacotherapy intake and improvement of quality of life persist following cessation of treatment. Successful AIT is associated with suppression of allergic inflammatory cells such as mast cells, eosinophils and basophils in target organs. Furthermore, AIT down-regulates type 2 innate lymphoid cells and allergen-specific type 2 T-helper (Th2) cells. The immunologic tolerant state following AIT is associated with the induction of distinct phenotypes of regulatory T-cells (T-regs) including interleukin (IL)-10-, IL-35- and transforming growth factor (TGF)-β- producing T-regs and FoxP3 + T-regs. B-cell responses, including the induction of IL-10 + regulatory B-cells (B-regs) and the production of IgG4-associated blocking antibodies are also induced following successful AIT. These events are associated with the suppression of antigen-specific Th2 responses and delayed immune deviation in favour of Th1 type responses. Insight into the mechanisms of AIT has allowed identification of novel biomarkers with potential to predict the clinical response to AIT and also novel therapeutic strategies for more effective and safer AIT.

Allergen-specific IgE measurement with the IMMULITE 2000 system: intermethod comparison of detection performance for allergen-specific IgE antibodies from Korean allergic patients.

PubMed

Lee, Yong Won; Sohn, Jung Ho; Lee, Jae-Hyun; Hong, Chein-Soo; Park, Jung-Won

2009-03-01

Intermethod comparison between IMMULITE 2000 chemiluminescent enzyme immunoassay (CLEIA) and the established CAP test for allergen-specific IgE (sIgE) has only been evaluated by a few studies. We performed such an interassay comparison using 283 Korean allergic patients with the following: asthma (18.4%), allergic rhinitis (18.4%), both asthma and allergic rhinitis (14.5%), atopic dermatitis (21.9%), and others (26.8%). We compared the sIgE detection performance of both systems for 10 major inhalant allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blattela germanica, cat dander, dog hair, alder, birch, oak, ragweed, and mugwort) and four food allergens (egg white, cow milk, peanut, and shrimp). After 645 paired comparison tests, close association and significant correlation were observed between the results of both assays for most of these allergens (r=0.525-0.979, p<0.05, respectively), except for shrimp. Intermethod agreement based on sIgE detection was fair to good (74.1-100%, kappa=0.514-1.000, p<0.05, respectively) for most allergens except for B. germanica, ragweed, and shrimp. Although both assays showed good accuracy in ROC curve analysis, some minor differences were noted. IMMULITE 2000 CLEIA for sIgE detection showed fair to good intermethod correlation, association, agreement, and accuracy in comparison to the established CAP assay among Korean allergic patients. However, we should take into account the intermethod differences between both assays for clinical applications.

From Allergen Back to Antigen:. a Rational Approach to New Forms of Immunotherapy

NASA Astrophysics Data System (ADS)

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.

Efficacy and safety of 4 months of sublingual immunotherapy with recombinant Mal d 1 and Bet v 1 in patients with birch pollen-related apple allergy.

PubMed

Kinaciyan, Tamar; Nagl, Birgit; Faustmann, Sandra; Frommlet, Florian; Kopp, Stephan; Wolkersdorfer, Martin; Wöhrl, Stefan; Bastl, Katharina; Huber, Hans; Berger, Uwe; Bohle, Barbara

2018-03-01

Birch pollen-related apple allergy is among the most prevalent food allergies in adolescent/adult subjects and mainly results from sensitization to the major birch pollen allergen Bet v 1 and subsequent cross-reaction with the apple protein Mal d 1. However, specific immunotherapy with birch pollen has inconsistent effects on apple allergy. We sought to compare the safety and efficacy of sublingual immunotherapy (SLIT) with 2 formulations containing either rMal d 1 or rBet v 1 on birch pollen-related apple allergy. Sixty participants with birch pollen-related apple allergy were randomized to daily sublingual application of placebo (n = 20) or 25 μg of rMal d 1 (n = 20) or rBet v 1 (n = 20) for 16 weeks. Adverse events were regularly recorded. Sublingual challenges with standardized doses of rMal d 1, skin prick tests with recombinant allergens, and measurements of allergen-specific IgE and IgG 4 antibodies were performed before and after treatment. Both formulations caused comparable, mainly local adverse events. No systemic reactions occurred. Compared with the placebo and rBet v 1-treated groups, SLIT with rMal d 1 reduced rMal d 1-induced oral symptoms (P = .001 and P = .038) accompanied by longitudinally reduced rMal d 1-specific cutaneous reactions (P = .022) and enhanced IgG 4 /IgE ratios (P = .012). SLIT with rBet v 1 neither improved the clinical reactivity to rMal d 1 nor enhanced rMal d 1-specific IgG 4 /IgE ratios. Participants receiving placebo showed no allergen-specific changes. Sublingual treatment with a recombinant food allergen was safe and clinically effective, as determined by using standardized challenges. We present a promising approach for the effective treatment of birch pollen-related apple allergy. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Ragweed Pollen Allergy: Burden, Characteristics, and Management of an Imported Allergen Source in Europe.

PubMed

Chen, Kuan-Wei; Marusciac, Laura; Tamas, Paul Tudor; Valenta, Rudolf; Panaitescu, Carmen

2018-05-22

Ambrosia artemisiifolia, also known as common or short ragweed, is an invasive annual flowering herbaceous plant that has its origin in North America. Nowadays, ragweed can be found in many areas worldwide. Ragweed pollen is known for its high potential to cause type I allergic reactions in late summer and autumn and represents a major health problem in America and several countries in Europe. Climate change and urbanization, as well as long distance transport capacity, enhance the spread of ragweed pollen. Therefore ragweed is becoming domestic in non-invaded areas which in turn will increase the sensitization rate. So far 11 ragweed allergens have been described and, according to IgE reactivity, Amb a 1 and Amb a 11 seem to be major allergens. Sensitization rates of the other allergens vary between 10 and 50%. Most of the allergens have already been recombinantly produced, but most of them have not been characterized regarding their allergenic activity, therefore no conclusion on the clinical relevance of all the allergens can be made, which is important and necessary for an accurate diagnosis. Pharmacotherapy is the most common treatment for ragweed pollen allergy but fails to impact on the course of allergy. Allergen-specific immunotherapy (AIT) is the only causative and disease-modifying treatment of allergy with long-lasting effects, but currently it is based on the administration of ragweed pollen extract or Amb a 1 only. In order to improve ragweed pollen AIT, new strategies are required with higher efficacy and safety. © 2018 S. Karger AG, Basel.

Expression, purification and characterization of Der f 27, a new allergen from dermatophagoides farinae

PubMed Central

Lin, Jianli; Li, Meng; Liu, Yulin; Jiang, Congli; Wu, Yulan; Wang, Yuanyuan; Gao, Anjian; Liu, Zhigang; Yang, Pingchang; Liu, Xiaoyu

2015-01-01

The house dust mite (HDM), Dermatophagoidesfarinae (D. farina), is one of the most important indoor allergen sources and a major elicitor of allergic asthma; itscharacterization is important in the diagnosis and immunotherapy of mite allergen-relevant diseases. This study aims to characterize a novel allergen, the D. farinae-derived serpin (Der f 27). In this study, the total RNA of D. farinae was extracted, and the Der f 27 gene was cloned and expressed. The allergenicity of recombinant Der f 27 protein was determined by enzyme-linked immunosorbent assay, and Western-blotting with the sera of asthma patients, and skin prick test (SPT) in allergic human subjects. A r-Der f 27 allergic asthma mouse model was established. The cloned Der f 27 gene has been presented at the Gene Bank with an accession number of KM009995. The IgE levels of r-Der f 27 in the serum from r-Der f 27 SPT positive allergic patients were 3 folds more than healthy subjects. The Der f 27 SPT positive ratewas 42.1% in 19 DM-SPT positive patients. Airway hyperresponsiveness, serum specific IgE, and levels of interleukin-4 in the spleen cell culture supernatant were significantly increased in allergic asthma mice sensitized to r-Der f 27. In conclusion, Der f 27 is a new subtype of house mite allergen. PMID:26328010

Allergen-induced Th1 and Th2 cytokine secretion in relation to specific allergen sensitization and atopic symptoms in children.

PubMed

Jenmalm, M C; Van Snick, J; Cormont, F; Salman, B

2001-10-01

Allergic diseases are believed to be due to T helper (Th)2-like immunity to allergens in affected tissues, and immune responses to allergens are characterized by a cross-regulation between Th1 and Th2 cells. Atopic individuals may develop IgE antibodies to only one or more allergens. However, the mechanisms behind sensitization to a specific allergen, e.g. why an individual develops IgE to cat but not birch, are not known. Our aim was to study birch- and cat-induced Th1 and Th2 cytokine secretion in children who were sensitized to birch but not to cat, and vice versa. The subjects in the study were 60 12-year-old children. Seventeen of the children were sensitized (skin prick test and circulating IgE positive) to birch but not cat, 13 were sensitized to cat but not birch, 11 were sensitized both to birch and cat, and 19 children were skin prick test and circulating IgE negative. Forty-six children had a history of atopic symptoms, and 42 of them had current symptoms. Peripheral blood mononuclear cells were separated from venous blood and stimulated with cat or birch allergen. The levels of IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-gamma in the cell supernatants were analysed by ELISA. Sensitized children produced more of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 than non-sensitized atopic and non-atopic children in response to stimulation with the allergen they were sensitized to. High levels of the Th2 cytokines IL-4 and IL-5 and low levels of the anti-inflammatory cytokine IL-10 were associated with atopic symptoms, and high cat-induced IL-9 levels with asthma. The Th2 cytokines IL-4, IL-5, IL-9 and IL-13 were all commonly detected in sensitized children after stimulation with the specific, in contrast to an unrelated, allergen. Atopic symptoms were associated with increased levels of IL-4 and IL-5 and tended to be associated with low levels of IL-10, and asthma with high cat-induced IL-9 levels.

Adjuvant effects of aluminium hydroxide-adsorbed allergens and allergoids - differences in vivo and in vitro.

PubMed

Heydenreich, B; Bellinghausen, I; Lund, L; Henmar, H; Lund, G; Adler Würtzen, P; Saloga, J

2014-06-01

Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde- or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4(+) T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo. © 2014 British Society for Immunology.

Structural studies of novel glycoconjugates from polymerized allergens (allergoids) and mannans as allergy vaccines.

PubMed

Manzano, Ana I; Javier Cañada, F; Cases, Bárbara; Sirvent, Sofia; Soria, Irene; Palomares, Oscar; Fernández-Caldas, Enrique; Casanovas, Miguel; Jiménez-Barbero, Jesús; Subiza, José L

2016-02-01

Immunotherapy for treating IgE-mediated allergies requires high doses of the corresponding allergen. This may result in undesired side effects and, to avoid them, hypoallergenic allergens (allergoids) polymerized with glutaraldehyde are commonly used. Targeting allergoids to dendritic cells to enhance cell uptake may result in a more effective immunotherapy. Allergoids coupled to yeast mannan, as source of polymannoses, would be suitable for this purpose, since mannose-binding receptors are expressed on these cells. Conventional conjugation procedures of mannan to proteins use oxidized mannan to release reactive aldehydes able to bind to free amino groups in the protein; yet, allergoids lack these latter because their previous treatment with glutaraldehyde. The aim of this study was to obtain allergoids conjugated to mannan by an alternative approach based on just glutaraldehyde treatment, taking advantage of the mannoprotein bound to the polymannose backbone. Allergoid-mannan glycoconjugates were produced in a single step by treating with glutaraldehyde a defined mixture of allergens derived from Phleum pratense grass pollen and native mannan (non-oxidized) from Saccharomyces cerevisae. Analytical and structural studies, including 2D-DOSY and (1)H-(13)C HSQC nuclear magnetic resonance spectra, demonstrated the feasibility of such an approach. The glycoconjugates obtained were polymers of high molecular weight showing a higher stability than the native allergen or the conventional allergoid without mannan. The allergoid-mannan glycoconjugates were hypoallergenic as detected by the IgE reactivity with sera from grass allergic patients, even with lower reactivity than conventional allergoid without mannan. Thus, stable hypoallergenic allergoids conjugated to mannan suitable for using in immunotherapy can be achieved using glutaraldehyde. In contrast to mannan oxidation, the glutaraldehyde approach allows to preserve mannoses with their native geometry, which may be

Impact of oral immunotherapy on quality of life in children with cow milk allergy: a pilot study.

PubMed

Carraro, S; Frigo, A C; Perin, M; Stefani, S; Cardarelli, C; Bozzetto, S; Baraldi, E; Zanconato, S

2012-01-01

Quality of life is negatively affected in children with food allergy. Oral immunotherapy is an approach to food allergy that leads to patient desensitization by administering gradually increasing amounts of a given food allergen. The aim of this pilot study is to evaluate how oral immunotherapy affects quality of life in children allergic to cow milk proteins. Thirty children (aged 3-12 years) with cow milk allergy were recruited. Their parents were provided with a validated disease specific quality of life questionnaire (the food allergy quality of life questionnaire -- parent form, FAQLQ-PF) before and again 2 months after completing an oral immunotherapy protocol with cow milk. A significant improvement in all the investigated domains -- emotional impact, food anxiety and social and dietary limitations -- was found. The separate analysis of the different age groups demonstrated that the emotional impact and the food-related anxiety improved in children older than 4, while the social domains improved in each age group. In this pilot experience, oral immunotherapy significantly improves quality of life in children with cow milk allergy. The improvement seems particularly evident in children over 4 years old, who are most likely to benefit from the oral immunotherapy approach. Further placebo-controlled studies are needed to confirm these preliminary results.

Quantitation of IgE antibody specific for ragweed and grass allergens: binding of radiolabeled allergens by solid-phase bond IgE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeiss, C.R.; Levitz, D.; Suszko, I.M.

1978-08-01

IgE antibody specific for multiple allergens extracted from grass and ragweed pollens was measured by radioimmunoassay. The assay depends on the interaction between IgE antibody bound to a polystyrene solid phase, /sup 125/I-labeled grass allergens (GA), and ragweed allergens (RW). The binding of /sup 125/I RW by serum IgE antibody from 37 allergic patients ranged from 0.2 ng to 75 ng RW protein (P) bound per ml. This binding of /sup 125/I RW by patient's IgE was paralleled by their IgE binding of /sup 125/I antigen E (AgE), a purified allergen from ragweed pollen (r = 0.90, p less thanmore » 0.001). Inhibition of patient's IgE binding of /sup 125/I RW by highly purified AgE ranged from 25 to 85% indicated individual differences in patient's IgE response to inhaled ragweed pollen. The binding of /sup 125/I GA by serum IgE antibody from 7 grass-sensitive patients ranged from 0.6 ng GA P bound per ml to 15 ng. This assay should be useful in the study of IgE responses to environmental agents containing multiple allergens and has the advantage that other antibody classes cannot interfere with the interaction between IgE antibody and labeled allergens.« less

Watermelon profilin: characterization of a major allergen as a model for plant-derived food profilins.

PubMed

Cases, Bárbara; Pastor-Vargas, Carlos; Dones, Félix Gil; Perez-Gordo, Marina; Maroto, Aroa S; de las Heras, Manuel; Vivanco, Fernando; Cuesta-Herranz, Javier

2010-01-01

Plant profilins have been reported as minor allergens. They are a well-known pan-allergen family responsible for cross-reactivity between plant-derived foods and pollens. Watermelon profilin has been reported to be a major allergen in watermelon (Citrullus lanatus).The aim of this study was to characterize recombinant watermelon profilin, confirming its reactivity for diagnostic purposes and the development of immunotherapy. Native profilin was purified from watermelon extract by affinity chromatography using poly-L-proline. Recombinant His-tagged profilin was produced in Pichia pastoris yeast using pPICZαA vector and purified by metal chelate affinity chromatography. ELISA and immunoblot were carried out with sera from 17 watermelon-allergic patients. Biological activity was tested by the basophil activation test. Native profilin and recombinant profilin were purified and identified by mass spectrometry. Both show similar IgE reactivity in vitro and are biologically active. Similarities were found in the IgE-binding patterns and biological activity of recombinant profilin and native profilin. Recombinant profilin may be a powerful tool for specific diagnosis. Copyright © 2010 S. Karger AG, Basel.

Pollen derived low molecular compounds enhance the human allergen specific immune response in vivo.

PubMed

Gilles-Stein, S; Beck, I; Chaker, A; Bas, M; McIntyre, M; Cifuentes, L; Petersen, A; Gutermuth, J; Schmidt-Weber, C; Behrendt, H; Traidl-Hoffmann, C

2016-10-01

Besides allergens, pollen release bioactive, low molecular weight compounds that modulate and stimulate allergic reactions. Clinical relevance of these substances has not been investigated to date. To elucidate the effect of a non-allergenic, low molecular weight factors from aqueous birch pollen extracts (Bet-APE < 3 kDa) on the human allergic immune response in vivo. Birch and grass pollen allergic individuals underwent skin prick testing with allergen alone, allergen plus Bet-APE < 3 kDa, or allergen plus pre-identified candidate substances from low molecular pollen fraction. Nasal allergen challenges were performed in non-atopic and pollen allergic individuals using a 3 day repeated threshold challenge battery. Subjects were either exposed to allergen alone or to allergen plus Bet-APE< 3 kDa. Local cytokine levels, nasal secretion weights, nasal congestion and symptom scores were determined. Skin prick test reactions to pollen elicited larger weals when allergens were tested together with the low molecular weight compounds from pollen. Similar results were obtained with candidate pollen-associated lipid mediators. In nasal lining fluids of allergic patients challenged with allergen plus Bet-APE < 3 kDa, IL-8 and IgE was significantly increased as compared to allergen-only challenged patients. These patients also produced increased amounts of total nasal secretion and reported more severe rhinorrhea than the allergen-only challenged group. Low molecular compounds from pollen enhance the allergen specific immune response in the skin and nose. They are therefore of potential clinical relevance in allergic patients. © 2016 John Wiley & Sons Ltd.

Grass pollen allergens globally: the contribution of subtropical grasses to burden of allergic respiratory diseases.

PubMed

Davies, J M

2014-06-01

Grass pollens of the temperate (Pooideae) subfamily and subtropical subfamilies of grasses are major aeroallergen sources worldwide. The subtropical Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass) species are abundant in parts of Africa, India, Asia, Australia and the Americas, where a large and increasing proportion of the world's population abide. These grasses are phylogenetically and ecologically distinct from temperate grasses. With the advent of global warming, it is conceivable that the geographic distribution of subtropical grasses and the contribution of their pollen to the burden of allergic rhinitis and asthma will increase. This review aims to provide a comprehensive synthesis of the current global knowledge of (i) regional variation in allergic sensitivity to subtropical grass pollens, (ii) molecular allergenic components of subtropical grass pollens and (iii) allergic responses to subtropical grass pollen allergens in relevant populations. Patients from subtropical regions of the world show higher allergic sensitivity to grass pollens of Chloridoideae and Panicoideae grasses, than to temperate grass pollens. The group 1 allergens are amongst the allergen components of subtropical grass pollens, but the group 5 allergens, by which temperate grass pollen extracts are standardized for allergen content, appear to be absent from both subfamilies of subtropical grasses. Whilst there are shared allergenic components and antigenic determinants, there are additional clinically relevant subfamily-specific differences, at T- and B-cell levels, between pollen allergens of subtropical and temperate grasses. Differential immune recognition of subtropical grass pollens is likely to impact upon the efficacy of allergen immunotherapy of patients who are primarily sensitized to subtropical grass pollens. The literature reviewed herein highlights the clinical need to standardize allergen preparations for both

Food allergy: immune mechanisms, diagnosis and immunotherapy

PubMed Central

Nadeau, Kari C.

2016-01-01

Food allergy is a pathological, potentially deadly, immune reaction triggered by normally innocuous food protein antigens. The prevalence of food allergies is rising and the standard of care is not optimal, consisting of food-allergen avoidance and treatment of allergen-induced systemic reactions with adrenaline. Thus, accurate diagnosis, prevention and treatment are pressing needs, research into which has been catalysed by technological advances that are enabling a mechanistic understanding of food allergy at the cellular and molecular levels. We discuss the diagnosis and treatment of IgE-mediated food allergy in the context of the immune mechanisms associated with healthy tolerance to common foods, the inflammatory response underlying most food allergies, and immunotherapy-induced desensitization. We highlight promising research advances, therapeutic innovations and the challenges that remain. PMID:27795547

Towards evidence-based medicine in specific grass pollen immunotherapy.

PubMed

Calderon, M; Mösges, R; Hellmich, M; Demoly, P

2010-04-01

When initiating grass pollen immunotherapy for seasonal allergic rhinoconjunctivitis, specialist physicians in many European countries must choose between modalities of differing pharmaceutical and regulatory status. We applied an evidence-based medicine (EBM) approach to commercially available subcutaneous and sublingual Gramineae grass pollen immunotherapies (SCIT and SLIT) by evaluating study design, populations, pollen seasons, treatment doses and durations, efficacy, quality of life, safety and compliance. After searching MEDLINE, Embase and the Cochrane Library up until January 2009, we identified 33 randomized, double-blind, placebo-controlled trials (including seven paediatric trials) with a total of 440 specific immunotherapy (SIT)-treated subjects in seven trials (0 paediatric) for SCIT with natural pollen extracts, 168 in three trials (0 paediatric) for SCIT with allergoids, 906 in 16 trials (five paediatric) for natural extract SLIT drops, 41 in two trials (one paediatric) for allergoid SLIT tablets and 1605 in five trials (two paediatric) for natural extract SLIT tablets. Trial design and quality varied significantly within and between SIT modalities. The multinational, rigorous trials of natural extract SLIT tablets correspond to a high level of evidence in adult and paediatric populations. The limited amount of published data on allergoids prevented us from judging the level of evidence for this modality.

Adjuvant effects of aluminium hydroxide-adsorbed allergens and allergoids – differences in vivo and in vitro

PubMed Central

Heydenreich, B; Bellinghausen, I; Lund, L; Henmar, H; Lund, G; Adler Würtzen, P; Saloga, J

2014-01-01

Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde-or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4+ T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo. PMID:24528247

Removing Peanut Allergen Ara h 1 from Peanut Extracts Using p-Aminobenzamidine

USDA-ARS?s Scientific Manuscript database

Rationale: Ara h 1 is one of 3 major allergens in peanut. Removing Ara h 1 from a peanut extract may produce a hypoallergenic peanut extract for immunotherapy and other purposes. Methods: Peanut extracts were treated overnight with and without 10 mM p-aminobenzamidine (pABA, a protease inhibitor) i...

Ana o 1 and Ana o 2 cashew allergens share cross-reactive CD4+ T-cell epitopes with other tree nuts

PubMed Central

Archila, Luis Diego; Chow, I-Ting; McGinty, John W.; Renand, Amedee; Jeong, David; Robinson, David; Farrington, Mary L.; Kwok, William.W.

2017-01-01

Background Allergies to cashew are increasing in prevalence, with clinical symptoms ranging from oral pruritus to fatal anaphylactic reaction. Yet, cashew-specific T-cell epitopes and T-cell cross-reactivity amongst cashew and other tree nut allergens in humans remain uncharacterized. Objectives In this study, we characterized cashew specific T-cell responses in cashew allergic subjects and examined cross-reactivity of these cashew specific cells toward other tree nut allergens. Methods CD154 up-regulation assay was used to determine immunodominance hierarchy among cashew major allergens at the T cell level. The phenotype, magnitude and functionality of cashew-specific T-cells was determined by utilizing ex vivo staining with MHC class II tetramers. Dual tetramer staining and proliferation experiments were used to determine cross-reactivity to other tree nuts. Results CD4+ T-cell responses were directed towards cashew allergens Ana o 1 and Ana o 2. Multiple Ana o 1 and Ana o 2 T-cell epitopes were then identified. These epitopes elicited either TH2 or TH2/TH17 responses in allergic subjects, which were either cashew unique epitope or cross-reactive epitopes. For clones that recognized the cross-reactive epitope, T-cell clones responded robustly to cashew, hazelnut and/or pistachio but not to walnut. Conclusions Phylogenetically diverse tree nut allergens can activate cashew reactive T-cells and elicit a TH2 type response at an epitope specific level. Clinical relevance Lack of cross-reactivity between walnut and cashew suggest that cashew peptide immunotherapy approach may not be most effective for walnut. PMID:27129138

Ana o 1 and Ana o 2 cashew allergens share cross-reactive CD4(+) T cell epitopes with other tree nuts.

PubMed

Archila, L D; Chow, I-T; McGinty, J W; Renand, A; Jeong, D; Robinson, D; Farrington, M L; Kwok, W W

2016-06-01

Allergies to cashew are increasing in prevalence, with clinical symptoms ranging from oral pruritus to fatal anaphylactic reaction. Yet, cashew-specific T cell epitopes and T cell cross-reactivity amongst cashew and other tree nut allergens in humans remain uncharacterized. In this study, we characterized cashew-specific T cell responses in cashew-allergic subjects and examined cross-reactivity of these cashew-specific cells towards other tree nut allergens. CD154 up-regulation assay was used to determine immunodominance hierarchy among cashew major allergens at the T cell level. The phenotype, magnitude and functionality of cashew-specific T cells were determined by utilizing ex vivo staining with MHC class II tetramers. Dual tetramer staining and proliferation experiments were used to determine cross-reactivity to other tree nuts. CD4(+) T cell responses were directed towards cashew allergens Ana o 1 and Ana o 2. Multiple Ana o 1 and Ana o 2 T cell epitopes were then identified. These epitopes elicited either TH 2 or TH 2/TH 17 responses in allergic subjects, which were either cashew unique epitope or cross-reactive epitopes. For clones that recognized the cross-reactive epitope, T cell clones responded robustly to cashew, hazelnut and/or pistachio but not to walnut. Phylogenetically diverse tree nut allergens can activate cashew-reactive T cells and elicit a TH 2-type response at an epitope-specific level. Lack of cross-reactivity between walnut and cashew suggests that cashew peptide immunotherapy approach may not be most effective for walnut. © 2016 John Wiley & Sons Ltd.

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

PubMed

Jordakieva, Galateja; Wallmann, Julia; Schmutz, René; Lemell, Patrick; Wegmann, Michael; Nittke, Thomas; Mittlböck, Martina; Fehrenbach, Heinz; Godnic-Cvar, Jasminka; Zieglmayer, René; Jensen-Jarolim, Erika

2014-01-01

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). 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. Our data revealed that, besides significant leukocyte dynamics, particularly erythrocytes are involved in acute hypersensitivity reactions to respiratory allergens. A rapid recruitment of erythrocytes to the lungs to compensate

Tumor-specific antigens and immunologic adjuvants in cancer immunotherapy.

PubMed

Seremet, Teofila; Brasseur, Francis; Coulie, Pierre G

2011-01-01

T cell-based cancer immunotherapy relies on advancements made over the last 20 years on the molecular mechanisms underlying the antigenicity of tumors. This review focuses on human tumor antigens recognized by T lymphocytes, particularly the reasons why some are tumor-specific but others are not, and on the immunologic adjuvants used in clinical trials on therapeutic vaccination with defined tumor antigens.

Cross-reactivity among non-specific lipid-transfer proteins from food and pollen allergenic sources.

PubMed

Morales, María; López-Matas, M Ángeles; Moya, Raquel; Carnés, Jerónimo

2014-12-15

Non-specific lipid-transfer proteins (nsLTPs) are a family of pan-allergens present in foods and pollen. However, sequence homology among them is limited. The objective of this study was to evaluate the IgE-mediated cross-reactivity between nsLTPs from different sources and evaluate the allergenic properties of LTPs from peach (Pru p 3) and pellitory (Par j 1/Par j 2), major fruit and pollen allergens. Both proteins were purified and characterised. Cross-reactivity studies among nsLTPs from different foods and pollens were performed by immunoblot inhibition using sera specific to peach or pellitory pollen. Cross-reactivity with Pru p 3 was observed in hazelnut, onion, corn, peanut and apple while in pollens, none of the extracts was inhibited with Par j 1/2. In conclusion, Pru p 3 did not inhibit LTPs from most fruits. Therefore, although Pru p 3 covers the largest number of epitopes, diagnosis with only this allergen may not detect all LTP sensitivities. Copyright © 2014 Elsevier Ltd. All rights reserved.

A differing pattern of association between dietary fish and allergen-specific subgroups of atopy.

PubMed

Andreasyan, K; Ponsonby, A-L; Dwyer, T; Kemp, A; Dear, K; Cochrane, J; Carmichael, A

2005-05-01

We examined the role of fish intake in the development of atopic disease with particular reference to the possibility of differential effects on allergen-specific subgroups of sensitization. The exposure of interest was parental report of fish intake by children aged 8 years at the 1997 Childhood Allergy and Respiratory Health Study (n = 499). The outcomes of interest were subgroups of atopy: house dust mite (HDM)-pure sensitization [a positive skin-prick test (SPT) > or = 2 mm to Der p or Der f only], ryegrass-pure sensitization (a positive SPT > or = 2 mm to ryegrass only); asthma and hay fever by allergen-specific sensitization. A significant association between fish intake and ryegrass-pure [adjusted odds ratio (AOR) 0.37 (0.15-0.90)] but not HDM-pure sensitization [AOR 0.87 (0.36-2.13)] was found. Fish consumption significantly decreased the risk for ryegrass-pure sensitization in comparison with HDM-pure sensitization [AOR 0.20 (0.05-0.79)]. We have demonstrated a differential effect of fish intake for sensitization to different aeroallergens. This may be due to the different timing of allergen exposure during early life. Further investigation of the causes of atopic disease should take into account allergen-specific subgroups.

Identification of allergens in the box jellyfish Chironex yamaguchii that cause sting dermatitis.

PubMed

Horiike, Takumi; Nagai, Hiroshi; Kitani, Seiichi

2015-01-01

Jellyfish stings cause painful, papular-urticarial eruptions due to the immediate allergic, acute toxic and persistent inflammatory responses. In spite of many marine accidents and their economic impact, modes of first-aid treatment remain conventional and specific allergen and medical treatment are not yet available. The purpose of this study was to define the specific allergen of the box jellyfish Chironex yamaguchii and to study the precise mechanism of the resulting dermatitis. We comprehensively studied the immunoglobulin-binding molecules from the box jellyfish C. yamaguchii with a purification procedure and Western blotting, using sera from 1 patient and from several controls. From the nematocyst wall and spine, we detected IgG-binding acidic glycoprotein (of 66 and 30 kDa) as determined by Western blot and ion-exchange chromatography. In addition, the 66-kDa protein was found to be an asparagine residue-coupled N-linked glycoprotein and the epitope resided in the protein fraction. We found that CqTX-A, the major toxic protein of the nematocyst, is also a heat-stable IgE-binding allergen. This was confirmed as a 45-kDa protein by Western blot from both nematocyst extracts and purified CqTX-A. The detection of these proteins may, in part, explain the combined immediate allergic-toxic and persistent allergic responses. Hopefully, our findings will lead to the development of specific venom immunotherapy for marine professional workers and tourists for jellyfish-sting dermatitis and anaphylaxis. © 2015 S. Karger AG, Basel.

Formation of disulfide bonds and homodimers of the major cat allergen Fel d 1 equivalent to the natural allergen by expression in Escherichia coli.

PubMed

Grönlund, Hans; Bergman, Tomas; Sandström, Kristofer; Alvelius, Gunvor; Reininger, Renate; Verdino, Petra; Hauswirth, Alexander; Liderot, Karin; Valent, Peter; Spitzauer, Susanne; Keller, Walter; Valenta, Rudolf; van Hage-Hamsten, Marianne

2003-10-10

Dander from the domestic cat (Felis domesticus) is one of the most common causes of IgE-mediated allergy. Attempts to produce tetrameric folded major allergen Fel d 1 by recombinant methods with structural features similar to the natural allergen have been only partially successful. In this study, a recombinant folded Fel d 1 with molecular and biological properties similar to the natural counterpart was produced. A synthetic gene coding for direct fusion of the Fel d 1 chain 2 N-terminally to chain 1 was constructed by overlapping oligonucleotides in PCR. Escherichia coli expression resulted in a non-covalently associated homodimer with an apparent molecular mass of 30 kDa defined by size exclusion chromatography. Furthermore, each 19,177-Da subunit displayed a disulfide pattern identical to that found in the natural Fel d 1, i.e. Cys3(1) Cys73(2), Cys44(1)-Cys48(2), Cys70(1)-Cys7(2), as determined by electrospray mass spectrometry after tryptic digestion. Circular dichroism analysis showed identical folds of natural and recombinant Fel d 1. Furthermore, recombinant Fel d l reacted specifically with serum IgE, inducing expression of CD203c on basophils and lymphoproliferative responses in cat-allergic patients. The results show that the overall fold and immunological properties of the recombinant Fel d 1 are very similar to those of natural Fel d 1. Moreover, the recombinant Fel d 1 construct provides a tool for defining the three-dimensional structure of Fel d 1 and represents a reagent for diagnosis and allergen-specific immunotherapy of cat allergy.

Using Antigen-Specific B Cells to Combine Antibody and T Cell-Based Cancer Immunotherapy.

PubMed

Wennhold, Kerstin; Thelen, Martin; Schlößer, Hans Anton; Haustein, Natalie; Reuter, Sabrina; Garcia-Marquez, Maria; Lechner, Axel; Kobold, Sebastian; Rataj, Felicitas; Utermöhlen, Olaf; Chakupurakal, Geothy; Theurich, Sebastian; Hallek, Michael; Abken, Hinrich; Shimabukuro-Vornhagen, Alexander; von Bergwelt-Baildon, Michael

2017-09-01

Cancer immunotherapy by therapeutic activation of T cells has demonstrated clinical potential. Approaches include checkpoint inhibitors and chimeric antigen receptor T cells. Here, we report the development of an alternative strategy for cellular immunotherapy that combines induction of a tumor-directed T-cell response and antibody secretion without the need for genetic engineering. CD40 ligand stimulation of murine tumor antigen-specific B cells, isolated by antigen-biotin tetramers, resulted in the development of an antigen-presenting phenotype and the induction of a tumor antigen-specific T-cell response. Differentiation of antigen-specific B cells into antibody-secreting plasma cells was achieved by stimulation with IL21, IL4, anti-CD40, and the specific antigen. Combined treatment of tumor-bearing mice with antigen-specific CD40-activated B cells and antigen-specific plasma cells induced a therapeutic antitumor immune response resulting in remission of established tumors. Human CEA or NY-ESO-1-specific B cells were detected in tumor-draining lymph nodes and were able to induce antigen-specific T-cell responses in vitro, indicating that this approach could be translated into clinical applications. Our results describe a technique for the exploitation of B-cell effector functions and provide the rationale for their use in combinatorial cancer immunotherapy. Cancer Immunol Res; 5(9); 730-43. ©2017 AACR . ©2017 American Association for Cancer Research.

Mimotope mapping as a complementary strategy to define allergen IgE-epitopes: peach Pru p 3 allergen as a model.

PubMed

Pacios, Luis F; Tordesillas, Leticia; Cuesta-Herranz, Javier; Compes, Esther; Sánchez-Monge, Rosa; Palacín, Arantxa; Salcedo, Gabriel; Díaz-Perales, Araceli

2008-04-01

Lipid transfer proteins (LTPs) are the major allergens of Rosaceae fruits in the Mediterranean area. Pru p 3, the LTP and major allergen of peach, is a suitable model for studying food allergy and amino acid sequences related with its IgE-binding capacity. In this work, we sought to map IgE mimotopes on the structure of Pru p 3, using the combination of a random peptide phage display library and a three-dimensional modelling approach. Pru p 3-specific IgE was purified from 2 different pools of sera from peach allergic patients grouped by symptoms (OAS-pool or SYS-pool), and used for screening of a random dodecapeptide phage display library. Positive clones were further confirmed by ELISA assays testing individual sera from each pool. Three-dimensional modelling allowed location of mimotopes based on analysis of electrostatic properties and solvent exposure of the Pru p 3 surface. Twenty-one phage clones were selected using Pru p 3-specific IgE, 9 of which were chosen using OAS-specific IgE while the other 12 were selected with systemic-specific IgE. Peptide alignments revealed consensus sequences for each pool: L37 R39 T40 P42 D43 R44 A46 P70 S76 P78 Y79 for OAS-IgE, and N35 N36 L37 R39 T40 D43 A46 S76 I77 P78 for systemic-IgE. These 2 consensus sequences were mapped on the same surface of Pru p 3, corresponding to the helix 2-loop-helix 3 region and part of the non-structured C-terminal coil. Thus, 2 relevant conformational IgE-binding regions of Pru p 3 were identified using a random peptide phage display library. Mimotopes can be used to study the interaction between allergens and IgE, and to accelerate the process to design new vaccines and new immunotherapy strategies.

Marker allergens of weed pollen - basic considerations and diagnostic benefits in the clinical routine: Part 16 of the Series Molecular Allergology.

PubMed

Stemeseder, Teresa; Hemmer, Wolfgang; Hawranek, Thomas; Gadermaier, Gabriele

The term weed is referring to plants used as culinary herbs and medicinal plants as well as ecologically adaptive and invasive segetal plants. In Europe, pollen of ragweed, mugwort, English plantain and pellitory are the main elicitors of weed pollen allergies. Presently, 35 weed pollen allergens have been identified. The most relevant belong to the protein families of pectate lyases, defensin-like proteins, non-specific lipid transfer proteins, and Ole e 1-like proteins. The sensitization frequency depends on geographic regions and might affect more than 50 % of pollen allergic patients in distinct regions. Due to overlapping flowering seasons, similar habitats, polysensitizations and cross-reactive (pan)-allergens, it is difficult to diagnose genuine weed pollen sensitization using pollen extracts. Marker allergens for component-resolved diagnostics are available for the important weed pollen. These are Amb a 1 (ragweed), Art v 1 (mugwort), Pla l 1 (English plantain) and Par j 2 (pellitory). Molecule-based approaches can be used to identify the primary sensitizer and thus enable selection of the appropriate weed pollen extracts for allergen immunotherapy.

199 Development of a National Guideline on Skin Testing and Immunotherapy

PubMed Central

Linnemann, Désirée Larenas; Ortega Martell, José Antonio; del Rio, Blanca; Rodriguez-Perez, Noel; Arias-Cruz, Alfredo; Estrada, Alan

2012-01-01

Background Several international guidelines exist on allergen immunotherapy (AIT) –eg American, European, British, Spanish, Italian- but local conditions that reign in each country limit their applicability. We present the steps we followed to develop a National Guideline on AIT, taking into account local legislation, extracts available, costs and patient preference. Methods Firstly a Nation-wide survey on the practice of skin testing and AIT was undertaken among all members of Mexican Allergist Societies. Secondly, based on the replies obtained with the survey clinical questions were formulated on critical points and issues susceptible for improvement, as diagnosed by the survey. Thirdly, all 6 Regional Allergist Societies were visited to obtain the opinion of their members on the clinical questions concerning how immunotherapy could best be practiced under local Mexican conditions. This led to the Consensed experience. Fourthly, 6 experts looked for the replies to the clinical questions reviewing the literature and assigning quality of evidence to the articles on the specific issues treated by each clinical question. Results To develop the final document the GRADE approach was used. For each clinical question both, knowledge from the local consensed experience and the evidence-based replies were taken into account, as well as cost, patient preference and safety to make a set of recommendations and suggestions on the most crucial aspects of skin testing and AIT. Forming centers of allergists in Mexico corrected the final draft. The final document came out as the January issue of Revista Mexicana Alergia and was presented by the authors in a National Course on Immunotherapy (May 2011), with—apart from the lectures—a more workshop-like part to allow for practical exercising and discussion. The updated questions on allergen immunotherapy for the final board exam are based on the Guideline. Allergy-residents developed a slide-show. In 2012 Regional Allergist

Allergoid-specific T-cell reaction as a measure of the immunological response to specific immunotherapy (SIT) with a Th1-adjuvanted allergy vaccine.

PubMed

von Baehr, V; Hermes, A; von Baehr, R; Scherf, H P; Volk, H D; Fischer von Weikersthal-Drachenberg, K J; Woroniecki, S

2005-01-01

Specific immunotherapy (SIT) is believed to modulate CD4+ T-helper cells. In order to improve safety, SIT vaccines are often formulated with allergoids (chemically modified allergens). Interaction between T-cells and allergoids is necessary to influence cellular cytokine expression. There have been few reports on identification the early cellular effects of SIT. Patients allergic to grass and/or mugwort pollen (n= 21) were treated with a 4-shot allergy vaccine (Pollinex Quattro) containing appropriate allergoids (grass/rye and/or mugwort) adsorbed to L-tyrosine plus a Th1 adjuvant, monophosphoryl lipid A (MPL). Fourteen grass-allergic patients served as untreated controls. Using the peripheral blood mononuclear cells of these patients, an optimized lymphocyte transformation test (LTT) was employed to monitor the in vitro proliferative response of T-cells to an allergoid challenge (solubilised Pollinex Quattro) before the first and last injection and then 2 and 20 weeks after the final injection. Control challenges utilised preparations of a similar pollen vaccine without the adjuvant MPL and a tree pollen vaccine with and without MPL. The LTT showed increased LTT stimulation indices (SI) in 17/20 SIT patients when the solublised vaccine preparation was used as a challenge before the last injection and 2 weeks after, in comparison to pre-treatment levels. Twenty weeks after therapy, the SI decreased to baseline level. A vaccine challenge without MPL gave lower SI levels. A challenge of a clinically inappropriate tree allergoid vaccine gave no response, and a nontreated group also showed no response. Following a short-course SIT adjuvated with MPL, challenges of allergoids were shown to activate allergen-specific T cells in vitro. There was an additional stimulating effect when the challenge was in combination with MPL. There were no non-specific effects of MPL, shown by the tree allergoid/MPL control. The timing of the response was closely correlated to the

BASALIT trial: double-blind placebo-controlled allergen immunotherapy with rBet v 1-FV in birch-related soya allergy.

PubMed

Treudler, R; Franke, A; Schmiedeknecht, A; Ballmer-Weber, B; Worm, M; Werfel, T; Jappe, U; Biedermann, T; Schmitt, J; Brehler, R; Kleinheinz, A; Kleine-Tebbe, J; Brüning, H; Ruëff, F; Ring, J; Saloga, J; Schäkel, K; Holzhauser, T; Vieths, S; Simon, J C

2017-08-01

Conflicting results exist on the effect of allergen immunotherapy (AIT) on pollen-related food allergy. We aimed to investigate the efficacy of one-year AIT with the folding variant (FV) of recombinant (r) Bet v 1 on birch-related soya allergy. Of 138 subjects with Bet v 1 sensitization, 82 were positive at double-blind placebo-controlled food challenge (DBPCFC) with soya. A total of 56 of 82 were randomized in the ratio of 2:1 (active: placebo). Per-protocol population (PPP) had received ≥150 μg of allergen or placebo preparation. lowest observed adverse effect levels (LOAEL), postinterventional occurrence of objective signs (objS) at any dose level, sIgE/IgG4 against Bet v 1 and Gly m 4. Between-group changes were investigated (ancova, Mann-Whitney U-test, Fisher exact test). Baseline characteristics including LOAELs were comparable in both groups with objS and subjS occurring in 82% and 95% of active (n = 38) vs 78% and 83% of placebo group (n = 18). After AIT, objS occurred in 24% and 47%, respectively. LOAEL group differences showed a beneficial tendency (P = 0.081) for LOAEL objective in PPP (30 active, 15 placebo). sIgG4 raised only in active group (Bet v 1: P = 0.054, Gly m 4: P = 0.037), and no relevant changes occurred for sIgE. Only 56% of the intended sample size was recruited. For the first time, we present data on the effect of rBet v 1-FV on birch-related soya allergy. rBet v 1-FV AIT induced significant immunogenic effects. Clinical assessment showed a tendency in favour of the active group but did not reach statistical significance. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multicolor flow-cytometric analysis of milk allergen-specific T-helper type 2 cells revealed coexpression of interleukin-4 with Foxp3.

PubMed

Yamawaki, Kazuo; Inuo, Chisato; Nomura, Takayasu; Tanaka, Kenichi; Nakajima, Yoichi; Kondo, Yasuto; Yoshikawa, Tetsushi; Urisu, Atsuo; Tsuge, Ikuya

2015-12-01

Allergen-specific T-helper type 2 (TH2) cells play an important role in the development of allergic inflammation; however, investigations of the properties of allergen-specific T cells have been challenging in humans. Despite clear evidence that forkhead box p3 (Foxp3) is expressed in conventional effector T cells, its function has remained unknown. To characterize allergen-specific TH2 cells in milk allergy, with particular focus on the expression of Foxp3. Twenty-one children with milk allergy and 11 children without milk allergy were studied. Peripheral blood mononuclear cells from subjects were stimulated with milk allergen for 6 hours and analyzed using multicolor flow cytometry to identify CD154(+) allergen-specific T-helper cells. Simultaneously, the expression of intracellular cytokines and Foxp3 was analyzed. The milk allergy group had significantly larger numbers of milk allergen-specific interleukin (IL)-4- and IL-5-producing CD4(+) T cells than the control group. Subjects in the milk allergy group had significantly more CD154(+)CD4(+) IL-10-producing cells and CD154(+)Foxp3(+)CD4(+) cells than those in the control group. In addition, the number of milk allergen-specific CD154(+)Foxp3(+)CD4(+) cells strongly correlated with that of CD154(+)IL4(+)CD4(+) cells. Bcl-2 expression in CD154(+)IL-4(+)Foxp3(+) T-helper cells was significantly lower compared with that in total CD4 cells. Increased numbers of IL-4-producing allergen-specific T-helper cells were found in patients with milk allergy. In addition, Foxp3 was coexpressed with IL-4 in allergen-specific TH2 cells from patients. This coexpression was associated with lower Bcl-2 levels and could contribute to the phenotype and function of TH2 cells. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Clinical Efficacy and Immune Regulation With Peanut Oral Immunotherapy

PubMed Central

Jones, Stacie M.; Pons, Laurent; Roberts, Joseph L.; Scurlock, Amy M.; Perry, Tamara T.; Kulis, Mike; Shreffler, Wayne G.; Steele, Pamela; Henry, Karen A.; Adair, Margaret; Francis, James M.; Durham, Stephen; Vickery, Brian P.; Zhong, Xiaoping; Burks, A. Wesley

2009-01-01

Background Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported. Objective The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT. Methods Peanut-allergic children underwent an OIT protocol including initial day escalation, build-up, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated. Results Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12–18 months, while IgG4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over 6–12 months. Peanut-specific FoxP3 T cells increased until 12 months and then decreased thereafter. Additionally, T cell microarrays showed downregulation of genes in apoptotic pathways. Conclusion OIT induces clinical desensitization to peanut, with significant longer term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT. PMID:19577283

Ole e 13 is the unique food allergen in olive: Structure-functional, substrates docking, and molecular allergenicity comparative analysis.

PubMed

Jimenez-Lopez, J C; Robles-Bolivar, P; Lopez-Valverde, F J; Lima-Cabello, E; Kotchoni, S O; Alché, J D

2016-05-01

Thaumatin-like proteins (TLPs) are enzymes with important functions in pathogens defense and in the response to biotic and abiotic stresses. Last identified olive allergen (Ole e 13) is a TLP, which may also importantly contribute to food allergy and cross-allergenicity to pollen allergen proteins. The goals of this study are the characterization of the structural-functionality of Ole e 13 with a focus in its catalytic mechanism, and its molecular allergenicity by extensive analysis using different molecular computer-aided approaches covering a) functional-regulatory motifs, b) comparative study of linear sequence, 2-D and 3D structural homology modeling, c) molecular docking with two different β-D-glucans, d) conservational and evolutionary analysis, e) catalytic mechanism modeling, and f) IgE-binding, B- and T-cell epitopes identification and comparison to other allergenic TLPs. Sequence comparison, structure-based features, and phylogenetic analysis identified Ole e 13 as a thaumatin-like protein. 3D structural characterization revealed a conserved overall folding among plants TLPs, with mayor differences in the acidic (catalytic) cleft. Molecular docking analysis using two β-(1,3)-glucans allowed to identify fundamental residues involved in the endo-1,3-β-glucanase activity, and defining E84 as one of the conserved residues of the TLPs responsible of the nucleophilic attack to initiate the enzymatic reaction and D107 as proton donor, thus proposing a catalytic mechanism for Ole e 13. Identification of IgE-binding, B- and T-cell epitopes may help designing strategies to improve diagnosis and immunotherapy to food allergy and cross-allergenic pollen TLPs. Copyright © 2016 Elsevier Inc. All rights reserved.

Mite allergoids coupled to nonoxidized mannan from Saccharomyces cerevisae efficiently target canine dendritic cells for novel allergy immunotherapy in veterinary medicine.

PubMed

Soria, Irene; Alvarez, Javier; Manzano, Ana I; López-Relaño, Juan; Cases, Bárbara; Mas-Fontao, Ana; Cañada, F Javier; Fernández-Caldas, Enrique; Casanovas, Miguel; Jiménez-Barbero, Jesús; Palomares, Oscar; Viñals-Flórez, Luis M; Subiza, José L

2017-08-01

We have recently reported that grass pollen allergoids conjugated with nonoxidized mannan of Saccharomyces cerevisae using glutaraldehyde results in a novel hypoallergenic mannan-allergen complex with improved properties for allergen vaccination. Using this approach, human dendritic cells show a better allergen uptake and cytokine profile production (higher IL-10/IL-4 ratio) for therapeutic purposes. Here we aim to address whether a similar approach can be extended to dogs using canine dendritic cells. Six healthy Spanish Greyhound dogs were used as blood donors to obtain canine dendritic cells (DC) derived from peripheral blood monocytes. Allergens from Dermatophagoides farinae mite were polymerized and conjugated with nonoxidized mannan. Nuclear magnetic resonance (NMR), gel electrophoresis (SDS-PAGE), immunoblotting and IgE-ELISA inhibition studies were conducted to evaluate the main characteristics of the allergoid obtained. Mannan-allergen conjugate and controls were assayed in vitro for canine DC uptake and production of IL-4 and IL-10. The results indicate that the conjugation of D. farinae allergens with nonoxidized mannan was feasible using glutaraldehyde. The resulting product was a polymerized structure showing a high molecular weight as detected by NMR and SDS-PAGE analysis. The mannan-allergen conjugate was hypoallergenic with a reduced reactivity with specific dog IgE. An increase in both allergen uptake and IL-10/IL-4 ratio was obtained when canine DCs were incubated with the mannan-allergen conjugate, as compared with the control allergen preparations (unmodified D. farinae allergens and oxidized mannan-allergen conjugate). We conclude that hypoallergenic D. farinae allergens coupled to nonoxidized mannan is a novel allergen preparation suitable for canine allergy immunotherapy targeting dendritic cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Identification of allergens by IgE-specific testing improves outcomes in atopic dermatitis.

PubMed

Will, Brett M; Severino, Richard; Johnson, Douglas W

2017-11-01

IgE quantitative assaying of allergens (IgEQAA) has long been implemented by allergists in determining patients' reactivities for allergic rhinitis and asthma, two of the three diagnoses in atopic syndrome. This test operates by measuring the patient's IgE response to different allergens and can identify potential triggers for a patient's symptoms. Despite this, IgEQAA has yet to see the same widespread use in the field of dermatology, specifically in the treatment of patients with atopic dermatitis (AD). The affected body surface area (BSA) at first presentation, IgEQAA classes, and total immunoglobulin E (IgE) concentration were taken retrospectively for 54 patients with AD. Of the 54 patients observed, 41 had an abnormally high total IgE concentration (76%). Additionally, it was observed that nine (17%) of our patients significantly improved after making lifestyle changes. Knowledge of the identified specific antigens can guide patients to make lifestyle modifications that may improve disease outcomes. IgEQAA and avoidance of allergens may help some patients with AD. © 2017 The International Society of Dermatology.

Specific immunotherapy of experimental myasthenia by genetically engineered APCs: the "guided missile" strategy.

PubMed

Drachman, D B; Wu, J-M; Miagkov, A; Williams, M A; Adams, R N; Wu, B

2003-09-01

Although treatment of MG with general immunosuppressive agents is often effective, it has important drawbacks, including suppression of the immune system as a whole, with the risks of infection and neoplasia, and numerous other adverse side effects. Ideally, treatment of MG should eliminate the specific pathogenic autoimmune response to AChR, without otherwise suppressing the immune system or producing other adverse side effects. Although antibodies to AChR are directly responsible for the loss of AChRs at neuromuscular junctions in MG, the AChR antibody response is T cell-dependent, and immunotherapy directed at T cells can abrogate the autoantibody response, with resulting benefit. As in other autoimmune diseases, the T cell response in MG is highly heterogeneous. The design of specific immunotherapy must take this heterogeneity into account and target the entire repertoire of AChR-specific T cells. We describe our investigation of a novel strategy for specific immunotherapy of MG, involving gene transfer to convert antigen-presenting cells (APCs) to "guided missiles" that target AChR-specific T cells, and that induce apoptosis and elimination of those T cells. This strategy uses the ability of APCs from a given individual to present the entire spectrum of AChR epitopes unique for that individual, and thereby to target the entire repertoire of antigen-specific T cells of the same individual. Using viral vectors, we have genetically engineered the APCs to process and present the most important domain of the AChR molecule, and to express a "warhead" of Fas ligand (FasL) to eliminate the activated AChR-specific T cells with which they interact. Our results show that the APCs express the appropriate gene products, and effectively and specifically eliminate AChR-specific T cells by the Fas/FasL pathway, while sparing T cells of other specificities.

In silico structural analysis of group 3, 6 and 9 allergens from Dermatophagoides farinae.

PubMed

Teng, Feixiang; Yu, Lili; Bian, Yonghua; Sun, Jinxia; Wu, Juansong; Ling, Cunbao; Yang, Li; Wang, Yungang; Cui, Yubao

2015-05-01

Dermatophagoides farinae (Hughes; Acari: Pyroglyphidae) are the predominant source of dust mite allergens, which provoke allergic diseases, such as rhinitis, asthma and eczema. Of the 30 allergen groups produced by D. farinae, the Der f 3, Der f 6 and Der f 9 allergens are all trypsin‑associated proteins, however little else is currently known about them. The present study used in silico tools to compare the amino acid sequences, and predict the secondary and tertiary structures of Der f 3, Der f 6 and Der f 9 allergens. Protein sequence alignment detected ~46% identity between Der f 3, Der f 6 and Der f 9. Furthermore, each protein was shown to contain three active sites and two highly conserved trypsin functional domains. Predictions of the secondary and tertiary structure identified α‑helices, β‑sheets and random coils. The active sites of the three proteins appeared to fold onto each other in a three‑dimensional model, constituting the active site of the enzyme. Epitope analysis demonstrated that Der f 3, Der f 6 and Der f 9 have 4‑5 potential epitopes located in random coils, and the epitope sequences of Der f 3, Der f 6 and Der f 9 were shown to overlap in two domains (at amino acids 83‑87 and 179‑180); however the residues in these two domains were not identical. The present study aimed to conduct a biochemical and genetic analysis of these three allergens, and to potentially contribute to the development of vaccines for allergen‑specific immunotherapy.

House dust mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes.

PubMed

Pevec, Branko; Radulovic Pevec, Mira; Stipic Markovic, Asja; Batista, Irena; Rijavec, Matija; Silar, Mira; Kosnik, Mitja; Korosec, Peter

2012-01-01

Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG(4), nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Decreased wheal sizes and VAS scores, negative challenges and increased sIgG(4) levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal

Polyphenol-rich pomegranate juice reduces IgE binding to cashew nut allergens.

PubMed

Li, Yichen; Mattison, Christopher P

2018-03-01

Food allergy negatively impacts quality of life and can be life-threatening. Cashew nuts can cause severe reactions in very small amounts, and they are included in a group of foods most commonly responsible for causing food allergy. Polyphenols and polyphenol-rich juices have been demonstrated to complex with peanut allergens. Here, the interaction between cashew nut allergens and polyphenol-rich juices is evaluated biochemically and immunologically. Various juices, including pomegranate (POM), blueberry (BB), and concord grape (CG) juices, were evaluated for polyphenol content and formation of polyphenol-cashew allergen complexes. Among the various juices studied, POM juice showed a greater capacity to form complexes with cashew proteins. Dynamic light scattering (DLS) demonstrated a sharp increase in cashew protein extract particle size to around 3580 nm, and fewer cashew proteins were resolved by electrophoresis after treatment with POM juice. Immunoassays demonstrated reduced IgG and IgE binding to cashew allergens due to allergen precipitation by POM juice. These observations support the formation of complexes between polyphenol and cashew proteins that can prevent antibody recognition of cashew allergens through allergen precipitation. POM juice treatment of cashew extract effectively reduces antibody binding through allergen precipitation, and these findings could be applied to the development of less allergenic cashew nut products and oral immunotherapy. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Enhanced glucocorticoid-induced leucine zipper in dendritic cells induces allergen-specific regulatory CD4(+) T-cells in respiratory allergies.

PubMed

Karaki, S; Garcia, G; Tcherakian, C; Capel, F; Tran, T; Pallardy, M; Humbert, M; Emilie, D; Godot, V

2014-05-01

Respiratory allergies rely on a defect of IL-10-secreting regulatory CD4(+) T-cells (IL-10-Tregs ) leading to excessive Th2-biased immune responses to allergens. According to clinical data, the restoration of allergen-specific IL-10-Tregs is required to control respiratory allergies and cure patients. The discovery of mechanisms involved in the generation of IL-10-Tregs will thus help to provide effective treatments. We previously demonstrated that dendritic cells (DCs) expressing high levels of the glucocorticoid-induced leucine zipper protein (GILZ) generate antigen-specific IL-10-Tregs . We suspect a defective expression of GILZ in the DCs of respiratory allergic patients and speculate that increasing its expression might restore immune tolerance against allergens through the induction of IL-10-Tregs . We assessed GILZ expression in blood DCs of patients and healthy nonallergic donors by qPCR. We compared the ability of patients' DCs to induce allergen-specific IL-10-Tregs before and after an in vivo up-regulation of GILZ expression by steroid administration, steroids being inducers of GILZ. We report lower levels of GILZ in DCs of respiratory allergic patients that return to normal levels after steroid administration. We show that patients' DCs with increased levels of GILZ generate allergen-specific IL-10-Tregs again. We further confirm unequivocally that GILZ is required in patients' DCs to activate these IL-10-Tregs . This proof of concept study shows that the re-establishment of GILZ expression in patients' DCs to normal levels restores their capacity to activate allergen-specific IL-10-Tregs . We thus highlight the up-regulation of GILZ in DCs as a new interventional approach to restore the immune tolerance to allergens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Novel T-cell epitopes of ovalbumin in BALB/c mouse: Potential for peptide-immunotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Marie; Mine, Yoshinori

The identification of food allergen T-cell epitopes provides a platform for the development of novel immunotherapies. Despite extensive knowledge of the physicochemical properties of hen ovalbumin (OVA), a major egg allergen, the complete T-cell epitope map of OVA has surprisingly not been defined in the commonly used BALB/c mouse model. In this study, spleen cells obtained from OVA-sensitized mice were incubated in the presence of 12-mer overlapping synthetic peptides, constructed using the SPOTS synthesis method. Proliferative activity was assessed by 72-h in vitro assays with use of the tetrazolium salt WST-1 and led to identification of four mitogenic sequences, i.e.,more » A39R50, S147R158, K263E274, and A329E340. ELISA analyses of interferon (IFN)-{gamma} and interleukin (IL)-4 productions in cell culture supernatants upon stimulation with increasing concentrations of peptides confirmed their immunogenicity. Knowledge of the complete T-cell epitope map of OVA opens the way to a number of experimental investigations, including the exploration of peptide-based immunotherapy.« less

Development and characterization of an allergoid of cat dander for immunotherapy.

PubMed

Sola, J P; Pedreño, Y; Cerezo, A; Peñalver-Mellado, M

2018-01-13

Allergy to cats is a frequent cause of sensitization to indoor allergens and currently there are few alternatives to specific immunotherapy with cat native extracts. The objective is to develop and characterize a new allergoid to increase the tools available for use in clinical practice. The allergoid cat dander extract (ACD) was developed from a native cat dander extract (NCD) by modification with glutaraldehyde, and the optimal process control was determined by SDS-PAGE, DOT BLOT and determination of free amine groups. The ACD was characterized in protein profile by SDS-PAGE, size exclusion chromatography (SEC) and peptide footprint. The allergenic profile of ACD was determined by immunoblot, IgE CAP inhibition and IgG competition ELISA. The major allergen content in NCD was obtained by the ELISA sandwich protocol and was extrapolated to ACD. The control process determined the optimal development of the allergoid. The ACD obtained contains 182.28μg/mg of protein and 11.90μg/mg of Fel d 1. SDS-PAGE and SEC confirmed the presence of high molecular weight proteins in ACD, and the peptide footprint showed the presence of Fel d 1 and Fel d 7. The high degree of polymerization was evidenced with the determination of the reduction of lysine residues in the allergoid, resulting 91.96%. The ACD showed a significant loss of allergenicity respect to NCD, while the IgG-binding capacity was maintained. The ACD obtained presents a good safety profile, so would be a good alternative for treatment of cat allergy. Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Cross-reactivity and epitope analysis of Pru a 1, the major cherry allergen.

PubMed

Scheurer, S; Son, D Y; Boehm, M; Karamloo, F; Franke, S; Hoffmann, A; Haustein, D; Vieths, S

1999-02-01

-anaphylactic allergen fragments or variants derived from the IgE-inducing pollen allergens may serve as useful tools for a new strategy of specific immunotherapy.

Minor allergen patterns in birch pollen allergen products-A question of pollen?

PubMed

Zimmer, J; Döring, S; Strecker, D; Trösemeier, J H; Hanschmann, K M; Führer, F; Vieths, S; Kaul, S

2017-08-01

Contrary to the scientific differentiation between major and minor allergens, the regulatory framework controlling allergen products in the EU distinguishes relevant and non-relevant allergens. Given the lack of knowledge on their clinical relevance, minor allergens are usually not controlled by allergen product specifications. Especially, in birch pollen (BP) allergen products, minor allergens are commonly disregarded. To quantify three minor allergens in BP allergen products from different manufacturers and to assess the influence of the utilized BP on minor allergen patterns. Apart from common quality parameters such as Bet v 1 content, Bet v 4, Bet v 6 and Bet v 7 were quantified in 70 BP allergen product batches from six manufacturers, using ELISA systems developed in-house. Batch-to-batch variability was checked for agreement with a variability margin of 50%-200% from mean of the given batches for individual allergen content. Subsequently, minor allergen patterns were generated via multidimensional scaling and related to information on the pollen lots used in production of the respective product batches. Like the already established Bet v 4 ELISA, the ELISA systems for quantification of Bet v 6 and Bet v 7 were successfully validated. Differences in minor allergen content between products and batch-to-batch consistency were observed. Correlations between minor and major allergen content were low to moderate. About 20% of batches exceeded the variability margin for at least one minor allergen. Interestingly, these fluctuations could not in all cases be linked to the use of certain BP lots. The impact of the observed minor allergen variability on safety and efficacy of BP allergen products can currently not be estimated. As the described differences could only in few cases be related to the used pollen lots, it is evident that additional factors influence minor allergens in BP allergen products. © 2017 John Wiley & Sons Ltd.

Animal models of allergen-induced tolerance in asthma: are T-regulatory-1 cells (Tr-1) the solution for T-helper-2 cells (Th-2) in asthma?

PubMed

Tournoy, K G; Hove, C; Grooten, J; Moerloose, K; Brusselle, G G; Joos, G F

2006-01-01

Non-specific anti-inflammatory medication is actually the treatment of choice for controlling the T-helper type 2 (Th-2) cell-driven airway inflammation in asthma. The induction of counterbalancing Th-1 cell clones, long considered a promising approach for immunotherapy, has failed to fulfil its promise because of potentially detrimental side-effects. This is therefore probably not a valid option for the treatment of asthma. With the increasing awareness that active immune mechanisms exist to control inflammatory responses, interest rises to investigate whether these can be exploited to control allergen-induced airway disease. The induction of antigen-specific T cells with suppressive characteristics (regulatory T cells) is therefore a potentially interesting approach. These regulatory T cells mediate tolerance in healthy, non-atopic individuals and have the potential of becoming an effective means of preventing allergen-induced airway inflammation and possibly of suppressing ongoing allergic immune responses. Here we review the available knowledge about allergen-induced suppressive immunity obtained from animal models taking into account the different developmental stages of allergic airway disease.

Allergen-specific IgG and IgA in serum and bronchoalveolar lavage fluid in a model of experimental feline asthma.

PubMed

Norris, C R; Byerly, J R; Decile, K C; Berghaus, R D; Walby, W F; Schelegle, E S; Hyde, D M; Gershwin, L J

2003-12-15

Allergic asthma, a Th2 cell driven response to inhaled allergens, has classically been thought of as predominantly mediated by IgE antibodies. To investigate the role of other immunoglobulin classes (e.g., IgG and IgA) in the immunopathogenesis of allergic asthma, levels of these allergen-specific immunoglobulins were measured in serum and mucosal fluids. Bermuda grass allergen (BGA)-specific IgG and IgA ELISAs in serum and bronchoalveolar lavage fluid (BALF) were developed and optimized in an experimental model of BGA-induced feline asthma. Levels of BGA-specific IgG and IgA significantly increased over time in serum and BALF after allergen sensitization. Additionally, these elevated levels of BGA-specific IgG and IgA were seen in conjunction with the development of an asthmatic phenotype indicated by positive intradermal skin tests, enhanced airways hyperreactivity, and increased eosinophil percentages in the BALF.

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

PubMed

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. © 2015 S. Karger AG, Basel.

Monitoring honeybee venom immunotherapy in children with the basophil activation test.

PubMed

Žitnik, Simona E K; Vesel, Tina; Avčin, Tadej; Šilar, Mira; Košnik, Mitja; Korošec, Peter

2012-03-01

New in vitro methods are essential for developing better follow-up criteria for venom immunotherapy (VIT). Thirty-one children with a history of honeybee venom-induced systemic anaphylaxis were included in this prospective, single-blinded study. The basophil CD63 activation test (BAT) was assessed before starting VIT, at the end of the build-up phase (day 5), 6 months later, and after 2-4 yr of VIT. Basophil CD63 activation test allowed identification of the culprit insect in 74% of honeybee venom-allergic children. In comparison, IgE reactivity was single positive in only 52% of children. Five days after starting VIT, BAT was highly comparable to before VIT. However, after 6 months and further after 2-4 yr of VIT, a significant and approximately fourfold decrease was demonstrated in CD63 response at sub-maximal 0.1 μg/ml allergen concentration, which mainly represents cellular sensitivity. No such differences were found at a higher 1 μg/ml of allergen concentration. Person-to-person analyses showed that after 2-4 yr of VIT, a marked CD63 decrease was evident in 85% of children. In addition, elevated basophil sensitivity measured before VIT was associated with the appearance of side effects observed during the build-up phase of VIT. Basophil CD63 allergen-specific sensitivity seems to be a promising tool for monitoring protective immune response in honeybee VIT. © 2011 John Wiley & Sons A/S.

205 Allergy Training and Immunotherapy in Latin America: How Survey-Results Lead to a Regional Overview

PubMed Central

Gomez, R. Maximiliano; Linnemann, Désirée Larenas; Passalacqua, Giovanni; González-Díaz, Sandra; Coce, Victor H.; Canonica, Giorgio Walter; Baena-Cagnani, Carlos E.

2012-01-01

Background In April 2011 a group of Latin American (LA) allergy experts, leaders in their countries in the area of immunotherapy, met in Cordoba, Argentina, to discuss how allergy and allergen-specific immunotherapy (ASIT) can be improved in the region. The need for a situational sketch was expressed. Methods A questionnaire on allergy training (AT), ASIT, extracts and legislation was sent out to 22 leaders in the field of nine LA countries to obtain an overview of the LA situation. Results Results are presented with descriptive statistics. All 22 questionnaires were returned (9 countries). AT in 56% of the surveyed LA countries is at the third-level of medical care, after a core-training of 2 to 3 years internal medicine or pediatrics; in 3 countries it is a second-level career and in one country there is no AT. Board certification with exam is only mandatory in a third of the countries; recertification being obtained without exam. Mostly, training is in general allergy; pediatric AT only exists in 2 countries. Both sublingual (SLIT, only in the form of drops) and subcutaneous (SCIT) immunotherapy are practiced in all countries, from the age of 3 years (mean, range 1–5 years) onward. As no strict legislation exists IT can be managed by non-allergists in 7/9 countries. Mixed extracts are used with mostly 3 to 5 allergens/vial (range 2 to 6-10 allergens/vial) and all countries have bacterial vaccine. SCIT extracts come from US and European (89%) and 56% local providers. SLIT extracts are almost exclusively from Europe (Spain), but in Argentine, Brazil, and Mexico also local SLIT extracts exist. There is rudimentary regulation concerning extract potency in 2 countries. IT is generally paid for by private patients. Insurance companies reimburse IT in 56% of the countries, the social security system in 33% and in one country selected third level governmental hospitals supply IT. Publications on adverse events with IT are starting to appear (3 countries) and 3

Comparison of intradermal dilutional testing, skin prick testing, and modified quantitative testing for common allergens.

PubMed

Peltier, Jacques; Ryan, Matthew W

2007-08-01

To compare and correlate wheal size using the Multi-Test II applicator with the endpoint obtained by intradermal dilutional testing (IDT) for 5 common allergens. To examine the safety of modified quantitative testing (MQT) for determining immunotherapy starting doses. Prospective comparative clinical study. A total of 134 subjects were simultaneously skin tested for immediate hypersensitivity using the Multi-Test II device and IDT. There was a 77% concordance between results from IDT and results from MQT. When there was a difference, MQT predicted a safer endpoint for starting immunotherapy in all but 2 cases. Wheal size by SPT is predictive of endpoint by IDT. MQT is nearly as effective as formal IDT in determining endpoint. Modified quantitative testing appears to be a safe alternative to IDT for determining starting doses for immunotherapy.

Markers of tolerance development to food allergens.

PubMed

Ponce, M; Diesner, S C; Szépfalusi, Z; Eiwegger, T

2016-10-01

IgE-mediated reactions to food allergens are the most common cause of anaphylaxis in childhood. Although allergies to cow's milk, egg, or soy proteins, in contrast to peanut and tree nut allergens, resolve within the first 6 years of life in up to 60% due to natural tolerance development, this process is not well understood. At present, there is no cure or treatment for food allergy that would result in an induction of tolerance to the symptom-eliciting food. Avoidance, providing an emergency plan and education, is the standard of treatment. Oral immunotherapeutic approaches have been proven reasonable efficacy; however, they are associated with high rates of side-effects and low numbers of patients achieving tolerance. Nevertheless, mechanisms that take place during oral immunotherapy may help to understand tolerance development. On the basis of these therapeutic interventions, events like loss of basophil activation and induction of regulatory lymphocyte subsets and of blocking antibodies have been described. Their functional importance at a clinical level, however, remains to be investigated in detail. Consequently, there is eminent need to understand the process of tolerance development to food allergens and define biomarkers to develop and monitor new treatment strategies for food allergy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetically modified α-amylase inhibitor peas are not specifically allergenic in mice.

PubMed

Lee, Rui-Yun; Reiner, Daniela; Dekan, Gerhard; Moore, Andrew E; Higgins, T J V; Epstein, Michelle M

2013-01-01

Weevils can devastate food legumes in developing countries, but genetically modified peas (Pisum sativum), chickpeas and cowpeas expressing the gene for alpha-amylase inhibitor-1 (αAI) from the common bean (Phaseolus vulgaris) are completely protected from weevil destruction. αAI is seed-specific, accumulated at high levels and undergoes post-translational modification as it traverses the seed endomembrane system. This modification was thought to be responsible for the reported allergenicity in mice of the transgenic pea but not the bean. Here, we observed that transgenic αAI peas, chickpeas and cowpeas as well as non-transgenic beans were all allergenic in BALB/c mice. Even consuming non-transgenic peas lacking αAI led to an anti-αAI response due to a cross-reactive response to pea lectin. Our data demonstrate that αAI transgenic peas are not more allergenic than beans or non-transgenic peas in mice. This study illustrates the importance of repeat experiments in independent laboratories and the potential for unexpected cross-reactive allergic responses upon consumption of plant products in mice.

Genetically Modified α-Amylase Inhibitor Peas Are Not Specifically Allergenic in Mice

PubMed Central

Dekan, Gerhard; Moore, Andrew E.; Higgins, T. J. V.; Epstein, Michelle M.

2013-01-01

Weevils can devastate food legumes in developing countries, but genetically modified peas (Pisum sativum), chickpeas and cowpeas expressing the gene for alpha-amylase inhibitor-1 (αAI) from the common bean (Phaseolus vulgaris) are completely protected from weevil destruction. αAI is seed-specific, accumulated at high levels and undergoes post-translational modification as it traverses the seed endomembrane system. This modification was thought to be responsible for the reported allergenicity in mice of the transgenic pea but not the bean. Here, we observed that transgenic αAI peas, chickpeas and cowpeas as well as non-transgenic beans were all allergenic in BALB/c mice. Even consuming non-transgenic peas lacking αAI led to an anti-αAI response due to a cross-reactive response to pea lectin. Our data demonstrate that αAI transgenic peas are not more allergenic than beans or non-transgenic peas in mice. This study illustrates the importance of repeat experiments in independent laboratories and the potential for unexpected cross-reactive allergic responses upon consumption of plant products in mice. PMID:23326368

[Health economics analysis of specific immunotherapy in allergic rhinitis accompanied with asthma].

PubMed

Chen, Jianjun; Xiang, Jisheng; Wang, Yanjun; Shi, Qiumei; Tan, Huifang; Kong, Weijia

2013-09-01

To investigate the cost-effectiveness of standardized specific immunotherapy (SIT) for allergic rhinitis patients accompanied with asthma (ARAS) in China. Forty ARAS patients sensitized with house dust mite (HDM) were administered with SIT (SIT group) or merely medicine treatment (control group). Alutard dermatophagoides pteronyssinus vaccine from ALK company was used for immunotherapy. The usage of symptom control medicine was according to the ARIA and GINA guideline. Cost-effectiveness ratio (CER) and Incremental cost-effectiveness ratio(ICER) analysis was conducted. The effectiveness was measured in terms of symptom scores, quality of life, objective improvement of rhinitis and asthma. Sensitive analysis was conducted to verify the stability of the results. The cost of SIT group for 1 year (6578 yuan) was higher than that of control group (1733.3 yuan), while the cost-effectiveness ratio and incremental cost-effectiveness ratio of SIT group were significant better than that of control group in all items. CER was 1686.7 yuan in SIT group compared with 3466.6 yuan in control group for nasal symptom scores, 4698.6 yuan in SIT group compared with 5777.8 yuan in control group for asthma symptom scores, 3462.1 yuan in SIT group compared with 8666.7 yuan in control group. The sensitive analysis of the price 10 percent higher or lower showed the same results. The cost-effectiveness of specific immunotherapy (SIT) for mite sensitized ARAS patients was better than that of merely medicine treatment.

Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens

PubMed Central

Gubin, Matthew M.; Zhang, Xiuli; Schuster, Heiko; Caron, Etienne; Ward, Jeffrey P.; Noguchi, Takuro; Ivanova, Yulia; Hundal, Jasreet; Arthur, Cora D.; Krebber, Willem-Jan; Mulder, Gwenn E.; Toebes, Mireille; Vesely, Matthew D.; Lam, Samuel S.K.; Korman, Alan J.; Allison, James P.; Freeman, Gordon J.; Sharpe, Arlene H.; Pearce, Erika L.; Schumacher, Ton N.; Aebersold, Ruedi; Rammensee, Hans-Georg; Melief, Cornelis J. M.; Mardis, Elaine R.; Gillanders, William E.; Artyomov, Maxim N.; Schreiber, Robert D.

2014-01-01

The immune system plays key roles in determining the fate of developing cancers by not only functioning as a tumour promoter facilitating cellular transformation, promoting tumour growth and sculpting tumour cell immunogenicity1–6, but also as an extrinsic tumour suppressor that either destroys developing tumours or restrains their expansion1,2,7. Yet clinically apparent cancers still arise in immunocompetent individuals in part as a consequence of cancer induced immunosuppression. In many individuals, immunosuppression is mediated by Cytotoxic T-Lymphocyte Associated Antigen-4 (CTLA-4) and Programmed Death-1 (PD-1), two immunomodulatory receptors expressed on T cells8,9. Monoclonal antibody (mAb) based therapies targeting CTLA-4 and/or PD-1 (checkpoint blockade) have yielded significant clinical benefits—including durable responses—to patients with different malignancies10–13. However, little is known about the identity of the tumour antigens that function as the targets of T cells activated by checkpoint blockade immunotherapy and whether these antigens can be used to generate vaccines that are highly tumour-specific. Herein, we use genomics and bioinformatics approaches to identify tumour-specific mutant proteins as a major class of T cell rejection antigens following αPD-1 and/or αCTLA-4 therapy of mice bearing progressively growing sarcomas and show that therapeutic synthetic long peptide (SLP) vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy. Whereas, mutant tumour antigen-specific T cells are present in progressively growing tumours, they are reactivated following treatment with αPD-1- and/or αCTLA-4 and display some overlapping but mostly treatment-specific transcriptional profiles rendering them capable of mediating tumour rejection. These results reveal that tumour-specific mutant antigens (TSMA) are not only important targets of checkpoint blockade therapy but also can be

An EAACI “European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI)”: the methodology

PubMed Central

2014-01-01

At present, there is no European report on clinically relevant systemic reactions due to the regular use of allergen immunotherapy (AIT), administered either subcutaneously or sublingually (SCIT and SLIT, respectively) outside clinical trials. Using an electronic survey and a “harmonised terminology” according to MedDRA, we aimed to prospectively collect systemic adverse reactions due to AIT from real life clinical settings. Under the framework of the EAACI, a team of European specialists in AIT, pharmacovigilance, epidemiology and drugs regulation set up a web-based prospective pilot survey to be conducted in three European countries (France, Germany and Spain). A designated “national coordinator” was responsible for following ethics requirements relative to each country and to select at least 30 doctors per country. Patients were recruited the same day they received their first dose of either SCIT or SLIT. Patient inclusion criteria were: adults and children, with IgE mediated pollen, house dust mite, Alternaria, and/or animal dander respiratory allergies who will initiate AIT. A list of 31 symptoms terms were extracted from the MedDRA (Medical Dictionary for Regulatory Activities) dictionary to harmonize the reporting of all adverse systemic reactions in this survey. The SurveyMonkey® online instrument was used by participant doctors to submit information directly to a blinded central database. Three questionnaires were generated: i) the Doctor Questionnaire, ii) the Patient Questionnaire and iii) the Adverse Reaction Questionnaire. A handbook and a mistake report form were given to each doctor. In this paper, we describe the methodology followed. PMID:25075276

In the strategies to prevent asthma exacerbations, allergic asthma needs specific treatment.

PubMed

Incorvaia, Cristoforo; Ridolo, Erminia

2015-04-01

No generally accepted definition of asthma exacerbation is thus far available, though in 2012 an expert committee endorsed by the National Institute of Health proposed such definition as "a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome". Graham and Eid reviewed the impact of asthma exacerbations, and noted that, analysing the outcomes with existing treatments, many patients with asthma remain symptomatic and experience exacerbations. This requires the introduction of new strategies to more effectively reduce the exacerbation risk, based on correct diagnosis, stopping smoking, correct inhaler technique, consistent adherence, weight management, and gaining control with the addition of medication". Indeed, as allergic asthma is the most common form, a specific approach by allergen immunotherapy should receive more attention. Actually, the efficacy of immunotherapy in allergic asthma, by the subcutaneous or the sublingual route, is supported by robust meta-analyses. The most important allergen source causing asthma is the house dust mite, but an increasing role for molds is apparent due to the ongoing climate change.

13-year overview of serious adverse drug reactions following subcutaneous specific immunotherapy with a chemically modified allergen preparation.

PubMed

Distler, Andreas; Pappelendam, Debbie

The Paul-Ehrlich-Institut (PEI) published an analysis of reports of adverse drug reactions (ADRs) in 2001 with test and therapy allergens from the period from 1991 to 2000. Possible risk factors were evaluated for the ADR reports classified as "serious". During the analyzed period, modified semi-depot preparations (allergoids) induced between 0.01 % and 0.0005 % serious systemic reactions, i. e. one serious ADR occurred in 10,000 to 200,000 injections. No information was provided regarding the respective incidences in relation to the individual companies or preparations. Within the scope of a 13-year analysis (2001-2013), the serious ADRs were analysed at HAL for the allergoid preparations PURETHAL® Pollen and Mites. As in the analysis of PEI, the frequency of serious ADRs was based on the estimated number of administered injections. A total of 46 cases with serious ADRs were received. In 26 % of the cases, a serious ADR occurred during initial treatment after the first injection. In 82.6 % of the cases, the serious ADR occurred within the 30-minute observation period in the practice. Adrenaline was administered as emergency treatment in seven cases. Hospitalisations were initiated by the treating physician or by patients themselves in 45 cases. The duration of the hospital stay varied from a few hours up to three days for further monitoring. Serious ADRs occurred in 11 cases with mites and in 35 cases with pollen. If it is assumed that there are six injections in each vial, this yields an incidence of 0.00061 % (1 : 164,000). The frequency with mites (0.00093 %) was slightly higher than with pollen (0.00055 %). The allergoid preparations (pollen and mite allergens) showed a very low risk of serious ADRs, which was close to the lower level of incidence of 0.0005 % for allergoid preparations published by the PEI.

High level expression, purification and physico- and immunochemical characterisation of recombinant Pen a 1: a major allergen of shrimp.

PubMed

Albrecht, Melanie; Alessandri, Stefano; Conti, Amedeo; Reuter, Andreas; Lauer, Iris; Vieths, Stefan; Reese, Gerald

2008-11-01

Well-characterised and immunologically active recombinant allergens are of eminent importance for improvement of diagnostic tools and immunotherapy of allergic diseases. The use of recombinant allergens has several advantages such as the more precise quantification of the active substance compared to allergen extracts and the reduced risk of contamination with other allergenic proteins compared to purified natural allergens. Optimised standard protocols for expression and purification and a detailed physico-chemical characterisation of such recombinant allergens are necessary to ensure consistent quality and comparability of results obtained with recombinant material. In this study the major allergen Pen a 1 of brown shrimp (Penaeus aztecus) was expressed in E. coli and purified in two steps by immobilised metal chelate-affinity chromatography (IMAC) and size-exclusion chromatography. Identity and purity were verified with N-terminal sequencing and peptide mass fingerprinting. Circular dichroism and NMR-spectroscopy indicated an alpha-helical flexible structure of rPen a 1 which is in accordance with the known structure of tropomyosins. Finally, the recombinant allergen proved to be immunologically reactive in IgE Western blot analysis and ELISA. This study provides a protocol for the preparation of recombinant shrimp tropomyosin in standardised quality.

Immunotherapy in lung cancer.

PubMed Central

Al-Moundhri, M.; O'Brien, M.; Souberbielle, B. E.

1998-01-01

More research and new treatment options are needed in all stages of lung cancer. To this end immunotherapy needs a revival in view of recent improved technologies and greater understanding of the underlying biology. In this review we discuss mechanisms of tumour immunotherapy, non-specific, specific and adoptive, with particular reference to a direct therapeutic action on all subtypes of lung cancer. PMID:9703271

Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies: An AIRWAYS Integrated Care Pathways (ICPs) programme item (Action Plan B3 of the European Innovation Partnership on active and healthy ageing) and the Global Alliance against Chronic Respiratory Diseases (GARD), a World Health Organization GARD research demonstration project.

PubMed

Calderon, M A; Demoly, P; Casale, T; Akdis, C A; Bachert, C; Bewick, M; Bilò, B M; Bohle, B; Bonini, S; Bush, A; Caimmi, D P; Canonica, G W; Cardona, V; Chiriac, A M; Cox, L; Custovic, A; De Blay, F; Devillier, P; Didier, A; Di Lorenzo, G; Du Toit, G; Durham, S R; Eng, P; Fiocchi, A; Fox, A T; van Wijk, R Gerth; Gomez, R M; Haathela, T; Halken, S; Hellings, P W; Jacobsen, L; Just, J; Tanno, L K; Kleine-Tebbe, J; Klimek, L; Knol, E F; Kuna, P; Larenas-Linnemann, D E; Linneberg, A; Matricardi, M; Malling, H J; Moesges, R; Mullol, J; Muraro, A; Papadopoulos, N; Passalacqua, G; Pastorello, E; Pfaar, O; Price, D; Del Rio, P Rodriguez; Ruëff, R; Samolinski, B; Scadding, G K; Senti, G; Shamji, M H; Sheikh, A; Sisul, J C; Sole, D; Sturm, G J; Tabar, A; Van Ree, R; Ventura, M T; Vidal, C; Varga, E M; Worm, M; Zuberbier, T; Bousquet, J

2016-01-01

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

Specific B-cell Epitope of Per a 1: A Major Allergen of American Cockroach (Periplaneta americana) and Anatomical Localization.

PubMed

Sookrung, Nitat; Khetsuphan, Thanyathon; Chaisri, Urai; Indrawattana, Nitaya; Reamtong, Onrapak; Chaicumpa, Wanpen; Tungtrongchitr, Anchalee

2014-07-01

Cockroach (CR) is a common source of indoor allergens, and Per a 1 is a major American CR (Periplaneta americana) allergen; however, several attributes of this protein remain unknown. This study identifies a novel specific B cell epitope and anatomical locations of Per a 1.0105. Recombinant Per a 1.0105 (rPer a 1.0105) was used as BALB/c mouse immunogen for the production of monoclonal antibodies (MAb). The MAb specific B cell epitope was identified by determining phage mimotopic peptides and pair-wise alignment of the peptides with the rPer a 1.0105 amino acid sequence. Locations of the Per a 1.0105 in P. americana were investigated by immunohistochemical staining. The rPer a 1.0105 (~13 kDa) had 100%, 98% and ≥90% identity to Per a 1.0105, Per a 1.0101, and Cr-PII, respectively. The B-cell epitope of the Per a 1.0105 specific-MAb was located at residues(99) QDLLLQLRDKGV(110) contained in all 5 Per a 1.01 isoforms and Per a 1.02. The epitope was analogous to the Bla g 1.02 epitope; however, this B-cell epitope was not an IgE inducer. Per a 1.0105 was found in the midgut and intestinal content of American CR but not in the other organs. The amount of the Per a 1 was ~544 ℃g per gram of feces. The novel Per a 1 B-cell epitope described in this study is a useful target for allergen quantification in samples; however, the specific MAb can be used as an allergen detection reagent. The MAb based-affinity resin can be made for allergen purification, and the so-purified protein can serve as a standard and diagnostic allergen as well as a therapeutic vaccine component. The finding that the Per a 1 is contained in the midgut and feces is useful to increase yield and purity when preparing this allergen.

Specific B-cell Epitope of Per a 1: A Major Allergen of American Cockroach (Periplaneta americana) and Anatomical Localization

PubMed Central

Sookrung, Nitat; Khetsuphan, Thanyathon; Chaisri, Urai; Indrawattana, Nitaya; Reamtong, Onrapak; Chaicumpa, Wanpen

2014-01-01

Purpose Cockroach (CR) is a common source of indoor allergens, and Per a 1 is a major American CR (Periplaneta americana) allergen; however, several attributes of this protein remain unknown. This study identifies a novel specific B cell epitope and anatomical locations of Per a 1.0105. Methods Recombinant Per a 1.0105 (rPer a 1.0105) was used as BALB/c mouse immunogen for the production of monoclonal antibodies (MAb). The MAb specific B cell epitope was identified by determining phage mimotopic peptides and pair-wise alignment of the peptides with the rPer a 1.0105 amino acid sequence. Locations of the Per a 1.0105 in P. americana were investigated by immunohistochemical staining. Results The rPer a 1.0105 (~13 kDa) had 100%, 98% and ≥90% identity to Per a 1.0105, Per a 1.0101, and Cr-PII, respectively. The B-cell epitope of the Per a 1.0105 specific-MAb was located at residues99 QDLLLQLRDKGV110 contained in all 5 Per a 1.01 isoforms and Per a 1.02. The epitope was analogous to the Bla g 1.02 epitope; however, this B-cell epitope was not an IgE inducer. Per a 1.0105 was found in the midgut and intestinal content of American CR but not in the other organs. The amount of the Per a 1 was ~544 ℃g per gram of feces. Conclusions The novel Per a 1 B-cell epitope described in this study is a useful target for allergen quantification in samples; however, the specific MAb can be used as an allergen detection reagent. The MAb based-affinity resin can be made for allergen purification, and the so-purified protein can serve as a standard and diagnostic allergen as well as a therapeutic vaccine component. The finding that the Per a 1 is contained in the midgut and feces is useful to increase yield and purity when preparing this allergen. PMID:24991456

Safety profile of hymenoptera venom immunotherapy (VIT) in monosensitized patients: lack of new sensitization to nontreated insect venom.

PubMed

Spoerl, D; Bircher, A J; Scherer, K

2011-01-01

Venom immunotherapy (VIT) has proven to be efficacious in reducing the severity of anaphylactic reactions following field stings in patients with Hymenoptera venom allergy. Due to sequence homologies in the allergens used in Hymenoptera vaccines, there is concern that immunotherapy could lead to sensitization to allergens to which patients were not previously sensitized. The relevance of such an undesired phenomenon is unclear. To investigate the incidence of sensitization to Hymenoptera venoms other than those to which the patients were already sensitized and to assess the overall safety profile of VIT in order to compare the risk-benefit ratio in a subpopulation of monosensitized individuals. We performed a retrospective analysis of specific immunoglobulin E (sIgE) levels in patients with no prior detectable sIgE to Hymenoptera venom other than the one for which they received VIT. We assessed the safety profile of VIT using serological and clinical parameters. Of the 56 monosensitized patients who had VIT, 3 (5%) developed sIgE to the other insect with no history of field sting to explain it. This rate was similar to the rate of new sensitization due to field stings during VIT. VIT was well-tolerated and levels of serological markers improved. No patient had a systemic anaphylactic reaction after having been stung by an insect other than the one he/she was desensitized for during follow-up. VIT seems to be safe with respect to clinically significant new sensitizations.

Component-resolved diagnostics in vernal conjunctivitis.

PubMed

Armentia, Alicia; Sanchís, Eugenia; Montero, Javier A

2016-10-01

Conventional diagnostic tests in allergy are insufficient to clarify the cause of vernal conjunctivitis. Component-resolved diagnostic (CRD) by microarray allergen assay may be useful in detecting allergens that might be involved in the inflammatory process. In a recent trial in patients suffered from eosinophilic esophagitis, after 2 years of the CRD-guided exclusion diet and specific immunotherapy, significant clinical improvement was observed, and 68% of patients were discharged (cure based on negative biopsy, no symptoms, and no medication intake). Our new objective was to evaluate IgE-mediated hypersensitivity by CRD in tears and serum from patients with vernal conjunctivitis and treat patients with identified triggering allergens by specific immunotherapy. Twenty-five patients with vernal conjunctivitis were evaluated. The identified triggering allergens were n Lol p 1 (11 cases), n Cyn d 1 (eight cases), group 4 and 6 grasses (six cases) and group 5 of grasses (five cases). Prick test and pollen IgE were positive in one case. Clinical improvement was observed in 13/25 vernal conjunctivitis patients after 1-year specific immunotherapy. CRD seems to be a more sensitive diagnostic tool compared with prick test and IgE detection. Specific CRD-led immunotherapy may achieve clinical improvements in vernal conjunctivitis patients.

Classification of current anticancer immunotherapies

PubMed Central

Vacchelli, Erika; Pedro, José-Manuel Bravo-San; Buqué, Aitziber; Senovilla, Laura; Baracco, Elisa Elena; Bloy, Norma; Castoldi, Francesca; Abastado, Jean-Pierre; Agostinis, Patrizia; Apte, Ron N.; Aranda, Fernando; Ayyoub, Maha; Beckhove, Philipp; Blay, Jean-Yves; Bracci, Laura; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Estaban; Cerundolo, Vincenzo; Clayton, Aled; Colombo, Mario P.; Coussens, Lisa; Dhodapkar, Madhav V.; Eggermont, Alexander M.; Fearon, Douglas T.; Fridman, Wolf H.; Fučíková, Jitka; Gabrilovich, Dmitry I.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giaccone, Giuseppe; Gilboa, Eli; Gnjatic, Sacha; Hoos, Axel; Hosmalin, Anne; Jäger, Dirk; Kalinski, Pawel; Kärre, Klas; Kepp, Oliver; Kiessling, Rolf; Kirkwood, John M.; Klein, Eva; Knuth, Alexander; Lewis, Claire E.; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Mach, Jean-Pierre; Mattei, Fabrizio; Mavilio, Domenico; Melero, Ignacio; Melief, Cornelis J.; Mittendorf, Elizabeth A.; Moretta, Lorenzo; Odunsi, Adekunke; Okada, Hideho; Palucka, Anna Karolina; Peter, Marcus E.; Pienta, Kenneth J.; Porgador, Angel; Prendergast, George C.; Rabinovich, Gabriel A.; Restifo, Nicholas P.; Rizvi, Naiyer; Sautès-Fridman, Catherine; Schreiber, Hans; Seliger, Barbara; Shiku, Hiroshi; Silva-Santos, Bruno; Smyth, Mark J.; Speiser, Daniel E.; Spisek, Radek; Srivastava, Pramod K.; Talmadge, James E.; Tartour, Eric; Van Der Burg, Sjoerd H.; Van Den Eynde, Benoît J.; Vile, Richard; Wagner, Hermann; Weber, Jeffrey S.; Whiteside, Theresa L.; Wolchok, Jedd D.; Zitvogel, Laurence; Zou, Weiping

2014-01-01

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches. PMID:25537519

Systemic reactions during maintenance immunotherapy with honey bee venom.

PubMed

Bousquet, J; Ménardo, J L; Velasquez, G; Michel, F B

1988-07-01

Immunotherapy with hymenoptera venoms is safe and effective in most patients but treatment failures have been reported. Five patients experienced systemic symptoms of anaphylaxis when they were in maintenance immunotherapy with honey bee venom. In one case, the patient presented a severe life-threatening reaction when stung by a honey bee. Three others had the development of new clinical sensitivity suggesting a re-sensitization. This occurred in the fifth patient after a severe viral infection. By means of a rush protocol and monthly doses of 200 to 400 micrograms of honey bee venom, the patients were subsequently protected efficiently. In most cases these reactions might have been predicted since patients experienced large local reactions prior to the systemic reactions when allergens were injected. Further, in four cases there was an increased skin test reactivity or raised serum honey bee venom IgE levels or both. In all patients, the levels of serum honey bee venom IgG was under 200 U/mL (IgG Pharmacia RAST).

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

An adjuvant free mouse model of oral allergenic sensitization to rice seeds protein

PubMed Central

2011-01-01

Background Rice is commonly known as a staple crop consumed worldwide, though with several rice proteins being reported for allergic properties in clinical studies. Thus, there is a growing need for the development of an animal model to better understand the allergenicity of rice proteins and the immunological and pathophysiological mechanisms underlying the development of food allergy. Methods Groups of BALB/c mice were sensitized daily with freshly homogenized rice flour (30 mg or 80 mg) without adjuvant by intragastric gavage. In addition, the mice were challenged with extracted rice flour proteins at several time points intragastrically. Hypersensitivity symptoms in mice were evaluated according to a scoring system. Vascular leakage, ELISA of rice protein-specific IgE, histopathology of small intestine, and passive cutaneous anaphylaxis were conducted on challenged mice. Results An adjuvant free mouse model of rice allergy was established with sensitized mice showing increased scratching behaviors and increased vascular permeability. Rice protein-specific IgE was detected after eighteen days of sensitization and from the fifth challenge onwards. Inflammatory damage to the epithelium in the small intestine of mice was observed beyond one month of sensitization. Passive cutaneous anaphylaxis results confirmed the positive rice allergy in the mouse model. Conclusions We introduced a BALB/c mouse model of rice allergy with simple oral sensitization without the use of adjuvant. This model would serve as a useful tool for further analysis on the immunopathogenic mechanisms of the various rice allergens, for the evaluation of the hypersensitivity of rice or other cereal grains, and to serve as a platform for the development of immunotherapies against rice allergens. PMID:21605393

Allergen Sensitization Pattern by Sex: A Cluster Analysis in Korea.

PubMed

Ohn, Jungyoon; Paik, Seung Hwan; Doh, Eun Jin; Park, Hyun-Sun; Yoon, Hyun-Sun; Cho, Soyun

2017-12-01

Allergens tend to sensitize simultaneously. Etiology of this phenomenon has been suggested to be allergen cross-reactivity or concurrent exposure. However, little is known about specific allergen sensitization patterns. To investigate the allergen sensitization characteristics according to gender. Multiple allergen simultaneous test (MAST) is widely used as a screening tool for detecting allergen sensitization in dermatologic clinics. We retrospectively reviewed the medical records of patients with MAST results between 2008 and 2014 in our Department of Dermatology. A cluster analysis was performed to elucidate the allergen-specific immunoglobulin (Ig)E cluster pattern. The results of MAST (39 allergen-specific IgEs) from 4,360 cases were analyzed. By cluster analysis, 39items were grouped into 8 clusters. Each cluster had characteristic features. When compared with female, the male group tended to be sensitized more frequently to all tested allergens, except for fungus allergens cluster. The cluster and comparative analysis results demonstrate that the allergen sensitization is clustered, manifesting allergen similarity or co-exposure. Only the fungus cluster allergens tend to sensitize female group more frequently than male group.

The quest for bacterial allergens.

PubMed

Nordengrün, Maria; Michalik, Stephan; Völker, Uwe; Bröker, Barbara M; Gómez-Gascón, Lidia

2018-04-26

Allergies are complex diseases featuring local tissue inflammation, which is characterized by an exaggerated type 2 immune response to environmental compounds known as allergens. Pollens, environmental fungi, and house dust mites are examples of common allergens. Bacteria have a dual role in allergy. Usually, they are associated with protection, however, certain bacterial species promote the development and exacerbation of allergic inflammation. Notably, IgE antibodies specific for bacterial antigens are found in the sera of allergic individuals. This implies that some bacterial factors are allergens, eliciting a specific type 2 immune response. However, to date, only a few of these are molecularly defined. This review summarizes the current knowledge about known bacterial allergens, and it provides an overview of the available techniques for the discovery of new allergens as well as for measuring the immune responses directed against them. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Use of Humanized RS-ATL8 Reporter System for Detection of Allergen-Specific IgE Sensitization in Human Food Allergy.

PubMed

Ali, Eman Ali; Nakamura, Ryosuke; Falcone, Franco H

2017-01-01

Allergen-specific Immunoglobulin E (IgE) determination lies at the heart of diagnosis of sensitization to food and other allergens. In the past few years, reporter systems capable of detecting the presence of allergen-specific IgE have been developed by several labs. These rely on humanized rat basophil leukemia cell lines stably transfected with reporter genes such as firefly luciferase. In this chapter, we describe protocols for the use of the RS-ATL8 cell line (IgE cross-linking-induced luciferase expression; EXiLE) in 96-well and 384-well formats. We also describe optional treatment steps for enveloped virus and complement inactivation.

Hot Topics in Primary Care: Sublingual Immunotherapy: A Guide for Primary Care.

PubMed

Meltzer, Eli O

2017-04-01

Allergen immunotherapy (AIT), the only potential disease-modifying treatment for allergic disease, has been used for more than a century. Hankin et al showed significant reduction in pharmacy, outpatient, and inpatient resources in the 6 months following vs the 6 months preceding AIT in Medicaid-enrolled children with allergic rhinitis (AR). A 2013 analysis showed sustained cost reduction over 18 months in patients with AR treated with AIT compared with matched control subjects not treated with AIT.

Total and Toxocara canis larval excretory/secretory antigen- and allergen-specific IgE in atopic and non-atopic dogs.

PubMed

Zwickl, Lena L M N; Joekel, Deborah E; Fischer, Nina M; Rostaher, Ana; Thamsborg, Kristian; Deplazes, Peter; Favrot, Claude

2018-06-01

Total IgE concentrations are higher in dogs than in humans. Persistent Toxocara canis larval infection is prevalent in dogs and is associated with substantial specific antibody reactions. A correlation, however, between total IgE and T. canis-specific antibody levels in dogs has not been evaluated. To determine the relationship between total IgE, T. canis-specific IgG and IgE, and allergen-specific IgE levels in atopic and non-atopic dogs, and to evaluate possible confounding factors. Sera of 30 atopic and 30 non-atopic client-owned dogs. Total IgE, T. canis-specific antibody and allergen-specific IgE levels were evaluated by ELISA. Total IgE, T. canis-specific antibody and allergen-specific IgE levels were significantly higher in non-atopic compared to atopic dogs. A positive correlation was demonstrated between T. canis-specific IgG and T. canis-specific IgE; T. canis-specific IgG and total IgE; T. canis-specific IgE and total IgE; and allergen-specific IgE and total IgE. No differences were detected on the basis of age, gender, vaccination status; deworming or season between atopic and non-atopic dogs. Previous immunomodulatory treatment and cause of atopy did not influence antibody levels of atopic dogs. Toxocara canis-specific IgE appears to be a major component of total IgE in dogs. Total and T. canis-specific IgE levels are higher in non-atopic compared to atopic dogs. It is speculated that T. canis infection may have a protective effect against the development of canine atopic dermatitis and/or that elevations in total serum IgE level are often not associated with atopic dermatitis. © 2018 ESVD and ACVD.

Efficacy of sublingual specific immunotherapy on allergic asthma and rhinitis in children's real life.

PubMed

De Castro, G; Zicari, A M; Indinnimeo, L; Tancredi, G; di Coste, A; Occasi, F; Castagna, G; Giancane, G; Duse, M

2013-08-01

Sublingual-specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. We performed a case-control study to evaluate the effect of SLIT in children with allergic asthma and rhinitis. The study plan included 140 patients (age 6-14 yr, 43% girls and 57% boys) presenting allergic rhinitis and/or asthma, 70 treated with SLIT actively for three years and 70 controls never treated with specific immunotherapy (only symptomatic drugs). Rhinitis Symptom Score (RSS), Asthma Symptom Score (ASS) and Medication Score (MS) were evaluated at beginning and during the 3 years of immunotherapy. results: There was a significant improvement of RSS (mean ± SD) in the SLIT group: baseline 5.31 ± 2.01, third year 1.38 ± 1.06 (p < 0.0001 vs baseline). baseline 5.00 ± 1.08, third year 4.68 ± 1.152 (P ¼ NS). ASS (mean ± SD) in the SLIT group: baseline 4.09 ± 2.21, third year 1.23 ± 1.4 (p < 0.0001 vs baseline). baseline 4.04 ± 2.46, third year 3.62 ± 2.26 (p ¼ NS). MS (mean ± SD) in the SLIT group: baseline 3.30 ± 1.4, third year 0.88 ± 1.26 (p < 0.0001 vs baseline). baseline 3.19 ± 1.23, third year 3.39 ± 1.12 (p ¼ NS). There are no statistically significant differences among monosensitized/polysensitized patients and at different age ranges. None of the patients included reported severe systemic reactions or anaphylaxis. During the treatment, the active group showed sustained reductions in mean asthma and rhinitis symptom scores when compared with controls to confirm the efficacy and safety of sublingual immunotherapy.

[Cluster-immunotherapy in seasonal allergic rhinitis: safety aspects of induction therapy with depot allergoids (Purethal)].

PubMed

Hansen, I; Hörmann, K; Stuck, B A; Schneider-Gêne, S; Mösges, R; Klimek, L

2003-08-01

Specific immunotherapy (SIT) represents the only specific treatment that can be offered to allergic patients apart from allergen avoidance. SIT has been widely used in pollen allergic rhinitis. Clinical efficacy has been demonstrated in several controlled clinical trials and depends on the specific allergen the individual patient is sensitive to, the quality and total amount of allergen applied, and the SIT schedule. In classic SIT, gradually increasing dosages of the allergen extract are injected subcutaneously. Several dosage schedules for subcutaneous SIT can be applied. In Cluster-SIT, 2 - 3 injections per day of treatment are given once a week during induction treatment. In this study, we investigated 64 patients (33 female, 31 male) from 18 to 54 years (26.9 +/- 5.1 years) in terms of side-effects of Cluster-SIT during induction treatment. The total amount of enlarged local reactions (> grade 1) was n = 77 or 15.2 % of all injections. Of these, 68 (88 %) were classified as immediate reactions, 8 (11 %) were late phase reactions and 1 (1 %) was immediate as well as late phase reaction. Of all enlarged local reactions, 48 (62 %) were grade 1 reactions, 13 (17 %) were grade 2 reactions, 13 (17 %) were grade 3 reactions and 1 (1 %) was a grade 4 reaction. The total amount of systemic reactions was n = 22 or 4.3 % of all injections. Of these, 19 (86 %) were classified as immediate reactions, 3 (14 %) were delayed reactions. Of all systemic reactions, 18 (82 %) were grade 1 reactions and 4 (18 %) grade 2 reactions. Grade 3 or grade 4 reactions did not occur. There were no differences in gender or age regarding the occurrence of side effects (all p > 0.05). Frequency and severity of adverse side effects in Cluster-SIT correspond to those in other dosage schedules. On behalf of security aspects, Cluster-SIT could become an interesting alternative dosage schedule for dose increase during SIT. Furthermore, in Cluster-SIT with allergoids, induction treatment can be

Clinical relevance is associated with allergen-specific wheal size in skin prick testing

PubMed Central

Haahtela, T; Burbach, G J; Bachert, C; Bindslev-Jensen, C; Bonini, S; Bousquet, J; Bousquet-Rouanet, L; Bousquet, P J; Bresciani, M; Bruno, A; Canonica, G W; Darsow, U; Demoly, P; Durham, S R; Fokkens, W J; Giavi, S; Gjomarkaj, M; Gramiccioni, C; Kowalski, M L; Losonczy, G; Orosz, M; Papadopoulos, N G; Stingl, G; Todo-Bom, A; von Mutius, E; Köhli, A; Wöhrl, S; Järvenpää, S; Kautiainen, H; Petman, L; Selroos, O; Zuberbier, T; Heinzerling, L M

2014-01-01

Background Within a large prospective study, the Global Asthma and Allergy European Network (GA2LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. Objective To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. Methods The GA2LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. Results Depending on the allergen, from 40% (blatella) to 87–89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. Conclusion These ‘reading keys’ for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use. PMID:24283409

Characteristic motifs for families of allergenic proteins

PubMed Central

Ivanciuc, Ovidiu; Garcia, Tzintzuni; Torres, Miguel; Schein, Catherine H.; Braun, Werner

2008-01-01

The identification of potential allergenic proteins is usually done by scanning a database of allergenic proteins and locating known allergens with a high sequence similarity. However, there is no universally accepted cut-off value for sequence similarity to indicate potential IgE cross-reactivity. Further, overall sequence similarity may be less important than discrete areas of similarity in proteins with homologous structure. To identify such areas, we first classified all allergens and their subdomains in the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/) to their closest protein families as defined in Pfam, and identified conserved physicochemical property motifs characteristic of each group of sequences. Allergens populate only a small subset of all known Pfam families, as all allergenic proteins in SDAP could be grouped to only 130 (of 9318 total) Pfams, and 31 families contain more than four allergens. Conserved physicochemical property motifs for the aligned sequences of the most populated Pfam families were identified with the PCPMer program suite and catalogued in the webserver Motif-Mate (http://born.utmb.edu/motifmate/summary.php). We also determined specific motifs for allergenic members of a family that could distinguish them from non-allergenic ones. These allergen specific motifs should be most useful in database searches for potential allergens. We found that sequence motifs unique to the allergens in three families (seed storage proteins, Bet v 1, and tropomyosin) overlap with known IgE epitopes, thus providing evidence that our motif based approach can be used to assess the potential allergenicity of novel proteins. PMID:18951633

Generalized pustular psoriasis - A model disease for specific targeted immunotherapy, systematic review.

PubMed

Boehner, Alexander; Navarini, Alexander A; Eyerich, Kilian

2018-05-31

Generalized pustular psoriasis (GPP) psoriasis is a rare, multisystemic skin disease characterized by recurrent episodes of pustulation. GPP can be life-threatening and is often difficult to treat. In the era of precision medicine in dermatology, GPP stands exemplary for both challenges and chances - while new treatments offer great hope, there is urgent need for better definition and stratification of this severe and heterogeneous disease. Our objective was to systematically review the literature for evidence of efficacy of targeted immunotherapy and their mode of action in the context of clinical phenotype, classification and pathogenesis of adult GPP. Classifying GPP is challenging since clinical criteria for description and diagnosis are not consistent between expert centers. We therefore defined diagnostic feasibility of the reviewed cases by assessing four criteria: compatible clinical history, typical dermatological features and/or diagnostic histopathology, consistent clinical pictures and the DITRA status. Pathogenesis of GPP is mediated by pathways that partly overlap plaque type psoriasis, with a more pronounced activity of the innate immune system. Both IL-1 and IL-36 but also IL-17 play a major role in disease formation. We ascertained a total of 101 published cases according to our predefined criteria and identified TNF-α, IL-12/23, IL-17 and IL-1β as targets for immunotherapy for the treatment of GPP. Of those cases, 61% showed complete response and 27% partial response to targeted immunotherapy. Only 12% experienced weak or no response. These data indicate that specific immunotherapy can be used to effectively treat GPP, with most evidence existing for anti-IL-17 agents. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

DNA-based approaches to the treatment of allergies.

PubMed

Spiegelberg, Hans L; Raz, Eyal

2002-02-01

Although excellent pharmacological treatments for allergies exist, they do not change the underlying pathogenesis of allergic diseases and do not cure the disease. Only allergen-specific immunotherapy, the injection of small but increasing amounts of allergen, has been shown to change a pre-existing allergic Th2 immune response to a non-allergic Th1 response. However, since injection of allergen is associated with the risk of allergic and sometimes even life-threatening anaphylactic reactions, immunotherapy is no longer used as extensively as in the past. In the search for a novel immunotherapy having a low risk-to-benefit ratio, immunostimulatory CpG motif DNA sequences have recently been shown to provide an excellent tool for designing safer and more efficient forms of allergen immunotherapy. These DNA-based immunotherapeutics include allergen gene vaccines, immunization with allergen-DNA conjugates and immunomodulation with immunostimulatory oligodeoxynucleotides. All three DNA-based immunotherapeutics have been shown to be very effective in animal models of allergic diseases and, at present, allergen-DNA conjugates are being tested for their safety and efficacy in allergic patients. This review describes the preclinical findings and the data of the first clinical trials in allergic patients of DNA-based immunotherapeutics for allergic disorders.

Clinical relevance is associated with allergen-specific wheal size in skin prick testing.

PubMed

Haahtela, T; Burbach, G J; Bachert, C; Bindslev-Jensen, C; Bonini, S; Bousquet, J; Bousquet-Rouanet, L; Bousquet, P J; Bresciani, M; Bruno, A; Canonica, G W; Darsow, U; Demoly, P; Durham, S R; Fokkens, W J; Giavi, S; Gjomarkaj, M; Gramiccioni, C; Kowalski, M L; Losonczy, G; Orosz, M; Papadopoulos, N G; Stingl, G; Todo-Bom, A; von Mutius, E; Köhli, A; Wöhrl, S; Järvenpää, S; Kautiainen, H; Petman, L; Selroos, O; Zuberbier, T; Heinzerling, L M

2014-03-01

Within a large prospective study, the Global Asthma and Allergy European Network (GA(2) LEN) has collected skin prick test (SPT) data throughout Europe to make recommendations for SPT in clinical settings. To improve clinical interpretation of SPT results for inhalant allergens by providing quantitative decision points. The GA(2) LEN SPT study with 3068 valid data sets was used to investigate the relationship between SPT results and patient-reported clinical relevance for each of the 18 inhalant allergens as well as SPT wheal size and physician-diagnosed allergy (rhinitis, asthma, atopic dermatitis, food allergy). The effects of age, gender, and geographical area on SPT results were assessed. For each allergen, the wheal size in mm with an 80% positive predictive value (PPV) for being clinically relevant was calculated. Depending on the allergen, from 40% (blatella) to 87-89% (grass, mites) of the positive SPT reactions (wheal size ≥ 3 mm) were associated with patient-reported clinical symptoms when exposed to the respective allergen. The risk of allergic symptoms increased significantly with larger wheal sizes for 17 of the 18 allergens tested. Children with positive SPT reactions had a smaller risk of sensitizations being clinically relevant compared with adults. The 80% PPV varied from 3 to 10 mm depending on the allergen. These 'reading keys' for 18 inhalant allergens can help interpret SPT results with respect to their clinical significance. A SPT form with the standard allergens including mm decision points for each allergen is offered for clinical use. © 2013 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Advanced generation anti-prostate specific membrane antigen designer T cells for prostate cancer immunotherapy.

PubMed

Ma, Qiangzhong; Gomes, Erica M; Lo, Agnes Shuk-Yee; Junghans, Richard P

2014-02-01

Adoptive immunotherapy by infusion of designer T cells (dTc) engineered with chimeric antigen receptors (CARs) for tumoricidal activity represents a potentially highly specific modality for the treatment of cancer. In this study, 2nd generation (gen) anti-prostate specific membrane antigen (PSMA) dTc were developed for improving the efficacy of previously developed 1st gen dTc for prostate cancer immunotherapy. The 1st gen dTc are modified with chimeric immunoglobulin-T cell receptor (IgTCR) while the 2nd gen dTc are engineered with an immunoglobulin-CD28-T cell receptor (IgCD28TCR), which incorporates a CD28 costimulatory signal for optimal T cell activation. A 2nd gen anti-PSMA IgCD28TCR CAR was constructed by inserting the CD28 signal domain into the 1st gen CAR. 1st and 2nd gen anti-PSMA dTc were created by transducing human T cells with anti-PSMA CARs and their antitumor efficacy was compared for specific activation on PSMA-expressing tumor contact, cytotoxicity against PSMA-expressing tumor cells in vitro, and suppression of tumor growth in an animal model. The 2nd gen dTc can be optimally activated to secrete larger amounts of cytokines such as IL2 and IFNγ than 1st gen and to proliferate more vigorously on PSMA-expressing tumor contact. More importantly, the 2nd gen dTc preserve the PSMA-specific cytotoxicity in vitro and suppress tumor growth in animal models with significant higher potency. Our results demonstrate that 2nd gen anti-PSMA designer T cells exhibit superior antitumor functions versus 1st gen, providing a rationale for advancing this improved agent toward clinical application in prostate cancer immunotherapy. © 2013 Wiley Periodicals, Inc.

Evaluation of stability of allergen extracts for sublingual immunotherapy during transport under unfavourable temperature conditions with an innovative thermal insulating packaging.

PubMed

Puccinelli, P; Natoli, V; Dell'albani, I; Scurati, S; Incorvaia, C; Barbieri, S; Masieri, S; Frati, F

2013-10-01

Many pharmaceutical and biotechnological products are temperature-sensitive and should normally be kept at a controlled temperature, particularly during transport, in order to prevent the loss of their stability and activity. Therefore, stability studies should be performed for temperature-sensitive products, considering product characteristics, typical environmental conditions, and anticipating environmental extremes that may occur during product transport in a specific country. Staloral products for sublingual immunotherapy are temperature sensitive and are labelled for maintenance under refrigerated conditions (2-8°C). Given the peculiar climatic context of Italy and the great temperature fluctuations that may occur during transport, this study was aimed at evaluating the impact of a new engineered thermal insulating packaging for Staloral. In particular, the purpose was to assess whether the new packaging could create a container condition able to preserve the stability and immunological activity of the product during the transport phase throughout Italy. The results showed that the range of temperatures that can affect the product, in the area surrounding the product packaging, may reach a peak of 63°C during transport under the most unfavourable climatic conditions, i.e. in a non-refrigerated van during the summer season, from the site of production in France to the patient's house in Catania, the city with the highest temperatures in Italy. However, the highest temperature reached inside the vaccine did not exceed 45°C over a period of about 2 h. The ELISA inhibition test on samples subjected to the extreme temperature conditions previously defined (45°C) showed an immunological activity higher than 75% of that initially measured and was comparable to those obtained with samples stored at controlled temperature (5°C). This means that, even in the worst case scenario, the structure of the allergen extracts is not influenced and the vaccine potency is

Macrophages induce an allergen-specific and long-term suppression in a mouse asthma model.

PubMed

Vissers, J L M; van Esch, B C A M; Hofman, G A; van Oosterhout, A J M

2005-12-01

Increasing evidence suggests that macrophages (Mphi) play a crucial downregulatory role in the initiation and progression of allergic asthma. Recently, the current authors demonstrated that ovalbumin (OVA)-loaded Mphi (OVA-Mphi) suppress subsequent OVA-induced airway manifestations of asthma and that this effect could be potentiated upon selective activation. In the present study, the authors further delineated the underlying pathway by which Mphi exert this immunosuppressive effect. To examine the migration of OVA-Mphi, cells were labelled with 5'chloromethylfluorescein diacetate (CMFDA) and were administered (i.v.) into OVA-sensitised BALB/c mice. After 20 h, the relevant organs were dissected and analysed using fluorescent microscopy. Allergen-specificity was investigated by treating OVA-sensitised mice with keyhole limpet haemocyanin (KLH)-Mphi activated with immunostimulatory sequence oligodeoxynucleotide (ISS-ODN). By lengthening the period between treatment and challenge to 4 weeks it was examined whether OVA-Mphi exerted an immunosuppressive memory response. Strikingly, CMFDA-labelled Mphi were not trapped in the lungs, but migrated to the spleen. ISS-ODN-stimulated KLH-Mphi failed to suppress OVA-induced airway manifestations of asthma. Moreover, treatment with ISS-ODN-stimulated OVA-Mphi was still effective after lengthening the period between treatment and challenge. These data demonstrate that allergen-loaded macrophages can induce an indirect immunosuppressive response that is allergen-specific and long lasting, which are both hallmarks of a memory lymphocyte response.

Health economic analysis of allergen immunotherapy for the management of allergic rhinitis, asthma, food allergy and venom allergy: A systematic overview.

PubMed

Asaria, M; Dhami, S; van Ree, R; Gerth van Wijk, R; Muraro, A; Roberts, G; Sheikh, A

2018-02-01

The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost-effectiveness of AIT for these conditions. We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations. Twenty-three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost-effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost-effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost-effectiveness threshold of £20 000/quality-adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost-effective with an incremental cost-effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling

Update on equine allergies.

PubMed

Fadok, Valerie A

2013-12-01

Horses develop many skin and respiratory disorders that have been attributed to allergy. These disorders include pruritic skin diseases, recurrent urticaria, allergic rhinoconjunctivitis, and reactive airway disease. Allergen-specific IgE has been detected in these horses, and allergen-specific immunotherapy is used to ameliorate clinical signs. The best understood atopic disease in horses is insect hypersensitivity, but the goal of effective treatment with allergen-specific immunotherapy remains elusive. In this review, updates in pathogenesis of allergic states and a brief mention of the new data on what is known in humans and dogs and how that relates to equine allergic disorders are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

The clinical efficacy of in vitro allergen-specific IgE antibody test in the diagnosis of allergic children with asthma.

PubMed

Chou, Tzn-Yu; Wu, Kuo-Yao; Shieh, Chi-Chang; Wang, Jiu-Yao

2002-01-01

Asthma is a very common respiratory allergic disease in Taiwan. The aims of this study were to investigate the allergen-sensitized profile and its relationship with serum total IgE levels in allergic asthmatic children in Taiwan. Moreover, the number of allergens to be tested for the most efficient and effective diagnosis of allergic diseases was also examined. Total IgE and IgE specific for a panel of common aeroallergens were assayed in 200 serum samples of asthmatic children using Pharmacia CAP system (Pharmacia, Uppsala, Sweden). House dust mites Der p (Dermatophagoides pteronyssinus), Der f (Dermatophagoides farinae), and Bt (Blomia Tropicalis) had the highest sensitized rates at 82.5%, 82.0%, and 72%, respectively. Candida albican (14.0%) and Bermuda grass (8.0%) were the most common sensitized fungus and pollen in our subjects, respectively. The accumulated sensitized rate (10%) for pollens was lower than those of fungus (21.5%) and house dust allergens (84%). The average serum total IgE of the allergen-negative asthmatic children (n=30) was significantly lower than that of children with at least one allergen sensitized asthma (n=170) (377.9 +/- 123.6 vs. 1117.8 +/- 235.7 IU/ml, p<0.05). The level of total IgE was significantly correlated with the concentrations of mite-specific IgE antibodies, but not with the numbers of allergen sensitized. In addition, the detection rate was 84% when the 4 most common allergens (Der p, Der f, Dog dander, and cockroach) were tested, similar to the result after testing for all 12.

Cellular immunotherapy for malignant gliomas.

PubMed

Lin, Yi; Okada, Hideho

2016-10-01

Cancer immunotherapy has made much progress in recent years. Clinical trials evaluating a variety of immunotherapeutic approaches are underway in patients with malignant gliomas. Thanks to recent advancements in cell engineering technologies, infusion of ex vivo prepared immune cells have emerged as promising strategies of cancer immunotherapy. Herein, the authors review recent and current studies using cellular immunotherapies for malignant gliomas. Specifically, they cover the following areas: a) cellular vaccine approaches using tumor cell-based or dendritic cell (DC)-based vaccines, and b) adoptive cell transfer (ACT) approaches, including lymphokine-activated killer (LAK) cells, γδ T cells, tumor-infiltrating lymphocytes (TIL), chimeric antigen receptor (CAR)-T cells and T-cell receptor (TCR) transduced T cells. While some of the recent studies have shown promising results, the ultimate success of cellular immunotherapy in brain tumor patients would require improvements in the following areas: 1) feasibility in producing cellular therapeutics; 2) identification and characterization of targetable antigens given the paucity and heterogeneity of tumor specific antigens; 3) the development of strategies to promote effector T-cell trafficking; 4) overcoming local and systemic immune suppression, and 5) proper interpretation of imaging data for brain tumor patients receiving immunotherapy.

Bioavailability of House Dust Mite Allergens in Sublingual Allergy Tablets Is Highly Dependent on the Formulation.

PubMed

Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare

2017-01-01

In sublingual immunotherapy (SLIT), the immune system is addressed by solubilized allergen that interacts with immunocompetent cells of the oral mucosa, the efficiency of which is governed by 2 main factors of SLIT allergen bioavailability: the allergen concentration and the mucosal contact time. Recently, 3 house dust mite (HDM) SLIT tablets were developed that differ with regard to allergen content, nominal strength (maintenance doses: 6 SQ-HDM/10,000 Japanese Allergen Units [JAU], 12 SQ-HDM/ 20,000 JAU, and 300 IR/57,000 JAU), and formulation (freeze-dried/compressed). Here, the importance of the SLIT tablet formulation for HDM major allergen bioavailability is examined. The HDM major allergen content, tablet disintegration times, and allergen release kinetics were determined. Dissolution kinetics (allergen concentration vs. time) of Der f 1, Der p 1, and Der 2 were measured. Area under the curve (AUC) was used as a surrogate parameter for allergen bioavailability. The release of HDM major allergens from the freeze-dried tablets was complete after 30 s, while only partial release was achieved with the compressed tablets, even after prolonged dissolution. At 1 min, i.e., the recommended sublingual holding time for the freeze-dried tablets, the allergen bioavailability (AUC) of the compressed 300 IR/57,000 JAU tablet was 4.7-fold (Der f 1), 10.8-fold (Der p 1), and 23.6-fold (Der 2) lower than that of the freeze-dried 12 SQ-HDM/20,000 JAU tablet and similar to (Der f 1) and 5.3-fold (Der p 1) and 12.5-fold (Der 2) lower than that of the freeze-dried 6 SQ-HDM/10,000 JAU tablet. SLIT tablet allergen bioavailability depends highly on the tablet formulation. Only the fast-dissolving freeze-dried tablets provide maximal delivery of soluble allergens and achieve allergen concentrations that reflect the nominal tablet strengths within the recommended sublingual holding time. © 2017 S. Karger AG, Basel.

The prevalence and diagnostic value of specific IgE antibodies to inhalant, animal and plant food, and ficus allergens in patients with natural rubber latex allergy.

PubMed

Ebo, D G; Bridts, C H; Hagendorens, M M; De Clerck, L S; Stevens, W J

2003-01-01

It is well recognised that natural rubber latex allergy can be associated with serological cross-reactivity to plant allergens, especially tropical fruits and Ficus. In contrast, data on the frequency and clinical value of specific IgE antibodies against these allergens remain rare. In addition, little is known about the prevalence and diagnostic value of specific IgE antibodies to classical inhalant and animal allergens in NRL allergic patients. The purpose of this study was to investigate the prevalence, the sensitivity, and the specificity of these different specific IgE antibodies in patients suffering from NRL allergy. Serum samples of 42 NRL allergic adults were investigated. All had a history of NRL allergy confirmed by a positive skin test for latex and a positive latex-specific IgE. Samples were analysed for IgE antibodies against 9 plant food allergens (avocado, banana, chestnut, fig, kiwi, papaya, peanut, pineapple and tomato) and Ficus benjamina. A specific IgE quantification for 3 animal food allergens (codfish, cow's milk, egg's white) and 8 common inhalant allergens (Dermatophagoïdes pteronyssinus, birch pollen, timothy grass pollen, mugwort pollen, cat and dog epithelium, Aspergillus fumigatus and Cladosporium herbarum) was also performed. Because double blind placebo-controlled challenges could not be considered, for ethical reasons, patient's food allergy or immediate hypersensitivity for Ficus and inhalant allergens was documented by a standardised questionnaire. Diagnosis of atopy was based on a relevant history and the presence of a specific IgE antibody to at least one classical inhalant allergen. For some IgE determinations presence or absence of cross-reactivity was investigated by CAP-inhibition tests. A specific IgE antibody to at least one of the investigated inhalant and animal food allergens was found in respectively 76% and 12% of the serum samples. A plant food-specific IgE antibody was observed in 88% of the serum samples, most

Sensitive and specific detection of potentially allergenic almond (Prunus dulcis) in complex food matrices by Taqman(®) real-time polymerase chain reaction in comparison to commercially available protein-based enzyme-linked immunosorbent assay.

PubMed

Röder, Martin; Vieths, Stefan; Holzhauser, Thomas

2011-01-24

Currently, causative immunotherapies are lacking in food allergy. The only option to prevent allergic reactions in susceptible individuals is to strictly avoid the offending food. Thus, reliable labelling of allergenic constituents is of major importance, but can only be achieved if appropriate specific and sensitive detection techniques for foods with allergenic potential are available. Almond is an allergenic food that requires mandatory labelling on prepackaged foods and belongs to the genus Prunus. Species of this genus are phylogenetically closely related. We observed commercially available almond specific ELISA being highly cross-reactive with other foods of the Prunoideae family, resulting in a false-positive detection of up to 500,000 mg kg(-1) almond. Previously published PCR methods were reported to be cross-reactive with false positive results >1200 mg kg(-1). We describe the development of a novel almond specific real-time PCR, based on mutated mismatch primers and sequence specific Taqman(®) probe detection, in comparison with two quantitative commercially available ELISA. PCR sensitivity was investigated with chocolate, chocolate coating and cookies spiked between 5 and 100,000 mg kg(-1) almond. In all matrices almond was reproducibly detected by real-time PCR at the lowest spike level of 5 mg kg(-1). Further, between 100 and 100,000 mg kg(-1) spiked almond, the method featured good correlation between quantified copy numbers and the amount of spiked almond. Within this range a similar relation between detectable signal and amount of almond was observed for both PCR and ELISA. In contrast to ELISA the Taqman(®) real-time PCR method was highly specific in 59 food items with negligible cross-reactivity for a very limited number of Prunoideae foods. The real-time PCR analysis of 24 retail samples was in concordance with ELISA results: 21% (n=5) contained undeclared almond. This is the first completely disclosed real-time PCR method for a specific and

Recombinant allergen-based IgE testing to distinguish bee and wasp allergy.

PubMed

Mittermann, Irene; Zidarn, Mihaela; Silar, Mira; Markovic-Housley, Zora; Aberer, Werner; Korosec, Peter; Kosnik, Mitja; Valenta, Rudolf

2010-06-01

The identification of the disease-causing insect in venom allergy is often difficult. To establish recombinant allergen-based IgE tests to diagnose bee and yellow jacket wasp allergy. Sera from patients with bee and/or wasp allergy (n = 43) and patients with pollen allergy with false-positive IgE serology to venom extracts were tested for IgE reactivity in allergen extract-based tests or with purified allergens, including nonglycosylated Escherichia coli-expressed recombinant (r) Api m 1, rApi m 2, rVes v 5, and insect cell-expressed, glycosylated rApi m 2 as well as 2 natural plant glycoproteins (Phl p 4, bromelain). The patients with venom allergy could be diagnosed with a combination of E coli-expressed rApi m 1, rApi m 2, and rVes v 5 whereas patients with pollen allergy remained negative. For a group of 29 patients for whom the sensitizing venom could not be identified with natural allergen extracts, testing with nonglycosylated allergens allowed identification of the sensitizing venom. Recombinant nonglycosylated allergens also allowed definition of the sensitizing venom for those 14 patients who had reacted either with bee or wasp venom extracts. By IgE inhibition studies, it is shown that glycosylated Api m 2 contains carbohydrate epitopes that cross-react with natural Api m 1, Ves v 2, natural Phl p 4, and bromelain, thus identifying cross-reactive structures responsible for serologic false-positive test results or double-positivity to bee and wasp extracts. Nonglycosylated recombinant bee and wasp venom allergens allow the identification of patients with bee and wasp allergy and should facilitate accurate prescription of venom immunotherapy. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

High correlation of specific IgE sensitization between birch pollen, soy and apple allergens indicates pollen-food allergy syndrome among birch pollen allergic patients in northern China.

PubMed

Hao, Guo-Dong; Zheng, Yi-Wu; Wang, Zhi-Xiang; Kong, Xing-Ai; Song, Zhi-Jing; Lai, Xu-Xin; Spangfort, Michael D

2016-05-01

Birch pollen sensitization and associated pollen-food syndrome among Chinese allergic patients have not been investigated. Sera from 203 allergic patients from the northern part of China and collected during February to July 2014 were investigated. Specific immunoglobulin E (IgE) against birch pollen extract Bet v and major birch pollen allergen Bet v 1 were measured using the ADVIA Centaur. The presence of major apple allergen Mal d 1 and soy bean allergen Gly m 4 specific IgE was measured by ImmunoCAP 100. Among the 203 sera, 34 sera (16.7%) had specific IgE to Bet v and of these, 28 sera (82.4%) contained Bet v 1-specific IgE. Among the 28 sera with Bet v 1-specific IgE, 27 sera (96.4%) contained Mal d 1-specific IgE and 22 sera (78.6%) contained Gly m 4-specific IgE. Of the 34 Bet v-positive sera, 6 sera (17.6%) contained no specific IgE for Bet v 1, Mal d 1, or Gly m 4. Almost all Bet v-positive sera were donated during the birch pollen season. The prevalence of birch allergy among patients visiting health care during pollen season can be as high as 16.7% in Tangshan City. The majority of Chinese birch allergic patients are IgE-sensitized to the major birch pollen allergen Bet v 1 as well as to the major apple allergen Mal d 1 and soy bean allergen Gly m 4. A relatively high number of patients (17.6%) are IgE-sensitized to birch pollen allergen(s) other than Bet v 1. The high prevalence of specific IgE to Mal d 1 and Gly m 4 among Bet v 1-sensitized patients indicates that pollen-food allergy syndrome could be of clinical relevance in China.

Allergenically active components of cat allergen extracts.

PubMed

Anderson, M C; Baer, H

1981-09-01

The allergens involved in cat allergy have been studied in pelt extracts, saliva, serum, and urine. Using crossed immunoelectrophoresis (CIE) to examine the antigenic content, and crossed radioimmunoelectrophoresis (CRIE) and RAST to examine the allergenic content, it was found that allergen 1 of Dr. Ohman is the most important allergenic component, whereas albumin and several unidentified proteins play a minor role. Allergen 1 was not detectable in serum and urine. The allergenic and nonallergenic proteins of pelt extract and saliva were identical by CIE, suggesting that pelt extract proteins are mainly of salivary origin.

Immunotherapy for cow's milk allergy

PubMed Central

Takahashi, Masaya; Soejima, Kazukiko; Hatano, Yasuko; Minami, Hirotaka