Bavishi, Aakash A; Grammer, Leslie C; Pongracic, Jacqueline; Rychlik, Karen; Kumar, Rajesh; Zee, Phyllis; Greenberger, Paul A; Fishbein, Anna B
Circadian rhythms underlie many immune responses and allergic diseases. Subcutaneous immunotherapy (SCIT) can result in adverse reactions; however, it is unclear whether such reactions have a diurnal pattern. To assess whether the timing of SCIT affects the rate of adverse reactions. This study was a retrospective medical record review of adult patients (n = 289) who received SCIT at the Northwestern Medical Faculty Foundation, Chicago, Illinois, during a 10-year period (2004-2014). Injections were given in the outpatient setting. There were a total of 17,457 injections with 574 reactions. Covariates included age, sex, median income, asthma status, vial contents, number of injections, and previous immunotherapy reactions. Logistical regression was used to calculate the odds of having a reaction with time of SCIT administration as the primary determinate. Immunotherapy reactions occurred more frequently after afternoon or evening (pm) injections (328/8721 = 3.8%) vs morning (am) injections (246/8736 = 2.8%), (χ2 = 12.26, P < .01). Systemic reactions, defined as World Allergy Organization grade 1 or higher, did not have diurnal variation (59/8721 = 0.67% for pm vs am 56/8736 = 0.64% for morning; χ2 = 0.08; P = .77). pm injections resulted in higher odds of reaction compared with am injection in a fully adjusted logistic regression model (odds ratio = 1.43; 95% confidence interval, 1.20-1.70; P < .01). When considering time as 4 categories, the highest odds of reaction were noted for the period from 15:01 to 17:30 (odds ratio, 1.55; 95% confidence interval, 1.21-2.00; P < .01). pm injections of SCIT are associated with increased cutaneous reaction rates when compared with am injections. In patients experiencing bothersome local reactions, it may be beneficial to administer SCIT in the morning. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Khinchi, M S; Poulsen, Lars K.; Carat, F
Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed.......Both sublingual allergen-specific immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) have a documented clinical efficacy, but only few comparative studies have been performed....
Aasbjerg, K; Backer, V; Lund, G
BACKGROUND: IgE-mediated allergic rhinitis to grass pollen can successfully be treated with either allergen immunotherapy tablets (SLIT tablet) or SQ-standardized subcutaneous immunotherapy (SCIT). The efficacy of these two treatment modalities for grass allergy is comparable, but the immunological...
Sahin, E; Dizdar, D; Dinc, M E; Cirik, A A
Allergic rhinitis is strongly associated with the presence of house dust mites. This study investigated the long-term effects of allergen-specific immunotherapy. Allergen-specific immunotherapy was applied over three years. The study was based on a 10-year follow up of patients with allergic rhinitis. The study was conducted between 2001 and 2015. Skin prick test results and symptom scores were evaluated before (26 patients) and after 3 years (20 patients) of allergen-specific immunotherapy (using data from a previously published study), and 10 years after allergen-specific immunotherapy had ended (20 of 26 patients). The symptom scores before allergen-specific immunotherapy were significantly higher than those obtained after 3 years of allergen-specific immunotherapy and 10 years after allergen-specific immunotherapy (p 0.0175). Subcutaneous immunotherapy is an effective treatment for house dust mite induced allergic rhinitis.
Schulten, Véronique; Tripple, Victoria; Andersen, Kristian Aasbjerg
BACKGROUND: Allergen-specific immunotherapy is the only curative treatment for type I allergy. It can be administered subcutaneously (SCIT) or sublingually (SLIT). The clinical efficacy of these two treatment modalities appears to be similar, but potential differences in the immunological...... mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen allergic patients were randomized into groups receiving either SCIT...... was observed starting 10 months after treatment was commenced. At 24 months, T cell responses showed IL-5 levels significantly below the before treatment baseline. No significant reduction of IL-5 was observed in the SLIT or untreated group. However, a significant transient increase in IL-10 production after...
Schulten, Véronique; Tripple, Victoria; Andersen, Kristian Aasbjerg
mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous versus sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen allergic patients were randomized into groups receiving either SCIT......: The most dominant immunological changes on a cellular level was a decrease in IL-5 in the SCIT group and a significant, transient increase of IL-10 observed after 10 months of treatment in both treated groups. The distinct routes of AIT administration may induce different immune-modulatory mechanisms...
... efficacy in asthmatic patients. Herein, the immunoregulatory mechanisms underlying the beneficial effects of SIT are discussed with the ultimate aim to improve its treatment efficacy. Keywords: allergic asthma; immunotherapy; dendritic cell; regulatory T cells; Th2 lymphocytes; hyperresponsiveness; eosinophilia; IgE; IL-10 ...
Mahdy, Reda Abdel Rahman; Nada, Waled M; Marei, Ayman A
The study evaluated the treatment of cases with vernal keratoconjunctivitis by subcutaneous allergen-specific immunotherapy (SCIT) versus topical treatment according to clinical improvement and total serum immunoglobulin (Ig) E. Prospective randomized study. The study included 64 patients with bilateral vernal keratoconjunctivitis. Cases were divided into 2 groups: group 1, 32 patients who were subjected to topical treatment; and group 2, 32 patients who were subjected to intradermal skin reactions to different allergens. Prepared subcutaneous injections of different allergens were administered. Follow-up was performed to detect criteria of improvement according to clinical data and total serum IgE. The study revealed that the treatment by SCIT was more effective in improving the clinical symptoms and reducing the serum IgE than topical treatment because there was a greater reduction in symptoms in group 1 of immunotherapy (72%) than in group 2 of medical treatment (59%) (P vernal keratoconjunctivitis by SCIT was more effective than topical treatment in improving the clinical symptoms and reducing the total serum IgE.
Meadows, A.; Kaambwa, B.; Novielli, N.; Huissoon, A.; Fry-Smith, A; Meads, C; P. Barton; Dretzke, J
© Queen’s Printer and Controller of HMSO 2013 Severe allergic rhinitis uncontrolled by conventional medication can substantially affect quality of life. Immunotherapy involves administering increasing doses of a specific allergen, with the aim of reducing sensitivity and symptomatic reactions. Recent meta-analyses have concluded that both subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are more effective than placebo in reducing symptoms. It is uncertain which route o...
Calderón, M A; Simons, F E R; Malling, Hans-Jørgen
-presenting cells (mostly Langerhans and myeloid dendritic cells) exhibit a tolerogenic phenotype, despite constant exposure to danger signals from food and microbes. This reduces the induction of pro-inflammatory immune responses leading to systemic allergic reactions. Oral tissues contain relatively few mast......To cite this article: Calderón MA, Simons FER, Malling H-J, Lockey RF, Moingeon P, Demoly P. Sublingual allergen immunotherapy: mode of action and its relationship with the safety profile. Allergy 2012; 67: 302-311. ABSTRACT: Allergen immunotherapy reorients inappropriate immune responses...... in allergic patients. Sublingual allergen immunotherapy (SLIT) has been approved, notably in the European Union, as an effective alternative to subcutaneous allergen immunotherapy (SCIT) for allergic rhinitis patients. Compared with SCIT, SLIT has a better safety profile. This is possibly because oral antigen...
Levin, Mattias; King, Jasmine J.; Glanville, Jacob; Jackson, Katherine J. L.; Looney, Timothy J.; Hoh, Ramona A.; Mari, Adriano; Andersson, Morgan; Greiff, Lennart; Fire, Andrew Z.; Boyd, Scott D.; Ohlin, Mats
Background Specific immunotherapy (SIT) is the only treatment with proven long-term curative potential in allergic disease. Allergen-specific IgE is the causative agent of allergic disease, and antibodies contribute to SIT, but the effects of SIT on aeroallergen-specific B cell repertoires are not well understood. Objective To characterize the IgE sequences expressed by allergen-specific B cells, and track the fate of these B cell clones during SIT. Methods We have used high-throughput antibody gene sequencing and identification of allergen-specific IgE using combinatorial antibody fragment library technology to analyze immunoglobulin repertoires of blood and nasal mucosa of aeroallergen-sensitized individuals before and during the first year of subcutaneous SIT. Results Of 52 distinct allergen-specific IgE heavy chains from eight allergic donors, 37 were also detected by high-throughput antibody gene sequencing of blood, nasal mucosa, or both sample types. The allergen-specific clones had increased persistence, higher likelihood of belonging to clones expressing other switched isotypes, and possibly larger clone size than the rest of the IgE repertoire. Clone members in nasal tissue showed close mutational relationships. Conclusion Combining functional binding studies, deep antibody repertoire sequencing, and information on clinical outcomes in larger studies may in the future aid assessment of SIT mechanisms and efficacy. PMID:26559321
Linneberg, Allan; Jacobsen, Rikke Kart; Jespersen, Lasse
Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease. Little is known about potential effects of SCIT on the risk of other chronic immune-related diseases. Over the years, a few casuistic reports have caused concern that SCIT might ac...... as a trigger of autoimmune disease.......Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease. Little is known about potential effects of SCIT on the risk of other chronic immune-related diseases. Over the years, a few casuistic reports have caused concern that SCIT might act...
Kramer, Matthias F; Heath, Matthew D
We are living in an "aluminium age" with increasing bioavailability of the metal for approximately 125 years, contributing significantly to the aluminium body burden of humans. Over the course of life, aluminium accumulates and is stored predominantly in the lungs, bones, liver, kidneys and brain. The toxicity of aluminium in humans is briefly summarised, highlighting links and possible causal relationships between a high aluminium body burden and a number of neurological disorders and disease states. Aluminium salts have been used as depot-adjuvants successfully in essential prophylactic vaccinations for almost 100 years, with a convincing positive benefit-risk assessment which remains unchanged. However, allergen-specific immunotherapy commonly consists of administering a long-course programme of subcutaneous injections using preparations of relevant allergens. Regulatory authorities currently set aluminium limits for vaccines per dose, rather than per treatment course. Unlike prophylactic vaccinations, numerous injections with higher proportions of aluminium-adjuvant per injection are applied in subcutaneous immunotherapy (SCIT) and will significantly contribute to a higher cumulative life dose of aluminium. While the human body may cope robustly with a daily aluminium overload from the environment, regulatory cumulative threshold values in immunotherapy need further addressing. Based on the current literature, predisposing an individual to an unusually high level of aluminium, such as through subcutaneous immunotherapy, has the potential to form focal accumulations in the body with the propensity to exert forms of toxicity. Particularly in relation to longer-term health effects, the safety of aluminium adjuvants in immunotherapy remains unchallenged by health authorities - evoking the need for more consideration, guidance, and transparency on what is known and not known about its safety in long-course therapy and what measures can be taken to prevent or
Linneberg, Allan; Jacobsen, Rikke Kart; Jespersen, Lasse
Subcutaneous allergen-specific immunotherapy (SCIT) is a well-documented treatment of IgE-mediated allergic disease. Little is known about potential effects of SCIT on the risk of other chronic immune-related diseases. Over the years, a few casuistic reports have caused concern that SCIT might act...
Kim, Myoung-Eun; Kim, Jeong-Eun; Sung, Joon-Mo; Lee, Jin-Woo; Choi, Gil-Soon; Nahm, Dong-Ho
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.
Nahm, Dong Ho; Kim, Myoung Eun; Kwon, Byul; Cho, Su Mi; Ahn, Areum
The clinical usefulness of subcutaneous allergen immunotherapy (SCIT) in the treatment of atopic dermatitis (AD) is still controversial. We analyzed the clinical efficacy of SCIT in patients with AD and the clinical characteristics of patients showing a favorable clinical response to the treatment. Two hundred and fifty one patients with AD sensitized to house dust mite (HDM) were treated by SCIT using HDM extract. The clinical severity of AD was measured using the standardized clinical severity scoring system for AD (SCORAD) at baseline and 12 months. A favorable clinical response to SCIT was defined as a decrease in SCORAD value at 12 months greater than 50% compared to baseline value. Severe AD was defined as a baseline SCORAD value above 50. A favorable clinical response to SCIT was observed in 73.6% of patients. The proportion of patients showing a favorable clinical response to SCIT was significantly higher in patients with severe AD (90.6%) than patients with mild to moderated AD (63.7%) (p<0.001). Patients with severe AD showing a favorable clinical response had a significantly shorter duration of AD (12.3±8.5 years; mean±SD) than patients with severe AD showing no significant clinical response (20.6±10.9 years) (p<0.05) at baseline. SCIT could be a clinically useful therapeutic option for patients with severe AD sensitized to HDM. Early initiation of SCIT might provide a favorable clinical outcome in patients with severe AD sensitized to HDM.
Novak, Natalija; Bieber, Thomas; Hoffmann, Matthias; Fölster-Holst, Regina; Homey, Bernhard; Werfel, Thomas; Sager, Angelika; Zuberbier, Torsten
Exposure to house dust mites (HDMs) aggravates the course of atopic dermatitis (AD) in patients sensitized to HDMs. This study investigated the efficacy and safety of subcutaneous allergen-specific immunotherapy with the use of depigmented polymerized mite extract as an add-on therapy to basic (ie, topical and, as necessary, systemic) medication. Patients (n = 168) were recruited in a randomized, double-blind, placebo-controlled parallel group phase III study conducted in Germany (21 sites), in adult patients with AD aggravated by HDMs. The primary end points of the study were the assessments of the area under the curves of the total Severity Scoring Atopic Dermatitis (SCORAD) score and of the use of basic medication during the 18-month treatment period. Post hoc subgroup analyses were also performed. Overall efficacy analysis of the intention-to-treat and per-protocol study populations showed no statistically significant differences between the active treatment and placebo groups. However, the subgroup of patients with severe AD (SCORAD > 50) showed a statistically significant reduction of the median total SCORAD by 18% (P = .02) compared with placebo. The frequency of adverse reactions was similar in both groups, suggesting the safety of the active treatment. Although subcutaneous allergen-specific immunotherapy showed no statistically significant difference in the overall population of patients with AD, statistically significant reduction of the total SCORAD could be achieved in a subgroup of patients with severe AD. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Full Text Available Specific allergen immunotherapy (SIT is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases.
Feng, Shaoyan; Xu, Ying; Ma, Renqiang; Sun, Yueqi; Luo, Xi; Li, Huabin
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. 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. 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. 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.
importance as the allergen that is most often implicated as a trigger for asthma and perennial allergic rhinitis on aworldwide basis. Numerous studies have demonstrated the efficacy of subcutaneous immunotherapy (SCIT) using HDM allergen for both asthma and allergic rhinitis,4-6 and a smallernumberof studies......,theresults ofthestudybyVirchow et al are important and clinically relevant. In particular, instead of themorecommonapproach of studying patientswith milder asthma or those with only allergic rhinitis, this trial focused on themore challenging subset of patientswith asthma, thosewith inadequatesymptomcontrol despite......, these adherence rates are similar to those seen with SCIT and even with long-term pharmacotherapy for allergic disease and asthma.17 SLIT is currently approved for numerous allergens by the European regulatory authorities and is inwide use throughout Europe. In 2014, the US Food and Drug Administration announced...
Schmid, Johannes Martin; Dahl, Ronald; Hoffmann, Hans Jürgen
the immune response in allergic patients and results in an inhibition of the specific type 1 allergic response. This inhibition is mainly brought about by a change in the immunoglobulin response pattern from allergen specific IgE towards predominantly IgG. Seven days after vaccination with tetanus vaccine...
Cappella, Antonio; Durham, Stephen R.
Allergen specific immunotherapy involves the repeated administration of allergen products in order to induce clinical and immunologic tolerance to the offending allergen. Immunotherapy is the only etiology-based treatment that has the potential for disease modification, as reflected by longterm remission following its discontinuation and possibly prevention of disease progression and onset of new allergic sensitizations. Whereas subcutaneous immunotherapy is of proven value in allergic rhinitis and asthma there is a risk of untoward side effects including rarely anaphylaxis. Recently the sublingual route has emerged as an effective and safer alternative. Whereas the efficacy of SLIT in seasonal allergy is now well-documented in adults and children, the available data for perennial allergies and asthma is less reliable and particularly lacking in children. This review evaluates the efficacy, safety and longterm benefits of SCIT and SLIT and highlights new findings regarding mechanisms, potential biomarkers and recent novel approaches for allergen immunotherapy. PMID:23095870
Full Text Available Abstract Allergen-specific immunotherapy is a potentially disease-modifying therapy that is effective for the treatment of allergic rhinitis/conjunctivitis, allergic asthma and stinging insect hypersensitivity. However, despite its proven efficacy in these conditions, it is frequently underutilized in Canada. The decision to proceed with allergen-specific immunotherapy should be made on a case-by-case basis, taking into account individual patient factors such as the degree to which symptoms can be reduced by avoidance measures and pharmacological therapy, the amount and type of medication required to control symptoms, the adverse effects of pharmacological treatment, and patient preferences. Since this form of therapy carries the risk of anaphylactic reactions, it should only be prescribed by physicians who are adequately trained in the treatment of allergy. Furthermore, injections must be given under medical supervision in clinics that are equipped to manage anaphylaxis. In this article, the authors review the indications and contraindications, patient selection criteria, and the administration, safety and efficacy of allergen-specific immunotherapy.
Full Text Available Successful allergen-specific immunotherapy (AIT is associated with a marked decrease in symptoms on allergen exposure, a reduced requirement for 'rescue' anti-allergic drugs and improvement in patients' quality of life. These benefits persist for at least several years following discontinuation of immunotherapy - the hallmark of clinical and immunological tolerance. AIT has been shown to modulate both innate and adaptive immunological responses. Early suppression of innate effector cells of allergic inflammation (mast cells, basophils, regulation of pro-allergic T helper 2 type (Th 2 responses and IgE+ B cell responses have been shown to occur both in the tissue and in the peripheral blood during AIT. The allergen-tolerant state is associated with local and systemic induction of distinct populations of allergen-specific T regulatory cells including IL-10+ Tregs (Tr1 cells, TGF-P+ Tregs and FoxP3+ memory T regs. B cells are switched in favour of producing IgG (particularly IgG4 antibodies and associated blocking activity for IgE-dependent events, including basophil activation and IgE-facilitated allergen binding to B cells. An induction of IL-10+ B regulatory cells and alterations in dendritic cell subsets have also recently been described. These events are followed by the induction of T regulatory cells, suppression of allergen-specific T cell proliferation and immune deviation from Th2 in favour of Th1 responses. Alternative mechanisms of tolerance include apoptosis/deletion of antigen-specific memory Th2 cells and/or a failure of co-stimulation leading to T cell anergy.
Aliu, Have; Rask, Carola; Brimnes, Jens
Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the - treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development...
Pauli, Gabrielle; Malling, H-J
Subcutaneous immunotherapy is a well documented treatment of allergic rhinitis and asthma. The majority of the disadvantages of the treatment are related to the poor quality of the natural allergen extracts which can contain varying amounts of individual allergens including allergens to which...
EFFECTIVENESS OF SUBCUTANEOUS ALLERGEN-SPECIFIC IMMUNOTHERAPY WITH TREE POLLEN ALLERGEN EXTRACT ADSORBED ON CALCIUM PHOSPHATE IN CHILDREN WITH ALLERGIC RHINOCONJUNCTIVITIS: RESULTS OF A 2 YEAR-LONG OBSERVATION
N. V. Shakhova
Full Text Available The study was aimed at evaluating effectiveness and safety of subcutaneous allergen-specific immunotherapy (scASIT with tree pollen allergen extract adsorbed on calcium phosphate at allergic rhinoconjunctivitis in children. Patients and methods: open-label prospective study of 50 children and adolescents (5-17 years of age with allergic rhinoconjunctivitis caused by high sensitivity to tree pollen allergens. The first group involved the patients undergoing scASIT for 2 years 6 months (n = 23, the control group – the patients (n = 27 not undergoing any specific immunotherapy. Results: scASIT was accompanied by a statistically significant (in comparison with the control group reduction in intensity of rhinoconjunctivitis symptoms (6.1 ± 3.1; 11.8 ± 4.5; p = 0.00002, reduction in the use of symptomatic drugs (1.0 ± 0.4; 1.8 ± 0.3; p = 0.000004 and improvement of quality of all spheres of children’s life – physical (p = 0.001, social (p = 0.04, emotional (p = 0.001 and role functioning (p = 0.03. Systemic side reactions were not observed in the patients. Local reactions were observed in 23% of all allergen injections. Conclusions: the authors established high effectiveness and safety of scASIT with tree pollen allergen extract adsorbed on calcium phosphate suspension at allergic rhinoconjunctivitis in children.
Nurmatov, Ulugbek; Dhami, Sangeeta; Arasi, Stefania
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effective...
Pajno, G B; Fernandez-Rivas, M; Arasi, S
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...
Allergen-specific immunotherapy provides immediate, long-term and preventive clinical effects in children and adults: the effects of immunotherapy can be categorised by level of benefit -the centenary of allergen specific subcutaneous immunotherapy
Full Text Available Abstract Allergen Specific Immunotherapy (SIT for respiratory allergic diseases is able to significantly improve symptoms as well as reduce the need for symptomatic medication, but SIT also has the capacity for long-term clinical effects and plays a protective role against the development of further allergies and symptoms. The treatment acts on basic immunological mechanisms, and has the potential to change the pathological allergic immune response. In this paper we discuss some of the most important achievements in the documentation of the benefits of immunotherapy, over the last 2 decades, which have marked a period of extensive research on the clinical effects and immunological background of the mechanisms involved. The outcome of immunotherapy is described as different levels of benefit from early reduction in symptoms over progressive clinical effects during treatment to long-term effects after discontinuation of the treatment and prevention of asthma. The efficacy of SIT increases the longer it is continued and immunological changes lead to potential long-term benefits. SIT alone and not the symptomatic treatment nor other avoidance measures has so far been documented as the therapy with long-term or preventive potential. The allergic condition is driven by a subset of T-helper lymphocytes (Th2, which are characterised by the production of cytokines like IL-4, and IL-5. Immunological changes following SIT lead to potential curative effects. One mechanism whereby immunotherapy suppresses the allergic response is through increased production of IgG4 antibodies. Induction of specific IgG4 is able to influence the allergic response in different ways and is related to immunological effector mechanisms, also responsible for the reduced late phase hyperreactivity and ongoing allergic inflammation. SIT is the only treatment which interferes with the basic pathophysiological mechanisms of the allergic disease, thereby creating the potential for
Sturm, Gunter J; Varga, Eva-Maria; Roberts, Graham
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 auto-injector. This guideline aims to give...... 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...... 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. This article...
Díez Zuluaga, Libia Susana
Full Text Available Allergen specific immunotherapy is currently the only treatment that modifies the natural course of allergic diseases. Its present indications are asthma, rhinitis, conjunctivitis, atopic dermatitis and hymenoptera venom allergy. However, there still is some controversy regarding its safety and clinical utility. In this article, we present a review about the molecular mechanisms, indications, contraindications, safety and efficacy of immunotherapy in each one of these diseases, by means of illustrative cases.
Jongejan, Laurian; van Ree, Ronald; Poulsen, Lars K
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....
Ponda, Punita; Mithani, Sima; Kopyltsova, Yelena; Sison, Cristina; Gupta, Payel; Larenas, Désirée; Bonagura, Vincent R
Allergists around the world have different practice styles when administering subcutaneous aeroallergen immunotherapy (IT) in peak pollen seasons, especially when changing doses or frequency of IT. The Immunotherapy practice parameters do not specifically address this issue. Given the paucity of good data about adjustment of allergen immunotherapy during the pollen seasons, we examined whether a significant difference is present in the way allergists administer immunotherapy during allergy seasons. To quantify the practice styles of allergists who are members of the American Academy of Allergy, Asthma and Immunology (AAAAI), a self-reported electronic survey was disseminated in September 2010 with the help of the AAAAI Needs Assessment Committee. The responses were tallied and analyzed according to demographic information. A total of 1,201 allergists in the AAAAI responded to the survey. Most responders practice in an urban or suburban nonacademic practice in the United States and have been in practice for more than 10 years. The size of their practice was variable. Those in practice for more than 10 years were more likely to adjust the dose and frequency of immunotherapy in pollen seasons. This survey highlights the differences in the practice styles of AAAAI member allergists, and these differences may be associated with their demographic characteristics. Given the wide variability in how allergists adjust dose and frequency of immunotherapy during pollen seasons, establishing guidelines regarding this routine dilemma might help standardize the delivery of treatment to patients. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Larenas Linnemann, Désirée E S; Blaiss, Michael S
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.
Full Text Available This review presents up-to-date understanding of immunotherapy in the treatment of children with allergic asthma. The principal types of allergen immunotherapy (AIT are subcutaneous immunotherapy (SCIT and sublingual immunotherapy (SLIT. Both of them are indicated for patients with allergic rhinitis and/or asthma, who have evidence of clinically relevant allergen-specific IgE, and significant symptoms despite reasonable avoidance measures and/or maximal medical therapy. Studies have shown a significant decrease in asthma symptom scores and in the use of rescue medication, and a preventive effect on asthma onset. Although the safety profile of SLIT appears to be better than SCIT, the results of some studies and meta-analyses suggest that the efficacy of SCIT is better and that SCIT has an earlier onset than SLIT in children with allergic asthma. Severe, not controlled asthma, and medical error were the most frequent causes of SCIT-induced adverse events.
Renand, Amedee; Shamji, Mohamed H; Harris, Kristina M; Qin, Tielin; Wambre, Erik; Scadding, Guy W; Wurtzen, Peter A; Till, Stephen J; Togias, Alkis; Nepom, Gerald T; Kwok, William W; Durham, Stephen R
Three years treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The GRASS(∗) trial demonstrated that two years treatment via either route was effective in suppressing the response to nasal allergen challenge, although was insufficient for inhibition one year after discontinuation. To examine in the GRASS trial the time-course of immunologic changes during two years sublingual and subcutaneous immunotherapy and for one year after treatment discontinuation. We performed multi-modal immunomonitoring to assess allergen-specific CD4 T cell properties, in parallel with analysis of local mucosal cytokine responses induced by nasal allergen exposure and humoral immune responses that included IgE-dependent basophil activation and measurement of serum inhibitory activity for allergen-IgE binding to B cells (IgE-Facilitated Allergen Binding). All three of these distinct arms of the immune response displayed significant and coordinate alterations during 2 years allergen desensitization, followed by reversal at 3 years, reflecting a lack of a durable immunological effect. Whereas frequencies of antigen-specific Th2 cells in peripheral blood determined by HLA class II tetramer analysis most closely paralleled clinical outcomes, IgE-antibody dependent functional assays remained partially inhibited one year following discontinuation. Two years of allergen immunotherapy were effective but insufficient for long-term tolerance. Allergen-specific Th2 cells most closely paralleled the transient clinical outcome and it is likely that recurrence of the T cell 'drivers' of allergic immunity abrogated the potential for durable tolerance. On the other hand, persistence of IgE-blocking antibody one year after discontinuation may be an early indicator of a pro-tolerogenic mechanism. Copyright © 2017. Published by Elsevier Inc.
Zimmer, J; Bonertz, A; Vieths, S
All allergen products for allergen immunotherapy currently marketed in the European Union are pharmaceutical preparations derived from allergen-containing source materials like pollens, mites and moulds. Especially this natural origin results in particular demands for the regulatory requirements governing allergen products. Furthermore, the development of regulatory requirements is complicated by the so far missing universal link between certain quality parameters, in particular biological potency, on the one hand and clinical efficacy on the other hand. As a consequence, each allergen product for specific immunotherapy has to be assessed individually for its quality, safety and efficacy. At the same time, biological potency of allergen products is most commonly determined using IgE inhibition assays based on human sera relative to product-specific in house references, ruling out full comparability of products from different manufacturers. This review article aims to summarize the current quality requirements for allergen products including the special requirements implemented for control of chemically modified allergen extracts (allergoids). Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.
Full Text Available Franco Frati,1 Cristoforo Incorvaia,2 Marie David,3 Silvia Scurati,3 Simona Seta,4 Guglielmo Padua,4 Eleonora Cattaneo,1 Carlo Cavaliere,5 Alessia Di Rienzo,6 Ilaria Dell'Albani,1 Paola Puccinelli11Medical and Scientific and Regulatory Department, Stallergenes, Milan, Italy; 2Allergy/Pulmonary Rehabilitation, ICP Hospital, Milan, Italy; 3Laboratoire Stallergenes, Antony, France; 4Marketing Department, Stallergenes, Milan, Italy; 5Ear, Nose and Throat Department, University Sapienza, Rome, Italy; 6Azienda Sanitaria Locale, Allergology Service, Frosinone, ItalyAbstract: The house dust mite is a major cause of respiratory allergy worldwide. The management of mite allergy is based on avoidance measures, drug treatment, and allergen immunotherapy, but only allergen immunotherapy is able to modify the natural history of the disease. Injectable subcutaneous immunotherapy was introduced a century ago, while sublingual immunotherapy was proposed in the 1980s and emerged in the ensuing years as an effective and safe option to subcutaneous immunotherapy. However, the quality of the extracts to be used in allergen immunotherapy is crucial for the success of treatment. The mite extract for sublingual immunotherapy known as Staloral 300 was developed to offer optimal characteristics concerning the mite culture medium, standardization, and allergen dose. Double-blind, placebo-controlled trials with Staloral 300 have provided a substantial part of the clinical evidence analyzed in a meta-analysis of the efficacy of allergen immunotherapy in mite-induced rhinitis and asthma. Safety and tolerability are very good, mild local reactions in the mouth being the most common side effect. This makes it feasible to carry out sublingual immunotherapy for the 3–5-year duration needed to achieve long-lasting tolerance to the specific allergen. The performance of Staloral 300 may provide optimal conditions for an effective and safe sublingual immunotherapy in patients with
Dhami, S; Zaman, H; Varga, E-M
BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety...
Jennifer M. Rolland
Full Text Available Allergen-specific immunotherapy (SIT involves the administration of gradually increasing amounts of an allergen extract to reduce clinical symptoms of allergy. Well-controlled clinical trials have demonstrated the efficacy of SIT in the treatment of allergic diseases, including rhinoconjunctivitis and asthma, and best practice protocols have been established. Nevertheless, application of this potentially curative treatment is restricted, largely due to the risk of serious adverse events, especially in asthmatics. Although efficacy is high for venom-induced allergy, success rates for the more common aeroallergen-induced disease range from 60 to 80% depending on the allergen. The practice of SIT is currently being refined following major advances in our knowledge of basic immune mechanisms. In particular, new T cell-targeted strategies are being explored with the awareness of the pivotal role allergen-specific T cells play in initiating and regulating the immune response to allergens. Current SIT induces decreased IgE class switching and eosinophil activation by downregulating production of the T helper (Th 2-type cytokines interleukin (IL-4 and IL-5. Therefore, allergen preparations that have ablated IgE binding while retaining T cell reactivity should still be clinically effective but have substantially improved safety. These approaches include the use of small peptides based on dominant T cell epitopes of allergens and chemically modified or recombinant allergen molecules. Both approaches have already been tested, with promising results, in animal models; peptide immunotherapy has been shown effective in clinical trials. Defined hypoallergenic molecules or peptides offer ease of standardization in addition to efficacy and safety and will result in more widespread use of SIT in clinical practice. Elucidation of mechanisms for downregulating Th2-predominant responses to allergen by SIT will enable the development of laboratory assays for
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.
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
Lourenço, Edmir Américo
Full Text Available Introduction The relevance of allergic rhinitis is unquestionable. This condition affects people's quality of life and its incidence has increased over the last years. Objective Thus, this study aims to analyze the effectiveness of subcutaneous injectable immunotherapy in cases of nasal itching, sneeze, rhinorrhea and nasal congestion in allergic rhinitis patients. Methods In the present study, the same researcher analyzed the records of 281 patients. Furthermore, the researchers identified allergens through puncture cutaneous tests using standardized extracts containing acari, fungi, pet hair, flower pollen, and feathers. Then, the patients underwent treatment with subcutaneous specific immunotherapy, using four vaccine vials for desensitization, associated with environmental hygiene. The authors analyzed conditions of nasal itching, sneeze, rhinorrhea, and nasal congestion throughout the treatment, and assigned them with a score ranging from zero (0, meaning absence of these symptoms to three (3, for severe cases. The symptoms were statistically compared in the beginning, during, and after treatment. Results In this study, authors analyzed the cases distribution according to age and the evolution of symptomatology according to the scores, comparing all phases of treatment. The average score for the entire population studied was 2.08 before treatment and 0.44 at the end. These results represent an overall improvement of ∼79% in symptomatology of allergic rhinitis in the studied population. Conclusion The subcutaneous immunotherapy as treatment of allergic rhinitis led to a reduction in all symptoms studied, improving the quality of life of patients, proving itself as an important therapeutic tool for these pathological conditions.
Zuidmeer-Jongejan, Laurian; Huber, Hans; Swoboda, Ines
BACKGROUND: The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. OBJECTIVES: Preclinical characterization and good manufacturing practice (GMP) production...... chromatography and mass spectrometry. Allergenicity was assessed by ImmunoCAP inhibition and basophil histamine release assay, immunogenicity by immunization of laboratory animals and stimulation of patients' peripheral blood mononuclear cells (PBMCs). Reference molecules were purified wild-type Cyp c 1 (natural.......e. hypoallergenicity with retained immunogenicity. These results have warranted first-in-man immunotherapy studies to evaluate the safety of this innovative vaccine. © 2015 S. Karger AG, Basel....
Garbani, M; Xia, W; Rhyner, C; Prati, M; Scheynius, A; Malissen, B; Engqvist, H; Maurer, M; Crameri, R; Terhorst, D
Immunomodulatory interventions play a key role in the treatment of infections and cancer as well as allergic diseases. Adjuvants such as micro- and nanoparticles are often added to immunomodulatory therapies to enhance the triggered immune response. Here, we report the immunological assessment of novel and economically manufactured microparticle adjuvants, namely strontium-doped hydroxyapatite porous spheres (SHAS), which we suggest for the use as adjuvant and carrier in allergen-specific immunotherapy (ASIT). Scanning electron microscopy revealed that the synthesis procedure developed for the production of SHAS results in a highly homogeneous population of spheres. Strontium-doped hydroxyapatite porous spheres bound and released proteins such as ovalbumin (OVA) or the major cat allergen Fel d 1. SHAS-OVA were taken up by human monocyte-derived dendritic cells (mdDCs) and murine DCs and did not have any necrotic or apoptotic effects even at high densities. In a murine model of ASIT for allergic asthmatic inflammation, we found that OVA released from subcutaneously injected SHAS-OVA led to a sustained stimulation of both CD4 + and CD8 + T cells. Allergen-specific immunotherapy with SHAS-OVA as compared to soluble OVA resulted in similar humoral responses but in a higher efficacy as assessed by symptom scoring. We conclude that SHAS may constitute a suitable carrier and adjuvant for ASIT with great potential due to its unique protein-binding properties. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Kristiansen, Maria; Dhami, Sangeeta; Netuveli, Gopal
in relation to its longer-term effects for this outcome. There was however a reduction in the short-term risk of those with allergic rhinitis developing asthma (RR=0.40; 95%CI 0.29 to 0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence...... asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer-term. We are unable to comment on the cost-effectiveness of AIT.......Background: There is a need to establish the effectiveness, cost-effectiveness and safety of allergen immunotherapy (AIT) for the prevention of allergic disease. Methods:Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using...
Shamji, Mohamed H; Layhadi, Janice A; Scadding, Guy W; Cheung, Delica K M; Calderon, Moises A; Turka, Laurence A; Phippard, Deborah; Durham, Stephen R
Immunotherapy inhibits basophil histamine release, but the assay is cumbersome, and no one has studied the effects of immunotherapy withdrawal. Intracellular fluorochrome-labeled diamine oxidase (DAO) was used as a novel functional readout of basophil histamine release after immunotherapy. Results were compared with conventional basophil surface expression of activation markers. Subcutaneous immunotherapy (SCIT)-treated patients (n = 14), sublingual immunotherapy (SLIT)-treated patients (n = 12), participants who completed 3 years of treatment with grass pollen sublingual immunotherapy (the SLIT-TOL group; n = 6), patients with untreated seasonal allergic rhinitis (SAR; n = 24), and nonatopic control subjects (n = 12) were studied. Intracellularly labeled DAO(+) and surface expression of CD203c(bright), CD63(+), and CD107a(+) on chemoattractant receptor-homologous molecule expressed on TH2 lymphocytes (CRTh2)-positive basophils were measured by means of flow cytometry. Serum IgG4 levels and serum inhibitory activity for IgE-allergen complex binding to B cells (IgE-FAB) and basophil histamine release were also determined. Proportions of allergen-stimulated DAO(+)CRTh2(+) basophils were higher in participants in the SCIT, SLIT, and SLIT-TOL groups (all P pollen immunotherapy. Intracellularly labeled DAO expression by basophils merits further investigation as a surrogate biomarker for monitoring efficacy and tolerance after immunotherapy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
James, Louisa K; Shamji, Mohamed H; Walker, Samantha M; Wilson, Duncan R; Wachholz, Petra A; Francis, James N; Jacobson, Mikila R; Kimber, Ian; Till, Stephen J; Durham, Stephen R
Grass pollen immunotherapy for allergic rhinitis is a disease-modifying treatment that results in long-term clinical tolerance lasting years after treatment discontinuation. Active treatment is associated with generation of inhibitory grass pollen-specific IgG antibodies capable of blocking allergen-IgE interactions. We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy. We conducted a 4-year study in which patients who had moderate-to-severe allergic rhinitis underwent a randomized, double-blind, placebo-controlled discontinuation of subcutaneous grass pollen immunotherapy. All subjects received grass pollen immunotherapy injections for 2 years (n = 13), followed by a further 2 years of either active (n = 7) or placebo (n = 6) injections. Clinical outcomes included seasonal symptoms and use of rescue medication. Serum specimens were collected at baseline and after 2 and 4 years for quantification of allergen-specific IgG antibodies. Sera were also tested for IgG-dependent inhibitory bioactivity against IgE-allergen binding in cellular assays by using flow cytometry and confocal microscopy to detect binding of IgE-grass pollen allergen complexes to B cells. Clinical improvement was maintained after 2 years of discontinuation. Although immunotherapy-induced grass pollen-specific IgG1 and IgG4 levels decreased to near-preimmunotherapy levels during discontinuation, inhibitory bioactivity of allergen-specific IgG antibodies was maintained unchanged. Grass pollen immunotherapy induces a subpopulation of allergen-specific IgG antibodies with potent inhibitory activity against IgE that persists after treatment discontinuation and that could account for long-term clinical tolerance. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Bonertz, A; Roberts, G C; Hoefnagel, M
Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory...
Elliott, Jesse; Kelly, Shannon E; Johnston, Amy; Skidmore, Becky; Gomes, Tara; Wells, George A
Allergic rhinitis and asthma are important public health concerns, yet there is no consensus about the benefits and harms of allergen-specific immunotherapy to treat these conditions. We performed an umbrella review of systematic reviews summarizing the current evidence for the benefits and harms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). We searched MEDLINE, Embase, the Cochrane Library and the grey literature from Jan. 1, 2010 to Nov. 20, 2016 for systematic reviews of randomized controlled trials or prospectively controlled studies involving children or adults with allergic rhinitis or asthma. Outcomes were summarized narratively (benefits: total combined symptom-medication score, symptom score, medication score, disease-specific quality of life, adherence; harms: anaphylaxis, death, local and systemic reactions). Twenty-three systematic reviews were included. SCIT and SLIT were more effective than placebo for most outcomes. SCIT was better than SLIT at improving medication and symptom scores, with no differences in quality of life; however, data were limited for this comparison. Anaphylaxis and death were infrequently reported. Few reviews assessed benefits or harms among children. Allergen immunotherapy appears to be effective among patients with allergic rhinitis and asthma. The safety of allergen immunotherapy is not conclusively established, although death and anaphylaxis appear to be rare. PROSPERO no.: CRD42015024590. Copyright 2017, Joule Inc. or its licensors.
Nurmatov, Ulugbek; Dhami, Sangeeta; Arasi, Stefania
BACKGROUND: 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...... 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 (SLIT) and one study evaluated epicutaneous immunotherapy...
Netterlid, Eva; Hindsén, Monica; Siemund, Ingrid; Björk, Jonas; Werner, Sonja; Jacobsson, Helene; Güner, Nuray; Bruze, Magnus
Persistent, itching nodules have been reported to appear at the injection site after allergen-specific immuno-therapy with aluminium-precipitated antigen extract, occasionally in conjunction with contact allergy to aluminium. This study aimed to quantify the development of contact allergy to aluminium during allergen-specific immunotherapy. A randomized, controlled, single-blind multicentre study of children and adults entering allergen-specific immunotherapy was performed using questionnaires and patch-testing. A total of 205 individuals completed the study. In the 3 study groups all subjects tested negative to aluminium before allergen-specific immunotherapy and 4 tested positive after therapy. In the control group 4 participants tested positive to aluminium. Six out of 8 who tested positive also had atopic dermatitis. Positive test results were found in 5/78 children and 3/127 adults. Allergen-specific immunotherapy was not shown to be a risk factor for contact allergy to aluminium. Among those who did develop aluminium allergy, children and those with atopic dermatitis were more highly represented.
Allergen Immunotherapy (AIT) is able to restore a physiological Th1 response and Tregs function. This effect is allergen-specific, even though it has been reported that it may also be non-specific, such as also extended to allergens not used in AIT. This immunological phenomenon may also be of clinical nature. This case report shows that a poly-allergic patient, successfully treated with Parietaria extract, also achieved a clinical tolerance towards other causal allergens, such as mites and cat. Of course, this was an anecdote, but it is reasonable to prospect the hypothesis that a bystander clinical effect may be observed during AIT in poly-allergic patients.
Linneberg, Allan; Madsen, Flemming; Skaaby, Tea
After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic.......After 100 years of experience with allergen-specific immunotherapy (SIT), an issue that is still unresolved is whether SIT can act as a trigger of, or as a risk factor for, autoimmune disease. We searched the literature for evidence on this topic....
Vissers, Joost L. M.; van Esch, Betty C. A. M.; Hofman, Gerard A.; Kapsenberg, Martien L.; Weller, Frank R.; van Oosterhout, Antoon J. M.
Background: Human studies have demonstrated that allergen immunotherapy induces memory suppressive responses and IL-10 production by allergen-specific T cells. Previously, we established a mouse model in which allergen immunotherapy was effective in the suppression of allergen-induced asthma
Halken, Susanne; Larenas-Linnemann, Desiree; Roberts, Graham; Calderón, Moises A; Angier, Elisabeth; Pfaar, Oliver; Ryan, Dermot; Agache, Ioana; Ansotegui, Ignacio J; Arasi, Stefania; Du Toit, George; Fernandez-Rivas, Montserrat; Geerth van Wijk, Roy; Jutel, Marek; Kleine-Tebbe, Jörg; Lau, Susanne; Matricardi, Paolo M; Pajno, Giovanni B; Papadopoulos, Nikolaos G; Penagos, Martin; Santos, Alexandra F; Sturm, Gunter J; Timmermans, Frans; van Ree, R; Varga, Eva-Maria; Wahn, Ulrich; Kristiansen, Maria; Dhami, Sangeeta; Sheikh, Aziz; Muraro, Antonella
Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for the prevention of (i) development of allergic comorbidities in those with established allergic diseases, (ii) development of first allergic condition, and (iii) allergic sensitization. This guideline has been developed using the Appraisal of Guidelines for Research & Evaluation (AGREE II) framework, which involved a multidisciplinary expert working group, a systematic review of the underpinning evidence, and external peer-review of draft recommendations. Our key recommendation is that a 3-year course of subcutaneous or sublingual AIT can be recommended for children and adolescents with moderate-to-severe allergic rhinitis (AR) triggered by grass/birch pollen allergy to prevent asthma for up to 2 years post-AIT in addition to its sustained effect on AR symptoms and medication. Some trial data even suggest a preventive effect on asthma symptoms and medication more than 2 years post-AIT. We need more evidence concerning AIT for prevention in individuals with AR triggered by house dust mites or other allergens and for the prevention of allergic sensitization, the first allergic disease, or for the prevention of allergic comorbidities in those with other allergic conditions. Evidence for the preventive potential of AIT as disease-modifying treatment exists but there is an urgent need for more high-quality clinical trials. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
Eifan, Aarif O; Calderon, Moises A; Durham, Stephen R
There is an increasing prevalence of atopic diseases such as allergic rhinitis and asthma with house dust mite (HDM) being the common allergen that is highly associated with allergic rhinitis and asthma. Allergen avoidance and pharmacotherapy are part of treatment but it has proved difficult to change the course of HDM-related allergic diseases. Allergen immunotherapy (AIT) has been in use for the past century and has been shown to be effective in the treatment of allergic respiratory disease. This review exclusively focuses on HDM-AIT and discusses the differences in clinical efficacy and safety, long-term effect after discontinuation and immunological changes observed in both HDM-subcutaneous immunotherapy (SCIT) and HDM-sublingual immunotherapy (SLIT) in the treatment of allergic rhinitis and asthma in both pediatric and adult populations. The majority of studies involved small numbers of patients, variable doses of major allergens and are of variable quality. There is good evidence for HDM-SCIT efficacy and its long-term effect in adults and children, whereas at the present time, evidence for HDM-SLIT is unconvincing, particularly in children. In carefully selected patients, HDM-SCIT is effective and safe. More definitive trials are needed before HDM-SLIT can be recommended in routine practice for rhinitis and/or asthma.
Dhami, Sangeeta; Nurmatov, Ulugbek; Roberts, Graham; Pfaar, Oliver; Muraro, Antonella; Ansotegui, Ignacio J.; Calderon, Moises; Cingi, Cemal; Demoly, Pascal; Durham, Stephen; van Wijk, Ronald Gerth; Halken, Susanne; Hamelmann, Eckard; Hellings, Peter; Jacobsen, Lars; Knol, Edward; Larenas Linnemann, Desiree; Lin, Sandra; Maggina, Vivian; Oude-Elberink, Hanneke; Pajno, Giovanni; Panwankar, Ruby; Pastorello, Elideanna; Pitsios, Constantinos; Rotiroti, Giuseppina; Timmermans, Frans; Tsilochristou, Olympia; Varga, Eva-Maria; Wilkinson, Jamie; Williams, Andrew; Worm, Margitta; Zhang, Luo; Sheikh, Aziz
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT
Halken, Susanne; Larenas-Linnemann, Desiree; Roberts, Graham; Calderón, Moises A.; Angier, Elisabeth; Pfaar, Oliver; Ryan, Dermot; Agache, Ioana; Ansotegui, Ignacio J.; Arasi, Stefania; Du Toit, George; Fernandez-Rivas, Montserrat; Geerth van Wijk, Roy; Jutel, Marek; Kleine-Tebbe, Jörg; Lau, Susanne; Matricardi, Paolo M.; Pajno, Giovanni B.; Papadopoulos, Nikolaos G.; Penagos, Martin; Santos, Alexandra F.; Sturm, Gunter J.; Timmermans, Frans; van Ree, R.; Varga, Eva-Maria; Wahn, Ulrich; Kristiansen, Maria; Dhami, Sangeeta; Sheikh, Aziz; Muraro, Antonella
Allergic diseases are common and frequently coexist. Allergen immunotherapy (AIT) is a disease-modifying treatment for IgE-mediated allergic disease with effects beyond cessation of AIT that may include important preventive effects. The European Academy of Allergy and Clinical Immunology (EAACI) has
Dhami, Sangeeta; Nurmatov, Ulugbek; Roberts, Graham; Pfaar, Oliver; Muraro, Antonella; Ansotegui, Ignacio J; Calderon, Moises; Cingi, Cemal; Demoly, Pascal; Durham, Stephen; van Wijk, Ronald Gerth; Halken, Susanne; Hamelmann, Eckard; Hellings, Peter; Jacobsen, Lars; Knol, Edward; Linnemann, Desiree Larenas; Lin, Sandra; Maggina, Vivian; Oude-Elberink, Hanneke; Pajno, Giovanni; Panwankar, Ruby; Pastorello, Elideanna; Pitsios, Constantinos; Rotiroti, Giuseppina; Timmermans, Frans; Tsilochristou, Olympia; Varga, Eva-Maria; Wilkinson, Jamie; Williams, Andrew; Worm, Margitta; Zhang, Luo; Sheikh, Aziz
BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Allergic Rhinoconjunctivitis. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT
Ariano, Renato; Berto, Patrizia; Tracci, Daniela; Incorvaia, Cristoforo; Frati, Franco
Only a few studies analyzed the pharmacoeconomics of allergen immunotherapy compared with drug treatment in subjects with allergic rhinitis and asthma. This study was aimed at evaluating whether allergen immunotherapy has an economic advantage on standard antiallergic drugs in patients with pollen-induced rhinitis and asthma. Thirty patients with rhinitis and asthma caused by Parietaria pollen were included in the study, 20 (11 men and 9 women; mean age, 35.45 +/- 10.45 years) were treated with subcutaneous immunotherapy by a Parietaria judaica extract (Alustal, Stallergénes, Antony, France) by a conventional build-up schedule in 12 weeks and a maintenance treatment every 4 weeks for 3 years, and 10 (6 men and 4 women; mean age, 31.90 +/- 10.97 years) were treated with antiallergic drugs. Each patient was evaluated before starting the treatment and annually for 6 years in the pollen period of Parietaria by means of nose, eyes, and lung symptom scores, along with drug consumption registered in diary cards. In other specifically designated cards general practitioner's or specialist's visits, the number of desensitizing injections and the number of boxes of antiallergic drugs were registered. A significant difference in favor of immunotherapy plus drug treatment versus drug treatment alone was observed, reaching a cost reduction of approximately 15% the second year and 48% the third year, with a highly statistical significance that was maintained up to the sixth year, i.e., 3 years after stopping immunotherapy, when an 80% reduction was found. The net saving for each patient at the final evaluation corresponded to euros 623 (dollars 830)/year. These findings confirm some previous observations in studies from Germany and the United States that subcutaneous immunotherapy has significant economic advantages over antiallergic drug treatment in the long term.
Häfner, Dietrich; Gödicke, Viola; Narkus, Annemie
A set of standard clinical chemistry and hematology parameters are usually measured during clinical studies. The major outcome of these standard tests is to control that the drug investigated does not lead to pathophysiological changes in respective organs or blood. In some cases based on scientific rationale such tests may not be needed. In this paper we report on a standard set of clinical chemistry and hematology laboratory parameters measured before and after treatment in three different immunotherapy studies, representing different routes of administration and different formulations. Thirteen hematological laboratory parameters and eight clinical chemistry parameters were evaluated from three double-blind, placebo-controlled, randomized, multi-centre, phase III studies. The three studies include one with sublingual immunotherapy (n = 185), one subcutaneous immunotherapy trial with an aluminium hydroxide-adsorbed recombinant hypoallergenic Bet v1-FV (n = 211) and one with pre-seasonal subcutaneous immunotherapy with a 6-grass pollen allergoid (n = 154). Allergen specific immunotherapy with both administration forms and formulations respectively did not show any influence on any of the 21 laboratory parameters analyzed. Few patients had a change in laboratory parameters from within normal range at baseline to either below or above at end-of-treatment. No differences between active and placebo were seen with respect to number of patients with such a change. This study with different preparations and routes of application indicates that the value of repeated measurements of standard clinical chemistry and hematology parameters during allergen immunotherapy should be discussed further.
Calderon Moises A
Full Text Available Abstract Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy. Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies. Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals’ quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases. Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in
Full Text Available Abstract The FAST project (Food Allergy Specific Immunotherapy aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT, using subcutaneous injections with aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1 and lipid transfer protein (Pru p 3, respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models, SCIT with alum-absorbed hypoallergens will be evaluated in phase I/IIa and IIb randomized double-blind placebo-controlled (DBPC clinical trials, with the DBPC food challenge as primary read-out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication.
Sturm, Gunter J; Varga, Eva-Maria; Roberts, Graham; Mosbech, Holger; Bilò, M Beatrice; Akdis, Cezmi A; Antolín-Amérigo, Darío; Cichocka-Jarosz, Ewa; Gawlik, Radoslaw; Jakob, Thilo; Kosnik, Mitja; Lange, Joanna; Mingomataj, Ervin; Mitsias, Dimitris I; Ollert, Markus; Oude Elberink, Joanna N G; Pfaar, Oliver; Pitsios, Constantinos; Pravettoni, Valerio; Ruëff, Franziska; Sin, Betül Ayşe; Agache, Ioana; Angier, Elizabeth; Arasi, Stefania; Calderón, Moises A; Fernandez-Rivas, Montserrat; Halken, Susanne; Jutel, Marek; Lau, Susanne; Pajno, Giovanni B; van Ree, Ronald; Ryan, Dermot; Spranger, Otto; van Wijk, Roy Gerth; Dhami, Sangeeta; Zaman, Hadar; Sheikh, Aziz; Muraro, Antonella
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, H1 -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 auto-injector. 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. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Aryan, Zahra; Compalati, Enrico; Comapalati, Enrico; Canonica, Giorgio Walter; Rezaei, Nima
Atopic asthma in childhood with the tendency to persist into adult life is an important issue in pediatrics. Allergen-specific immunotherapy (SIT) is the only curative treatment option for these children, being directed to the causes of the disease. The Th2 phenotype is a predominant immunological pattern in atopic asthma and SIT leads to apoptosis/anergy of T cells and induces immune-regulatory responses and immune deviation towards Th1. Many factors can affect the safety and efficacy of SIT, such as pattern of sensitization, allergy vaccine (allergen extracts, adjuvants and conjugated molecules), route of administration (subcutaneous or sublingual) and different treatment schedules. Overall, asthma symptoms and medication scores usually decrease following a SIT course and the most common observed side effects are restricted to local swelling, erythema and pruritus. Compared with conventional pharmacotherapy, SIT may be more cost effective, providing a benefit after discontinuation and a steroid-sparing effect. In addition, it can prevent new sensitizations in monosensitized asthmatic children. Microbial supplements such as probiotics, immunomodulatory substances like anti-IgE/leukotrienes, antibodies and newer allergen preparations such as recombinant forms have been tested to improve the efficacy and safety of SIT with inconclusive results. In conclusion, SIT provides an appropriate solution for childhood asthma that should be employed more often in clinical practice. Further studies are awaited to improve current knowledge regarding the mechanisms behind SIT and determine the most appropriate materials and schedule of immunotherapy for children with asthma.
van Oosterhout, A. J.; van Esch, B.; Hofman, G.; Hofstra, C. L.; van Ark, I.; Nijkamp, F. P.; Kapsenberg, M. L.; Savelkoul, H. F.; Weller, F. R.
In the present study, we investigated whether allergen immunotherapy is effective in a murine model with immunologic and pathophysiologic features reminiscent of allergic asthma. Ovalbumin-sensitized mice received increasing (1 microgram to 1 mg) subcutaneous doses of ovalbumin twice a week for 8 wk
Full Text Available Background. Allergen-specific immunotherapy as elimination procedures is the only method of treatment and prevention of allergic disorders formation and exacerbation of clinical symptoms. One of the approaches to molecular diagnosis is choice of allergen for allergen-specific immunotherapy (ASIT. The purpose of our study was to identify possible reasons of failure of ASIT with pollen allergens (predominantly weeds in children with seasonal allergic rhinitis (hay fever and/or bronchial asthma based on studying hypersensitivity to the allergens, analysis of anamnestic data. Materials and methods. Allergy skin prick tests were conducted to 192 children (middle age 9.8 ± 2.7 years with the seasonal symptoms of rhinitis and/or bronchial asthma according to standard methodology with pollen allergens of Immunolog Ltd (Vinnytsia. We evaluated positive results as 5 mm and higher diameter of papula/hyperemia. The anamnestic survey was carried out in 52 patients by means of the questionnaire that contained questions about cross allergy (pollen-food, oral allergy syndrome, concomitant pathology of upper respiratory tract and effectiveness of АSІТ, which is elaborated by us. Results. The skin prick tests show that in 192 patients, who have hay fever, ragweed, sunflower sensibilization predominates (56 and 58 %, correspondingly. About 10–20 % of children are sensitive to cereals (ryegrass, fescue. To the allergens of poplar, acacia, couch-grass, oak, mint, nettle, walnut, the positive reactions of prick tests were observed in 3–7 children, that is 1.5–3.6 %. According to our results, 23 % of patients had sensibilization to 5 and more pollen allergens. 52 % of children had concomitant food allergy, 15 % of patients have reactions of the lips, oral cavity when using certain products, mostly tomatoes, nuts, seeds (they were diagnosed oral allergy syndrome. Also, one third of children have varying degrees of adenoid hypertrophy, tonsils hypertrophy
Datta, Ankur; Moitra, Saibal; Das, Prasanta K; Mondal, Somnath; Omar Faruk, Sk Md; Hazra, Iman; Tripathi, Santanu K; Chaudhuri, Swapna
To study the apoptosis of Foxp3+ Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy. Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed. Allergen sensitization-challenge increases Annexin-V, Fas, FasL, caspases-8, 9, 3 cytochrome-C, APAF-1, Bax, perforin-1 and granzyme-B on Treg cells which is decreased following intranasal immunotherapy. On the other hand, Bcl-2 expression is decreased in allergy and increased by immunotherapy. Apoptosis of Treg cells is increased following allergen sensitization-challenge via extrinsic, intrinsic and perforin/granzyme pathways and allergen immunotherapy decreased the sensitivity to apoptosis of Treg cells.
Pajno, Giovanni Battista; Bernardini, Roberto; Peroni, Diego; Arasi, Stefania; Martelli, Alberto; Landi, Massimo; Passalacqua, Giovanni; Muraro, Antonella; La Grutta, Stefania; Fiocchi, Alessandro; Indinnimeo, Luciana; Caffarelli, Carlo; Calamelli, Elisabetta; Comberiati, Pasquale; Duse, Marzia
Allergen-specific immunotherapy (AIT) is currently recognized as a clinically effective treatment for allergic diseases, with a unique disease-modifying effect. AIT was introduced in clinical practice one century ago, and performed in the early years with allergenic extracts of poor quality and definition. After the mechanism of allergic reaction were recognized, the practice of AIT was refined, leading to remarkable improvement in the efficacy and safety profile of the treatment. Currently AIT is accepted and routinely prescribed worldwide for respiratory allergies and hymenoptera venom allergy. Both the subcutaneous (SCIT) and sublingual (SLIT) routes of administration are used in the pediatric population.AIT is recommended in allergic rhinitis/conjunctivitis with/without allergic asthma, with an evidence of specific IgE-sensitization towards clinically relevant inhalant allergens. Long-term studies provided evidence that AIT can also prevent the onset of asthma and of new sensitizations. The favorable response to AIT is strictly linked to adherence to treatment, that lasts 3-5 years. Therefore, several factors should be carefully evaluated before starting this intervention, including the severity of symptoms, pharmacotherapy requirements and children and caregivers' preference and compliance.In recent years, there have been increasing interest in the role of AIT for the treatment of IgE-associated food allergy and extrinsic atopic dermatitis. A growing body of evidence shows that oral immunotherapy represents a promising treatment option for IgE-associated food allergy. On the contrary, there are still controversies on the effectiveness of AIT for patients with atopic dermatitis.This consensus document was promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP) to provide evidence-based recommendations on AIT in order to implement and optimize current prescription practices of this treatment for allergic children.
Nurmatov, Ulugbek; Dhami, S; Arasi, S.
-effectiveness of AIT in the management of food allergy. Methods: 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...... 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......Background: 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...
Dhami, S.; Nurmatov, U.; Arasi, S.; Khan, T.; Asaria, M.; Zaman, H.; Agarwal, A.; Netuveli, G.; Roberts, G.; Pfaar, O.; Muraro, A.; Ansotegui, I. J.; Calderon, M.; Cingi, C.; Durham, S.; van Wijk, R. Gerth; Halken, S.; Hamelmann, E.; Hellings, P.; Jacobsen, L.; Knol, E.; Larenas-Linnemann, D.; Lin, S.; Maggina, P.; Moesges, R.; Elberink, H. Oude; Pajno, G.; Panwankar, R.; Pastorello, E.; Penagos, M.; Pitsios, C.; Rotiroti, G.; Timmermans, F.; Tsilochristou, O.; Varga, E. -M.; Schmidt-Weber, C.; Wilkinson, J.; Williams, A.; Worm, M.; Zhang, L.; Sheikh, A.
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the
Dahl, Ronald; Kapp, Alexander; Colombo, Giselda; deMonchy, Jan G. R.; Rak, Sabina; Emminger, Waltraud; Rivas, Montserrat Fernandez; Ribel, Mette; Durham, Stephen R.
Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking.
Ciprandi, G; Silvestri, M; Buttafava, S; Frati, F
Even though the Parietaria pollen season may be rather long, many physicians think that Parietaria pollen is a perennial allergen present along the whole year. In fact, many doctors prefer to prescribe allergen immunotherapy (AIT) in Parietaria allergic patients, using continuous courses. On the other hand, physicians usually prescribe pre-co-seasonal AIT course for other pollen allergies. This study aimed at investigating whether a single pre-co-seasonal AIT course could be effective in Parietaria allergic patients. Globally, 59 subjects (31 males, mean age 35.9 years) were retrospectively evaluated. All were treated with SLIT as a pre-co-seasonal course: 33 with Parietaria extract and 26 with birch extract. Patients' perception of symptom severity and medication use was assessed by visual analogue scale, comparing the previous pollen season and the present. The Parietaria 2012 pollen season started from the 60(th) day and ended at the 205(th) day of 2012. A single pre-co-seasonal SLIT course was able to significantly (p Parietaria pollen season in Genoa lasted about six months and a single pre-co-seasonal SLIT Parietaria course could be sufficient to reduce symptom severity and medication use.
Zuidmeer-Jongejan, Laurian; Huber, Hans; Swoboda, Ines; Rigby, Neil; Versteeg, Serge A.; Jensen, Bettina M.; Quaak, Suzanne; Akkerdaas, Jaap H.; Blom, Lars; Asturias, Juan; Bindslev-Jensen, Carsten; Bernardi, Maria L.; Clausen, Michael; Ferrara, Rosa; Hauer, Martina; Heyse, Jet; Kopp, Stephan; Kowalski, Marek L.; Lewandowska-Polak, Anna; Linhart, Birgit; Maderegger, Bernhard; Maillere, Bernard; Mari, Adriano; Martinez, Alberto; Mills, E. N. Clare; Neubauer, Angela; Nicoletti, Claudio; Papadopoulos, Nikolaos G.; Portoles, Antonio; Ranta-Panula, Ville; Santos-Magadan, Sara; Schnoor, Heidi J.; Sigurdardottir, Sigurveig T.; Stahl-Skov, Per; Stavroulakis, George; Stegfellner, Georg; Vázquez-Cortés, Sonia; Witten, Marianne; Stolz, Frank; Poulsen, Lars K.; Fernandez-Rivas, Montserrat; Valenta, Rudolf; van Ree, Ronald
The FAST (food allergy-specific immunotherapy) project aims at developing safe and effective subcutaneous immunotherapy for fish allergy, using recombinant hypoallergenic carp parvalbumin, Cyp c 1. Preclinical characterization and good manufacturing practice (GMP) production of mutant Cyp (mCyp) c
Chaker, Adam M; Shamji, Mohamed H; Dumitru, Florentina A; Calderon, Moises A; Scadding, Guy W; Makatsori, Melina; Jones, Ieuan; He, Qiuling A; Subramanian, Kulandayan K; Arm, Jonathan P; Durham, Stephen R; Schmidt-Weber, Carsten B
Allergen immunotherapy is currently the only disease-modifying treatment available for allergic rhinitis and allergic asthma. We sought to evaluate the induction of sustained tolerance to allergen when anti-IL-4 was combined with a suboptimal course of grass pollen subcutaneous immunotherapy (SCIT) using the allergen-induced skin late-phase response (LPR) and exploratory immune monitoring as surrogate markers of therapeutic response. In this randomized, double-blind, 3-group parallel design trial, 37 participants with seasonal allergic rhinitis received suboptimal SCIT (30,000 standardized quality units) in combination with anti-IL-4 (VAK694) and suboptimal SCIT (30,000 standardized quality units) plus placebo antibody or double placebo (placebo SCIT and placebo antibody) restricted to 13 weeks before the grass pollen season. The primary end point was the size of the LPR at 12 months. Exploratory end points included measures of the immunomodulatory activity of treatment by using IL-4 and IL-10 FluoroSpot assays, flow cytometry of T cells, and measurement of IgE, IgG4, and facilitated antigen binding. Both active treatment arms led to a substantial and sustained reduction of the LPR with no additional suppression with addition of anti-IL-4. Treatment with anti-IL-4 and SCIT compared with SCIT alone led to a sustained reduction in allergen-specific IL-4-producing cell counts (P pollen season. The combination of anti-IL-4 with SCIT provided no additional benefit over SCIT alone in suppressing the allergen-induced skin LPR. A larger trial is needed to assess whether the observed ex vivo downregulation of TH2 responses might translate into clinical benefit. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Kleine-Tebbe, J; Ackermann-Simon, J; Hanf, G
Allergen-specific immunotherapy (SIT, desensitization) is applied monthly with subcutaneous injections (SCIT) or sublingually (SLIT) with droplets or tablets on a daily basis. Numerous immunological changes during SIT induce long-lasting tolerance. Efficacy has been demonstrated by a number of controlled studies for insect venom hypersensitivity (SCIT), allergic rhinoconjunctivitis (SCIT, SLIT particularly in grass pollen allergy), and allergic asthma (SCIT > SLIT). SIT is indicated in children and adults with severe allergic reactions from insect venoms (e.g., bee, wasp) or cumbersome symptoms from pollen, house dust mites or mold allergens and proven immediated-type allergy. Contraindications must be considered individually. SIT is performed for 3 years, in case of venom allergy 3-5 years. Severe systemic reactions are rare after SCIT. After SLIT rather local allergic symptoms of short duration occur in the mouth and throat. At present, the number prescriptions for SIT has decreased due to inadequate reimbursement of allergy-related services (diagnostics, therapies, monitoring). In the future, inferior medical care of allergic patients in Germany is expected, who until now have benefited from the preventive effects of SIT (reduced risk of developing asthma and new allergic sensitizations).
Full Text Available Marie-Luise Lemberg,1 Till Berk,2 Kija Shah-Hosseini,1 Elena-Manja Kasche,1,3 Ralph Mösges1 1Faculty of Medicine, Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany; 2Department of Trauma Surgery, University Hospital Zurich, Zurich, Switzerland; 3Center for Dermatology, Specific Allergology and Environmental Medicine, Hamburg, Germany Background: Many placebo-controlled studies have demonstrated that allergen immunotherapy (AIT is an effective therapy for treating allergies. Both commonly used routes, subcutaneous (SCIT and sublingual immunotherapy (SLIT, require high patient adherence to be successful. In the literature, numbers describing adherence vary widely; this investigation compares these two routes of therapy directly.Methods: All data were retrieved from the patient data management system of a center for dermatology, specific allergology, and environmental medicine in Germany. All 330 patients (aged 13–89 years included in this study had commenced AIT between 2003 and 2011, thus allowing a full 3-year AIT cycle to be considered for each investigated patient.Results: In this specific center, SCIT was prescribed to 62.7% and SLIT to 37.3% of all included patients. The total dropout rate of the whole patient cohort was 34.8%. Overall, SLIT patients showed a higher dropout rate (39.0% than did SCIT patients (32.4%; however, the difference between these groups was not significant. Also, no significant difference between the overall dropout rates for men and for women was observed. A Kaplan–Meier curve of the patient collective showed a remarkably high dropout rate for the first year of therapy.Conclusion: The analysis presented in this single-center study shows that most patients who discontinue AIT do so during the first year of therapy. Patients seem likely to finish the 3-year therapy cycle if they manage to adhere to treatment throughout the first year. Strategies for preventing
A. S. Fedorov
Full Text Available Allergen-specific immunotherapy (ASIT is the most effective method of allergy treatment which consists of exposure to small doses of antigen responsible for development of allergic condition in the particular patient. Therefore, one may achieve desensitization to this antigen. The history of ASIT application lasts for more than 100 years, and, over this time, huge clinical evidence for the usage of the method has been accumulated. Use of ASIT causes reduction of allergy symptoms and treatment needs and, moreover, it has the potential for long-term clinical benefit, by preventing the development of allergy and its symptoms. The treatment affects basic immunological mechanisms responsible for the development of clinical symptoms. ASIT is an antiinflammatory, pathogenetic and prophylactic treatment of allergic airway disease. The review considers the results of major clinical trials of the ASIT applications for treatment of allergic diseases of the respiratory system (allergic rhinitis and bronchial asthma. Various schemes of ASIT are discussed including its different variants (injectable and sublingual ASIT, the issues of preparation choice for ASIT from those currently available on the pharmaceutical market, patient selection criteria, and the issues of modern molecular allergodiagnostic (allergic sensitization mapping of the patient at molecular level, in order to optimize them. Immunological mechanisms of ASIT are also considered, since appropriate views are rather contraversial. The ASIT effect is mediated through the following basic immunological mechanisms: the suppressed increase of the eosinophil concentrations, reduced duration of the delayed hypersensitivity phase, as well as initiation and maintenance of the Th2-to-Th1-like immune response transition. Regulatory T-cells play a major role in implementation of the immunological mechanism in ASIT, they have a significant impact on the Th2 response suppression. Such suppression may proceed
Calderon, Moises A; Cox, Linda; Casale, Thomas B; Mösges, Ralph; Pfaar, Oliver; Malling, Hans-Jørgen; Sastre, Joaquin; Khaitov, Musa; Demoly, Pascal
A patient's knowledge of his/her allergic condition and treatment is a key factor in adherence and effectiveness. To assess patients' understanding of allergy and acceptance of allergen immunotherapy on the basis of (i) information given by their physician at the time of prescription and (ii) a new communication template viewed some months later, we performed an Internet-based survey of patient panels in France, Germany, Spain, the USA and Russia. The survey participants were either recent "early abandoners" (having discontinued allergen immunotherapy before the end of the prescribed course) or "non-starters" (having decided not to initiate a course of allergen immunotherapy recommended by their physician). All participants completed an on-line questionnaire immediately before and immediately after viewing the new communication template. The study's main objectives were to validate the new communication template and to assess its impact on anticipated willingness to initiate or resume allergen immunotherapy. We surveyed a total of 261 patients (France: 57; Germany: 51; Spain: 52; USA: 51; Russia: 50), comprising 127 "early abandoners" and 134 "non-starters". The mean time since symptom onset and selection for the study was 14.5 years. Subcutaneous allergen immunotherapy had been prescribed in 60 % of cases. Twenty-eight percent of the participants did not know for which allergy they were being treated. Early abandoners reported a perception of low effectiveness (39 %) and complained about expense (39 %) and practical constraints (32 %). Twenty-two percent of the non-starters feared side effects. The communication template was considered to be clear (by 92 % of the patients), convincing (by 75 %) and reassuring (by 89 %); 80 % of the participants felt better informed afterwards, and 67 % stated that viewing the communication template would have made them more likely to continue or initiate allergen immunotherapy (overall willingness score: 5.65 out of 10
Ridolo, E; Incorvaia, C; Senna, G E; Montagni, M; Olivieri, E; Canonica, G W
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.
Wachholz, Petra A; Soni, Nanna Kristensen; Till, Stephen J; Durham, Stephen R
Among atopic individuals, levels of allergen-specific IgG antibodies have been inversely associated with the degree of allergen sensitization. Additionally, allergen-specific IgG antibodies are markedly increased by allergen injection immunotherapy. These observations have led to proposals that allergen-specific IgG antibodies might have protective properties in atopic individuals. We hypothesized that after grass pollen immunotherapy, these antibodies disrupt IgE-dependent allergen processing by antigen-presenting cells. We have developed a novel flow cytometric assay based on detection of allergen-IgE binding to the low-affinity IgE receptor on B cells to examine the blocking effects of sera collected from 18 patients who participated in a double-blind, controlled trial of grass pollen immunotherapy for 1 year. In all 10 patients who received active therapy, there was induction of activity that inhibited allergen-IgE binding to B cells (P =.02, vs placebo subjects), as well as subsequent allergen presentation to T cells. This activity copurified with IgG and was allergen specific, because sera taken from patients treated with grass pollen immunotherapy but who were also birch pollen sensitive did not inhibit IgE-birch pollen allergen binding to B cells. We conclude that allergen-specific IgG antibodies induced by immunotherapy can disrupt formation of allergen-IgE complexes that bind to antigen-presenting cells and facilitate allergen presentation.
Reyes Moreno, Arturo; Castrejón Vázquez, María Isabel; Miranda Feria, Alfonso Javier
The allergic asthma is the reversible chronic inflammatory process at the airways, secondary to exaggerate reply to the allergens exposition, its treatment includes: avoiding the exposure to allergens, pharmacology therapy and the specific immunotherapy with allergens (ITA), which is based on the growing dosages of the extract allergenic; the objectives are to modify the immune response and to improve the allergic disease. The ITA can fail due to causes attributable to the patient, vaccine-inherent causes and/or factors related to the allergic disease. To determine the main causes of specific immunotherapy with allergens' failure in our hospital. In the present study 126 records of patients with allergic asthma treated in the extern consultation service of the clinical immunology and allergy department of the CMN 20 de Noviembre, ISSSTE, were reviewed from January 1996 to December 2001. It was found that specific immunotherapy with allergens, failed in 32 (23%) patients. Main causes of failure were: 1) withdrawal in the vaccine application in 19 (59%) patients; 2) high serum levels of IgE. The co-morbidities that contribute to poor responses to the treatment were: obesity, gastroesofageal reflux and chronic rhynosinusitis. Specific immunotherapy with allergens is an alternative method of allergic asthma's treatment which has been approved by national and international medical consensus. Main causes of failure in our hospital are the abandon of treatment and high serum levels of IgE, as well as the existence of other conditions.
Dreborg, S; Lee, T H; Kay, A B; Durham, S R
One hundred years ago, Noon [Lancet 1911;1:1572-1573], using conjunctival provocation testing (CPT), was the first to demonstrate the effectiveness of subcutaneous immunotherapy (SCIT) in grass-allergic subjects with hay fever. In this centenary year, we present data that, by use of CPT and allergen-specific IgG, replicate this observation and additionally confirm the allergen specificity of SCIT by using a double-blind design employing either grass or mite SCIT in dual grass- and mite-allergic individuals. Twenty adults (11 females) with perennial rhinoconjunctivitis and exacerbation of symptoms during the grass pollen season and in the autumn had immediate skin and conjunctival sensitivity and raised specific IgE to both Dermatophagoides farinae and Phleum pratense. Participants were randomly assigned to either timothy or D. farinae immunotherapy for 3 years. CPT and specific IgG tests to both allergens were performed annually. After 3 years, subjects gave their blinded overall evaluation. Six mild-to-moderate general reactions occurred in 2 timothy- and 4 mite-treated patients. Four of these patients and 2 other patients withdrew from the study. Seven patients in each group completed the study. After 3 years of immunotherapy, the timothy CPT threshold concentration had increased 16- fold in timothy-treated patients (p < 0.05; between-group change, p < 0.05). The increase in the mite CPT threshold in mite- compared to grass-treated patients was 31-fold (p < 0.05). The overall assessment of conjunctival sensitivity was highly significant in favour of treatment (p < 0.015), as was that of allergen-specific IgG (p < 0.0001). Allergen immunotherapy is allergen species-specific, as judged by decreased conjunctival sensitivity and changes in allergen-specific IgG concentrations. Copyright © 2011 S. Karger AG, Basel.
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
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.
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
Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial.
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
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 2 years following discontinuation of treatment. 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. A randomized double-blind, placebo-controlled, 3-parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg 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 of treatment, and at 3 years (1 year after treatment discontinuation). Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 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 vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5
Scadding, G W; Eifan, A O; Lao-Araya, M; Penagos, M; Poon, S Y; Steveling, E; Yan, R; Switzer, A; Phippard, D; Togias, A; Shamji, M H; Durham, S R
Nasal allergen provocations may be useful in investigating the pathophysiology of allergic rhinitis and effects of treatments. To use grass pollen nasal allergen challenge (NAC) to investigate the effects of allergen immunotherapy in a cross-sectional study. We studied nasal and cutaneous responses in untreated subjects with seasonal grass-pollen allergic rhinitis (n = 14) compared with immunotherapy-treated allergics (n = 14), plus a nonatopic control group (n = 14). Volunteers underwent a standardized NAC with 2000 biological units of timothy grass allergen (equivalent to 1.3 μg major allergen, Phl p5). Nasal fluid was collected and analysed by ImmunoCAP and multiplex assays. Clinical response was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Cutaneous response was measured by intradermal allergen injection. Retrospective seasonal symptom questionnaires were also completed. Immunotherapy-treated patients had lower symptom scores (P = 0.04) and higher PNIF (P = 0.02) after challenge than untreated allergics. They had reduced early (P = 0.0007) and late (P < 0.0001) skin responses, and lower retrospective seasonal symptom scores (P < 0.0001). Compared to untreated allergics, immunotherapy-treated patients had reduced nasal fluid concentrations of IL-4, IL-9 and eotaxin (all P < 0.05, 8 h level and/or area under the curve comparison), and trends for reduced IL-13 (P = 0.07, area under the curve) and early-phase tryptase levels (P = 0.06). Nasal allergen challenge is sensitive in the detection of clinical and biological effects of allergen immunotherapy and may be a useful surrogate marker of treatment efficacy in future studies. © 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.
Schmid, J. M.; Dahl, R.; Hoffmann, H. J.
Background: Allergen specific immunotherapy is the only disease modifying treatment of allergic diseases. It induces complex cellular and humoral changes leading to an inhibition of type-1 allergic reactions. Method: Twenty four young grass pollen allergic adults suffering from seasonal rhino...
Howarth, P; Malling, Hans-Jørgen; Molimard, M
To cite this article: Howarth P, Malling H-J, Molimard M, Devillier P. Analysis of allergen immunotherapy studies shows increased clinical efficacy in highly symptomatic patients. Allergy 2012; 67: 321-327. ABSTRACT: Background: The assessment of allergen immunotherapy (AIT) efficacy...... them. Thus, clinical studies of AIT can neither establish baseline symptom levels nor limit the enrolment of patients to those with the most severe symptoms. Allergen immunotherapy treatment effects are therefore diluted by patients with low symptoms for a particular pollen season. The objective...... of this analysis was to assess the effect possible to achieve with AIT in the groups of patients presenting the most severe allergic symptoms. Methods: Study centres were grouped into tertiles categorized according to symptom severity scores observed in the placebo patients in each centre (low, middle and high...
Calderon, Moises A; Cox, Linda; Casale, Thomas B
of prescription and (ii) a new communication template viewed some months later, we performed an Internet-based survey of patient panels in France, Germany, Spain, the USA and Russia. The survey participants were either recent "early abandoners" (having discontinued allergen immunotherapy before the end...... of the prescribed course) or "non-starters" (having decided not to initiate a course of allergen immunotherapy recommended by their physician). All participants completed an on-line questionnaire immediately before and immediately after viewing the new communication template. The study's main objectives were...... to validate the new communication template and to assess its impact on anticipated willingness to initiate or resume allergen immunotherapy. RESULTS: We surveyed a total of 261 patients (France: 57; Germany: 51; Spain: 52; USA: 51; Russia: 50), comprising 127 "early abandoners" and 134 "non...
Grier, Thomas J; Converse, Lorie M; Rekkerth, Donna J; Renahan, Kevin E
Current summaries of effective maintenance dose ranges for subcutaneous immunotherapy (SCIT) are based on administration of 0.5-mL volumes. Extract formulations delivering equivalent dose ranges for practices using different injection volumes have not been reported, and calculation of the final glycerin concentrations in these solutions remains an inconvenient and repetitive process. To create math-free guides for allergen doses and glycerin concentrations that identify the extract concentrate volumes required to deliver doses within the ranges cited in the 2011 immunotherapy practice parameters for clinicians using 5.0-mL maintenance vials and injection volumes ranging from 0.2 to 1.0 mL. Algebraic calculations were performed to determine the specific combinations of extract concentrate strengths, volumes of these products in patient vaccines, and injection volumes needed for administration of target allergen doses spanning the current SCIT practice parameter recommendations. For each product or group (nonstandardized extracts), tables were constructed to define the allergen doses provided by various combinations of extract concentrate volumes and injection volumes. The values within the effective dose ranges for each product were highlighted to facilitate comparisons of specific conditions relevant to allergy specialists. Glycerin tables were also created to permit convenient assessments of the final concentrations of this stabilizer in patient prescriptions. SCIT dosing and glycerin tables are useful tools to assist allergists with practice decisions that involve variable patient formulas and injection volumes and can help identify suitable conditions for treatment of patients presenting with diverse allergen sensitivities and specificity profiles. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Arroabarren, Esozia; Tabar, Ana I; Echechipía, Susana; Cambra, Koldo; García, Blanca E; Alvarez-Puebla, Maria J
Subcutaneous immunotherapy (SCIT) discontinuation data in children remain scarce. We sought for differences in the clinical efficacy of 3 vs. 5 yr of SCIT in children with dust mite respiratory allergy. We performed a 5-yr, phase IV prospective study. After the first year, the patients were randomized to 3 (IT3) or 5 yr of treatment (IT5). Efficacy was assessed at 3rd and 5th year by symptom and medication scores and visual analog scales (VAS). Skin tests with common allergens and in vitro assessments were also performed. Eighty-one children (mean age: 9 yr) were randomly assigned to 3 (IT3: 41) or 5 yr (IT5: 40) of immunotherapy. After 3 years, rhinitis global scores decreased in IT3 (44%; p = 0.002) and in IT5 (50%; p = 0.001). Asthma global, symptom and medication scores decreased by 100% in IT3 (p = 0.001) and IT5 (p = 0.001). VAS scores also diminished significantly (IT3: 70%, p = 0.001; IT5: 62.5%; p = 0.001). At 5th year, global rhinitis scores were reduced an additional 30% in IT5 children. Comparisons between both groups did not show differences in rhinitis (p = 0.055), asthma global scores (p = 0.948) or VAS scores at 5th year. Twenty percent of IT5 (p = 0.002) and 7% of IT3 children (p = 0.705) developed new sensitizations. At 5th year, sIgG4 determinations decreased in IT3 without significant variations in IT5. Three years of SCIT induced significant improvement in children with dust mite respiratory allergy, but a 5-yr course added clinical improvement in rhinitis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Berings, Margot; Karaaslan, Cagatay; Altunbulakli, Can; Gevaert, Philippe; Akdis, Mübeccel; Bachert, Claus; Akdis, Cezmi A
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 IgG4 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 IgG4 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.
Canonica, Giorgio Walter; Passalacqua, Giovanni; Incorvaia, Cristoforo; Cadario, Gianni; Fiocchi, Alessandro; Senna, Gianenrico; Rossi, Oliviero; Romano, Antonino; Scala, Enrico; Romano, Catello; Ingrassia, Antonino; Zambito, Marcello; Dell'Albani, Ilaria; Frati, Franco
The efficacy of allergen immunotherapy (AIT) is well supported by evidence from trials and meta-analyses. However, its actual performance in daily practice may be diminished by several pitfalls, including inappropriate patient selection, and, especially, the use of allergen extracts of insufficient quality. We performed a survey, the Allergen Immunotherapy Decision Analysis, to evaluate which criteria specialists use to choose products for sublingual immunotherapy (SLIT) in adult patients suffering from allergic respiratory disease. We surveyed a total of 169 Italian allergists randomly chosen from a database belonging to a market research company (Lexis Ricerche, Milan, Italy). The survey was performed between October and November 2012 under the aegis of the European Center for Allergy Research Foundation and consisted of a questionnaire-based electronic survey prepared by a scientific board of 12 AIT experts. The questionnaire comprised two parts, the first of which contained 14 items to be ranked by each participant according to the importance assigned to each when choosing SLIT products. The physicians' rankings assigned major importance to the level of evidence-based validation of efficacy and safety, standardization of the product, efficacy based on personal experience, and defined content(s) of the major allergen(s) in micrograms. The results of this survey show that Italian allergists rank the quality-related characteristics of allergen extracts as highly important when choosing products for AIT. The allergists' preference for high-quality products should be addressed by regulatory agencies and by producers.
Calderón, M A; Larenas, D; Kleine-Tebbe, J
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 prod...
Ola B Nilsson
Full Text Available BACKGROUND: Dog dander extract used for diagnosis and allergen-specific immunotherapy is often of variable and of poor quality. OBJECTIVE: To assemble four well-established dog allergen components into one recombinant folded protein for improved diagnosis and vaccination of allergy to dog. METHODS: A linked molecule, comprising the four dog lipocalin allergens Can f 1, Can f 2, Can f 4 and Can f 6 was constructed. The tetrameric protein was structurally characterized by small angle X-ray scattering, and compared with each single recombinant lipocalin allergen or an equimolar mix of the four allergens by analytical size exclusion chromatography, circular dichroism, allergen-specific IgE in serum by ELISA and allergen-dependent capacity to activate basophils. The immunogenicity of the fusion protein was evaluated in immunized mice by assessing splenocyte proliferation and antibody production. RESULTS: The linked tetrameric construct was produced as a soluble fusion protein, with the specific folds of the four individual allergens conserved. This multi-allergen molecule was significantly more efficient (p<0.001 than each single recombinant allergen in binding to dog-specific IgE, and the epitope spectrum was unaffected compared to an equimolar mix of the four allergens. Basophil degranulation revealed that the biologic activity of the linked molecule was retained. Immunization of mice with the linked construct induced comparable allergen-specific IgG responses with blocking capacity towards all included allergens and generated comparably low T-cell responses. CONCLUSION: We provide the first evidence for a linked recombinant molecule covering the major dog allergens for potential use in diagnostics and allergy vaccination of dog allergic patients.
Dhami, Sangeeta; Nurmatov, Ulugbek; Varga, Eva-Maria; Sturm, Gunter; Muraro, Antonella; Akdis, Cezmi A.; Antolin-Amerigo, Dario; Bilo, M. Beatrice; Bokanovic, Danijela; Calderon, Moises A.; Cichocka-Jarosz, Ewa; Oude Elberink, Joanna N. G.; Gawlik, Radoslaw; Jakob, Thilo; Kosnik, Mitja; Lange, Joanna; Mingomataj, Ervin; Mitsias, Dimitris I.; Mosbech, Holger; Pfaar, Oliver; Pitsios, Constantinos; Pravettoni, Valerio; Roberts, Graham; Rueeff, Franziska; Sin, Betul Ayse; Sheikh, Aziz
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the
Dhami, Sangeeta; Nurmatov, Ulugbek; Pajno, Giovanni Battista; Fernandez-Rivas, Montserrat; Muraro, Antonella; Roberts, Graham; Akdis, Cezmi; Alvaro-Lozano, Montserrat; Beyer, Kirsten; Bindslev-Jensen, Carsten; Burks, Wesley; du Toit, George; Ebisawa, Motohiro; Eigenmann, Philippe; Knol, Edward; Makela, Mika; Nadeau, Kari Christine; O'Mahony, Liam; Papadopoulos, Nikolaos; Poulsen, Lars; Sackesen, Cansin; Sampson, Hugh; Santos, Alexandra; van Ree, Ronald; Timmermans, Frans; Sheikh, Aziz
BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for IgE-mediated food allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in IgE-mediated food
Virchow, Johann Christian; Backer, Vibeke; Kuna, Piotr
IMPORTANCE: The house dust mite (HDM) sublingual allergen immunotherapy (SLIT) tablet is a potential novel treatment option for HDM allergy-related asthma. OBJECTIVES: To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticos...
Dhami, S.; Zaman, H.; Varga, Eva-Maria; Sturm, G. J.; Muraro, A.; Akdis, C. A.; Antolin-Amerigo, D.; Bilo, M. B.; Bokanovic, Danijela; Calderon, M. A.; Cichocka-Jarosz, E.; Elberink, J. N. G. Oude; Gawlik, R.; Jakob, T.; Kosnik, M; Lange, J; Mingomataj, Ervin; Mitsias, Dimitris I.; Mosbech, H; Ollert, Markus; Pfaar, O.; Pitsios, Constantinos; Pravettoni, V.; Roberts, G.; Rueff, F.; Sin, Betul Ayse; Asaria, M.; Netuveli, G.; Sheikh, A.
Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of
Full Text Available Abstract Background Grass pollen is a major cause of respiratory allergy worldwide and contain a number of allergens, some of theme (Phl p 1, Phl p 2, Phl p 5, and Phl 6 from Phleum pratense, and their homologous in other grasses are known as major allergens. The administration of grass pollen extracts by immunotherapy generally induces an initial rise in specific immunoglobulin E (sIgE production followed by a progressive decline during the treatment. Some studies reported that immunotherapy is able to induce a de novo sensitisation to allergen component previously unrecognized. Methods We investigated in 30 children (19 males and 11 females, mean age 11.3 years, 19 treated with sublingual immunotherapy (SLIT by a 5-grass extract and 11 untreated, the sIgE and sIgG4 response to the different allergen components. Results Significant increases (p Conclusions These findings confirm that the initial phase of SLIT with a grass pollen extract enhances the sIgE synthesis and show that the sIgE response concerns the same allergen components which induce IgE reactivity during natural exposure.
I. M. Gaiduk
Full Text Available Aims of study: evaluation of immunological parameters in course of sublingual allergen-specific immunotherapy with tree pollen mixture in children with hay fever.Materials and methods: the study included one-hundred patients 5 to 18 years of age with hay fever (pollen rhinitis, rhinoconjunctivitis and/or asthma. Allergen-specific immunotherapy was administered pre-seasonally for three consecutive years. Cytokinechanges were studied in blood serum and in lavages from nasal cavity. Samples assessed before treatment and after 2nd and 3rd courses SLIT completion.Results: increased serum concentrations of IL-10, IFNγ, and decreased IL-4 contents were revealed in the course of treatment. No significant changes in cytokineconcentrations were detectable in nasal lavages.Conclusions: the changes revealed correspond to a shift of T cell response profile towards Th1 pathway, thus confirming pathogenetic effects of sublingual allergen-specific
Mohammad Reza Zandkarimi
Full Text Available Background: Allergen immunotherapy involves the administration of gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure. This study evaluated the clinical efficacy of immunotherapy with extracts of common aeroallergens North-East of Iran in asthma and allergic rhinitis. Material and Methods: In this prospective study 156 cases were chosen randomley. The mean age of patients was 37 years (range 5-65 years. The patients with mild to moderate asthma and allergic rhinitis and history of atopy were selected for immunotherapy when they showed no effective response to medical treatment.Immunotherapy materials were made from common aeroallergens in north-eastern region of Iran by Dome Hollister US company. Immunotherapy schedule for injection of the extract with vial dilution of 1:10000pg was one injection every week for ten weeks and one injection with dilution of 1:1000pg every other week for the other ten weeks and one injection monthly from dilution of 1:100pg for two years. Results: One hundred twenty (77% of cases had allergic rhinitis 29(18.5% cases had allergic asthma and 7(4.5% cases were mixed. Mean age of patients were 37 years old. 48(30.8% cases were male. Analysis of efficacy of treatment showed that immunotherapy significantlyimproved the signs and symptoms of all the groups. In allergic rhinitis group 84(70% cases completely improved, 22(18.4% patients moderately responded and no response to immunotherapy was observed in 14(11.6% patients. In allergic asthma group, 22(75% cases completely improved 4(13.6% cases moderately responded and no response to immunotherapy was detected in 3(11.4% cases. In mixed group, 3(42.8% cases completely improved, 3(42.8% cases moderately responded and no response was observed in 1(14.4% case. Conclusion: Specific allergen immunotherapy for patients with allergic persistent
Cox, Linda; Esch, Robert E; Corbett, Mark; Hankin, Cheryl; Nelson, Michael; Plunkett, Greg
To discuss recent issues pertinent to allergen immunotherapy practice in the United States. Allergen extract preparation guidelines, updated allergen immunotherapy practice parameter (AIPP) guidelines, and evolving trends in how immunotherapy outcomes will be measured and assessed. Allergen extract preparation guidelines have been established by 2 entities: the US Pharmacopeia and an American Academy of Allergy, Asthma, and Immunology/American College of Allergy, Asthma, and Immunology/Joint Council of Allergy, Asthma, and Immunology Joint Task Force. Minor differences exist between these guidelines, but both focus on aseptic techniques and require that compounding personnel pass a written examination and annual media fill test. The AIPP third update provides new dosing recommendations for Bermuda grass, imported fire ant, and nonstandardized extracts distinguishing between pollen (0.5 mL of a 1:100 or 1:200 vol/vol) and mold/fungi or cockroach (highest tolerated dose) extracts. Because of limited and sometimes conflicting data on high and low proteolytic-containing extract compatibility, the AIPP continues to recommend against mixing these together. Although the AIPP does not specifically recommend a specific diluent, recent evidence suggests normal saline may not be as effective a stabilizer for extract dilutions as glycerin or human serum albumin. Currently, immunotherapy efficacy is determined with subjective assessments that rely on patient reporting, but this may change as health care reform evolves. It will likely become more important for US allergy/immunology practices to demonstrate immunotherapy comparative-effectiveness and report quality measures. Recent comparative-effectiveness studies have demonstrated the cost-effectiveness of immunotherapy compared with symptomatic drug treatment. Copyright © 2011 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).
Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante
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.
Scholz, Fiona M; Burrows, Amanda K; Muse, Russell
Sublingual immunotherapy (SLIT) offers an alternative mode of allergen delivery to subcutaneous immunotherapy (SCIT) with the aim of inducing immunological tolerance. Currently, there are no published reports regarding the efficacy or safety of SLIT in horses. To describe the first case of several adverse events occurring in a horse subsequent to the repeat administration of SLIT. A seven-year-old, warmblood mare with a confirmed diagnosis of equine hypersensitivity dermatitis (EHD). Immunotherapy was recommended for management of EHD. Due to the temperament of the horse, the owner elected to proceed with SLIT. Thirty six hours after commencing SLIT, the mare developed scleral oedema, moderate dyspnoea and abdominal discomfort. SLIT was withdrawn for 10 days and re instituted using a ten-fold dilution of the original vaccine. Localized oedema and swelling of the tongue developed within 12 h of administration. At this juncture, SLIT was withdrawn. The horse was rechallenged with the SLIT allergen vehicle, 50% glycerine and no adverse reactions occurred. SCIT was commenced using the same allergens and no adverse events occurred with repeated administration. To the best of the authors' knowledge, this is the first reported case of adverse reactions developing subsequent to the administration of SLIT for the management of EHD. © 2016 ESVD and ACVD.
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)
Turkalj, Mirjana; Banic, Ivana; Anzic, Srdjan Ante
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
Calderón, M; Cardona, V; Demoly, P
Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals. Improved understanding of immunology has taught us a great deal about the underlying mechanisms involved in allergen immunotherapy; however, despite these developments, a number of important questions remain unanswered. Several of these questions relate to the practice of allergen immunotherapy in the clinic, such as: Is it possible to unify units of allergen potency? Which treatment schedules are best? Is allergen immunotherapy effective in all patient groups? Is there a dose-response relationship for efficacy and safety?, and Is there evidence for long-term effects following allergen immunotherapy? Others are related to new developments, such as new indications, or developments in the production of allergens. On the centenary of Noon's discovery, European experts in the field of immunotherapy met in Geneva under the aegis of the EAACI to discuss these controversial issues. This study presents outcomes and conclusions from these discussions. © 2012 John Wiley & Sons A/S.
Blank, Simon; Etzold, Stefanie; Darsow, Ulf
Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant...... major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due...... to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic...
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
Full Text Available Mirjana Turkalj,1,2 Ivana Banic,1 Srdjan Ante Anzic1 1Children’s Hospital Srebrnjak, Zagreb, 2Faculty of Medicine, JJ Strossmayer University of Osijek, Osijek, Croatia Abstract: 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. Keywords: allergic rhinitis, allergy, ragweed, allergen-specific immunotherapy, Ambrosia artemisiifolia
Calderon, M A; Gerth van Wijk, R; Eichler, I
This article is the result of consensus reached by a working group of clinical experts in paediatric allergology as well as representatives from an ethical committee and the European Medicine Agency (EMA). The manuscript covers clinical, scientific, regulatory and ethical perspectives on allergen....... The European Academy of Allergy and Clinical Immunology (EAACI) serves as the platform of such cooperation....
Blank, Simon; Etzold, Stefanie; Darsow, Ulf
Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant m...
Blank, Simon; Etzold, Stefanie; Darsow, Ulf; Schiener, Maximilian; Eberlein, Bernadette; Russkamp, Dennis; Wolf, Sara; Graessel, Anke; Biedermann, Tilo; Ollert, Markus; Schmidt-Weber, Carsten B
Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic grade HBV extracts which are approved for immunotherapy in numerous countries. The extracts were analyzed for their content of the major allergens Api m 1, Api m 2, Api m 3, Api m 5 and Api m 10. Using allergen-specific antibodies we were able to demonstrate the underrepresentation of relevant major allergens such as Api m 3, Api m 5 and Api m 10 in particular therapeutic extracts. Taken together, standardization of therapeutic extracts by determination of the total allergenic potency might imply the intrinsic pitfall of losing information about particular major allergens. Moreover, the variable allergen composition of different therapeutic HBV extracts might have an impact on therapy outcome and the clinical management of HBV-allergic patients with specific IgE to particular allergens.
Full Text Available Allergen-specific immunotherapy (SIT is the only available curative treatment of allergic diseases. Recent evidence provided a plausible explanation to its multiple mechanisms inducing both rapid desensitization and long-term allergen-specific immune tolerance, and suppression of allergic inflammation in the affected tissues. During SIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T cells, which suppress proliferative and cytokine responses against the allergen of interest. Regulatory T cells are characterized by IL-10 and TGF-beta secretion and expression of important cell surface suppressive molecules such as cytotoxic T lymphocyte antigen-4 and programmed death-1 that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Regulatory T cells and particularly IL-10 also have an influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies. In addition, development of allergen-specific B regulatory cells that produce IL-10 and develop into IgG4 producing plasma cells represent essential players in peripheral tolerance. These findings together with the new biotechnological approaches create a platform for development of the advanced vaccines. Moreover, reliable biomarkers could be selected and validated with the intention to select the patients who will benefit most from this immune-modifying treatment. Thus, allergen-SIT could provide a complete cure for a larger number of allergic patients and novel preventive approaches need to be elaborated.
Björstad, Åse; Cardell, Lars-Olaf; Hahn-Pedersen, Julie; Svärd, Mikael
In Sweden, approximately 6% of children and 10% of adults suffer from house dust mite (HDM) allergy with symptoms of allergic rhinitis and allergic asthma. Treatment is aimed at reducing HDM exposure and to control the symptoms of allergic rhinitis and allergic asthma by symptom-relieving pharmacotherapy. This pharmacotherapy is often effective, but some patients remain inadequately controlled. For these patients, allergy immunotherapy (AIT, subcutaneous or sublingual) with repeated administration of HDM allergen should be considered. The objective of this study was to compare the costs for sublingual AIT (SLIT; SQ® SLIT-tablet) to the costs for subcutaneous AIT (SCIT; SQ® SCIT) for the treatment of HDM allergy in a cost-minimisation analysis (CMA). The CMA included resources (and costs) for treatment, healthcare visits, travelling and lost productivity. Resource use based on Swedish clinical treatment practice and costs were obtained from medical price lists. Analyses were conducted from the societal, as well as healthcare perspective, by use of a time horizon of 3 years. The results show that SQ® SLIT-tablet is a cost-saving treatment as compared to SQ® SCIT for the treatment of HDM allergy (€6800 over 3 years). The results are mainly driven by the cost of healthcare visits and the frequency of SCIT administrations. In conclusion, cost-savings of €6800 over 3 years are expected from treating HDM allergy with SQ® SLIT-tablet as compared to SQ® SCIT, including costs for treatment, healthcare visits, travelling and lost productivity. The reduced number of healthcare visits compensates for higher medication costs.
Tater, Kathy Chu; Cole, William Elliott; Pion, Paul David
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.
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
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.
Morales, María; Gallego, Mayte; Iraola, Victor; Taulés, Marta; de Oliveira, Eliandre; Moya, Raquel; Carnés, Jerónimo
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.
González-Rioja, Roberto; Ibarrola, Ignacio; Arilla, M Carmen; Ferrer, Angel; Mir, Amparo; Andreu, Carmen; Martínez, Alberto; Asturias, Juan A
Despite the use of conventional allergen-specific immunotherapy in clinical practice, more defined, efficient, and safer allergy vaccines are required. The aim of the study was to obtain hypoallergenic molecules by deleting B-cell epitopes, which could potentially be applied to Parietaria judaica pollen allergy treatment. Three hybrid molecules (Q1, Q2, and Q3) derived from fragments of the 2 major P judaica pollen allergens, Par j 1 and Par j 2, were engineered by means of PCR. Hybrid structures were compared with their natural components by means of circular dichroism, and their biologic activities were compared by using T-cell proliferation assays. Their IgE-binding activity was determined with Western blotting, skin prick tests, and enzyme allergosorbent and ELISA inhibition tests. The hybrid proteins, especially Q2 and Q3, revealed significantly reduced IgE reactivity compared with the natural allergens, as well as with the whole P judaica extract. Furthermore, in vivo skin prick tests showed that the hybrid proteins had a significantly lower potency to induce cutaneous reactions than the whole P judaica extract. Two (Q1 and Q2) of the 3 hybrid proteins induced a comparable T-cell proliferation response as that produced by the whole extract and natural allergens. Considering its reduced anaphylactogenic potential, together with its conserved T-cell reactivity, the engineered Q2 protein could be used in safe and shortened schedules of allergen-specific immunotherapy against P judaica pollen allergy. Recombinant hybrid Q2 is able to induce T-cell proliferation, thus evidencing a potential therapeutic effect. Its reduced IgE-binding capacity envisages an excellent safety profile.
Rønborg, Steen; Johnsen, Claus R; Theilgaard, Sune; Winther, Anders; Hahn-Pedersen, Julie; Andreasen, Jakob Nørgaard; Olsen, Jens
Objectives Currently, patients with persistent moderate-to-severe house dust mite (HDM) allergic rhinitis despite use of symptom-relieving medication can be offered subcutaneously administered allergy immunotherapy (SQ SCIT; Alutard SQ) as standard care of treatment in Denmark. Recently, a HDM sublingually administered allergy immunotherapy tablet (SQ SLIT-tablet; ACARIZAX) has been developed for at-home treatment. The purpose of this analysis is to compare the costs related to treatment and administration of SQ SLIT-tablet and SQ SCIT. Methods Assuming equal efficacy between ther SQ SLIT-tablet and SQ SCIT, the cost-minimization analysis was the most appropriate for the comparison. According to guidelines and Summary of Product Characteristics, the treatment duration of SQ SLIT-tablet is 3 years and 3-5 years for SQ SCIT. The courses of treatment vary among patients and, therefore, the costs of treatment have been calculated for an average patient with HDM respiratory allergic disease (RAD) receiving either SQ SLIT-tablet or SQ SCIT. All costs associated with allergy immunotherapy were collected, i.e., cost of medication, administration and treatment setting, and discounted according to Danish guidelines. Comprehensive univariate sensitivity analyses were carried out. Results The treatment costs for an average patient with HDM RAD are €3094 for SQ SLIT-tablet and €3799 for SQ SCIT; however, when adding indirect costs to the calculations the total costs of the treatments are €3697 and €6717 for SQ SLIT-tablet and SQ SCIT, respectively. Therefore, if 2500 patients with HDM RAD were treated with SQ SLIT-tablet instead of SQ SCIT, it would elicit a saving to the healthcare system of ∼€1.8 million. The conclusion was robust to any changes in the sensitivity analysis. Conclusion With regards to the cost of treating Danish patients with HDM RAD, it is clearly cost-saving to treat patients with SQ SLIT-tablet compared to SQ SCIT.
Full Text Available Angel Moral,1 Victoria Moreno,2 Francisco Girón,3 David El-Qutob,4 José D Moure,5 Manuel Alcántara,6 Antonia Padial,7 Alberto G Oehling,8 Carmen Millán,9 Fernando de la Torre10 1Allergy Service, Hospital Virgen del Valle, Toledo, 2Allergy Service, Hospital Blanca Paloma, Huelva, 3Consulta Privada, Granada, 4Allergy Service, Clínica Atenea, Castellón, 5Pediatric Department, Complejo Hospitalario Universitario de Santiago, A Coruña, 6Allergy Service, Complejo Hospitalario de Jaén, Jaén, 7Allergy Service, Hospital Infanta Sofía, Madrid, 8Centro de Alergia y Asma Balear, Mallorca, 9Consulta Privada, Cádiz, 10ALK-Abelló, SA, Madrid, Spain Background: Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy.Patients and methods: A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months.Results: The most frequent adverse reaction was oral pruritus (13.7% of the patients. Most of the reactions were local (84.7% and immediate (93.5% and occurred during the initiation phase (60.6%. All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417, age (P=0.1801, years since the disease was first
Aasbjerg, K; Backer, V; Lund, G
with regular serum measurements of specific IgE, IgG4, IgE-blocking factor, facilitated antigen presentation (FAP), and basophil activation test (BAT). Nasal challenges were used to assess changes in nasal sensitivity. RESULTS: After 15 months of treatment IgG4, IgE-blocking factor, FAP, and BAT values...
Bonertz, A; Roberts, G; Slater, J E
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...
Aguilar-Pimentel, Juan Antonio; Graessel, Anke; Alessandrini, Francesca
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......)-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...
Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells.
Scadding, G W; Shamji, M H; Jacobson, M R; Lee, D I; Wilson, D; Lima, M T; Pitkin, L; Pilette, C; Nouri-Aria, K; Durham, S R
The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT). To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB). Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebo-treated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-beta mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT. Foxp3(+) cells were increased in the oral epithelium of SLIT- vs. placebo-treated atopics (P=0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P=0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT- compared with placebo-treated atopics (P=0.1 for both). IgG(1) and IgG(4) were increased following SLIT (Ppollen extract is associated with increased Foxp3(+) cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.
Van Ree, R; Van Leeuwen, W A; Dieges, P H; Van Wijk, R G; De Jong, N; Brewczyski, P Z; Kroon, A M; Schilte, P P; Tan, K Y; Simon-Licht, I F; Roberts, A M; Stapel, S O; Aalberse, R C
IgE titres tend to rise early after the start of immunotherapy, followed by a decline to pre-immunotherapy levels or lower. We were interested to know whether the early increase in IgE antibodies includes new specificities of IgE, and whether these responses persist. Sera of 64 patients undergoing grass pollen immunotherapy were tested for IgE against four purified grass pollen allergens: Lol p 1, 2, 3, and 5. At least two serum samples were taken, one before the start of therapy and one between 5 and 18 months after the first immunization (mean: 10 months). The mean IgE responses to Lol p 1, 2 and 3 showed a moderate but not significant increase. In contrast, the mean IgE response to Lol p 5 showed a significant decrease of > 30%. IgE against total Lohum perenne pollen extract moderately increased (> 20%), showing that a RAST for total pollen is not always indicative for the development of IgE against its major allergens. For > 40% of the patients it was found that IgE against one or more of the four allergens increased, while IgE against the remaining allergen(s) decreased. For 10 sera the ratio of IgE titres against at least two allergens changed by at least a factor of 5. The changes in specific IgE also included conversions from negative (< 0.1 RU) to positive (0.6 to 5.0 RU) for five patients. For two patients, the induction of these 'new' IgE antibodies against major allergens was shown to result in a response that was persistent over several years. Although active induction of new IgE specificities by immunotherapy was not really proven, the observations in this study indicate that monitoring of IgE against purified (major) allergens is necessary to evaluate changes in specific IgE in a reliable way.
Full Text Available In 1993 the European Academy of Allergy and Clinical Immunology was the first official organization to recognize that sublingual administration could be “promising route” for allergic desensitization. A few years later, the World Health Organization recommended this therapy as “a viable alternative to the injection route in adults.” The first meta-analysis showed sublingual allergen specific immunotherapy (SLIT effectiveness for allergic rhinitis and another study showed SLIT can actually help prevent the development of asthma both in adults and in children. The main goal of this review article is to present insight into the most up-to-date understanding of the clinical efficacy and safety of immunotherapy in the treatment of pediatric patients with allergic rhinitis and asthma. A literature review was performed on PubMed from 1990 to 2015 using the terms “asthma,” “allergic rhinitis,” “children,” “allergen specific immune therapy.” Evaluating data from double-blind placebo-controlled randomized clinical trials (DB-PC-RCTs, the clinical efficacy (assessed as the reduction of symptom score and the need of rescue medicament of SLIT for allergic rhinitis and allergic asthma, has been confirmed in various meta-analysis Outcomes such as rhinoconjunctivitis score and medication scores, combined scores, quality of life, days with severe symptoms, immunological endpoints, and safety parameters were all improved in the SLIT-tablet compared with placebo group. SLIT safety has been already proven in many DB-PC-RCTs and real-life settings. In accordance with all of the above mentioned, the goals for future trials and studies are the development of comprehensive guidelines for clinical practice on immunotherapy, embracing all the different potential participants. The importance of allergen immunotherapy is of special relevance in the pediatric age, when the plasticity and modulability of the immune system are maximal, and when
... Professionals Questions to Ask about Your Treatment Research Immunotherapy to Treat Cancer Immunotherapy is a type of ... from living organisms to treat cancer. What is Immunotherapy? View this video on YouTube. Types of Immunotherapy ...
Full Text Available Nowadays, treatment of food allergy only considered the avoidance of the specific food. However, the possibility of cross-reactivity makes this practice not very effective. Immunotherapy may exhibit as a good alternative to food allergy treatment. The use of hypoallergenic molecules with reduced IgE binding capacity but with ability to stimulate the immune system is a promising tool which could be developed for immunotherapy. In this study, three mutants of Pru p 3, the principal allergen of peach, were produced based on the described mimotope and T cell epitopes, by changing the specific residues to alanine, named as Pru p 3.01, Pru p 3.02, and Pru p 3.03. Pru p 3.01 showed very similar allergenic activity as the wild type by in vitro assays. However, Pru p 3.02 and Pru p 3.03 presented reduced IgE binding with respect to the native form, by in vitro, ex vivo, and in vivo assays. In addition, Pru p 3.03 had affected the IgG4 binding capacity and presented a random circular dichroism, which was reflected in the nonrecognition by specific antibodies anti-Pru p 3. Nevertheless, both Pru p 3.02 and Pru p 3.03 maintained the binding to IgG1 and their ability to activate T lymphocytes. Thus, Pru p 3.02 and Pru p 3.03 could be good candidates for potential immunotherapy in peach-allergic patients.
Full Text Available Allergic rhinitis is an immunologic disorder that develops in individuals who have produced allergen-specific immunoglobulin E in response to environmental exposures (most commonly to pollens, animal dander, insect debris, and molds. For patients with a severe allergy that is not responsive to environmental controls and pharmacotherapy or for those who do not wish to use medication for a lifetime, immunotherapy may be offered. Specific immunotherapy as practiced since hundred years in Western Europe and the USA. Different routes for specific immunotherapy have been evaluated, such as the subcutaneous, sublingual, oral, nasal, bronchial, and intra-lymphatic, the first 2 of these routes being the most commonly used today in clinical practice. In this article, subcutaneous and sublingual immunotherapy in allergic rhinitis is reviewed.
Taher, Yousef A.; Piavaux, Benoit J. A.; Gras, Renee; van Esch, Betty C. A. M.; Hofman, Gerard A.; Bloksma, Nanne; Henricks, Paul A. J.; van Oosterhout, Antoon J. M.
Background: The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. Objective: We examined (1) whether IDO activity is required during tolerance induction by allergen immunotherapy or for the subsequent suppressive
Full Text Available The records of patients from the Allergology Service in the Previsora Policlinic, Camagüey were revised to evaluate benefits and risks of the subcutaneous immunotherapy (ITSC with extracts of acari. The study was observational, analytic and retrospective of cases and controls in allergic rhinoconjunctivitis and bronchial asthma. A total of 160 subjects, older than 18 years old, were chosen. Eighty out of them had already received ITSC with dose increase during 13 weeks and maintenance with monthly injections during 18 months. A total of 80 patients who only received prevention measures and medications during the crises were paired. Questionnaires were applied for quality of rhinoconjunctivitis life and asthma, about the consumption of medications and the frequency of the crises. The adverse events were measured, as they were local and systemic to the cutaneous tests, to the ITSC and the different pharmacological treatments. There was a significant increase of the punctuation of life quality questionnaires, (p=0.011. The consumption of medications decreased in both the cases and the controls, without significant differences (p=0.083. The frequency of the rhinitis and asthma crises decrease in the group of ITSC (p=0.029. Slight local and systemic reactions were reported in both groups with Odds ratio (OR=2.029 in the ITSC group, with a 95% confidence interval of 1.114–3.967 (p=0.019. The results show that the subcutaneous immunotherapy with acari offers benefits and few risks to patients with allergic rhinoconjunctivitis and asthma.
Nelson, Harold S; Calderon, Moises A; Bernstein, David I; Casale, Thomas B; Durham, Stephen R; Andersen, Jens S; Esch, Robert; Cox, Linda S; Nolte, Hendrik
Progress has been made in the harmonization of efficacy and safety outcome measures for allergen immunotherapy (AIT) trials, but unresolved issues still remain. Furthermore, there are discrepancies in recommendations from professional medical societies and regulatory agencies regarding requirements for AIT trials. In this article, we reviewed published recommendations and current data from recent clinical trials, as well as the criteria applied by regulatory authorities for approval of AIT products, to provide updated considerations for conducting phase 3 AIT trials. Topics discussed include analysis of outcomes and trial designs for pediatric and asthma indications, as well as trial designs for perennial allergic rhinoconjunctivitis. In addition, the need for harmonization of safety reporting is emphasized. Considerations presented in this article may further effort to find common ground among professional medical societies and government agencies in developing future recommendations for AIT trial design.
Besh, O M; Radchenko, O M
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.
Full Text Available Abstract Asthma and rhinitis are often co-morbid conditions. As rhinitis often precedes asthma it is possible that effective treatment of allergic rhinitis may reduce asthma progression. The aim of our study is to investigate history of allergic rhinitis as a risk factor for asthma and the potential effect of allergen immunotherapy in attenuating the incidence of asthma. Hospital-referred non-asthmatic adults, aged 18–40 years between 1990 and 1991, were retrospectively followed up until January and April 2000. At the end of follow up, available subjects were clinically examined for asthma diagnosis and history of allergen specific immunotherapy, second-hand smoking and the presence of pets in the household. A total of 436 non-asthmatic adults (332 subjects with allergic rhinitis and 104 with no allergic rhinitis nor history of atopy were available for final analyses. The highest OR (odds ratio associated with a diagnosis of asthma at the end of follow-up was for the diagnosis of allergic rhinitis at baseline (OR, 7.8; 95%CI, 3.1–20.0 in the model containing the covariates of rhinitis diagnosis, sex, second-hand smoke exposure, presence of pets at home, family history of allergic disorders, sensitization to Parietaria judaica; grass pollen; house dust mites; Olea europea: orchard; perennial rye; and cat allergens. Female sex, sensitization to Parietaria judaica and the presence of pets in the home were also significantly predictive of new onset asthma in the same model. Treatment with allergen immunotherapy was significantly and inversely related to the development of new onset asthma (OR, 0.53; 95%CI, 0.32–0.86. In the present study we found that allergic rhinitis is an important independent risk factor for asthma. Moreover, treatment with allergen immunotherapy lowers the risk of the development of new asthma cases in adults with allergic rhinitis.
Polosa, Riccardo; Al-Delaimy, Wael K; Russo, Cristina; Piccillo, Giovita; Sarvà, Maria
Asthma and rhinitis are often co-morbid conditions. As rhinitis often precedes asthma it is possible that effective treatment of allergic rhinitis may reduce asthma progression. The aim of our study is to investigate history of allergic rhinitis as a risk factor for asthma and the potential effect of allergen immunotherapy in attenuating the incidence of asthma. Hospital-referred non-asthmatic adults, aged 18–40 years between 1990 and 1991, were retrospectively followed up until January and April 2000. At the end of follow up, available subjects were clinically examined for asthma diagnosis and history of allergen specific immunotherapy, second-hand smoking and the presence of pets in the household. A total of 436 non-asthmatic adults (332 subjects with allergic rhinitis and 104 with no allergic rhinitis nor history of atopy) were available for final analyses. The highest OR (odds ratio) associated with a diagnosis of asthma at the end of follow-up was for the diagnosis of allergic rhinitis at baseline (OR, 7.8; 95%CI, 3.1–20.0 in the model containing the covariates of rhinitis diagnosis, sex, second-hand smoke exposure, presence of pets at home, family history of allergic disorders, sensitization to Parietaria judaica; grass pollen; house dust mites; Olea europea: orchard; perennial rye; and cat allergens). Female sex, sensitization to Parietaria judaica and the presence of pets in the home were also significantly predictive of new onset asthma in the same model. Treatment with allergen immunotherapy was significantly and inversely related to the development of new onset asthma (OR, 0.53; 95%CI, 0.32–0.86). In the present study we found that allergic rhinitis is an important independent risk factor for asthma. Moreover, treatment with allergen immunotherapy lowers the risk of the development of new asthma cases in adults with allergic rhinitis. PMID:16381607
Durham, Stephen R; Yang, William H; Pedersen, Martin R; Johansen, Niels; Rak, Sabina
Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases. Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events. To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis. A multinational, multicenter, randomized, placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX; ALK-Abelló, Hørsholm, Denmark) or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks. Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T (P = .0710; P = .0470) compared with placebo. Significantly better rhinoconjunctivitis quality of life scores (P = .006) and an increased number of well days (P = .041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication use, 29%, P = .0120). No safety concerns were observed. This study confirms dose-dependent efficacy of the grass allergen tablet. Although further studies are required, the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy. For patients with grass pollen allergy, sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life.
Full Text Available Allergen-specific immunotherapy (AIT induces tolerance and shifts the Th2 response towards a regulatory T-cell profile. The underlying mechanisms are not fully understood, but dendritic cells (DC play a vital role as key regulators of T-cell responses. DCs interact with allergens via Fc receptors (FcRs and via certain C-type lectin receptors (CLRs, including CD209/DC-SIGN, CD206/MR and Dectin-2/CLEC6A. In this study, the effect of AIT on the frequencies as well as the FcR and CLR expression profiles of human DC subsets was assessed. PBMC was isolated from peripheral blood from seven allergic donors before and after 8 weeks and 1 year of subcutaneous AIT, as well as from six non-allergic individuals. Cells were stained with antibodies against DC subset-specific markers and a panel of FcRs and CLRs and analyzed by flow cytometry. After 1 year of AIT, the frequency of CD123+ DCs was increased and a larger proportion expressed FcεRI. Furthermore, the expression of CD206 and Dectin-2 was reduced on CD141+ DCs after 1 year of treatment and CD206 as well as Dectin-1 was additionally down regulated in CD1c+ DCs. Interestingly, levels of DNGR1/CLEC9A on CD141+ DCs were increased by AIT, reaching levels similar to cells isolated from non-allergic controls. The modifications in phenotype and occurrence of specific DC subsets observed during AIT suggest an altered capacity of DC subsets to interact with allergens, which can be part of the mechanisms by which AIT induces allergen tolerance.
Lundberg, Kristina; Rydnert, Frida; Broos, Sissela; Andersson, Morgan; Greiff, Lennart; Lindstedt, Malin
Allergen-specific immunotherapy (AIT) induces tolerance and shifts the Th2 response towards a regulatory T-cell profile. The underlying mechanisms are not fully understood, but dendritic cells (DC) play a vital role as key regulators of T-cell responses. DCs interact with allergens via Fc receptors (FcRs) and via certain C-type lectin receptors (CLRs), including CD209/DC-SIGN, CD206/MR and Dectin-2/CLEC6A. In this study, the effect of AIT on the frequencies as well as the FcR and CLR expression profiles of human DC subsets was assessed. PBMC was isolated from peripheral blood from seven allergic donors before and after 8 weeks and 1 year of subcutaneous AIT, as well as from six non-allergic individuals. Cells were stained with antibodies against DC subset-specific markers and a panel of FcRs and CLRs and analyzed by flow cytometry. After 1 year of AIT, the frequency of CD123+ DCs was increased and a larger proportion expressed FcεRI. Furthermore, the expression of CD206 and Dectin-2 was reduced on CD141+ DCs after 1 year of treatment and CD206 as well as Dectin-1 was additionally down regulated in CD1c+ DCs. Interestingly, levels of DNGR1/CLEC9A on CD141+ DCs were increased by AIT, reaching levels similar to cells isolated from non-allergic controls. The modifications in phenotype and occurrence of specific DC subsets observed during AIT suggest an altered capacity of DC subsets to interact with allergens, which can be part of the mechanisms by which AIT induces allergen tolerance. PMID:26863539
Blume, Steven W; Yeomans, Karen; Allen-Ramey, Felicia; Smith, Nancy; Kim, Harold; Lockey, Richard F; Nichol, Michael B
Allergy immunotherapy (AIT) is the only available treatment that alters the natural course of allergies and has possible disease-modifying effects. AIT is administered primarily via subcutaneous injection delivered in a physician's office. Few studies have been conducted in the United States or Canada to evaluate the costs of subcutaneous immunotherapy (SCIT). To (a) describe SCIT administration processes, resources, and costs and (b) characterize the patient population receiving SCIT. A multisite, prospective, observational time and motion study was conducted. Injection and wait times were collected by a third-party observer on 1 visit for each patient. Extract preparation processes were also observed. Site staff reported on treatment protocols, administrative time, supplies, and patient medical history. Patients responded to questionnaires on demographics, reasons for treatment, medication use, productivity, and travel time. Costs were estimated by applying unit costs to the time observations and the patient- and staff-reported data. A total of 670 SCIT patients were enrolled at 6 sites in the United States and 6 sites in Canada. Average age in the United States was 41 years (SD = 18) and 44 years (15) in Canada, with 10% of the patients aged ≥ 65 years. Annual incomes were over $100,000 for 40% of U.S. patients and 30% of Canadian patients. U.S. patients had over 4 times as many different allergens in their SCIT treatments as Canadian patients, with a mean of 18 versus 4. The most common reasons reported for starting SCIT was a "desire to cure allergies once and for all" (73%) and that "symptoms are not improved by allergy medications" (60%). Percentages of patients taking allergy medications in the 4 weeks prior to observation were 86% in the United States and 66% in Canada: antihistamines 75% United States, 54% Canada; inhaled corticosteroids 32% United States, 22% Canada. The predominant comorbidity was asthma, 43% United States, 24% Canada. Site
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
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
Nolte, Hendrik; Plunkett, Greg; Grosch, Karin; Larsen, Jorgen Nedergaard; Lund, Kaare; Bollen, Mirko
Consistency in composition and potency, particularly regarding major allergens, is crucial for the quality of extracts for allergen immunotherapy. To characterize the major allergen composition of house dust mite (HDM) extracts commercially available in the United States and the SQ HDM sublingual immunotherapy (SLIT) tablet, and to relate the composition to patient sensitization patterns. Der 1/Der 2 ratios were determined in 10,000- and 30,000-AU/mL HDM extracts from 5 US companies and the SQ HDM SLIT-tablet. Allergen content was analyzed by enzyme-linked immunosorbent assay and compared with an in-house reference. Sensitivity toward Der p 1, Der p 2, and Der p 10 was determined in serum from randomly selected subgroups of 220 individuals from North American and European SQ HDM SLIT-tablet trials. Mean Der 1/Der 2 ratios in US HDM extracts ranged from 0.4 to 20.5. For the SQ HDM SLIT-tablet (20 batches), variability did not exceed 12% regarding content of Der f 1 (SD, 11.9%; 95% confidence interval [CI], 0.94-1.06), Der p 1 (SD, 6.1%; 95% CI, 0.97-1.03), and combined Der 2 allergen (SD, 6.4%; 95% CI, 0.97-1.03), indicating a consistent Der 1/Der 2 ratio. High allergen sensitivity frequencies toward Der p 1 and Der p 2 were observed regardless of geographic region. Efficacy of the SQ HDM SLIT-tablet has been demonstrated in 5 clinical trials. The SQ HDM SLIT-tablet has efficacy potential for a broad range of patients because it includes a consistent 1:1 ratio of the 2 major HDM allergens to which individuals were most frequently sensitized across geographic regions. Efficacy has been demonstrated. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Zolkipli, Zaraquiza; Roberts, Graham; Cornelius, Victoria; Clayton, Bernie; Pearson, Sarah; Michaelis, Louise; Djukanovic, Ratko; Kurukulaaratchy, Ramesh; Arshad, S Hasan
Children born to atopic parents are at increased risk of sensitization to environmental allergens. We sought to demonstrate proof of concept for oral immunotherapy to high-dose house dust mite (HDM) allergen in infancy in the prevention of allergen sensitization and allergic diseases. This was a prospective, randomized, double-blind, placebo-controlled, proof-of-concept study involving 111 infants less than 1 year of age at high risk of atopy (≥ 2 first-degree relatives with allergic disease) but with negative skin prick test responses to common allergens at randomization. HDM extract (active) and appropriate placebo solution were administered orally twice daily for 12 months, and children were assessed every 3 months. Coprimary outcomes were cumulative sensitization to HDM and sensitization to any common allergen during treatment, whereas development of eczema, wheeze, and food allergy were secondary outcomes. All adverse events were recorded. There was a significant (P = .03) reduction in sensitization to any common allergen (16.0%; 95% CI, 1.7% to 30.4%) in the active (5 [9.4%]) compared with placebo (13 [25.5%]) treatment groups. There was no treatment effect on the coprimary outcome of HDM sensitization and the secondary outcomes of eczema, wheeze, and food allergy. The intervention was well tolerated, with no differences between active and placebo treatments in numbers or nature of adverse events. Prophylactic HDM oral immunotherapy is well tolerated in children at high heredity risk. The results met the trial's prespecified criteria for proof of concept in reducing sensitization to any allergen; however, no significant preventive effect was observed on HDM sensitization or allergy-related symptoms. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
James, Louisa K; Bowen, Holly; Calvert, Rosaleen A; Dodev, Tihomir S; Shamji, Mohamed H; Beavil, Andrew J; McDonnell, James M; Durham, Stephen R; Gould, Hannah J
Serum IgG(4) responses to allergen immunotherapy are well documented as blocking allergen binding to receptor-bound IgE on antigen-presenting cells and effector cells, but the molecular characteristics of treatment-induced IgG(4), particularly in relation to expressed antibody, are poorly defined. We aimed to clone and express recombinant IgG(4) from patients receiving grass pollen immunotherapy using single B cells to obtain matched heavy- and light-chain pairs. IgG(4)(+) B cells were enriched from blood samples taken from 5 patients receiving grass pollen immunotherapy. Matched heavy- and light-chain variable-region sequences were amplified from single IgG(4)(+) B cells. Variable regions were cloned and expressed as recombinant IgG(4). Binding analysis of grass pollen-specific IgG(4) was performed by using surface plasmon resonance. Functional assays were used to determine IgE blocking activity. In a separate experiment grass pollen-specific antibodies were depleted from serum samples to determine the proportion of grass pollen-specific IgG(4) within total IgG(4). Depletion of grass pollen-specific antibodies from serum led to a modest reduction in total IgG(4) levels. Matched heavy- and light-chain sequences were cloned from single IgG(4)(+) B cells and expressed as recombinant IgG(4). We identified an IgG(4) that binds with extremely high affinity to the grass pollen allergen Phl p 7. Furthermore, we found that a single specific mAb can block IgE-mediated facilitated allergen presentation, as well as IgE-mediated basophil activation. Although increases in IgG(4) levels cannot be wholly accounted for within the allergen-specific fraction, allergen immunotherapy might result in the production of high-affinity allergen-specific blocking IgG(4). Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Wu, Yabin; Long, Zhen; Huang, Yang; Huang, Xuanzhao
To evaluate the adverse reaction of standardized specific mite-allergen immunotherapy. One hundred and fifty-two patients diagnosed by the pediatric immunotherapy center of our hospital were treated with increasing doses of standardized specific mite-allergen injection. Before and 30 minutes after treatment, the peak expiratory flow (PEF) and pulmonary function for the maximum lung ventilation function were checked, and the adverse reactions were recorded. Six hundred and eighty-one injections were recorded. 84 injections (12.3%) caused immediate side effects, including 64 mild local adverse reactions (9.4%), 2 moderate local adverse reactions (0.3%), 18 systemic adverse reactions (2.6%) which were mild asthma, and no fatal anaphylactic shock and other serious adverse reactions were found. 50 injections (7.3%) cased delayed adverse reactions, all of which were mild local adverse reactions. The rate of immediate local adverse reactions and systemic adverse reactions in the maintenance treatment period was significantly higher than that in the initial treatment period (chi2 = 4.59, 19.82 respectively; P 0.05). The PEF change rate (-0.000 2 +/- 0.085 9) of the children at 681 injections and the MMEF change rate of the children at 109 injections (0.275 +/- 0.206) were not statistically different (t = -0.047, 1.39; P = 0.963, 0.166). Standardized specific mite-allergen immunotherapy is safe for children with allergic rhinitis and/or asthma.
Würtzen, Peter A; Gupta, Shashank; Brand, Stephanie; Andersen, Peter S
During allergen immunotherapy (AIT), the allergic patient is exposed to the disease-inducing antigens (allergens) in order to induce clinical and immunological tolerance and obtain disease modification. Large trials of grass AIT with highly standardized subcutaneous and sublingual tablet vaccines have been conducted to document the clinical effect. Induction of blocking antibodies as well as changes in the balance between T-cell phenotypes, including induction of regulatory T-cell subtypes, have been demonstrated for both treatment types. These observations increase the understanding of the immunological mechanism behind the clinical effect and may make it possible to use the immunological changes as biomarkers of clinical effect. The current review describes the recent mechanistic findings for subcutaneous immunotherapy and sublingual immunotherapy/tablet treatment and discusses how the observed immunological changes translate into a scientific foundation for the observed clinical effects of grass pollen immunotherapy and lead to new treatment strategies for grass AIT.
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
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.
Oksana M. Kurbacheva
Full Text Available Currently one of the factors of allergy predisposition is the increase in barrier permeability of the mucous membranes of the respiratory system and the gastrointestinal tract (GIT. It defines the probability of an emergence of an allergic response. To understand the mechanisms of the interaction of the mucous membranes of different systems that explain their common function is undoubtedly necessary for discussion of this problem. The features of microbiome influence and the changes of the microbiome state during the formation of the immune response to the contact with allergens are of particular interest. The structure of the epithelial barrier of the airwaysand GIT, and mechanisms of allergen transport through barrier systems with the subsequent interaction with the cells (? associated with barrier fabrics have been considered. The possible role of the barrier function of mucous membranes in conducting sublingual allergen-specific immunotherapy (SLIT is discussed.
Swoboda, Ines; De Weerd, Nicole; Bhalla, Prem L; Niederberger, Verena; Sperr, W R; Valent, Peter; Kahlert, Helga; Fiebig, Helmut; Verdino, Petra; Keller, Walter; Ebner, Christof; Spitzauer, Susanne; Valenta, Rudolf; Singh, Mohan B
More than 400 million individuals are sensitized to grass pollen allergens. Group 5 allergens represent the most potent grass pollen allergens recognized by more than 80 % of grass pollen allergic patients. The aim of our study was to reduce the allergenic activity of group 5 allergens for specific immunotherapy of grass pollen allergy. Based on B- and T-cell epitope mapping studies and on sequence comparison of group 5 allergens from different grasses, point mutations were introduced by site-directed mutagenesis in highly conserved sequence domains of Lol p 5, the group 5 allergen from ryegrass. We obtained Lol p 5 mutants with low IgE-binding capacity and reduced allergenic activity as determined by basophil histamine release and by skin prick testing in allergic patients. Circular dichroism analysis showed that these mutants exhibited an overall structural fold similar to the recombinant Lol p 5 wild-type allergen. In addition, Lol p 5 mutants retained the ability to induce proliferation of group 5 allergen-specific T cell lines and clones. Our results demonstrate that a few point mutations in the Lol p 5 sequence yield mutants with reduced allergenic activity that represent potential vaccine candidates for immunotherapy of grass pollen allergy.
Greenhawt, Matthew J; Vickery, Brian P
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 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.
Saeki, Mayumi; Nishimura, Tomoe; Kaminuma, Osamu; Suzuki, Kazuya; Takai, Toshiro; Mori, Akio; Takada, Kazuko; Takaiwa, Fumio; Hiroi, Takachika
Oral immunotherapy is potentially useful for the treatment of allergic diseases. We previously demonstrated that allergen-induced airway inflammation and immunoglobulin E (IgE) production in mice were suppressed by oral administration of high-dose transgenic (Tg) rice seeds (approximately 50 g/kg/day) expressing a T cell epitope of Dermatophagoides pteronyssinus group 1 allergen (Der p 1). However, this amount of Tg rice seeds was not realistic in our daily life. In this study, allergen-induced airway inflammation and IgE production following oral immunotherapy with a realistic (lowest) dose of Tg rice seeds were investigated. Mice orally administered with Tg or non-Tg rice seeds at approximately 5 g/kg/day for 1 week were immunized with recombinant Der p 1, and then challenged with the corresponding allergen. The infiltration of inflammatory cells into the airways and the levels of allergen-specific serum IgE were examined. Low-dose oral administration of Tg rice seeds significantly inhibited the allergen-induced infiltration of eosinophils and lymphocytes into the airways, but allergen-specific IgE synthesis was not changed. Low-dose oral immunotherapy with Tg rice seeds could suppress allergen-induced airway inflammation through mechanisms other than the downregulation of IgE synthesis. Copyright © 2012 S. Karger AG, Basel.
Liccardi, G; Calzetta, L; Salzillo, A; Billeri, L; Lucà, G; Rogliani, P
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.
Calderón, Moisés A; Bousquet, Jean; Canonica, G Walter; Cardell, Lars-Olaf; Fernandez de Rojas, Dolores Hernandez; Kleine-Tebbe, Jörg; Demoly, Pascal
Guidelines on the treatment of asthma, allergic rhinitis (AR), and allergen immunotherapy (AIT) lack recommendations for house dust mite (HDM) allergy. An expert panel reviewed current guidelines in the light of new data to assess whether guidelines could be improved. Most guidelines and key position papers did not provide specific recommendations on treatment of allergic asthma (AA) caused by HDM allergy, although some included AIT as a treatment option for AA in general. Around half of the guidelines stated that AIT with HDM extract was an effective treatment for AR, with several indicating sublingual immunotherapy as an option. This heterogeneity is caused by quality issues affecting studies of AIT with perennial allergens in patients with AA and AR, including use of different diagnosis and severity criteria, lack of consistent scoring or grading systems for primary and safety outcomes, and lack of consensus on treatment parameters. There is a need for well-designed clinical trials to serve as a basis for guideline recommendations. Although results from recent studies strengthen the evidence base for the efficacy and safety of sublingual immunotherapy in patients with HDM-induced AA and AR, their effect on subsequent guideline updates will depend on the methodology and evidence model used by each guideline. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Li, Lisha; Guan, Kai
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.
Karam, Marilyn; Holland, Christine; Yang, Zi; Samuels, Kiela; Sanders, Georgiana
Our previous pilot study conducted at the University of Michigan Health Services showed that fewer than 25% of the non-university allergen immunotherapy (AIT) prescribers adhered to AIT labeling guidelines which impacted both patients and healthcare personnel involved in AIT administration. We expand our study to characterize AIT labeling compliance and impact of practice variability at the "Big 10" University Health Services, and investigate prescribers motives for nonadherence to practice parameter guidelines. Three online surveys were distributed: AIT Administrator and Manager surveys for healthcare personnel at the "Big 10"; University Health Services and Physician Survey for physician members of the AAAAI. Data were analyzed using frequency/bivariate analysis and logistic regression. 21 AIT administrators from 10 University Health Services responded. 90.4% (20/21) felt labels containing all recommended practice parameter guidelines, components would decrease error; and standardization of labels, buildup and missed dose schedules would increase workflow efficiency (76%; 16/21). 90% (17/19) felt standardized protocols for treatment of systemic reactions would increase patient safety, workflow efficiency and comfort level of administrators. Only 28.6% of AIT extract vial labels at University Health Services were in accordance with practice parameter guidelines. Despite familiarity with the guidelines (91.5%; 697/762), only 64% (488/762) of surveyed physicians had practice parameter adherent AIT extracts labels with higher odds of a complete label when physicians were in group practice (odds ratio 1.51; [95% confidence interval, 1.06-2.15]; P=0.02). Reasons for nonadherence included having personalized labeling systems (55.4%, 174/314), unfamiliarity (14%, 44/314) and disagreement (9%, 29/314) with practice parameter guidelines. Poor adherence with AIT practice parameters labeling guidelines is an important concern in nonallergy offices. It is imperative that
Evaluation of two grass pollen extracts for immunotherapy by serum determinations of specific IgE and IgG4 antibodies towards purified Timothy grass pollen allergens (Phl p 1, 2, 4, 5, 6, 7, 11, 12 in patients undergoing hyposensitization treatment
Renato Enzo Rossi
Conclusions: These results indicate that grass pollen immunotherapy elicits an array of antibody specificities that reflect the allergen content and the potency of allergen extracts; this could be of pivotal importance to define optimal allergen extract doses.
Nouri-Aria, Kayhan T; Pilette, Charles; Jacobson, Mikila R; Watanabe, Hiroshi; Durham, Stephen R
Background IL-9 is an important stimulus for tissue infiltration by mast cells, a feature requiring concomitant activation of c-Kit. Objectives We assessed IL-9 expression and c-Kit + mast cells in the nasal mucosa of patients with allergic rhinitis during seasonal pollen exposure and observed the effects of allergen immunotherapy. Methods We studied 44 patients with seasonal rhinitis and asthma before and 2 years after a double-blind trial of grass pollen immunotherapy. Nasal mucosal IL-9 + cells and c-Kit + mast cells were assessed by means of immunochemistry. Cell types expressing IL-9 protein were determined by means of dual immunofluorescence. IL-9 mRNA-positive cells were assessed by means of in situ hybridization, and their phenotype was determined by using sequential immunohistochemistry and in situ hybridization. Results Nasal mucosal c-Kit + mast cells were increased during the pollen season ( P = .0001). IL-9 mRNA-positive cells also tended to increase ( P = .1) and correlated with nasal EG2 + eosinophils ( r = 0.47, P = .05) and IL-5 mRNA-positive cells ( r = 0.54, P = .02). The cell sources of IL-9 included T cells, eosinophils, neutrophils, and mast cells. When compared with placebo, successful pollen immunotherapy markedly inhibited seasonal increases in nasal mucosal c-Kit + mast cells ( P = .001) and the seasonal expression of IL-9 mRNA-positive cells ( P = .06). Immunotherapy also inhibited IL-9 protein expression from nonendothelial cell sources ( P = .0007). Conclusion IL-9 is upregulated in the nasal mucosa during the pollen season and correlates with tissue infiltration by eosinophils. Successful pollen immunotherapy is associated with inhibition of seasonal increases in both nasal c-Kit + mast cells and eosinophils. This effect might be explained, at least in part, by the reduced local expression of IL-9.
Bonura, A; Passantino, R; Costa, M A; Montana, G; Melis, M; Bondì, M Luisa; Butteroni, C; Barletta, B; Corinti, S; Di Felice, G; Colombo, P
Parietaria pollen is one of the major cause of pollinosis in the southern Europe. Specific immunotherapy is the only treatment able to modify the natural outcome of the disease restoring a normal immunity against allergens. We designed a recombinant molecule (PjEDloop1) comprised of genetic-engineered variants of the major allergens of the Parietaria pollen (Par j 2/Par j 1). Purity and chemical-physical properties of the derivative were analysed by RP-HPLC chromatography and Photon Correlation Spectroscopy. Immunological activity was evaluated by means of Western blotting, ELISA inhibition and PBMC proliferation assay in 10 Parietaria allergic patients. Basophil activation was studied in six subjects. The immunogenicity of the hybrid was studied looking at the immune responses induced in a mouse model of sensitization. The PjEDloop1 hybrid was produced as a purified recombinant protein with high stability in solution. Western blot, ELISA inhibition and basophil activation test showed that the PjEDloop1 displays a remarkable reduced IgE binding and anaphylactic activity. CD3 reactivity was conserved in all patients. Mice immunization with the rPjEDloop1 induced antibodies and T cell responses comparable to that obtained by the wild type allergens. Such antibodies shared the specificities to rPar j 1 and rPar j 2 with human IgE antibodies. Our results demonstrated that a mutant hybrid expressing genetically engineered forms of the major P. judaica allergens displayed reduced allergenicity and retained T cell reactivity for the induction of protective antibodies in vaccination approaches for the treatment of Parietaria pollinosis. © 2011 Blackwell Publishing Ltd.
Full Text Available Abstract Background Little information is available on the effect of allergen-specific immunotherapy on airway responsiveness and markers in exhaled air. The aims of this study were to assess the safety of immunotherapy with purified natural Alt a1 and its effect on airway responsiveness to direct and indirect bronchoconstrictor agents and markers in exhaled air. Methods This was a randomized double-blind trial. Subjects with allergic rhinitis with or without mild/moderate asthma sensitized to A alternata and who also had a positive skin prick test to Alt a1 were randomized to treatment with placebo (n = 18 or purified natural Alt a1 (n = 22 subcutaneously for 12 months. Bronchial responsiveness to adenosine 5'-monophosphate (AMP and methacholine, exhaled nitric oxide (ENO, exhaled breath condensate (EBC pH, and serum Alt a1-specific IgG4 antibodies were measured at baseline and after 6 and 12 months of treatment. Local and systemic adverse events were also registered. Results The mean (95% CI allergen-specific IgG4 value for the active treatment group increased from 0.07 μg/mL (0.03-0.11 at baseline to 1.21 μg/mL (0.69-1.73, P 4 value increased nonsignificantly from 0.09 μg/mL (0.06-0.12 at baseline to 0.13 μg/mL (0.07-0.18 at 6 months and to 0.11 μg/mL (0.07-0.15 at 12 months of treatment. Changes in the active treatment group were significantly higher than in the placebo group both at 6 months (P Conclusion Although allergen-specific immunotherapy with purified natural Alt a1 is well tolerated and induces an allergen-specific IgG4 response, treatment is not associated with changes in AMP or methacholine responsiveness or with significant improvements in markers of inflammation in exhaled air. These findings suggest dissociation between the immunotherapy-induced increase in IgG4 levels and its effect on airway responsiveness and inflammation.
Asaria, M.; Dhami, S.; van Ree, R.; Gerth van Wijk, R.; Muraro, A.; Roberts, G.; Sheikh, A.
Background: 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
Asaria, M; Dhami, S; van Ree, R; Gerth van Wijk, R; Muraro, A; Roberts, G; Sheikh, A
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
Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi
Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient’s daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure...
Bødtger, Uffe; Poulsen, L K; Jacobi, H H
BACKGROUND: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America...
Bødtger, U; Poulsen, Lars K.; Jacobi, H H
There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America....
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
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.
Full Text Available Over the last decades allergic diseases has become a major health problem worldwide. The only specific treatment to date is allergen specific immunotherapy (ASIT. Although it was shown that ASIT generates allergen-tolerant T cells, detailed mechanism underlying its activity is still unclear and there is no reliable method to monitor its effectiveness. The aim of our study was to evaluate ASIT influence on the frequency of forkhead box P3 (FoxP3 Tregs in allergic children with various clinical manifestations. The relative number of FoxP3 Tregs in 32 blood samples from allergic children at baseline and/or after 1 year of ASIT was assessed by flow cytometry. In the entire studied group, the percentage of FoxP3 Tregs did not increase 1 year after ASIT. Nevertheless, the percentage of FoxP3 Tregs after ASIT significantly increased in children with respiratory allergy (conjunctivitis, asthma, and rhinitis coexisting with nonrespiratory manifestations (food allergy and/or atopic dermatitis, whereas, in patients with respiratory allergy only, the percentage of FoxP3 Tregs decreased. To the best of our knowledge, this is the first report showing various differential FoxP3 Tregs response to ASIT in allergic children. FoxP3 Tregs number could be useful in treatment monitoring. Further studies are warranted to confirm these observations.
Dahl, Ronald; Kapp, Alexander; Colombo, Giselda; De Monchy, Jan G. R.; Rak, Sabina; Emminger, Waltraud; Riis, Bente; Gronager, Pernille M.; Durham, Stephen R.
Background: This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abello A/S, Horsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy.
McDougall, Stuart A; Heath, Matthew D; Kramer, Matthias F; Skinner, Murray A
Investigation into the absorption, distribution and elimination of aluminium in rat after subcutaneous aluminium adjuvant formulation administration using ICP-MS is described. Assays were verified under the principles of a tiered approach. There was no evidence of systemic exposure of aluminium, in brain or in kidney. Extensive and persistent retention of aluminium at the dose site was observed for at least 180 days after administration. This is the first published work that has quantified aluminium adjuvant retention based on the quantity of aluminium delivered in a typical allergy immunotherapy course. The results indicate that the repeated administration of aluminium-containing adjuvants will likely contribute directly and significantly to an individual's body burden of aluminium.
Colombo, Paolo; Trapani, Antonino; Geraci, Domenico; Golino, Massimiliano; Gianguzza, Fabrizio; Bonura, Angela
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.
Incorvaia, Cristoforo; Mauro, Marina; Ridolo, Erminia
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.
Belmans, Jochen; Van Woensel, Matthias; Creyns, Brecht; Dejaegher, Joost; Bullens, Dominique M; Van Gool, Stefaan W
Immunotherapeutic strategies for glioblastoma, the most frequent malignant primary brain tumor, aim to improve its disastrous consequences. On top of the standard treatment, one strategy uses T cell activation by autologous dendritic cells (DC) ex vivo loaded with tumor lysate to attack remaining cancer cells. Wondering whether 'targeting' in vivo DCs could replace these ex vivo ones, immunogenic autologous tumor lysate was used to treat glioma-inoculated mice in the absence of ex vivo loaded DCs. Potential immune mechanisms were studied in two orthotopic, immunocompetent murine glioma models. Pre-tumoral subcutaneous lysate treatment resulted in a survival benefit comparable to subcutaneous DC therapy. Focussing on the immune response, glioma T cell infiltration was observed in parallel with decreased amounts of regulatory T cells. Moreover, these results were accompanied by the presence of strong tumor-specific immunological memory, shown by complete survival of a second glioblastoma tumor, inoculated 100 days after the first one. Finally, in combination with temozolomide, survival of established glioma in mice could be increased. Our results show the potential of immunogenic autologous tumor lysate used to treat murine glioblastoma, which will be worthwhile to study in clinical trials as it has potential as a cost-efficient adjuvant treatment strategy for gliomas.
Rak, Sabina; Yang, William H; Pedersen, Martin R; Durham, Stephen R
The effect of sublingual immunotherapy on quality of life (QoL) was examined in patients with grass pollen-induced rhinoconjunctivitis. Patients (n = 855) were randomised to once-daily grass allergen tablets (2,500; 25,000; or 75,000 SQ-T Phleum pratense extract; GRAZAX or placebo. Treatment was initiated 8 weeks before the start of the grass pollen season and continued throughout. If symptoms were present, patients received loratadine or placebo rescue medication. There were three major findings: in patients using loratadine, grass allergen tablets provided QOL benefits over placebo; Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score was 17% (p = 0.006) and 20% (p = 0.020) greater with 75,000 SQ-T tablet than with placebo at first and second seasonal visit, respectively; in patients not using loratadine, grass allergen tablets improved QoL more than placebo; RQLQ score was 21% greater (p = 0.021) with 75,000 SQ-T tablet at second seasonal visit; grass tablets (without loratadine) had a greater effect on QoL than loratadine alone. RQLQ score was 26% (p = 0.014) greater with 75,000 SQ-T tablets than loratadine at second seasonal visit. These data show that sublingual immunotherapy with grass allergen tablets improves QOL in allergic rhinoconjunctivitis, reduces symptoms, and that this effect is greater than rescue antihistamine alone.
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
Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G4 which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG4 specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG4 antibodies are developed is under debate. We sought to analyze the epitope specificities of IgE and IgG4 antibodies from sera of patients who received AIT. 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG4 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/IgG4 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 EC50 for IgE-mediated mediator release induced by rBet v 1a_11x was determined. The reduction of IgE and IgG4 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 IgG4 to 66.1% and 64.9%, respectively. Serum IgE and IgG4 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 IgG4 which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG4 might stimulate the development of epitope-specific diagnostics and therapeutics. © 2016 John Wiley & Sons Ltd.
Shin, Ji Hyeon; Kim, Do Hyun; Kim, Boo Young; Kim, Sung Won; Hwang, Se Hwan; Lee, Joohyung; Kim, Soo Whan
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.
Shamji, M H; Kappen, J H; Akdis, M
be administered either subcutaneously (SCIT) or sublingually (SLIT) (3-12). Although AIT is effective, the degree of remission strongly varies depending on the complex interaction between patient, allergy, symptomatology and vaccines used for AIT (3-9). Clinical management of patients receiving AIT and efficacy...... in randomised controlled trials for drug development could be significantly enhanced if there were means to identify those who are most likely to respond, when to stop treatment, how to predict relapse and when to perform booster AIT. Furthermore, biomarkers in AIT can play a central role in personalized...
Ariano, R; Panzani, R C; Chiapella, M; Augeri, G; Falagiani, P
Local Intranasal Immunotherapy (LII) is a new approach to the treatment of allergic rhinitis due to the pollen of Parietaria officinalis. The aim of this study was to verify the usefulness of LII and to determine the proper doses. Twenty adult patients all presenting a sensitization to the pollen of Parietaria officinalis were randomly divided into two groups: 15 received the treatment and five were the control group. Treatment started before the beginning of the pollinic season of Parietaria officinalis and continued during the season. The extract used was an active extract of macronized powder Parietaria officinalis pollen in increasing doses. Doses were determined periodically with specific nasal provocation tests. Results in the treated group compared to the control group were statistically significant if one considers the increase in threshold sensitivity in the nasal provocation test, the diminution of clinical symptomatology and the quantity of drug required to control symptoms in the treated group. The side effects were few; it was only in one case that the treatment had to be interrupted. LII for allergic rhinitis due to the pollen of Parietaria officinalis seems an effective and practicable method even during the pollinic season.
Maina, Elisa; Devriendt, Bert; Cox, Eric
Food allergen-specific sublingual immunotherapy (FA-SLIT) is considered to be a novel, safe and effective approach in dogs with adverse food reactions (AFR). To investigate changes in key cytokines associated with FA-SLIT. Eleven dogs with confirmed AFR. Participants received either dose escalation of FA-SLIT or placebo over a six month period. Oral food challenge was performed at the beginning and end of the study, along with clinical examinations and collection of skin surface bacterial cytology and blood. Peripheral blood mononuclear cells were stimulated with the culprit food antigen. ELISA methods were used to quantify Interleukin (IL)-10, IFN-γ, IL-4 and IL-17A in the supernatant of stimulated cells. IL-10 and IFN-γ levels were significantly increased at the end of the study in the treatment group (T), compared with the placebo group (P), whereas no changes were found in IL-4 levels. IL-17A levels were decreased in both groups (but more profoundly in T). Bacterial scores on the skin were positively correlated with IL-17A and inversely correlated with IL-10 concentrations. Interleukins were not correlated with clinical scores. FA-SLIT may modulate the allergic response toward Th1 and Treg cell phenotypes, and induction of tolerance in dogs with AFR. Therefore, FA-SLIT may be a tool to desensitize dogs with AFR. However, more data on a larger number of cases and a broader panel of cytokines are needed to corroborate these findings, and to elucidate the mechanism of action for responses to FA-SLIT by dogs with AFR. © 2017 ESVD and ACVD.
Toletone, Alessandra; Voltolini, Susanna; Passalacqua, Giovanni; Dini, Guglielmo; Bignardi, Donatella; Minale, Paola; Massa, Emanuela; Signori, Alessio; Troise, Costantino; Durando, Paolo
To describe (i) the clinical characteristics of workers, exposed to hymenoptera stings, with an ascertained diagnosis of Hymenoptera Venom Allergy (HVA), (ii) the specific role of occupational exposure, (iii) the effect of Venom Immunotherapy (VIT) in reducing the severity of allergic episodes in workers exposed to repeated stings of hymenoptera, and (iv) the management of the occupational consequences caused by allergic reactions due to hymenoptera stings. Between 2000 and 2013 an observational study, including patients referred to the regional reference hospital of Liguria, Italy, with an ascertained diagnosis of HVA and treated with VIT, was performed. A structured questionnaire was administered to all patients to investigate the occupational features of allergic reactions. These were graded according to standard systems in patients at the first episode, and after re-stings, during VIT. One-hundred and 8four out of the 202 patients referred had a complete data set. In 32 (17.4%) patients, the allergic reaction occurred during work activities performed outdoor. Of these, 31.2% previously stung by hymenoptera at work, and receiving VIT, were re-stung during occupational activity. The grades of reaction developed under VIT treatment resulted clinically less severe than of those occurred at the first sting (p-value = 0.031). Our findings confirmed the clinical relevance of HVA, and described its occupational features in outdoor workers with sensitization, stressing the importance of an early identification and proper management of the professional categories recognized at high risk of hymenoptera stings. The Occupational Physician should be supported by other specialists to recommend appropriate diagnostic procedures and the prescription of VIT, which resulted an effective treatment for the prevention of episodes of severe reactions in workers with a proven HVA.
Bødtger, Uffe; Ejrnaes, A M; Hummelshoj, L
parameters. Changes in IgG allergen binding and VAS were significantly correlated (sigma = 0.72; p ... is a poor marker of decreased allergen-specific sensitivity to birch pollen, both as a single measurement and as delta values....
Full Text Available OBJECTIVE: Allergic rhinitis (AR is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT, but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years.
Madsen, F; Frølund, L; Christensen, M
BACKGROUND AND OBJECTIVE: Subcutaneous allergen-specific immunotherapy (SCIT) is an effective treatment for patients with allergic asthma and rhinitis. SCIT may be performed in many different ways and good safety profiles have been published. Other studies, however, have reported high frequencies...
Rotiroti, Giuseppina; Shamji, Mohamed; Durham, Stephen R; Till, Stephen J
Subcutaneous immunotherapy with high-dose grass pollen was first described more than 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. In contrast, low-dose subcutaneous immunotherapy has not shown clinical benefit. Uncontrolled reports from the early 20th century describe low-dose allergen inoculation directly into the dermis, an immunologically active area containing abundant dendritic cells and lymphatics. We sought to investigate the effect of low-dose intradermal grass pollen administration on cutaneous reactivity to allergen. Thirty adults sensitized to grass and tree pollens were randomized to receive (1) 6 repeat intradermal injections at 2-week intervals of grass pollen extract (estimated 7 ng of the major grass allergen Phl p 5 per injection), (2) 2 intradermal injections separated by 10 weeks, or (3) a single intradermal injection at 10 weeks. At the end of the study, cutaneous early and late responses were measured after double-blind intradermal injection with grass and birch pollen. Participants who received 6 fortnightly intradermal grass pollen injections had markedly smaller cutaneous late responses to grass pollen than control subjects who received 2 injections separated by 10 weeks (P pollen-specific IgG antibodies. Suppression was observed whether late responses were measured on the arms or the back. However, early responses were equivalent in all groups. Low-dose intradermal allergen, like conventional subcutaneous high-dose immmunotherapy, suppresses allergen-induced cutaneous late responses in a manner that is allergen specific, systemic, and associated with induction of IgG antibodies. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Full Text Available Allergic rhinitis is the most prevalent type I allergy in industrialized countries. Pollen scattering from trees or grasses often induces seasonal allergic rhinitis, which is known as pollinosis or hay fever. The causative pollen differs across different areas and times of the year. Impaired performance due to pollinosis and/or medication used for treating pollinosis is considered to be an important reason for the loss of concentration and productivity in the workplace. Antigen-specific immunotherapy is an only available curative treatment against allergic rhinitis. Subcutaneous injection of allergens with or without adjuvant has been commonly used as an immunotherapy; however, recently, sublingual administration has come to be considered a safer and convenient alternative administration route of allergens. In this review, we focus on the safety and protocol of subcutaneous and sublingual immunotherapy against seasonal allergic rhinitis. We also describe an approach to selecting allergens for the vaccine so as to avoid secondary sensitization and adverse events. The biomarkers and therapeutic mechanisms for immunotherapy are not fully understood. We discuss the therapeutic biomarkers that are correlated with the improvement of clinical symptoms brought about by immunotherapy as well as the involvement of Tr1 and regulatory T cells in the therapeutic mechanisms. Finally, we focus on the current immunotherapeutic approach to treating Japanese cedar pollinosis, the most prevalent pollinosis in Japan, including sublingual immunotherapy with standardized extract, a transgenic rice-based edible vaccine, and an immunoregulatory liposome encapsulating recombinant fusion protein.
Pilette, Charles; Nouri-Aria, Kayhan T; Jacobson, Mikila R; Wilcock, Louisa K; Detry, Bruno; Walker, Samantha M; Francis, James N; Durham, Stephen R
Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF-beta-producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J chain-containing) Abs to the major allergen Phl p 5 were determined by ELISA before and after a 2-year double-blind trial of grass pollen (Phleum pratense) injection IT. Nasal TGF-beta expression was assessed by in situ hybridization. Sera from five IT patients were fractionated for functional analysis of the effects of IgA and IgG Abs on IL-10 production by blood monocytes and allergen-IgE binding to B cells. Serum Phl p 5-specific IgA2 Abs increased after a 2-year treatment (approximately 8-fold increase, p = 0.002) in contrast to IgA1. Increases in polymeric Abs to Phl p 5 (approximately 2-fold increase, p = 0.02) and in nasal TGF-beta mRNA (p = 0.05) were also observed, and TGF-beta mRNA correlated with serum Phl p 5 IgA2 (r = 0.61, p = 0.009). Post-IT IgA fractions triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding to B cells as observed with IgG fractions. This study shows for the first time that the IgA response to IT is selective for IgA2, correlates with increased local TGF-beta expression, and induces monocyte IL-10 expression, suggesting that IgA Abs could thereby contribute to the tolerance developed in IT-treated allergic patients.
Devillier, Philippe; Dreyfus, Jean-François; Demoly, Pascal; Calderón, Moisés A
The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible. We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo. Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast. In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact
Plant, Jon D; Neradilek, Moni B
Canine atopic dermatitis is a common pruritic skin disease often treated with allergen immunotherapy (AIT). AIT in dogs traditionally begins with attempting to identify clinically relevant environmental allergens. Current allergen testing methodologies and immunotherapy techniques in dogs are not standardized. Immunotherapy with a mixture of allergenic extracts selected based on regional aerobiology rather than intradermal tests or serum IgE assays has been described. The objective of this study was to evaluate the effectiveness of regionally-specific immunotherapy in dogs with atopic dermatitis. The medical records of a veterinary dermatology referral clinic were searched for dogs with atopic dermatitis that began regionally-specific subcutaneous immunotherapy from June, 2010 to May, 2013. An overall assessment of treatment effectiveness (excellent, good, fair, or poor) was assigned based upon changes in pruritus severity, lesion severity, and the reduction in concurrent medication(s) during a follow-up period of at least 270 days. Baseline characteristics that might predict treatment success were analyzed with the Spearman's correlation and the Kruskal-Wallis tests. Of the 286 dogs that began regionally-specific immunotherapy (RESPIT) during a 3 year period, 103 met the inclusion criteria. The overall response to RESPIT was classified as excellent in 19%, good in 38%, fair in 25%, and poor in 18% of dogs. The response classification correlated significantly with a reduction in pruritus severity (r = 0.72, p atopic dermatitis in dogs.
van Ree, R.; van Leeuwen, W. A.; Dieges, P. H.; van Wijk, R. G.; de Jong, N.; Brewczyski, P. Z.; Kroon, A. M.; Schilte, P. P.; Tan, K. Y.; Simon-Licht, I. F.; Roberts, A. M.; Stapel, S. O.; Aalberse, R. C.
BACKGROUND: IgE titres tend to rise early after the start of immunotherapy, followed by a decline to pre-immunotherapy levels or lower. OBJECTIVES: We were interested to know whether the early increase in IgE antibodies includes new specificities of IgE, and whether these responses persist. METHODS:
Full Text Available 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.
Fukuda, Ken; Ishida, Waka; Harada, Yosuke; Wakasa, Yuhya; Takagi, Hidenori; Takaiwa, Fumio; Fukushima, Atsuki
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.
Jae Hyun Lim
Full Text Available The aim of this study is to identify the effects of sublingual immunotherapy (SLIT on immunologic parameters and bronchial-hyper-responsiveness in children with allergic rhinitis to house-dust mite (HDM, through long-term follow-up cohort.Among the Allergic Rhinitis Cohort Study for Kids, pediatric patients who visited the hospital for rhinitis symptoms and proven allergy to HDM through skin prick test were studied. In this cohort, 37 patients received SLIT more than 3-years (SLIT group, and 184 patients received only pharmacologic therapy (non-SLIT group were included in this study. The results of skin prick test, eosinophil percent and count, total immunoglobulin E (IgE, and bronchial provocation test at initial and 3-year followed-up were compared in the two groups.After 3 year follow-up, only the serum eosinophil percent decreased more significantly in SLIT group than that in the non-SLIT group. New-sensitization rate other than HDM between SLIT and non-SLIT group did not show any significant differences. The distribution of sensitized allergen other than HDM showed increasing tendency after 3 years in both groups. Older age and a small number of sensitized allergen affected the improvement of bronchial hyper-responsiveness regardless of SLIT.HDM SLIT in allergic rhinitis children for 3 years in Korea does not affect prevention of new sensitization and poly-sensitization rate increment, and improvement of bronchial hyper-responsiveness.
Lim, Jae Hyun; Kim, Jin Youp; Han, Doo Hee; Lee, Chul Hee; Hong, Seung-No; Wee, Jee Hye; Park, Sue K; Rhee, Chae-Seo
The aim of this study is to identify the effects of sublingual immunotherapy (SLIT) on immunologic parameters and bronchial-hyper-responsiveness in children with allergic rhinitis to house-dust mite (HDM), through long-term follow-up cohort. Among the Allergic Rhinitis Cohort Study for Kids, pediatric patients who visited the hospital for rhinitis symptoms and proven allergy to HDM through skin prick test were studied. In this cohort, 37 patients received SLIT more than 3-years (SLIT group), and 184 patients received only pharmacologic therapy (non-SLIT group) were included in this study. The results of skin prick test, eosinophil percent and count, total immunoglobulin E (IgE), and bronchial provocation test at initial and 3-year followed-up were compared in the two groups. After 3 year follow-up, only the serum eosinophil percent decreased more significantly in SLIT group than that in the non-SLIT group. New-sensitization rate other than HDM between SLIT and non-SLIT group did not show any significant differences. The distribution of sensitized allergen other than HDM showed increasing tendency after 3 years in both groups. Older age and a small number of sensitized allergen affected the improvement of bronchial hyper-responsiveness regardless of SLIT. HDM SLIT in allergic rhinitis children for 3 years in Korea does not affect prevention of new sensitization and poly-sensitization rate increment, and improvement of bronchial hyper-responsiveness.
Mirone, C; Albert, F; Tosi, A; Mocchetti, F; Mosca, S; Giorgino, M; Pecora, S; Parmiani, S; Ortolani, C
The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America. We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia. Thirty-two patients (18 M/14 F, mean age 36.78, range 23-60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 microg of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial. Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and PAmbrosia.
Full Text Available Eighty patients with allergic conjunctivitis were treated with immunotherapy employing specific allergens. Sixty-two percent of these showed beneficial response. In cases of vernal conjunctivitis needing topical steroid preparations frequently for control of symptoms, immunotherapy is worth attempting to cause remission of symptoms.
Steveling, Esther Helen; Lao-Araya, Mongkol; Koulias, Christopher; Scadding, Guy; Eifan, Aarif; James, Louisa K; Dumitru, Alina; Penagos, Martin; Calderón, Moisés; Andersen, Peter Sejer; Shamji, Mohamed; Durham, Stephen R
Seasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20-25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined. This is a randomized, double-blind, single-centre, placebo controlled, two arm time course study based in the United Kingdom comparing sublingual allergy immunotherapy tablet (GRAZAX(®), ALK-Abello Horsholm, Denmark) plus standard treatment with placebo plus standard treatment. Up to 50 moderate to severe grass pollen allergic participants will be enrolled to ensure randomisation of at least 44. Further, we shall enrol 20 non-atopic volunteers. Screening will be completed before eligible atopic participants are randomised to one of the two treatment arms in a 1 to 1 ratio. The primary endpoint will be the total nasal symptom score assessed over 60 min following grass pollen nasal allergen challenge after 12 months of treatment. Clinical assessments and/or mechanistic analyses on blood, nasal fluid, brushing and biopsies will be performed at baseline at 1, 2, 3, 4 (coinciding with the peak pollen season), 6 and 12 months of treatment. After 12 months of treatment, unblinding will take place. Those atopic participants receiving active treatment will continue therapy for another 12 months followed by a post treatment phase of 12 months. Assessments and collection of biologic samples from these participants will take place again at 24 and at 36 months from the start of treatment. The 20 healthy, non
Schmid, Johannes Martin; Dahl, Ronald; Hoffmann, Hans Jürgen
Johannes Martin Schmid, Ronald Dahl, and Hans Juergen Hoffmann Department of Respiratory Medicine, Aarhus, Denmark Background: The major effect of SCIT is a change in allergen specific immunoglobulin. We measure the contribution of competing immunoglobulin to the effect of SCIT in patients......X with an about six-fold decrease in cellular sensitivity. Conclusion: We found an increasing protective effect of SCIT after 1 year of treatment measured by basophil activation test. During the early treatment period, this effect is primarily based on a shift towards protecting IgX, while there seems...
Coop, Christopher A
The objective of this article is to review the available studies regarding mold immunotherapy. A literature search was conducted in MEDLINE to identify peer-reviewed articles related to mold immunotherapy using the following keywords: mold, allergy, asthma, and immunotherapy. In addition, references cited within these articles were also reviewed. Articles were selected based on their relevance to the topic. Allergic responses to inhaled mold antigens are a recognized factor in allergic rhinitis and asthma. There are significant problems with respect to the production of relevant allergen material for the diagnosis and treatment of mold allergy with immunotherapy. Mold allergens contain proteases and should not be mixed with other allergens for immunotherapy. Most of the immunotherapy studies focus on two molds, Alternaria and Cladosporium. There is a lack of randomized placebo-controlled trials when evaluating the efficacy of mold immunotherapy with trials only focusing on immunotherapy to Alternaria and Cladosporium. Additional studies are needed regarding mold allergy and immunotherapy focusing on which molds are important for causing allergic disease.
Full Text Available Jose Luis Justícia1, Eva Baró2, Victoria Cardona3, Pedro Guardia4, Pedro Ojeda5, José Maria Olaguíbel6, José Maria Vega7, Carmen Vidal81Medical Department, Stallergenes Ibérica, Barcelona, Spain; 2Health Outcomes Research Department, 3D Health Research, Barcelona, Spain; 3Hospital Vall d'Hebron, Barcelona, Spain; 4Hospital Virgen Macarena, Sevilla, Spain; 5Clínica de Asma y Alergia Dres. Ojeda, Madrid, Spain; 6Complejo Hospitalario de Navarra, Pamplona, Spain; 7Hospital Regional Universitario Carlos Haya Málaga, Spain; 8Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, SpainBackground: Allergen-specific immunotherapy (SIT is a treatment capable of modifying the natural course of allergy, so ensuring good adherence to SIT is fundamental. Up until now there has not existed an instrument specifically developed to measure patient satisfaction with SIT, although its assessment could help us to comprehend better and improve treatment adherence and effectiveness. The aim of this study was to develop an instrument to measure adult patient satisfaction with SIT.Methods: Items were generated from a literature review, focus groups with allergic adult patients undergoing SIT, and a meeting with experts. Potential items were administered to allergic patients undergoing SIT in an observational, cross-sectional, multicenter study. Item reduction was based on quantitative and qualitative criteria. A preliminary assessment of feasibility, reliability, and validity of the retained items was performed.Results: An initial pool of 70 items was administered to 257 patients undergoing SIT. Fifty-four items were eliminated resulting in a provisional instrument with 16 items. Factor analysis yielded four factors that were identified as perceived efficacy, activities and environment, cost-benefit balance, and overall satisfaction, explaining 74.8% of variance. Ceiling and floor effects were negligible for overall score. Overall score was
Gulbin Bingol Karakoc
Full Text Available Background. Allergen-specific immunotherapy (SIT is one of the important regimens for the treatment of allergic diseases. Predictive tests for the clinical response to SIT are limited. In this study we aimed to evaluate whether specific IgE/total IgE levels can predict clinical improvement in monosensitized patients to house dust mite treated with immunotherapy. Patients and Methods. We analyzed 32 patients who had undergone 2 years of SIT. Serum t-IgE and s-IgE levels, and serum s-IgE/t-IgE ratios were calculated and tested for correlation with clinical response to SIT. Asthma symptom score (ASS, rhinitis symptom score (RSS, pulmonary functions and visual analogue scales (VAS were evaluated at the beginning and after 2 years. Results. There were 17 boys and 15 girls with the mean age of 10.78±3.03 years. The mean serum house dust mite s-IgE level was 128.62±142.61 kU/L, t-IgE 608.90±529.98 IU/mL, and s-IgE/t-IgE ratio 33.83±53.18. Before immunotherapy, ASS was 6.23±1.63, RSS; 8.20±1.88, VAS; 7.38±2.01, FEV1 (%; 89.14±8.48, PEF (%; 88.93±13.57, and after 2 years, these values were determined as 1.90±1.10, 3.05±1.39, 1.35±1.24, 97.6±11.26, and 97.0±11.55, respectively. s-IgE/t-IgE ratio was correlated with change in RSS (r=−0.392, P=0.08 and VAS (r=−0.367, P=0.05. Conclusion. Although SIT is very effective treatment, all patients do not benefit from treatment. We assumed that s-IgE/t-IgE ratio would be useful to predict the clinical response to SIT.
Anzengruber, Julia; Bublin, Merima; Bönisch, Eva; Janesch, Bettina; Tscheppe, Angelika; Braun, Matthias L; Varga, Eva-Maria; Hafner, Christine; Breiteneder, Heimo; Schäffer, Christina
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
Frew, Anthony J; Powell, Richard J; Corrigan, Christopher J; Durham, Stephen R
Specific immunotherapy is widely used to treat allergic rhinitis, but few large-scale clinical trials have been performed. We sought to assess the efficacy and safety of specific immunotherapy with 2 doses of Alutard grass pollen in patients with moderately severe seasonal allergic rhinitis inadequately controlled with standard drug therapy. We performed a double-blind, randomized, placebo-controlled study of 410 subjects (203 randomized to 100,000 standardized quality units [SQ-U] maintenance, 104 to 10,000 SQ-U, and 103 to placebo). Three hundred forty-seven (85%) completed treatment. Groups were well matched for demographics and symptoms. Across the whole pollen season, mean symptom and medication scores were 29% and 32% lower, respectively, in the 100,000-SQ-U group compared with those in the placebo group (both P pollen season, mean symptom and medication scores were 32% and 41% lower, respectively, than those in the placebo group. The 10,000-SQ-U group had 22% less symptoms than the placebo group over the whole season (P pollen reduced symptoms and medication use and improved the quality of life of subjects with moderately severe hay fever. The 100,000-SQ-U regimen was more effective, but the 10,000-SQ-U regimen caused fewer side effects.
Melzer, Jonathan M; Driskill, Brent R; Clenney, Timothy L; Gessler, Eric M
Allergic fungal sinusitis (AFS) is a condition that has an allergic basis caused by exposure to fungi in the sinonasal tract leading to chronic inflammation. Despite standard treatment modalities, which typically include surgery and medical management of allergies, patients still have a high rate of recurrence. Subcutaneous immunotherapy (SCIT) has been used as adjuvant treatment for AFS. Evidence exists to support the use of sublingual immunotherapy (SLIT) as a safe and efficacious method of treating allergies, but no studies have assessed the utility of SLIT in the management of allergic fungal sinusitis. A record review of cases of AFS that are currently or previously treated with sublingual immunotherapy from 2007 to 2011 was performed. Parameters of interest included serum IgE levels, changes in symptoms, Lund-McKay scores, decreased sensitization to fungal allergens associated with AFS, and serum IgE levels. Ten patients with diagnosed AFS were treated with SLIT. No adverse effects related to the use of SLIT therapy were identified. Decreases in subjective complaints, exam findings, Lund-McKay scores, and serum IgE levels were observed. Thus, sublingual immunotherapy appears to be a safe adjunct to the management of AFS that may improve patient outcomes. © The Author(s) 2015.
Brehler, Randolf; Klimek, Ludger; Kopp, Matthias Volkmar; Christian Virchow, Johann
It is estimated that up to 24% of the population in Germany suffers from allergic rhinoconjunctivitis and 5% from allergic asthma. Allergic rhinoconjunctivitis is closely related to other atopic diseases. This review is based on pertinent publications retrieved by a selective search of the Medline database, guidelines from Germany and abroad, and Cochrane meta-analyses. Specific immunotherapy (SIT) is the only diseases-modifying treatment option for allergies. Meta-analysis reveals standardized mean differences in allergic rhinitis symptom scores of -0.73 for subcutaneous immunotherapy (SCIT) and -0.49 for sublingual immunotherapy (SLIT); the corresponding mean differences in medication scores are -0.57 and -0.32, respectively. The treatment should be carried out for at least three years. It is indicated when the symptoms are severe and allergen avoidance is not a realistic option. The efficacy of treatment depends on the allergen dose; thus, every allergen preparation should be evaluated individually, independent of route of administration. SCIT can cause systemic adverse effects, including anaphylaxis. SLIT is safer but often causes allergic symptoms of the oral mucosa at the beginning of treatment. Even though the efficacy of SIT is well documented, it is still underused. SIT should be offered as standard treatment to patients suffering from allergic rhinitis.
Passalacqua, Giovanni; Nowak-Węgrzyn, Anna; Canonica, Giorgio Walter
Sublingual immunotherapy (SLIT) is increasingly used worldwide, and several products have been recently registered as drugs for respiratory allergy by the European Medicine Agency and the Food and Drug Administration. Concerning inhalant allergens, the safety of SLIT is overall superior to that of subcutaneous immunotherapy in terms of systemic adverse events. No fatality has been ever reported, and episodes of anaphylaxis were described only exceptionally. Looking at the historical and recent trials, most (>90%) adverse events are "local" and confined to the site of administration. For this reason, a specific grading system has been developed by the World Allergy Organization to classify and describe local adverse events. There is an increasing amount of literature concerning oral desensitization for food allergens, referred to as oral immunotherapy. Also, in this case, local side effects are predominant, although systemic adverse events are more frequent than with inhalant allergens. We review herein the description of local side effects due to SLIT, with a special focus on large trials having a declared sample size calculation. The use of the Medical Dictionary for Regulatory Activities nomenclature for adverse events is mentioned in this context, as recommended by regulatory agencies. It is expected that a uniform classification/grading of local adverse events will improve and harmonize the surveillance and reporting on the safety of SLIT. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Burge, H A; Rogers, C A
Outdoor allergens are an important part of the exposures that lead to allergic disease. Understanding the role of outdoor allergens requires a knowledge of the nature of outdoor allergen-bearing particles, the distributions of their source, and the nature of the aerosols (particle types, sizes, dynamics of concentrations). Primary sources for outdoor allergens include vascular plants (pollen, fern spores, soy dust), and fungi (spores, hyphae). Nonvascular plants, algae, and arthropods contribute small numbers of allergen-bearing particles. Particles are released from sources into the air by wind, rain, mechanical disturbance, or active discharge mechanisms. Once airborne, they follow the physical laws that apply to all airborne particles. Although some outdoor allergens penetrate indoor spaces, exposure occurs mostly outdoors. Even short-term peak outdoor exposures can be important in eliciting acute symptoms. Monitoring of airborne biological particles is usually by particle impaction and microscopic examination. Centrally located monitoring stations give regional-scale measurements for aeroallergen levels. Evidence for the role of outdoor allergens in allergic rhinitis is strong and is rapidly increasing for a role in asthma. Pollen and fungal spore exposures have both been implicated in acute exacerbations of asthma, and sensitivity to some fungal spores predicts the existence of asthma. Synergism and/or antagonism probably occurs with other outdoor air particles and gases. Control involves avoidance of exposure (staying indoors, preventing entry of outdoor aerosols) as well as immunotherapy, which is effective for pollen but of limited effect for spores. Outdoor allergens have been the subject of only limited studies with respect to the epidemiology of asthma. Much remains to be studied with respect to prevalence patterns, exposure and disease relationships, and control. PMID:10931783
Mueller, R S; Janda, J; Jensen-Jarolim, E; Rhyner, C; Marti, E
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.
Hulya Anil; Koray Harmanci
Allergic rhinitis is an immunologic disorder that develops in individuals who have produced allergen-specific immunoglobulin E in response to environmental exposures (most commonly to pollens, animal dander, insect debris, and molds). For patients with a severe allergy that is not responsive to environmental controls and pharmacotherapy or for those who do not wish to use medication for a lifetime, immunotherapy may be offered. Specific immunotherapy as practiced since hundred years in Wester...
Roberts, A M; Van Ree, R; Cardy, S M; Bevan, L J; Walker, M R
We previously described the isolation of three identical complementary DNA (cDNA) clones, constructed from Orchard/Cocksfoot grass (Dactylis glomerata) anther messenger RNA (mRNA), expressing a 140,000 MW beta-galactosidase fusion protein recognized by IgE antibodies in atopic sera. Partial nucleotide sequencing and inferred amino acid sequence showed greater than 90% homology with the group II allergen from Lolium perenne (Lol II) indicating they encode the group II equivalent, Dac g II. Western blot immunoprobing of recombinant lysates with rabbit polyclonal, mouse monoclonal and human polyclonal antisera demonstrates immunological identity between recombinant Dac g II, Lol p I and Lol p II. Similar cross-identity is observed with pollen extracts from three other grass species: Festuca rubra, Phleum pratense and Anthoxanthum odoratum. Recombinant Dac g II was recognized by species- and group-cross-reactive human IgE antibodies in 33% (4/12) of sera randomly selected from grass-sensitive individuals and in 67% (14/21) of sera from patients receiving grass pollen immunotherapy, whilst 0/4 sera from patients receiving venom immunotherapy alone contained Dac g II cross-reactive IgE. Cross-reactive IgG4 antibodies were detectable in 95% of sera from grass pollen immunotherapy patients. These preliminary data suggest that conventional grass pollen allergoid desensitization immunotherapy may induce IgE responses to a cross-reactive epitope(s) co-expressed by grass pollen groups I and II (and possibly group III) allergens.
Pomés, Anna; Mueller, Geoffrey A; Randall, Thomas A; Chapman, Martin D; Arruda, L Karla
This review addresses the most recent developments on cockroach allergen research in relation to allergic diseases, especially asthma. The number of allergens relevant to cockroach allergy has recently expanded considerably up to 12 groups. New X-ray crystal structures of allergens from groups 1, 2, and 5 revealed interesting features with implications for allergen standardization, sensitization, diagnosis, and therapy. Cockroach allergy is strongly associated with asthma particularly among children and young adults living in inner-city environments, posing challenges for disease control. Environmental interventions targeted at reducing cockroach allergen exposure have provided conflicting results. Immunotherapy may be a way to modify the natural history of cockroach allergy and decrease symptoms and asthma severity among sensitized and exposed individuals. The new information on cockroach allergens is important for the assessment of allergen markers of exposure and disease, and for the design of immunotherapy trials.
Mitsias, Dimitris I; Kalogiros, Lampros A; Papadopoulos, Nikolaos G
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.
Poddighe, Dimitri; Licari, Amelia; Caimmi, Silvia; Marseglia, Gian Luigi
Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient's daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness.
Asturias, Juan Andres
Recombinant allergens are a promising alternative to crude allergen extracts for diagnosis and therapy of allergic diseases. Genetically modified allergen derivatives with reduced allergenic activity but retaining their immunogenicity have also been produced to increase safety and specificity of allergen-specific immunotherapy. When a limited number of allergens are responsible for most of the allergenic activity, fusion proteins comprising these major allergens can be used to simplify vaccine development. Three different allergen fusions of Par j 1 and Par j 2, the major allergens from Parietaria judaica, were characterized. Two of them (Q1 and Q2) showing reduced allergenicity but conserved immunogenicity represent suitable candidates for allergen-specific immunotherapy against P. judaica pollen allergy.
Wang, Jian; Huang, Ying; Zhang, Xue-Li; Huang, Xia; Xu, Xiao-Wen; Liang, Fan-Mei
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 (Presponses 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.
Saeki, Mayumi; Nishimura, Tomoe; Kaminuma, Osamu; Mori, Akio; Hiroi, Takachika
Allergen-specific immunotherapy (IT) has been shown to provide clinical benefit for patients with allergic diseases. At present, subcutaneous and sublingual ITs are mainly authorized for clinical treatment. Oral administration of allergens seems to be the easiest way to achieve IT, though it has yet to be translated to the clinical setting, mainly due to the requirement of a large amount of allergens. Plants, especially rice seeds, have recently been recognized as superior allergen carriers for oral administration, because of their high productivity, stability and safety. Therefore, in order to establish clinically applicable oral IT, we have been developing transgenic rice seeds (Tg rice), in which major epitopes of cedar pollen allergens or house-dust mites (HDM) are expressed. The efficacy of this orally administered Tg rice was confirmed in murine models of allergic rhinitis and bronchial asthma. In the safety study of the Tg rice, no adverse effects on cynomolgus macaques were observed. In this review, we summarized the current state and future prospects of allergen-specific IT, focusing particularly on oral IT with allergen-expressing Tg rice. Copyright © 2013 S. Karger AG, Basel.
El-Qutob, David; Mencia, Gemma; Fernandez-Caldas, Enrique
Allergic diseases are a major health problem worldwide. The therapeutic approaches to treat allergic rhinitis (AR) and allergic asthma (AA) fall in three major categories. The first step is allergen avoidance, or reduction of exposure to the offending allergen(s). The second and most widely used therapeutic practice is the prescription of relevant medication to reduce symptoms. The third therapeutic element is specific allergy vaccination, also known as allergen specific immunotherapy. Allergen-specific immunotherapy (SIT) is the only etiologic treatment of allergic disorders that can alter the natural course of the disease. In this review, recent advances in immunotherapy and relevant patents are presented. General vaccine modifications could be applied for any type of allergen. New specific modifications in allergic vaccines have been developed for a variety of allergies such as house dust mites, horse, cat, parvalbumin and from birch, ragweed and parietaria pollen.
Dhami, Sangeeta; Nurmatov, Ulugbek; Arasi, Stefania
the effectiveness, cost-effectiveness and safety of AIT in the management of allergic rhinoconjunctivitis METHODS: We searched 15 international biomedical databases for published, in progress and unpublished evidence. Studies were independently screened by two reviewers against pre-defined eligibility criteria...... and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random...
Dhami, Sangeeta; Nurmatov, Ulugbek; Roberts, Graham
in the management of allergic rhinoconjunctivitis. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically...... appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. CONCLUSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT....
Halken, Susanne; Larenas-Linnemann, Desiree; Roberts, Graham
) has developed a clinical practice guideline to provide evidence-based recommendations for AIT for prevention of i) development of allergic comorbidities in those with established allergic diseases, ii) development of first allergic condition and iii) allergic sensitization. This guideline has been...
Roberts, G; Pfaar, O; Akdis, C A
systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product...
could be demonstrated in 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.
Schmid, Johannes Martin; Würtzen, Peter Adler; Dahl, Ronald
(Alutard SQ) or to an open control group. IgE and IgG4 concentrations were determined for the major allergens Phl p 1 or Phl p 5 by using ImmunoCAP and for 8 grass pollen molecules by using Immuno Solid-phase Allergy Chip (ISAC) before treatment and after updosing. RESULTS: Levels of specific IgE against...
Poulsen, L K; Lundberg, L; Søndergaard, I
In a previous study guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes prepared from antigen and specific IgG) IT was compared....... In contrast to IgE, mean group titers of IgG1 and IgG2 in the groups receiving active or combined IT rose drastically during the first part of therapy and closely paralleled the clinical response during the rest of the study period. However, in the individual animals, no correlations were found between immune...... with placebo. In the present study methods were evaluated for determination of the allergen-specific IgE and IgG. IgE was determined by the passive cutaneous anaphylactic test (PCA) and the variability of this test on different strains of the recipient guinea pig was investigated. The same strain as used...
Sambugaro, R; Puccinelli, P; Burastero, S E; Di Rienzo, V
Sublingual administration of allergens is a safe and effective alternative to subcutaneous immunotherapy in patients with respiratory allergies. A drawback to this therapeutic approach is the relatively long and complex management of the induction phase. To determine whether different induction regimens affect the outcome of sublingual immunotherapy. Adult and pediatric patients with allergic rhinoconjunctivitis and/or asthma were included in the study. Ten subjects served as controls and received symptomatic treatments. Forty-three subjects were allocated to sublingual immunotherapy, with three different induction protocols (8-, 15- and 20-day, respectively). Symptom and medication scores, skin test results and (in asthmatic patients) FEV1 values were monitored for two years. Adverse effects were recorded. All induction regimens produced a significant improvement in symptom and medication usage (p protocol is safe and effective. Our results encourage the usage of shorter induction regimens, which produce better compliance with this therapy.
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.
Maina, Elisa; Cox, Eric
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.
Sánchez, Jorge; Cardona, Ricardo; Caraballo, Luis; Serrano, Carlos; Ramírez, Ruth; Díez, Susana; García, Elizabeth; Segura, Ana María; Cepeda, Alfonso; Minotas, María
Allergies comprise a set of highly prevalent diseases. When allergic processes are not controlled, they can endanger patients' health and lives, and have an important economic and social impact. The aim of this paper is to present a practical consensus of the scientific evidence on the use of immunotherapy in allergic diseases. A collaborative review made by various institutes and universities in Colombia was carried out upon request of the Asociación Colombiana de Alergia, Asma e Imunología, led by general practitioners, allergists, immunologists, internists and paediatricians with experience in the field of allergies. As a result, based on current national and international scientific evidence, we describe in detail what immunotherapy is about, its indications, contraindications and its economic and health benefits. Conclusions show immunotherapy as a clinically effective and safe treatment, which can substantially reduce the cost of the overall treatment of allergic patients.
Søndergaard, I; Poulsen, L K; Osterballe, O
Detailed evaluation of the IgE and IgG-subclass immune response during immunotherapy can now be performed by crossed radio immunoelectrophoresis (CRIE). Some new concepts are introduced facilitating the handling of the vast amount of data obtained by quantitating the immune response. These concepts...... are "distance" between antibody responses and "immune response width". The 20 patients included in this study were pollen-allergic patients who underwent specific immunotherapy in a 3-year prospective study. It was found that the immune response during immunotherapy was restricted to IgG1 and IgG4 antibodies...... and decreased towards six. For the IgG4 antibodies the number of reactions increased towards 15 antigens and decreased towards four. The increase is generally paralleled by an increase in quantitative immune response as well. For some of the antigens a rise in the IgE antibodies is contrasted by a fall...
Full Text Available BACKGROUND: Allergen-mediated cross-linking of IgE antibodies bound to the FcepsilonRI receptors on the mast cell surface is the key feature of the type I allergy. If an allergen is a homodimer, its allergenicity is enhanced because it would only need one type of antibody, instead of two, for cross-linking. METHODOLOGY/PRINCIPAL FINDINGS: An analysis of 55 crystal structures of allergens showed that 80% of them exist in symmetric dimers or oligomers in crystals. The majority are transient dimers that are formed at high protein concentrations that are reached in cells by colocalization. Native mass spectrometric analysis showed that native allergens do indeed form transient dimers in solution, while hypoallergenic variants of them exist almost solely in the monomeric form. We created a monomeric Bos d 5 allergen and show that it has a reduced capability to induce histamine release. CONCLUSIONS/SIGNIFICANCE: The results suggest that dimerization would be a very common and essential feature for allergens. Thus, the preparation of purely monomeric variants of allergens could open up novel possibilities for specific immunotherapy.
Verra, N.; Jansen, R.; Groenewegen, G.; Mallo, H.; Kersten, M. J.; Bex, A.; Vyth-Dreese, F. A.; Sein, J.; van de Kasteele, W.; Nooijen, W. J.; de Waal, M.; Horenblas, S.; de Gast, G. C.
The purpose of the study was to determine toxicity, efficacy and immunologic effects of concurrent subcutaneous injections of low-dose interleukin-2 (LD-IL-2), granulocyte-monocyte colony-stimulating factor (GM-CSF) and interferon-alpha 2b (IFNalpha) in progressive metastatic renal cell carcinoma.
Grier, Thomas J; Hall, Dawn M; Duncan, Elizabeth A; Coyne, Terrance C
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
Slovick, Anna; Douiri, Abdel; Muir, Rachel; Guerra, Andrea; Tsioulos, Konstantinos; Hay, Evie; Lam, Emily P S; Kelly, Joanna; Peacock, Janet L; Ying, Sun; Shamji, Mohamed H; Cousins, David J; Durham, Stephen R; Till, Stephen J
Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy. We sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis. We randomly assigned 93 adults with grass pollen-induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment. There was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, -172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, -11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense-specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03). Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory
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.
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
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)
Turkalj M; Banic I; Anzic SA
Mirjana Turkalj,1,2 Ivana Banic,1 Srdjan Ante Anzic1 1Children’s Hospital Srebrnjak, Zagreb, 2Faculty of Medicine, JJ Strossmayer University of Osijek, Osijek, Croatia Abstract: 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 im...
Thomas, Wayne R
HDM allergy is associated with asthma, allergic rhinitis and atopic dermatitis. In many countries childhood asthma is predominantly found in HDM-allergic children with their probability of developing disease being proportional to their IgE antibody titers and the early development of Th2 responses. While the pathogenesis is complex and increasingly linked to infection the immunologically-based allergen immunotherapy and anti-IgE antibody therapy are highly beneficial. Immunotherapy could be a short-term treatment providing lifelong relief but the current regimens depend on repeated administration of allergen over years. Immunological investigations point to a contribution of responses outside the Th2 pathway and multiple potential but unproven control mechanisms. Over half of the IgE antibodies are directed to the group 1 and 2 allergens with most of remainder to the group 4, 5, 7 and 21 allergens. This hierarchy found in high and low responders provides a platform for introducing defined allergens into immunotherapy and defined reagents for investigation.
Hessenberger, Michael; Weiss, Richard; Weinberger, Esther E; Boehler, Christof; Thalhamer, Josef; Scheiblhofer, Sandra
Two main shortcomings of classical allergen-specific immunotherapy are long treatment duration and low patient compliance. Utilizing the unique immunological features of the skin by transcutaneous application of antigen opens new approaches not only for painless vaccine delivery, but also for allergen-specific immunotherapy. Under certain conditions, however, barrier disruption of the skin favors T helper 2-biased immune responses, which may lead to new sensitizations. In a prophylactic approach, an infra-red laser device was employed, producing an array of micropores of user-defined number, density, and depth on dorsal mouse skin. The grass pollen allergen Phl p 5 was administered by patch with or without the T helper 1-promoting CpG oligodeoxynucleotide 1826 as adjuvant, or was subcutaneously injected. Protection from allergic immune responses was tested by sensitization via injection of allergen adjuvanted with alum, followed by intranasal instillation. In a therapeutic setting, pre-sensitized mice were treated either by the standard method using subcutaneous injection or via laser-generated micropores. Sera were analyzed for IgG antibody subclass distribution by ELISA and for IgE antibodies by a basophil mediator release assay. Cytokine profiles from supernatants of re-stimulated lymphocytes and from bronchoalveolar lavage fluids were assessed by flow cytometry using a bead-based assay. The cellular composition of lavage fluids was determined by flow cytometry. Application of antigen via micropores induced T helper 2-biased immune responses. Addition of CpG balanced the response and prevented from allergic sensitization, i.e. IgE induction, airway inflammation, and expression of T helper 2 cytokines. Therapeutic efficacy of transcutaneous immunotherapy was equal compared to subcutaneous injection, but was superior with respect to suppression of already established IgE responses. Transcutaneous immunotherapy via laser-generated micropores provides an efficient
Full Text Available Scientific background: Allergic rhinitis (AR exhibits a prevalence of approx. 20% in Germany and causes enormous costs in the health care system. Specific immunotherapy (SIT is considered to be the only potentially causal therapy for AR and mainly administered by two routes, subcutaneous (SCIT and sublinguale (SLIT. SIT promises a reduction of symptoms and the need for medication in patients with AR. Research questions: The question arises, to what extent is SIT effective and cost effective in the treatment of AR and which ethical-social and legal aspects have to be considered regarding its application. Methods: The literature search was accomplished in the electronic data bases MEDLINE, EMBASE etc. in February 2008. The medical evaluation was based on systematic reviews of blinded, randomised controlled studies (RCT. The economic evaluation included health-economic studies on the basis of RCT. Additionally, it was also searched for publications explicitly addressing ethical-social and legal aspects of the use of SIT. Results: Medical evaluationTwo reviews on SCIT and three on SLIT were included in the medical evaluation. For the evaluation of SIT with grass pollen results for short and medium-term effects are considered from several studies, for SIT with other seasonal allergens (e. g. tree pollen and with house dust mite allergens from clearly fewer studies and for SIT with other perennial allergens only from a few. The reviews report a significant reduction of the symptom and medication score in favour of SCIT with seasonal allergens and recognise the effectiveness at least for grass pollen allergens. Also for other seasonal allergens SCIT is appraised as effective. The reviews about SLIT determine a significant reduction of the symptom and the medication score in favour of SLIT vs. placebo in short and medium term follow-up in evaluations across all allergens. The subgroup analyses show a significant reduction of the symptom and medication
Bonyadi, MR. (PhD; Ezzati, F. (MSc
Background and objective: Being exposed to different allergens, followed by the production of specific IgE, has an important role in causing atopic dermatitis, recognizing the allergens and applying immunotherapy for treatment. We aimed to determine the frequency of common allergens in the patients suffering from atopic dermatitis. Material and Methods: In this descriptive- analytical study the serum level of total IgE and frequency of specific IgE were measured by Immunoblotting method again...
Poulsen, L K; Lundberg, L; Søndergaard, I
Guinea pigs inbred for their ability to develop respiratory anaphylaxis to experimental antigens have been used for comparison of different forms of immunotherapy (IT). Passive, active and combined (immune complexes between antigen and specific IgG) IT were compared with placebo. The bronchial...... reactivity of the animals to the antigen was monitored regularly before, during (35 weeks) and after IT (20 weeks). Animals treated with passive IT did not improve clinically. Active and combined IT abolished most symptoms within 7 weeks of treatment. During the post-treatment period, animals from both...
Full Text Available SLIT ([i]sublingual immunotherapy[/i], induces allergen-specific immune tolerance by sublingual administration of a gradually increasing dose of an allergen. The mechanism of SLIT is comparable to those during SCIT (subcutaneous immunotherapy, with the exception of local oral dendritic cells, pre-programmed to elicit tolerance. In the SLIT dose, to achieve the same efficacy as in SCIT, it should be 50–100 times higher with better safety profile. The highest quality evidence supporting the efficacy of SLIT lasting 1 – 3 years has been provided by the large scale double-blind, placebo-controlled (DBPC trials for grass pollen extracts, both in children and adults with allergic rhinitis. Current indications for SLIT are allergic rhinitis (and conjunctivitis in both children and adults sensitized to pollen allergens (trees, grass, [i]Parietaria[/i], house dust mites ([i]Dermatophagoides pteronyssinus, Dermatophagoides farinae[/i], cat fur, as well as mild to moderate controlled atopic asthma in children sensitized to house dust mites. There are positive findings for both asthma and new sensitization prevention. Severe adverse events, including anaphylaxis, are very rare, and no fatalities have been reported. Local adverse reactions develop in up to 70 – 80% of patients. Risk factors for SLIT adverse events have not been clearly identified. Risk factors of non-adherence to treatment might be dependent on the patient, disease treatment, physician-patient relationship, and variables in the health care system organization.
BACKGROUND/OBJECTIVES: Sublingual immunotherapy was first described in 1986. Since then, its use has been increased as an alternative to subcutaneously administered immunotherapy in the treatment of allergic rhinitis. The most common side effects are of oropharyngeal and gastrointestinal in natur...
Immunotherapy is a cancer treatment that helps your immune system fight cancer. It is a type of biological therapy. Biological therapy uses substances ... t yet use immunotherapy as often as other cancer treatments, such as surgery, chemotherapy, and radiation therapy. ...
Keiding, Hans; Jørgensen, Kasper P.
the therapy has been in use in order to assess the impact of national therapeutic practices on the results of health economic assessments. Data are obtained from a clinical trial carried out in 2001-2002. To evaluate the cost-effectiveness of immunization we have added data on resource use in Austria, Denmark......Background: Seasonal allergic rhinoconjunctivitis can, for some people, reduce quality of life and the ability to cope with everyday tasks. Scope: In this paper we investigate the cost-effectiveness of immunization therapy with Alutard SQ (ASQ) and compare the cost-effectiveness in countries where......, Finland, Germany, the Netherlands, and Sweden. Findings: The computations result in cost-effectiveness ratios for allergen immunization between €10 000 and €20 000 per QALY even without provision for indirect costs, and achieving dominance in most countries where indirect costs have also been taken...
Bordas-Le Floch, Véronique; Groeme, Rachel; Chabre, Henri; Baron-Bodo, Véronique; Nony, Emmanuel; Mascarell, Laurent; Moingeon, Philippe
Pollen allergens from short ragweed (Ambrosia artemisiifolia) cause severe respiratory allergies in North America and Europe. To date, ten short ragweed pollen allergens belonging to eight protein families, including the recently discovered novel major allergen Amb a 11, have been recorded in the International Union of Immunological Societies (IUIS) allergen database. With evidence that other components may further contribute to short ragweed pollen allergenicity, a better understanding of the allergen repertoire is a requisite for the design of proper diagnostic tools and efficient immunotherapies. This review provides an update on both known as well as novel candidate allergens from short ragweed pollen, identified through a comprehensive characterization of the ragweed pollen transcriptome and proteome.
Gamazo, Carlos; Gastaminza, Gabriel; Ferrer, Marta; Sanz, María L; Irache, Juan M
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.
Rondón, C; Campo, P; Salas, M; Aranda, A; Molina, A; González, M; Galindo, L; Mayorga, C; Torres, M J; Blanca, M
The effects of allergen immunotherapy (AIT) on local allergic rhinitis (LAR) are largely unknown. We conducted the first randomized, double-blind, placebo-controlled (DBPC), phase II trial of D. pteronyssinus (DP) subcutaneous AIT (DP-AIT) on LAR (clinicaltrials.gov identifier: NCT02123316). Thirty-six LAR patients received Pangramin PLUS DP or placebo for 24 months. The primary endpoints were symptoms, medication scores, and medication-free days. The secondary included skin test, serum specific IgE and IgG4, nasal allergen provocation test (NAPT), and adverse events. AIT-DP produced significant improvements in both primary and secondary endpoints vs placebo. After 12 months of AIT-DP, we detected a significant and marked increase in allergen tolerance with negative NAPT in 50% of patients, and significant increases of serum sIgG4. Immunotherapy was well tolerated; no systemic reactions were reported. This study demonstrated that AIT-DP is a safe and clinically effective treatment for LAR, confirming that LAR is a new indication for AIT. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Aasbjerg, Kristian; Backer, Vibeke
Treatment for seasonal allergic rhinitis induced by airborne allergens can be divided into two major groups: symptom-dampening drugs, such as antihistamines and corticosteroids, and disease-modifying drugs in the form of immunotherapy. It has been speculated that depot-injection corticosteroids...... given once or twice a year are a safe and patient-friendly alternative to the time-consuming immunotherapy. Our data indicate otherwise....
... Pregnancy Healthy Food Shopping Healthy Drinks for Kids Immunotherapy KidsHealth > For Parents > Immunotherapy Print A A A ... Immunity Types of Immunotherapy Side Effects Outlook About Immunotherapy Immunotherapy, also known as targeted therapy or biotherapy, ...
Tatiana A. Slavyanakaya
Full Text Available Abstract Allergen specific immunotherapy (AIT has been the only pathogenetically relevant treatment of IgE-mediated allergic diseases (ADs for many years. The use of AIT for atopic dermatitis (AD treatment is dubious and has both followers and opponents. The improvement of subcutaneous AIT (SCIT and introduction of Sublingual immunotherapy (SLIT gives prospects of their application both for adults and children suffering from AD. This review presents results of scientific research, system and meta-analyses that confirm the clinical efficacy of AIT for children with AD who has the sensitization to allergens of house dust mite, grass and plant pollen suffering from co-occurring respiratory ADs and with moderate and severe course of allergic AD. There have been analyzed the most advanced achievements in AIT studies as well as there have been specified the unmet needs in AD. The preliminary diagnostics of IgE-mediated AD and pathophysiological disorders, including immune ones, will allow a doctor to develop appropriate comprehensive treatment algorithm for children’s AD aimed at its correction. The including of AIT to the children’s comprehensive therapy program is reasonable only if AD has the allergic form. It is necessary better to design the randomized research studies and to acquire extended clinical practice in children with AD. Use of the successes of molecular-based allergy diagnostics will help to optimize and personalize the process of selecting the necessary allergens to determine the most appropriate vaccines for children considering the results of the allergen component diagnostics. The strategy of treatment of children with AD in future will be based on individual target therapy.
de Jongste Johan C
Full Text Available Abstract Background For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized double-blind placebo-controlled study was designed to establish the efficacy of sublingual immunotherapy with house dust mite allergen compared to placebo treatment in 6 to18-year-old children with allergic rhinitis and a proven house dust mite allergy in primary care. Described here are the methodology, recruitment phases, and main characteristics of the recruited children. Methods Recruitment took place in September to December of 2005 and 2006. General practitioners (in south-west Netherlands selected children who had ever been diagnosed with allergic rhinitis. Children and parents could respond to a postal invitation. Children who responded positively were screened by telephone using a nasal symptom score. After this screening, an inclusion visit took place during which a blood sample was taken for the RAST test. Results A total of 226 general practitioners invited almost 6000 children: of these, 51% was male and 40% Conclusion Our study was designed in accordance with recent recommendations for research on establishing the efficacy of sublingual immunotherapy; 98% of the target sample size was achieved. This study is expected to provide useful information on sublingual immunotherapy with house dust mite allergen in primary care. The results on efficacy and safety are expected to be available by 2010. Trial registration the trial is registered as ISRCTN91141483 (Dutch Trial Register
The treatment of allergies often involves pharmacological therapy and recommendations by healthcare workers that the allergen should be avoided. Allergen-specific immunotherapy has emerged as an alternative to effectively decrease the immunoglobulin (Ig) E:IgG4 ratio. Two routes of administration are described, ...
Rogers, Christine Anne; Burge, Harriet A
Outdoor allergens are an important part of the exposures that lead to allergic disease. Understanding the role of outdoor allergens requires a knowledge of the nature of outdoor allergen-bearing particles, the distributions of their source, and the nature of the aerosols (particle types, sizes, dynamics of concentrations). Primary sources for outdoor allergens include vascular plants (pollen, fern spores, soy dust), and fungi (spores, hyphae). Nonvascular plants, algae, and arthropods contrib...
Full Text Available Abstract Background Subcutaneous Immunotherapy (SCIT modifies the allergic response and relieves allergic symptoms. SCIT is the only and a very effective treatment for insect venom allergy. We hypothesized that basophil sensitivity, measured through the basophil activation test, would decrease during SCIT up dosing. Expression of CD203c was compared to CD63 as marker for basophil activation, using a Bland Altman plot and ROC curves. Methods Patients (n = 18 starting subcutaneous SCIT for wasp allergy with an up dosing scheme of 7 to 11 weeks were enrolled. Heparinised blood samples were drawn at weeks 1-4, 7 and at the first maintenance visit. Basophils were stimulated at 7 log dilutions of V. vespula allergen for 15 min, and were stained with CD203c and CD63. Basophils were identified as CD203c+ leukocytes, and the proportion of CD63+ and CD203c+ cells were plotted against allergen concentration. A sigmoid curve was fitted to the points, and the allergen concentration at which half of the maximal activation was achieved, LC50, was calculated. In another series of experiments, LC50 calculated in whole blood (AP was subtracted from LC50 calculated with basophils suspended in plasma from a nonatopic donor (HS to determine the protective effect of soluble factors in blood of patients treated with SCIT. Results Heparin blood basophil activation was similar through CD63 and CD203c. Basophils were significantly more sensitized three weeks after initiation of SCIT compared to baseline (p Conclusion Basophil activation is a versatile and sensitive tool that measures changes in the humoral immune response to allergen during SCIT.
Edwards, Thomas S; Wise, Sarah K
Sublingual immunotherapy (SLIT) is effective for the treatment of allergic rhinitis and allergic asthma in adults and children. In a limited number of studies, SLIT efficacy has been demonstrated for the treatment of food allergy. SLIT has a higher safety profile versus subcutaneous immunotherapy, although some systemic reactions have been reported. Appropriate patient selection, meticulous patient education, and routine follow-up are key for the safe and effective administration of SLIT. With organization and attention to detail, adding SLIT to one's practice can provide a highly valued patient service. Copyright © 2017 Elsevier Inc. All rights reserved.
Cairns, Linda; Aspeslagh, Sandrine; Anichini, Andrea
This report covers the Immunotherapy sessions of the 2016 Organisation of European Cancer Institutes (OECI) Oncology Days meeting, which was held on 15th-17th June 2016 in Brussels, Belgium. Immunotherapy is a potential cancer treatment that uses an individual's immune system to fight the tumour....... In recent years significant advances have been made in this field in the treatment of several advanced cancers. Cancer immunotherapies include monoclonal antibodies that are designed to attack a very specific part of the cancer cell and immune checkpoint inhibitors which are molecules that stimulate...... or block the inhibition of the immune system. Other cancer immunotherapies include vaccines and T cell infusions. This report will summarise some of the research that is going on in this field and will give us an update on where we are at present....
Full Text Available Vast amounts of allergen sequence data have been accumulated, thus complicating the identification of specific allergenic proteins when performing diagnostic allergy tests and immunotherapy. This study aims to rank the importance/potency of the allergens so as to logically reduce the number of allergens and/or allergenic sources. Meta-analysis of 62 allergenic sources used for intradermal testing on 3,335 allergic patients demonstrated that in southern China, mite, sesame, spiny amaranth, Pseudomonas aeruginosa, and house dust account for 88.0% to 100% of the observed positive reactions to the 62 types of allergenic sources tested. The Kolmogorov-Smironov Test results of the website-obtained allergen data and allergen family featured peptides suggested that allergen research in laboratories worldwide has been conducted in parallel on many of the same species. The major allergens were reduced to 21 representative allergens, which were further divided into seven structural classes, each of which contains similar structural components. This study therefore has condensed numerous allergenic sources and major allergens into fewer major representative ones, thus allowing for the use of a smaller number of allergens when conducting comprehensive allergen testing and immunotherapy treatments.
S Dean Rider
Full Text Available Euroglyphus maynei is a house dust mite commonly found in homes worldwide and is the source of allergens that sensitize and induce allergic reactions in humans. It is the source of species-specific allergens as well as allergens that are cross-reactive with the allergens from house dust mites Dermatophagoides farinae and D. pteronyssinus, and the ectoparasitic scabies mite Sarcoptes scabiei. The genomics, proteomics and molecular biology of E. maynei and its allergens have not been as extensively investigated as those of D. farinae, D. pteronyssinus, and S. scabiei where natural and recombinant allergens from these species have been characterized. Until now, little was known about the genome of E. maynei and it allergens but this information will be important for producing recombinant allergens for diagnostic and therapeutic purposes and for understanding the allergic response mechanism by immune effector cells that mediate the allergic reaction. We sequenced and assembled the 59 Mb E. maynei genome to aid the identification of homologs for known allergenic proteins. The predicted proteome shared orthologs with D. farinae and S. scabiei, and included proteins with homology to more than 30 different groups of allergens. However, the majority of allergen candidates could not be assigned as clear orthologs to known mite allergens. The genomic sequence data, predicted proteome, and allergen homologs identified from E. maynei provide insight into the relationships among astigmatid mites and their allergens, which should allow for the development of improved diagnostics and immunotherapy.
, and dysphagia. Sublingual immunotherapy (SLIT) was first described in 1986. Following this description, the use has greatly increased in the treatment of allergic rhinitis, as an alternative to subcutaneously administered immunotherapy. Side effects are commonly of oropharyngeal and gastrointestinal nature...... to administration of sublingual immunotherapy for house dust mite in allergic rhinitis. The patient had to stop the SLIT after two weeks of administration due to GORD. The cessation resulted in rapid resolution of symptoms....
Mösges, Ralph; Kasche, Elena M; Raskopf, Esther; Singh, Jaswinder; Sohlich, Lea; Astvatsatourov, Anatoli; Shah-Hosseini, Kija; Pirotton, Sabine; Haazen, Ludo; Durham, Stephen R; Legon, Thierry; Zadoyan, Gregor; Shamji, Mohamed H
A novel subcutaneous allergen immunotherapy formulation (gpASIT+(™) ) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity, and safety. This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170, or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3, and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks, and after completion. Grass pollen-specific immunoglobulins were analysed before and after treatment. CPT response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP versus 25.6% of patients receiving placebo (modified per protocol set). Also, 39% of patients in the 170 μg-group became non-reactive to CPT versus 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 μg), 3.1-fold (170 μg), and 3.9-fold (370 μg) (mPP). Three-week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
This thesis is about visualization and characterization of the tissue-device interaction during subcutaneous injection. The tissue pressure build-up during subcutaneous injections was measured in humans. The insulin pen FlexTouchr (Novo Nordisk A/S) was used for the measurements and the pressure...... build-up was evaluated indirectly from the changes in the flow rate between subcutaneous injections and air injections. This method enabled the tissue counter pressure to be evaluated without a formal clinical study approval. The measurements were coupled to a model for the pressure evolution...... in subcutaneous tissue, based on mass conservation and flow in a porous medium. From the measurements the flow permeability and bulk modulus of the tissue were determined. In the adipose tissue the drug forms a bolus from where it is absorbed by the blood capillaries. The spatial distribution of the injected...
Feuille, Elizabeth; Nowak-Węgrzyn, Anna
Oral immunotherapy (OIT) is a promising investigational therapy for food allergy. Clinical trials in peanut, milk, egg, and wheat allergy provide evidence that OIT can effectively desensitize a majority of individuals to a food allergen. While a portion of subjects demonstrate sustained unresponsiveness, the majority regain sensitivity with allergen avoidance. The safety and tolerability of OIT continue to limit its use in some patients. Virtually all studies report adverse reactions that are more frequent during dose escalation but may also occur during maintenance therapy. Recent studies have identified adjunctive therapies (such as omalizumab) which may mitigate adverse effects. There is a paucity of data on the long-term safety and efficacy of OIT. Further study is required before OIT is ready for routine clinical practice. This review is intended to provide the reader with an up-to-date understanding of OIT, including its mechanisms, efficacy, safety profile, and potential utility in clinical practice. © 2016 S. Karger AG, Basel.
Didier, Alain; Worm, Margitta; Horak, Friedrich
Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies.......Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies....
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
, for example, itching, swelling, irritation, ulceration of the oropharynx and nausea, abdominal pain, diarrhoea, and vomiting. More severe side effects are dominated by systemic and respiratory tract manifestations. RESULTS: In this clinical case, the author reports a right-sided transient tinnitus lasting...... for 48 h after administration of sublingual immunotherapy for house dust mite in allergic rhinitis. CONCLUSIONS: This case provide important insights for clinical practice, as tinnitus has not been previously reported as a side effect of sublingual immunotherapy with house dust mite allergens....
de Bot, Cindy M A; Moed, Heleen; Berger, Marjolein Y; Röder, Esther; de Groot, Hans; de Jongste, Johan C; van Wijk, Roy Gerth; van der Wouden, Johannes C
For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized double-blind placebo-controlled study was designed to establish the efficacy of sublingual immunotherapy with house dust mite allergen compared to placebo treatment in 6 to 18-year-old children with allergic rhinitis and a proven house dust mite allergy in primary care. Described here are the methodology, recruitment phases, and main characteristics of the recruited children. Recruitment took place in September to December of 2005 and 2006. General practitioners (in south-west Netherlands) selected children who had ever been diagnosed with allergic rhinitis. Children and parents could respond to a postal invitation. Children who responded positively were screened by telephone using a nasal symptom score. After this screening, an inclusion visit took place during which a blood sample was taken for the RAST test. A total of 226 general practitioners invited almost 6000 children: of these, 51% was male and 40% <12 years of age. The target sample size was 256 children; 251 patients were finally included. The most frequent reasons given for not participating were: absence or mildness of symptoms, absence of house dust mite allergy, and being allergic to grass pollen or tree pollen only. Asthma symptoms were reported by 37% of the children. Of the enrolled children, 71% was sensitized to both house dust mite and grass pollen. Roughly similar proportions of children were diagnosed as being sensitized to one, two, three or four common inhalant allergens. Our study was designed in accordance with recent recommendations for research on establishing the efficacy of sublingual immunotherapy; 98% of the target sample size was achieved. This study is expected to provide useful information on
Yang, Lin; Zhu, Rongfei
House dust mite (HDM) is a predominant source of indoor aeroallergen worldwide, which induces allergic diseases including allergic rhinoconjunctivitis, allergic asthma, atopic eczema and other allergic skin diseases. Allergen specific immunotherapy (AIT) is the only potential disease-modifying treatment of HDM allergic subjects. However, AIT remains underused due to no universally accepted allergen standardization and a shortage of rigorous clinical studies to confirm safety and efficacy. With the effort of doctors and researchers in allergy field, efficacy, safety, standardization and strategy of AIT are being continuously developed. This review presents the updated research based on recently published trials and meta-analyses.
Huang, Fang-Liang; Liao, En-Chih; Yu, Sheng-Jie
Over the past few decades, allergic diseases have become increasingly prevalent worldwide. House dust mite (HDM) is the most important domestic source for allergic diseases such as allergic rhinitis, asthma and atopic dermatitis. Dermatophagoides pteronyssinus (Der p) is the major environmental allergen in southeast Asia because of the humid and warm environment is suitable for its growth. In the recent year, role of HDM allergen in allergic inflammation through innate immune system has been well studied. Toll-like receptors (TLRs), protease-activated receptors (PARs) and DC-SIGN could be activated by different HDM major allergens and proinflammatory cytokines also be upregulated. Treatment efficacy for HDM allergy is unsatisfied to the patients and the medication is limited. Immunotherapy provided an alternative option for treating HDM allergy through targeted to the mechanisms of allergic reaction and represented a long-term symptoms relief. Gene specific immunotherapy was currently being developed and it could decrease allergic inflammation and improve the efficacy of treatment. In this report, we reviewed recent studies about the role of HDM allergy in innate immune system and its immunotherapy. Understanding the HDM allergen induced signal transduction pathway and developed allergen specific immunotherapy could help physicians to create precise diagnosis and solve unmet need in HDM allergy. Copyright © 2017 Elsevier GmbH. All rights reserved.
Gouw, Launce G., E-mail: firstname.lastname@example.org [Departments of Oncology, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Jones, Kevin B. [Departments of Orthopaedic Surgery, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Sharma, Sunil [Departments of Oncology, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States); Randall, R. Lor [Departments of Orthopaedic Surgery, Huntsman Cancer Institute at the University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 (United States)
Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis.
R. Lor Randall
Full Text Available Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis.
Roeder, Esther; Berger, Marjolein Y.; de Groot, Hans; van Wijk, Roy Gerth
Allergen-specific immunotherapy is one of the cornerstones of allergic rhinoconjunctivitis treatment. Since the development of non-invasive administration forms with better safety profiles, there is an increasing tendency to prescribe immunotherapy in youngsters. However, no overview is available on
Ipci, Kagan; Oktemer, Tugba; Muluk, Nuray Bayar; Şahin, Ethem; Altıntoprak, Niyazi; Bafaqeeh, Sameer Ali; Kurt, Yasemin; Mladina, Ranko; Šubarić, Marin; Cingi, Cemal
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.
Durham, S R; Walker, S M; Varga, E M; Jacobson, M R; O'Brien, F; Noble, W; Till, S J; Hamid, Q A; Nouri-Aria, K T
Pollen immunotherapy is effective in selected patients with IgE-mediated seasonal allergic rhinitis, although it is questionable whether there is long-term benefit after the discontinuation of treatment. We conducted a randomized, double-blind, placebo-controlled trial of the discontinuation of immunotherapy for grass-pollen allergy in patients in whom three to four years of this treatment had previously been shown to be effective. During the three years of this trial, primary outcome measures were scores for seasonal symptoms and the use of rescue medication. Objective measures included the immediate conjunctival response and the immediate and late skin responses to allergen challenge. Cutaneous-biopsy specimens obtained 24 hours after intradermal allergen challenge were examined for T-cell infiltration and the presence of cytokine-producing T helper cells (TH2 cells) (as evidenced by the presence of interleukin-4 messenger RNA). A matched group of patients with hay fever who had not received immunotherapy was followed as a control for the natural course of the disease. Scores for seasonal symptoms and the use of rescue antiallergic medication, which included short courses of prednisolone, remained low after the discontinuation of immunotherapy, and there was no significant difference between patients who continued immunotherapy and those who discontinued it. Symptom scores in both treatment groups (median areas under the curve in 1995, 921 for continuation of immunotherapy and 504 for discontinuation of immunotherapy; P=0.60) were markedly lower than those in the group that had not received immunotherapy (median value in 1995, 2863). Although there was a tendency for immediate sensitivity to allergen to return late after discontinuation, there was a sustained reduction in the late skin response and associated CD3+ T-cell infiltration and interleukin-4 messenger RNA expression. Immunotherapy for grass-pollen allergy for three to four years induces prolonged
Brown, Simon G A; Heddle, Robert J
Worldwide, eight genera of ants have been associated with sting allergy. Until recently only whole ant body extracts have been used for immunotherapy. The purpose of this review is to examine recent advances in the understanding of ant venom allergy and treatment using venom immunotherapy. Public health problems due to severe ant sting anaphylaxis are not confined to the imported fire ant of North America. Pachycondyla sennaarensis (samsum ant), Pachycondyla chinensis, and Myrmecia pilosula (jack jumper ant) also appear to pose notable threats. The risk to humans from a particular species probably depends on complex interactions between likelihood of human contact, insect aggression, efficiency of the venom delivery apparatus, and venom allergenicity. The highest population prevalence of clinical ant sting allergy so far (3.0%) was reported from south-eastern Australia, due mainly to M. pilosula. Prospective follow-up of untreated people suggests that those older than 30 years with a history of severe reactions (respiratory compromise or hypotension) will benefit most from venom immunotherapy. Whereas the efficacy of ant whole body extract immunotherapy remains to be proven, ant venom immunotherapy has been demonstrated to reduce the risk of systemic reactions to M. pilosula from 72% to 3%. Although a simple method of venom extraction has been developed, small market size means that the treatment may never become widely available. Ant venom immunotherapy is feasible and highly efficacious. However, the limited geographical distribution of each species presents a major challenge to making venom extracts available for clinical use.
Codina, Rosa; Lockey, Richard F
To review the use of pollen for the production of allergen extracts to diagnose and treat allergic diseases, examine the associated regulations, and highlight candidate areas for improvement. A PubMed search was performed using focused keywords combined with a review of regulatory documents and industry guidelines. The information obtained through literature, documents, and industry was scrutinized and used with personal experience and expertise to write this article. Both genetic and environmental factors affect the allergenic composition of pollen because it is a biologically active pharmaceutical ingredient obtained from nature. The potential effect of airborne contaminants in pollen requires major attention but can be properly addressed through careful collection practices, combined with a proper interpretation of the data on purity obtained for each pollen lot. The regulations associated with pollen used to manufacture allergen extracts in the United States and Europe and the numbers of pollen allergen extracts commercially available in both areas of the world differ. A critical parameter to select the appropriate extracts for diagnosis and allergen immunotherapy is to understand the phenomenon of cross-reactivity among pollen families, genera, and species. Physicians should be aware of the factors responsible for the qualitative and quantitative composition of pollen allergen extracts and the associated regulations to produce suitable extracts to diagnose and treat allergic diseases. Collaboration and cooperation among allergen manufacturing companies and regulatory agencies are necessary. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Etto, Tamara; de Boer, Carmela; Prickett, Sara; Gardner, Leanne M; Voskamp, Astrid; Davies, Janet M; O'Hehir, Robyn E; Rolland, Jennifer M
Bahia grass pollen (BaGP) is a major cause of allergic rhinitis. Subcutaneous allergen-specific immunotherapy is effective for grass pollen allergy, but is unsuitable for patients with moderate to severe asthma due to the risk of anaphylaxis. T cell-reactive but IgE nonreactive peptides provide a safer treatment option. This study aimed to identify and characterize dominant CD4(+) T cell epitope peptides of the major BaGP allergen, Pas n 1. Pas n 1-specific T cell lines generated from the peripheral blood of BaGP-allergic subjects were tested for proliferative and cytokine response to overlapping 20-mer Pas n 1 peptides. Cross-reactivity to homologous peptides from Lol p 1 and Cyn d 1 of Ryegrass and Bermuda grass pollen, respectively, was assessed using Pas n 1 peptide-specific T cell clones. MHC class II restriction of Pas n 1 peptide T cell recognition was determined by HLA blocking assays and peptide IgE reactivity tested by dot blotting. Three Pas n 1 peptides showed dominant T cell reactivity; 15 of 18 (83%) patients responded to one or more of these peptides. T cell clones specific for dominant Pas n 1 peptides showed evidence of species-specific T cell reactivity as well as cross-reactivity with other group 1 grass pollen allergens. The dominant Pas n 1 T cell epitope peptides showed HLA binding diversity and were non-IgE reactive. The immunodominant T cell-reactive Pas n 1 peptides are candidates for safe immunotherapy for individuals, including those with asthma, who are allergic to Bahia and possibly other grass pollens. Copyright © 2012 S. Karger AG, Basel.
Powell, R J; Frew, A J; Corrigan, C J; Durham, S R
Treatment of allergic rhinitis with subcutaneous allergen immunotherapy is effective in terms of reductions in symptoms and seasonal use of reliever medication. Its effect on quality of life (QoL), reflecting the impact of symptoms on work/school performance and leisure activities is, however, important and often overlooked. To assess effect on QoL of specific immunotherapy with two doses of Alutard SQ Phleum pratense in patients with moderately to severe seasonal allergic rhinoconjunctivitis inadequately controlled by standard drug therapy. Double-blind, randomized, placebo-controlled study of 410 patients with seasonal allergic rhinoconjunctivitis. Participants were randomized (2 : 1 : 1) to receive Alutard SQ P. pratense (ALK-Abelló) at maintenance doses of 100,000 SQ-U (203 subjects), 10,000 SQ-U (104 subjects) or placebo (103 subjects) given by subcutaneous injections. The groups were well matched for demographics and baseline symptoms. Quality of life was assessed using the Rhinoconjunctivitis Quality of Life Questionnaire which covers seven domains of health before and in the peak of the pollen season. While all domain scores were significantly improved when comparing 100,000 SQ-U with placebo, two domain scores were significantly improved when comparing 10,000 SQ-U with placebo. When comparing 100,000 SQ-U with 10,000 SQ-U, four domain scores were significantly improved. Treatment with Alutard SQ significantly improved the seasonal QoL of patients suffering from allergic rhinoconjunctivitis. The improvement was more pronounced and wider ranging in patients who received the higher 100,000 SQ-U maintenance dose.
Calabria, Christopher W; Coop, Christopher A; Tankersley, Michael S
The mechanism of local reactions is not well defined. Glycerin, an excellent preservative used commonly in immunotherapy extracts, is a recognized irritant. This study was undertaken to examine whether higher glycerin concentration in immunotherapy extracts is associated with an increase in local reaction rates during immunotherapy. A retrospective analysis of electronic immunotherapy records over a 12-month period was performed from a single site. A small local reaction was defined as induration and/or erythema at the injection site smaller than or equal to the size of the patient's palm. A large local reaction was defined as a reaction larger than the patient's palm. Over the 12-month period, 360 patients received a total of 9678 immunotherapy injections. For all injections, the total local reaction rate was 16.3% (1574/9678), the small local reaction rate was 15.9% (1536/9678), and the large local reaction rate was 0.4% (38/9678). For aeroallergens, small local reaction rates increased significantly with increasing allergen concentrations, from 7.3% (1:1000 vol/vol) to 23.0% (1:1 vol/vol; P glycerin concentration. Large local reactions were infrequent and did not significantly increase with allergen or glycerin concentration. Small local, but not large local, reaction rates increase with higher allergen concentration, number, and volume. Higher glycerin concentrations (even 50%) are not associated with significantly higher small or large local reaction rates.
Full Text Available Although patients with a history of hymenoptera venom anaphylaxis showed significantly reduced plasma levels of angiotensin-I and angiotensin-II compared to controls, there is no study in the literature to investigate the renin angiotensin aldosterone system (RAAS in patients with anaphylactic reaction induced by immunotherapy. The purpose of this study is to determine the role of the renin angiotensin aldosterone system in patients who had an anaphylactic reaction induced by allergen immunotherapy with pollen, house-dust and mold extracts. Plasma levels of angiotensin-I, angiotensin-II, angiotensin converting enzyme and aldosterone were measured in 20 patients who experienced anaphylaxis during allergen immunotherapy. The control group consisted of 15 immunotherapy patients without any history of anaphylaxis. The Mann–Whitney U-test was performed for comparison of the two groups, and a P value less than 0.05 was considered statistically significant. Angiotensin-I, angiotensin-II, angiotensin converting enzyme and aldosterone levels were similar in both the study and control groups and no statistical significance was found between the two groups (P > 0.05. The RAAS does not appear to play a role in the pathogenesis of anaphylactic reactions due to allergen immunotherapy with pollen, house-dust and mold extracts.
Moscato, Gianna; Pala, Gianni; Sastre, Joaquin
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.
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
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.
Aasbjerg, Kristian; Dalhoff, Kim Peder; Backer, Vibeke
Allergic rhinitis (AR) triggered by grass pollen is a common disease, affecting millions of people worldwide. Treatment consists of symptom-alleviating drugs, such as topical corticosteroids or antihistamines. Another option is potentially curative immunotherapy, currently available as sublingual...... and subcutaneous treatment. We investigated the potential differences in the prevalence and severity of adverse events related to subcutaneous and sublingual immunotherapy (SLIT) against grass pollen-induced AR. A thorough literature search was performed with PubMed and EMBASE. The findings were compared...... no systematically collected safety data. No sufficiently powered randomized trials comparing sublingual and subcutaneous immunotherapy (SCIT) were available, but general safety assessments indicate that sublingual tablet treatment is safer than subcutaneous treatment. Not all commonly used immunotherapy drugs...
Röder, Martin; Weber, Wolfgang
The fundamental requirement when testing for and ensuring compliance with legally required labelling regulations is the reliable analysis of food allergens. This can be carried out by means of either DNA (deoxyribonucleic acid) or protein detection. Protein detection has the advantage of directly detecting the allergenic component and can currently be carried out using immunological (enzyme-linked immunosorbent assay [ELISA])/lateral flow devices [LFD]) or mass spectrometry-based techniques. DNA detection is indirect, but allows the presence of food allergens to be validated through the use of another marker. Each method has its pros and cons, which have to be considered on a case-by-case basis. ELISA is quantitative, quick and easy to carry out and has high sensitivity. LFD testing is ideal for industrial applications, as the tests can be carried out on-site. Both antibody-based tests may have problems with processed foods and false positive results. Mass-spectrometric techniques show a lot of promise, but are currently still time-consuming and complex to carry out. They also run into problems with processed foods and their degree of sensitivity is matrix and parameter dependent. For these reasons, this technique is only occasionally used. Polymerase chain reaction (PCR) provides the highest specificity and, depending on the target sequence, a very good to good level of sensitivity. Despite the high stability of DNA, PCR is still subject to the influence of processing and matrix related factors. Due to natural variation and production-related changes in the structures relevant in the process of detection, all methods exhibit a relatively high level of uncertainty of measurement. At present, there is no method which provides the absolute correct quantification. However, by means of laboratory-based analyses it is possible to calibrate for the allergen in question and thus be able to make reliable measurements using methods that are already available.
... Merck, indicated for immunotherapy for diagnosed ragweed pollen induced allergic rhinitis, with or... HUMAN SERVICES Food and Drug Administration Allergenic Products Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of...
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
Nouri, Noura; Garbe, Claus
Intralesional immunotherapy supplements systemic treatments and often achieves higher remission rates as compared to systemic therapy. Its indication is metastatic melanoma with limited tumor burden, particularly in loco-regional metastasis and distant soft tissue metastasis. This review describes intralesional immunotherapy with talimogene laherparepvec (T-VEC), with velimogene aliplasmid (Allovectin-7) and with intralesional interleukin-2. These therapies function exclusively by activating the immune system. Furthermore, Rose Bengal and electrochemotherapy have been included, as bystander effects have been observed with these treatments. Objective remissions are achieved in a higher percentage with intralesional immunotherapies, such as intralesional interleukin-2 with up to 69% of complete remissions, as compared to systemic treatment. Therefore, intralesional immunotherapy may act as supplement in the armament against metastatic melanoma. In particular, for patients with multiple cutaneous and subcutaneous metastases (20—≥ 100) and in patients with subcutaneous bulky disease intralesional immunotherapy can improve the disease outcome. The exact role of intralesional immunotherapy in the age of immune checkpoint blockade has still to be determined. A number of clinical trials are on the way in order to better understand synergistic actions of intralesional and systemic immunotherapy.
de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roder, Esther; Hop, Wim C. J.; de Groot, Hans; de Jongste, Johan C.; van Wijk, Roy Gerth; Bindels, Patrick J. E.; van der Wouden, Johannes C.
Background: Sublingual immunotherapy (SLIT) as a therapy for the treatment of allergic rhinitis in children might be acceptable as an alternative for subcutaneous immunotherapy. However, the efficacy of SLIT with house dust mite extract is not well established. Objective: To investigate whether SLIT
C.M.A. de Bot (Cindy); H. Moed (Heleen); M.Y. Berger (Marjolein); E. Röder (Esther); H. de Groot (Hans); J.C. de Jongste (Johan); R. Gerth van Wijk (Roy); J.C. van der Wouden (Hans)
textabstractBackground. For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A
de Bot, Cindy M. A.; Moed, Heleen; Berger, Marjolein Y.; Roder, Esther; de Groot, Hans; de Jongste, Johan C.; van Wijk, Roy Gerth; van der Wouden, Johannes C.
Background: For respiratory allergic disorders in children, sublingual immunotherapy has been developed as an alternative to subcutaneous immunotherapy. Sublingual immunotherapy is more convenient, has a good safety profile and might be an attractive option for use in primary care. A randomized
Twaroch, Teresa E; Curin, Mirela; Swoboda, Ines
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
Twaroch, Teresa E; Curin, Mirela; Valenta, Rudolf; Swoboda, Ines
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.
Full Text Available Although pharmacological therapy and allergen avoidance are effective means of managing allergic disease, allergen-specific immunotherapy is able to treat not only the symptoms, but also the underlying causes of the disease. Sublingual immuno-therapy (SLIT has been shown to be effective in patients with allergic diseases. It has demonstrated long-term clinical benefits and shown the potential to modify the course of allergic disease in children with rhinitis, conjunctivitis, and asthma. The precise mechanisms of SLIT remain unclear, but antigen-presenting cells in the oral mucosa may induce regulatory T-cells that suppress the allergic immune response by increasing production of interleukin-10. SLIT has also been shown to increase allergen-specific IgG antibodies that antagonize and block the allergic response. SLIT was well tolerated in all reported, double-blinded, placebo-controlled, randomized trials. SLIT is an ideal means of treating the pediatric population because of its excellent safety and good compliance. However, the optimal dose and duration of SLIT require further investigation.
... this page: //medlineplus.gov/ency/patientinstructions/000903.htm Immunotherapy for cancer To use the sharing features on ... 4 treat melanoma of the skin. Non-specific Immunotherapies These therapies boost the immune system in more ...
Praticò, Andrea D; Leonardi, Salvatore
Food allergy is a worldwide issue, with an estimated prevalence of 2-10%. An effective treatment is not available for people affected and the only management is the avoidance of the allergen. Oral immunotherapy and sublingual immunotherapy have been tested by several authors, in particular for milk, egg and peanuts allergy, with significant results in term of desensitization induction. The achievement of tolerance is by the contrary doubtful, with different results obtained. In this review, we reviewed protocols of oral and sublingual immunotherapy for food allergy published in literature, mainly against milk, egg and peanut. At present, immunotherapy does not represent the gold standard in the treatment of food allergy, even if it can desensitize patients.
Vidal-Quist, J C; Ortego, F; Rombauts, S; Castañera, P; Hernández-Crespo, P
Products manufactured from mass-cultured house dust mites, currently commercialized for the diagnosis and immunotherapy of allergy, are heterogeneous in terms of allergen composition and thus present concerns to regulatory authorities. The most abundant species, Dermatophagoides pteronyssinus (Trouessart) (Astigmata: Pyroglyphidae), produces 19 allergenic proteins. Many of these are putatively involved in mite digestive physiology and metabolism. This study aimed to evaluate the effects of mite-rearing media on allergen production. Mites were adapted to feed on culture media supplemented with proteins, lipids, carbohydrates or beard shavings, and collected to quantify major allergens (Der p 1 and 2) by immunodetection, transcription of allergen genes by real-time quantitative polymerase chain reaction, and allergen-related enzymatic activities. All culture media significantly affected the content of major allergens. Modification of macronutrients in the diet produced minor effects on the transcription of allergen genes, but significantly altered mite allergen-related activities. The most remarkable impacts were detected in mites feeding on beard shavings and were reflected in reductions in the content of major allergens, alterations in the transcription of nine allergen genes, and changes in eight allergen-related activities. These results demonstrate the importance of culture media to the quality and consistency of mite extracts used for pharmaceuticals, and highlight the need to further elucidate allergen production by mites in the laboratory and in domestic environments. © 2017 The Royal Entomological Society.
Apostolovic, D.; Luykx, D.; Warmenhoven, H.; Verbart, D.; Stanic-Vucinic, D.; Jong, G.A.H. de; Velickovic, T.C.; Koppelman, S.J.
Conglutins, the major peanut allergens, Ara h 2 and Ara h 6, are highly structured proteins stabilized by multiple disulfide bridges and are stable towards heat-denaturation and digestion. We sought a way to reduce their potent allergenicity in view of the development of immunotherapy for peanut
Halken, Susanne; Lau, Susanne; Valovirta, Erkka
immunotherapy (SLIT) has also been investigated in children. SCIT, especially with grass and birch pollens but also house dust mites, is an effective treatment in children with allergic rhinitis and asthma when a significant part of their symptoms are caused by these allergens. A long-term effect up to 12 yr...... after discontinuation of SCIT with timothy allergen has been shown. Efficacy and safety of SLIT in pollen allergic rhinoconjunctivitis have been demonstrated in adults. The evidence in children is a little less convincing, and more data is needed. The clinical relevance, long-term results and the size...... of the effect, as well as the dose, the treatment regimen and duration has not been sufficiently elaborated. It is demonstrated that SCIT has the potential for preventing the development of asthma in children with allergic rhinoconjunctivitis. Also one randomized study indicates a preventive effect of SLIT...
Yu, Wong; Freeland, Deborah M Hussey; Nadeau, Kari C
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.
Calderon, M A; Demoly, P; Casale, T
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. © 2016 The Author(s)....
Calderon, M A; Demoly, P; Casale, T
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.......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...
Bøgh, Katrine Lindholm; Madsen, Charlotte Bernhard
Food allergy is a major health problem in the Western countries, affecting 3-8% of the population. What makes a dietary protein a food allergen has not yet been established, though several characteristics have been proposed to be shared by the food allergens. One of the features believed...... potential exist. Resistance to digestion is therefore a test parameter included in the safety assessment of the allergenic potential of novel proteins in genetically modified foods. In recent years, the association between resistance to digestion and allergenic potential has been challenged. When reviewing...... existing data from digestibility studies on known food allergens, it becomes evident that food allergens do not necessarily resist digestion. However, the choice of assay conditions, the method used for detection of residual intact protein as well as fragments hereof greatly influences the outcome. Studies...
Allergens play an essential role in atopic dermatitis, either intrinsic or extrinsic. They provoke cutaneous inflammation via IgE-dependent and cell-mediated immune reactions. Food allergens have a well-known contribution to disease activity of atopic dermatitis, especially in infants and young children. However, the importance of inhaled allergens is still under investigation. For clinical implication, identification of individualized allergens is an ideal strategy for better control of atopic dermatitis and avoidance of atopic march. The aim of this article is to discuss the common allergens in atopic dermatitis (AD), the specificity and sensitivity of laboratory tests for allergens, and the clinical effect of various preventions.
Ejrnaes, Anne M; Bødtger, Uffe; Larsen, Jørgen N
Allergen-specific IgG antibodies induced by specific immunotherapy (SIT) interfere with the allergen-IgE interaction, and act as blocking antibodies in vitro. It has been hypothesised that IgG4, as opposed to other IgG subclasses, is particularly important in this function, which may play a role...
Cantillo, José Fernando; Fernández-Caldas, Enrique; Puerta, Leonardo
Allergies caused by mosquito bites may produce local or systemic reactions. The inhalation of mosquito allergens may also cause asthma and/or allergic rhinoconjunctivitis in sensitized individuals. The mechanisms implicated in the development of these immune responses involve IgE antibodies, different subtypes of IgG and proinflammatory cytokines as well as basophils, eosinophils and mast cells. Several allergenic components have been identified in the saliva and bodies of mosquitoes and some of these are present in different mosquito species. The most common species implicated in allergic reactions belong to the genera Aedes, Culex and Anopheles. Several Aedes aegypti allergens have been cloned and sequenced. The recombinant molecules show IgE reactivity similar to that of the native allergens, making them good candidates for the diagnosis of mosquito allergies. Allergen-specific immunotherapy with mosquito extracts induces a protective response characterized by a decreased production of IgE antibodies, increased IgG levels, a reduction in the severity of cutaneous and respiratory symptoms and the need for medication. The aims of this review are to summarize the progress made in the characterization of mosquito allergens and discuss the types of immune responses induced by mosquito bites and the inhalation of mosquito allergens in atopic individuals. © 2015 S. Karger AG, Basel
Gadermaier, G; Wopfner, N; Wallner, M; Egger, M; Didierlaurent, A; Regl, G; Aberger, F; Lang, R; Ferreira, F; Hawranek, T
Ragweed (Ambrosia artemisiifolia) and mugwort (Artemisia vulgaris) pollen is the main cause of allergic reactions in late summer and autumn. The differential diagnosis between ragweed and mugwort pollen allergy is a frequent problem encountered by allergologists in areas where both plants are present due to shared antigenic structures and overlapping flowering seasons. To evaluate the sensitization pattern of weed allergic patients towards a large panel of purified allergens in the microarray format and by enzyme-linked immunosorbent assay (ELISA). Eight ragweed and six mugwort pollen allergens were purified from natural source or expressed as recombinant proteins in Escherichia coli. Allergens were spotted on protein microarray slides or coated onto ELISA plates. Sera from 19 ragweed and/or mugwort allergic individuals were used to determine the reactivity towards single molecules in both assays. All ragweed allergic individuals were sensitized to Amb a 1, among them 30% were monosensitized to the major ragweed allergen. Art v 1 and Art v 3 were recognized by 89% of mugwort pollen-allergic patients. Extensive cross-reactivity was observed for both patient groups mainly involving the pan-allergens profilin and nonspecific lipid transfer proteins. Comparable IgE profiles were obtained with both allergen microarray and ELISA methods. Molecule-based diagnosis provides essential information for the differential diagnosis between ragweed and mugwort pollen allergy and for the selection of the appropriate allergen source for specific immunotherapy.
The 7S vicilin and 11S legumin seed storage globulins belong to the cupin protein superfamily and are major food allergens in many of the “big eight” food allergen groups. Korean pine vicilin and pecan vicilin are thus predicted to be food allergens. Recombinant vicilins were expressed in E. coli an...
Armentia-Medina, A; Tapias, J A; Martín, J F; Ventas, P; Fernández, A
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.
Alija, Hava; Rask, Carola; Brimnes, Jens
The prevalence of IgE mediated allergic diseases is increasing dramatically in industrialized countries. Sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficacious treatment for IgE mediated allergic diseases, but requires protracted treatment duration. Even though SLIT...... is considered to have a better safety profile than subcutaneous immunotherapy, SLIT can still cause adverse events requiring clinical supervision for the first administration. Optimization of SLIT, by reducing the administration dose and treatment duration, would improve safety profile. For this purpose...
Allergy immunotherapy tablets (AIT) have expanded the treatment options for patients suffering from respiratory allergies. Efficacy is established in adults and children for two different commercially available grass AITs. The ALK grass AIT has an efficacy comparable to subcutaneous immunotherapy (SCIT), with a proven disease-modifying effect after treatment completion. Safety profiles favour AIT over SCIT. Studies suggest that tablets in all aspects are superior to sublingual drops. AITs for other allergies including house dust mite and birch and ragweed pollen are in development. © 2011 John Wiley & Sons A/S.
Francis, James N; James, Louisa K; Paraskevopoulos, Giannis; Wong, Cheukyee; Calderon, Moises A; Durham, Stephen R; Till, Stephen J
Grass pollen immunotherapy is an effective treatment for seasonal allergic rhinitis that provides the opportunity to study the induction and maintenance of allergen-specific immune tolerance. We investigated the relationship between clinical responsiveness, regulatory cytokine production, and antibody responses to allergen during 1 year of immunotherapy. Eighteen subjects with severe seasonal allergic rhinitis were randomized double-blind to receive active or placebo injections of an alum-adsorbed grass pollen vaccine (Alutard SQ). Subjects underwent repeated testing of early- and late-phase skin responses to intradermal allergen, and cellular responses to grass pollen allergen were tested. Sera were tested for allergen-specific IgG4, IgA, and inhibitory activity in biologic assays of IgE responses. Grass pollen immunotherapy was effective in reducing overall symptom scores (P < .05) and conjunctival reactivity (P < .05). In the active group significant IL-10 production occurred early at low allergen doses and at a similar time as inhibition of late skin responses at 2 to 4 weeks. Serum allergen-specific IgG4, IgA, and inhibitory antibody activity for basophil histamine release and IgE-facilitated allergen binding to B cells occurred later, at 6 to 12 weeks, at higher allergen doses and preceded inhibition of early skin responses. IL-10 responses occur early but at immunotherapy doses that are not clinically effective. Later induction of inhibitory antibodies, including IgG4 and IgA, might be required for efficacy through modulation of IgE-mediated events.
Nouri-Aria, Kayhan T; Wachholz, Petra A; Francis, James N; Jacobson, Mikila R; Walker, Samantha M; Wilcock, Louisa K; Staple, Steven Q; Aalberse, Robert C; Till, Stephen J; Durham, Stephen R
T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings. We studied the role of IL-10 in the induction of clinical, cellular, and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis. Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen (Phleum pratense, Phl P) immunotherapy. We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy, but only during the pollen season. IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA(+) cells. These changes were not observed in placebo-treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA signals were colocalized to CD3(+) T cells and CD68(+) macrophages, respectively, whereas only 1-2% of total CD3(+) cells and 4% of macrophages expressed IL-10. Following immunotherapy, peripheral T cells cultured in the presence of grass pollen extract also produced IL-10. Immunotherapy resulted in blunting of seasonal increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold increases in Phl p 5-specific IgG, and 100-fold increases in Phl p 5-specific IgG4. Post-immunotherapy serum exhibited inhibitory activity, which coeluted with IgG4, and blocked IgE-facilitated binding of allergen-IgE complexes to B cells. Both the increases in IgG and the IgG "blocking" activity correlated with the patients' overall assessment of improvement. Thus, grass pollen immunotherapy may induce allergen-specific, IL-10-dependent "protective" IgG4 responses.
M. Calderon (Moises); P. Demoly; T.B. Casale (Thomas); C.A. Akdis; C. Bachert (Claus); Bewick, M.; Bilò, B.M.; B. Bohle (B.); S. Bonini (Sergio); A. Bush (Andrew); Caimmi, D.P.; G. Canonica (Gwalter); D. Cardona (Doris); A.M. Chiriac (A.); L. Cox (Linda); A. Custovic; F. de Blay; Devillier, P.; Didier, A.; Di Lorenzo, G.; G. Du Toit (George); S.R. Durham (Stephen); C. Eng (Charis); A. Fiocchi (Alessandro); Fox, A.T.; R.G. van Wijk (Roy Gerth); Gomez, R.M.; Haathela, T.; S. Halken (Susanne); P.W. Hellings (P.); L. Jacobsen; P.M. Just; Tanno, L.K.; J. Kleine-Tebbe (Jörg); L. Klimek (Ludger); E.F. Knol (Edward Frank); P. Kuna; D. Larenas-Linnemann (Désirée); A. Linneberg (Allan); Matricardi, M.; H.-J. Malling; Moesges, R.; Mullol, J.; Muraro, A.; N. Papadopoulos; G. Passalacqua (Giovanni); Pastorello, E.; O. Pfaar (Oliver); D. Price (David); P.R. Del Rio (P. Rodriguez); Ruëff, R.; Samolinski, B.; G.K. Scadding; Senti, G.; Shamji, M.H.; A. Sheikh (Aziz); J.C. Sisul (J.); D. Solé (D.); G.J. Sturm; Tabar, A.; R. Van Ree; Ventura, M.T.; C. Vidal (Carmen); E.M. Varga; M. Worm (M.); T. Zuberbier (Torsten); J. Bousquet (Jean)
textabstractAllergic 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
Oseroff, Carla; Sidney, John; Vita, Randi; Tripple, Victoria; McKinney, Denise M; Southwood, Scott; Brodie, Tess M; Sallusto, Federica; Grey, Howard; Alam, Rafeul; Broide, David; Greenbaum, Jason A; Kolla, Ravi; Peters, Bjoern; Sette, Alessandro
A panel of 133 allergens derived from 28 different sources, including fungi, trees, grasses, weeds, and indoor allergens, was surveyed utilizing prediction of HLA class II-binding peptides and ELISPOT assays with PBMC from allergic donors, resulting in the identification of 257 T cell epitopes. More than 90% of the epitopes were novel, and for 14 allergen sources were the first ever identified to our knowledge. The epitopes identified in the different allergen sources summed up to a variable fraction of the total extract response. In cases of allergens in which the identified T cell epitopes accounted for a minor fraction of the extract response, fewer known protein sequences were available, suggesting that for low epitope coverage allergen sources, additional allergen proteins remain to be identified. IL-5 and IFN-γ responses were measured as prototype Th2 and Th1 responses, respectively. Whereas in some cases (e.g., orchard grass, Alternaria, cypress, and Russian thistle) IL-5 production greatly exceeded IFN-γ, in others (e.g., Aspergillus, Penicillum, and alder) the production of IFN-γ exceeded IL-5. Thus, different allergen sources are associated with variable polarization of the responding T cells. The present study represents the most comprehensive survey to date of human allergen-derived T cell epitopes. These epitopes might be used to characterize T cell phenotype/T cell plasticity as a function of seasonality, or as a result of specific immunotherapy treatment or varying disease severity (asthma or rhinitis).
Protocol for a double-blind randomised controlled trial of low dose intradermal grass pollen immunotherapy versus a histamine control on symptoms and medication use in adults with seasonal allergic rhinitis (PollenLITE).
Slovick, Anna; Douiri, Abdel; Kelly, Joanna; Guerra, Andrea; Muir, Rachel; Tsioulos, Konstantinos; Murphy, Caroline; Shamji, Mohamed H; Ying, Sun; Durham, Stephen R; Till, Stephen J
Subcutaneous immunotherapy with high dose grass pollen (typically microgram quantities) was first described over 100 years ago. This treatment suppresses allergen-induced cutaneous late responses, with lesser effects on early responses. We previously reported that repeated 2-weekly intradermal injections of grass pollen - containing approximately 7 ng of major allergen Phl p 5 - led to a progressive suppression of the allergen-induced cutaneous response, and that by the sixth injection, this was inhibited by over 90%. The purpose of this trial is to investigate the clinical efficacy of intradermal desensitisation with low doses (i.e. nanogram quantities) of grass pollen allergen for seasonal allergic rhinitis. The Pollen Low dose Intradermal therapy Evaluation (PollenLITE) is a single centre double-blind randomised parallel group controlled trial of the efficacy and safety of intradermal grass pollen injections plus standard treatment, versus histamine injections plus standard treatment, in adults with moderate-severe grass pollen-induced allergic rhinitis ('summer hay fever'). A minimum of ninety adults with a history of moderate-severe persistent allergic rhinitis during the UK grass pollen season will be randomised into two equal groups to receive 7 or 8 intradermal injections of grass pollen extract (containing approximately 7 ng of major allergen Phl p 5) or histamine, before the grass pollen season. In the summer, participants will score their symptoms, medication requirements, visual analogue scores, and complete EuroQOL (EQ-5D-5 L) and mini Rhinoconjunctivitis Quality of Life Questionnaires. Global assessments will also be recorded at the end of the pollen season. Blood samples will be collected from all participants for mechanistic immune assays. Skin punch biopsies will also be collected in 40 participants selected at random from intradermal injection sites after the grass pollen season for mechanistic assays. Finally, to investigate if the
Wang, Daniel; Gilbert, Jill; Kim, Young J
Recurrent and/or metastatic head and neck cancer portends a poor prognosis with traditional treatments, but current immunotherapy with immune checkpoint inhibitors has the potential to improve these clinical outcomes. This review focuses on the major breakthroughs that have led to the current understanding of immunotherapy in head and neck cancer as well as the future direction of the field. Ultimately, this understanding will guide clinicians on the selection of patients with head and neck cancer and practical considerations before starting immunotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.
Bergman, Philip J
The ideal cancer immunotherapy agent should be able to discriminate between cancer and normal cells, be potent enough to kill small or large numbers of tumor cells, and be able to prevent recurrence of the tumor. Tumor immunology and immunotherapy are among the most exciting and rapidly expanding fields; cancer immunotherapy is now recognized as a pillar of treatment alongside traditional modalities. This article highlights approaches that seem to hold particular promise in human clinical trials and many that have been tested in veterinary medicine. Copyright © 2017 Elsevier Inc. All rights reserved.
Chen, Xueni; Dreskin, Stephen C
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.
Gray, B N; Walker, C; Andrewartha, L; Freeman, S; Bennett, R C
A controlled, randomised clinical trial of immunotherapy was performed in 301 patients with stage B or C colorectal cancer. The immunotherapy treatment consisted of 18 vaccinations over a 2 year period following surgery with a combination of BCG given by scarification plus subcutaneous injection of Vibrio cholera neuraminidase (VCN)-modified autologous tumour cells. Five year follow-up has now been completed in all patients. The immunotherapy did not alter either the disease-free interval or the overall survival of patients in comparison with a control group of patients not receiving immunotherapy.
More often than not, cancer immunotherapies that work in adults are used in modified ways in children. Seldom are new therapies developed just for children, primarily because of the small number of pediatric patients relative to the adult cancer patient
In an early phase NCI clinical trial, two patients with metastatic cervical cancer had a complete disappearance of their tumors after receiving treatment with a form of immunotherapy called adoptive cell transfer.
Jacobsen, L; Niggemann, B; Dreborg, S
BACKGROUND: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. OBJECTIVE: We......: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination....
for all the methods using uncertainty analysis . The recommended approach for the allergen risk assessment was implemented in a Shiny application with the R software. Thus, allergen risk assessment can be performed easily by non-statisticians with the interactive application....... Allergen and Allergy Management) aims at developing strategies for food allergies based on evidences. Especially, food allergen risk assessment helps food producers or authorities to make decisions on withdrawing a food product from the market or adding more information on the label when allergen presence...... is unintended. The risk assessment method has three different kinds of input. The exposure is calculated from the product consumption and the allergen contamination in the food product. The exposure is then compared to the thresholds to which allergic individuals react in order to calculate the chance...
Full Text Available Two cases of subcutaneous granuloma annulare are reported. Clinical presentation was in the form of hard subcutaneous nodules, histopathology confirmed the clinical diagnosis. The cases were unique because of onset in adult age, occurrence over unusual sites and absence of classical lesions of granuloma annulare elsewhere.
Zhang, Jin; Wu, Li-Shuan; Fan, Wei; Zhang, Xiao-Ling; Jia, Hui-Xia; Li, Yu; Yin, Ya-Fang; Hu, Jian-Jun; Lu, Meng-Zhu
Proteomic analysis was used to generate a map of Populus deltoides CL. "2KEN8" mature pollen proteins. By applying 2-D electrophoresis, we resolved 403 protein spots from mature pollen. Using the matrix-assisted laser desorption/ionization time time-of-flight/time-of-flight tandem mass spectrometry method, we identified 178 distinct proteins from 218 protein spots expressed in mature pollen. Moreover, out of these, 28 proteins were identified as putative allergens. The expression patterns of these putative allergen genes indicate that several of these genes are highly expressed in pollen. In addition, the members of profilin allergen family were analyzed and their expression patterns were compared with their homologous genes in Arabidopsis and rice. Knowledge of these identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with poplar pollen allergy.
Francis, James N; Till, Stephen J; Durham, Stephen R
Immunotherapy involves the modulation of allergen-specific T-cell responses, either T(H)2-to-T(H)1 immune deviation or, in bee venom-treated patients, induction of IL-10 production by CD4+CD25+ T cells. IL-10-producing CD4+CD25+ regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. The aim of this study was to evaluate the role of IL-10 production and CD4+CD25+ T cells in the response to grass pollen immunotherapy. PBMCs were isolated from patients after 1 year of grass pollen immunotherapy and from matched untreated atopic and healthy control subjects. After 6 days of in vitro stimulation with Phleum pratense, production of IL-10, IL-5, IL-4, and IFN-gamma and proliferation and numbers of CD4+CD25+ T cells were measured. T cells were then stimulated for a further 5 hours with phorbol 12-myristate 13-acetate and ionomycin and assessed for intracellular IL-10 by means of flow cytometry. Patients undergoing immunotherapy produced significantly more IL-10 than atopic control subjects (patients undergoing immunotherapy, 116 +/- 21 pg/mL [n = 11]; atopic patients, 30 +/- 5 pg/mL [n = 11]; P pollen immunotherapy results in a population of circulating T cells that express the IL-10(+) CD4+CD25+ phenotype in response to allergen restimulation.
Full Text Available Immunotherapy is considered to be the only curative treatment for allergic diseases such as pollinosis, perennial rhinitis, asthma, and food allergy. The sublingual route is widely applied for immunotherapy for allergy, instead of the conventional administration by subcutaneous route. A recent meta-analysis of sublingual immunotherapy (SLIT has shown that this approach is safe, has positive clinical effects, and provides prolonged therapeutic effects after discontinuation of treatment. However, the mechanism of SLIT and associated biomarkers are not fully understood. Biomarkers that change after or during SLIT have been reported and may be useful for response monitoring or as prognostic indicators for SLIT. In this review, we focus on the safety, therapeutic effects, including prolonged effects after treatment, and new methods of SLIT. We also discuss response monitoring and prognostic biomarkers for SLIT. Finally, we discuss immunological mechanisms of SLIT with a focus on oral dendritic cells and facilitated antigen presentation.
Ponce, M; Diesner, S C; Szépfalusi, Z; Eiwegger, T
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.
Dhami, Sangeeta; Nurmatov, Ulugbek; Halken, Susanne
in the prevention of allergic disease. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using...... established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. DISCUSSION: The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT. This article is protected by copyright. All rights reserved....
Dhami, Sangeeta; Nurmatov, Ulugbek; Pajno, Giovanni Battista
allergy. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established...... instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. DISCUSSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT....
Sturm, Gunter J.; Varga, Eva-Maria; Roberts, Graham; Mosbech, Holger; Bilò, M. Beatrice; Akdis, Cezmi A.; Antolín-Amérigo, Darío; Cichocka-Jarosz, Ewa; Gawlik, Radoslaw; Jakob, Thilo; Kosnik, Mitja; Lange, Joanna; Mingomataj, Ervin; Mitsias, Dimitris I.; Ollert, Markus; Oude Elberink, Joanna N. G.; Pfaar, Oliver; Pitsios, Constantinos; Pravettoni, Valerio; Ruëff, Franziska; Sin, Betül Ayşe; Agache, Ioana; Angier, Elizabeth; Arasi, Stefania; Calderón, Moises A.; Fernandez-Rivas, Montserrat; Halken, Susanne; Jutel, Marek; Lau, Susanne; Pajno, Giovanni B.; van Ree, Ronald; Ryan, Dermot; Spranger, Otto; van Wijk, Roy Gerth; Dhami, Sangeeta; Zaman, Hadar; Sheikh, Aziz; Muraro, Antonella
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
Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 10, No 2 (2012) >. Log in or Register to get access to full text downloads.
Schiener, Maximilian; Graessel, Anke; Ollert, Markus
Stings of hymenoptera can induce IgE-mediated hypersensitivity reactions in venom-allergic patients, ranging from local up to severe systemic reactions and even fatal anaphylaxis. Allergic patients' quality of life can be mainly improved by altering their immune response to tolerate the venoms...... on state of the art diagnostic and therapeutic options as well as on novel directions trying to improve therapy....
De Blay, F; Bessot, J C; Pauli, G
As the number of proteins recognized as causing allergic respiratory diseases increases, new aero allergens have appeared in the animal and vegetable realms, both in home and professional environments. Lepidoglyphus destructor and Blomia tropicalis, two mites found in storage areas, are particularly important in agricultural areas and in homes. Over the last ten years, the frequency of reactions to cockroaches has also increased in several countries. The allergenicity of non-biting insects is a frequent cause of allergy in certain countries including Japan. Chironomides cause respiratory diseases in professional and outdoor environments. The important role of Alternaria, a mold, in producing severe asthma has also been demonstrated. The pathophysiology of pollen-induced asthma has been shown to result from pollen allergens carried by particles less than 5 microns in diameter. Cyprus and ash tree pollen also cause an increasing number of pollinoses and flowers can cause rhinitis and asthma. Respiratory allergy to Ficus benjamina inaugurated a new type of allergies caused airborne allergens from non-pollinating plants. Allergy to latex raises a particular problem for health care workers. The immunochemical structures of the major and minor airborne allergens are now better known and the homologous structures of different allergens largely explains certain cross-reactions. In the future, recombinant allergens will probably be used to better understand the role of allergens in inducing and maintaining the allergic reaction and should help in our approach to diagnosis and therapy.
Despite remarkable progress, cancer immunotherapies can be toxic to some patients. Learn how NCI-funded research will extend the benefits of immunotherapy to more patients through biomarker research and collaboration.
Emily F. Goode
Full Text Available Survival for patients with advanced oesophageal and stomach cancer is poor; together these cancers are responsible for more than a million deaths per year globally. As chemotherapy and targeted therapies such as trastuzumab and ramucirumab result in modest improvements in survival but not long-term cure for such patients, development of alternative treatment approaches is warranted. Novel immunotherapy drugs such as checkpoint inhibitors have been paradigm changing in melanoma, non-small cell lung cancer and urothelial cancers. In this review, we assess the early evidence for efficacy of immunotherapy in patients with gastroesophageal cancer in addition to considering biomarkers associated with response to these treatments. Early results of Anti- Programmed Cell Death Protein-1 (anti-PD-1, anti-PD-L1 and anti-Cytotoxic T-lymphocyte assosciated protein-4 (anti-CTLA4 trials are examined, and we conclude with a discussion on the future direction for immunotherapy for gastroesophageal cancer patients.
Colombo, Paolo; Bonura, Angela; Costa, Maria; Izzo, Vincenzo; Passantino, Rosa; Locorotondo, Giovanni; Amoroso, Saverio; Geraci, Domenico
Parietaria is a genus of dicotyledonous weeds of the Urticaceae family including several species and its pollen grain is one of the most important allergenic sources in the Mediterranean area. Species belonging to this genus induce IgE responses in approximately 10 million people. Identification of allergens by means of independent strategies suggest that the allergens of the two more common species, Parietaria judaica and Parietaria Officinalis, show molecular weights ranging between 10 and 14 kD and that the allergens of the two extracts are highly cross-reactive. Biochemical analysis and molecular cloning allowed the isolation and immunological characterization of the two major allergens of the P. judaica pollen, Par j 1 and Par j 2. Sequence comparison suggests that the P j major allergens of P. Judaica belong to the nonspecific lipid transfer protein family, and three-dimensional modeling by homology has revealed that both proteins present a very conserved structural motif composed of four alpha-helices. Immunological analysis has shown that Par j 1 and Par j 2 are able to bind most of the P. Judaica-specific IgE and some of their IgE determinants have been mapped. Recombinant Par j 1 and Par j 2 allergens have been shown to possess immunological properties equivalent to their natural counterpart and their availability represents a fundamental tool for the diagnosis and therapy of Parietaria pollen allergy. Copyright 2003 S. Karger AG, Basel
Saha, Bodhisattwa; Bhattacharya, Swati Gupta
Pollen grains from Phoenix sylvestris (date palm), a commonly cultivated tree in India has been found to cause severe allergic diseases in an increasing percentage of hypersensitive individuals. To unearth its allergenic components, pollen protein were profiled by two-dimensional gel electrophoresis followed by immunoblotting with date palm pollen sensitive patient sera. Allergens were identified by MALDI-TOF/TOF employing a layered proteomic approach combining conventional database dependent search and manual de novo sequencing followed by homology-based search as Phoenix sylvestris is unsequenced. Derivatization of tryptic peptides by acetylation has been demonstrated to differentiate the 'b' from the 'y' ions facilitating efficient de novo sequencing. Ten allergenic proteins were identified, out of which six showed homology with known allergens while others were reported for the first time. Amongst these, isoflavone reductase, beta-conglycinin, S-adenosyl methionine synthase, 1, 4 glucan synthase and beta-galactosidase were commonly reported as allergens from coconut pollen and presumably responsible for cross-reactivity. One of the allergens had IgE binding epitope recognized by its glycan moiety. The allergenic potency of date palm pollen has been demonstrated using in vitro tests. The identified allergens can be used to develop vaccines for immunotherapy against date palm pollen allergy. Identification of allergenic proteins from sources harboring them is essential in developing therapeutic interventions. This is the first comprehensive study on the identification of allergens from Phoenix sylvestris (date palm) pollen, one of the major aeroallergens in India using a proteomic approach. Proteomic methods are being increasingly used to identify allergens. However, since many of these proteins arise from species which are un-sequenced, it becomes difficult to interpret those using conventional proteomics. Date palm being an unsequenced species, the Ig
Toomey, Paul G; Vohra, Nasreen A; Ghansah, Tomar; Sarnaik, Amod A; Pilon-Thomas, Shari A
Gastrointestinal (GI) cancers are the most common human tumors encountered worldwide. The majority of GI cancers are unresectable at the time of diagnosis, and in the subset of patients undergoing resection, few are cured. There is only a modest improvement in survival with the addition of modalities such as chemotherapy and radiation therapy. Due to an increasing global cancer burden, it is imperative to integrate alternative strategies to improve outcomes. It is well known that cancers possess diverse strategies to evade immune detection and destruction. This has led to the incorporation of various immunotherapeutic strategies, which enable reprogramming of the immune system to allow effective recognition and killing of GI tumors. A review was conducted of the results of published clinical trials employing immunotherapy for esophageal, gastroesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers. Monoclonal antibody therapy has come to the forefront in the past decade for the treatment of colorectal cancer. Immunotherapeutic successes in solid cancers such as melanoma and prostate cancer have led to the active investigation of immunotherapy for GI malignancies, with some promising results. To date, monoclonal antibody therapy is the only immunotherapy approved by the US Food and Drug Administration for GI cancers. Initial trials validating new immunotherapeutic approaches, including vaccination-based and adoptive cell therapy strategies, for GI malignancies have demonstrated safety and the induction of antitumor immune responses. Therefore, immunotherapy is at the forefront of neoadjuvant as well as adjuvant therapies for the treatment and eradication of GI malignancies.
van Ree, R.; Aalberse, R. C.
From a group of 92 patients receiving grass pollen immunotherapy, and selected on grounds of high IgG4 titers against Lol p I, sera were tested for IgG4 antibodies against the glycosylated grass pollen allergen Lol p XI. In 72 of 92 cases IgG4 antibodies were demonstrated. The N-glycan of Lol p XI
Farrokhi, Shokrollah; Abbasirad, Narjes; Movahed, Ali; Khazaei, Hossein Ali; Pishjoo, Masoud; Rezaei, Nima
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.
Roder, Esther; Berger, Marjolein Y.; Hop, Wim C. J.; Bernsen, Roos M. D.; de Groot, Hans; van Wijk, Roy Gerth
Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in
M. Calderon (Moises); P. Demoly; R. Gerth van Wijk (Roy); J. Bousquet (Jean); A. Sheikh (Aziz); A.J. Frew (Antony J.); G.K. Scadding; C. Bachert (Claus); H.-J. Malling; Valenta, R. (Rudolph); Bilo, B. (Beatrice); A. Nieto (Antonio); C.A. Akdis; P.M. Just; C. Vidal (Carmen); E.M. Varga; Alvarez-Cuesta, E. (Emilio); B. Bohle (B.); A. Bufe (A.); W. Canonica (Walter); D. Cardona (Doris); R. Dahl; Didier, A. (Alain); S.R. Durham (Stephen); C. Eng (Charis); M. Fernandez Rivas (M.); L. Jacobsen; M. Jutel (M.); J. Kleine-Tebbe (Jörg); L. Klimek (Ludger); J. Lötvall (Jan); Moreno, C. (Carmen); R. Mösges; Muraro, A. (Antonella); B. Niggemann; G. Pajno (G.); G. Passalacqua (Giovanni); O. Pfaar (Oliver); S. Rak; G.E. Senna (Gianenrico); Senti, G. (Gabriela); E. Valovirta (Erkka); M. van Hage (Marianne); Virchow, J.C. (Johannes C); U. Wahn (Ulrich); N. Papadopoulos
textabstractAllergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the
Milovanovic, M; Heine, G; Zuberbier, T; Worm, M
Elevated specific IgE antibody levels are common in atopic individuals, caused by T-helper type 2-dominated B cell activation. The induction of antigen-specific IL-10 secreting T cells is discussed as an important mechanism during specific immunotherapy. By contrast the presence and function of B cell-derived IL-10 is not well defined yet. We investigated whether type-I allergen extracts induce IL-10 expression in human B cells and analysed its functional role on IgE production. Human peripheral B cells were stimulated with grass pollen, house dust mite (HDM) (Dermatophagoides pteronyssimus; Der p) and dog allergen extract. Expression of IL-10 by activated human B cells was determined by flow cytometric analysis and ELISA. Functional analysis considering immunoglobulin production was assayed by ELISA. The allergen extracts studied induced IL-10 expression in B cells. However, the ability to induce IL-10 differed between the allergen extracts. The most potent allergen extract was dog (169+/-28 pg/mL), followed by grass pollen (141+/-10 pg/mL) and HDM allergen (125+/-11 pg/mL). Upon allergen extract stimulation only CD27 expressing memory B cells produced IL-10 and co-expressed the very early activation antigen CD69. The addition of allergen extracts to B cells activated by anti-CD40 and IL-4 selectively inhibited IgE which was dependent on allergen extract-induced IL-10. By contrast the other immunoglobulin subclasses like IgA, IgG or IgM were not altered upon allergen extract challenge. Our data indicate that allergen-activated memory B cells can modulate IgE production through secretion of IL-10.
Full Text Available Subcutaneous zygomycosis, also known as basidiobolomycosis, is a rare disease caused by the fungus Basidiobolus ranarum. Since its first description in 1954, may cases have been reported. In India, so far only few cases have been described. We report this entity in a 3 year- old female child who had firm to hard swelling of the right upper extremely and chest. Histopathology showed short aseptate hyphae surrounded by eosinophilic material within the granulomatous tissue response, in the subcutaneous tissue. She responded dramatically to saturated solution of potassium iodide.
Full Text Available Proteomic analysis was used to generate a map of Populus deltoides CL. ‘2KEN8’ mature pollen proteins. By applying 2-D electrophoresis, we resolved 403 protein spots from mature pollen. Using the matrix-assisted laser desorption/ionization time time-of-flight/time-of-flight tandem mass spectrometry method, we identified 178 distinct proteins from 218 protein spots expressed in mature pollen. Moreover, out of these, 28 proteins were identified as putative allergens. The expression patterns of these putative allergen genes indicate that several of these genes are highly expressed in pollen. In addition, the members of profilin allergen family were analyzed and their expression patterns were compared with their homologous genes in Arabidopsis and rice. Knowledge of these identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with poplar pollen allergy.
Zhang, Jin; Wu, Li-Shuan; Fan, Wei; Zhang, Xiao-Ling; Jia, Hui-Xia; Li, Yu; Yin, Ya-Fang; Hu, Jian-Jun; Lu, Meng-Zhu
Proteomic analysis was used to generate a map of Populus deltoides CL. “2KEN8” mature pollen proteins. By applying 2-D electrophoresis, we resolved 403 protein spots from mature pollen. Using the matrix-assisted laser desorption/ionization time time-of-flight/time-of-flight tandem mass spectrometry method, we identified 178 distinct proteins from 218 protein spots expressed in mature pollen. Moreover, out of these, 28 proteins were identified as putative allergens. The expression patterns of these putative allergen genes indicate that several of these genes are highly expressed in pollen. In addition, the members of profilin allergen family were analyzed and their expression patterns were compared with their homologous genes in Arabidopsis and rice. Knowledge of these identified allergens has the potential to improve specific diagnosis and allergen immunotherapy treatment for patients with poplar pollen allergy. PMID:26284084
Aydin, Dogu; Berg, Jais O
We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help...
Full Text Available Two cases of subcutaneos granuloma annulare are reported. Clinical presentation was in the form of hard subcutaneous nodules; histopathology confirmed the clinical diagnosis. The cases were unique because of onset in adult hood, occurrence over unusual sites and absence of classical lesions of granuloma annulare elsewhere.
Kamdar, Toral; Bryce, Paul J
Food allergies are caused by immune responses to food proteins and represent a breakdown of oral tolerance. They can range from mild pruritus to life-threatening anaphylaxis. The only current consensus for treatment is food avoidance, which is fraught with compliance issues. For this reason, there has been recent interest in immunotherapy, which may induce desensitization and possibly even tolerance. Through these effects, immunotherapy may decrease the potential for adverse serious reactions with accidental ingestions while potentially leading to an overall health benefit. In this review, we discuss the mechanisms of food allergy and give an overview of the various immunotherapeutic options and current supporting evidence, as well as look towards the future of potential novel therapeutic modalities.
Lamm, D L; Thor, D E; Stogdill, V D; Radwin, H M
A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder. In addition, 9 patients at high risk for tumor recurrence were treated with bacillus Calmette-Guerin produced a self-limited cystitis and 1 complication (hydronephrosis) of immunotherapy was observed. Of the 57 randomized patients 54 were followed for 3 to 30 months. Tumor recurrence was documented in 13 of 26 controls (50 per cent) and only 6 of 28 patients (21 per cent) treated with bacillus Calmette-Guerin (p equals 0.027, chi-square). The interval free of disease was prolonged significantly with bacillus Calmette-Guerin treatment (p equals 0.014, generalized Wilcoxon test). Importantly, a simple purified protein derivative skin test distinguished those patients who responded to bacillus Calmette-Guerin immunotherapy from those who did not. Only 1 of 17 treated patients (6 per cent) whose purified protein derivative test converted from negative to positive had tumor recurrence compared to 5 recurrences (38 per cent) among the 13 patients whose test remained negative or had been positive before treatment (p equals 0.022, chi-square). Bacillus Calmette-Guerin was given to 10 patients with stage B transitional cell carcinoma who were not candidates for cystectomy and 7 are free of disease. Of 5 patients with carcinoma in situ 3 remain free of tumor after bacillus Calmette-Guerin treatment and 5 of 6 who had multiple recurrences after intravesical chemotherapy responded favorably to bacillus Calmette-Guerin immunotherapy.
Full Text Available Abstract Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body’s own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.
Herzberg, Benjamin; Fisher, David E
Harnessing the immune system to attack cancer cells has represented a holy grail for greater than 100years. While prospects of tumor-selective durable immune based therapies have provided small clinical signals for many decades, recent years have demonstrated a virtual explosion in progress. Melanoma has led the field of cancers in which immunotherapy has produced major clinical inroads. The most significant and impactful immunotherapies for melanoma utilize immune checkpoint inhibition to stimulate T cell mediated tumor killing. The major targets of checkpoint blockade have thus far been CTLA4 and PD1, two key receptors for central and peripheral immune tolerance. This review discusses current understanding of how these checkpoint blockade therapeutics have led to major clinical responses in patients with advanced melanoma. It is likely that we are poised to see significantly greater anti-cancer immunotherapy efficacy, both in improving response rates and durability for melanoma, and for other less immunogenic malignancies. Copyright © 2016 Elsevier Inc. All rights reserved.
Luís Miguel Lourenço Martins
Full Text Available 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.
Schenkelberger, V; Freitag, M; Altmeyer, P
The weeping fig, Ficus benjamina (Fb), is a relatively common indoor allergen. Many cases of perennial allergic rhinoconjunctivitis and allergic asthma caused by Fb hypersensitivity are not detected. These patients typically have proven sensitization to housedust mites and do not improve after avoidance of exposure (encasing) and specific immunotherapy. The number of Fb sensitizations is increasing in Germany, which can partly be explained by the cross-reactivity between Hevea brasiliensis (Hb) latex and Fb and the rapidly increasing number of mostly occupational latex allergies. But Fb itself is a potential sensitizer which is widely spread as ornamental plant in homes and offices. As relevant indoor allergen Fb ranks third after housedust mites and pets but before molds among our allergy patients. For diagnosis, prick-tests with Fb-latex seem to be more sensitive than in vitro-methods (RAST, CAPRAST). Fb plants should not be kept in the homes of atopic individuals or persons with latex (Hb) allergy.
Niederberger, V; Stübner, P; Spitzauer, S; Kraft, D; Valenta, R; Ehrenberger, K; Horak, F
The diagnosis of type I allergy, an IgE-antibody-mediated hypersensitivity disease affecting more than 25% of the population, is based on the measurement of allergen-specific serum IgE levels and provocation testing. Whether the determination of allergen- specific serum IgE levels can replace in vivo provocation testing for allergy diagnosis is a controversial issue. We used purified recombinant timothy grass and birch pollen allergens to compare by skin prick and nasal provocation testing as well as by serology in vivo sensitivity with antibody-binding capacity in 24 pollen allergic patients and eight control individuals. Results from biologic tests were correlated with each other and with allergen-specific IgE and IgG1-4 levels. IgE-reactive allergens induced immediate skin and nasal reactions, but the intensity of the allergic tissue reactions was not correlated with either the levels of allergen-specific IgE or the levels of allergen-specific IgG antibodies. Less frequently detected allergens with low IgE-binding capacity were able to induce strong allergic reactions comparable to those caused by major allergens with high IgE-binding capacity. In contrast, skin test and nasal provocation results were significantly correlated (r = 0.63, p components for specific immunotherapy.
Full Text Available Objective: To study skin sensitivity to various allergens in patients of nasobronchial allergy. Materials and Methods: 2880 skin prick tests with 60 allergens were performed in 48 patients of nasobronchial allergy. Results: Most common offending allergens were insects (21.2%, followed by dusts (12.0%, pollens (7.8%, animal dander (3.1%, and fungi (1.3%. The common insect antigen were locust female (33.3% followed by locust male (25%, grasshopper (20.8%, cricket (16.7%, cockroach female (16.7% and cockroach male (14.6%. Common dust allergens were house dust, wheat dust, cotton mill and paper dust. Among pollens, Amaranthus spinosus, Argemone mexicana, Adhatoda vasica, Ailanthus and Cannabis were found to be common allergens. In animal danders common offending allergens were cow dander and dog dander. Among fungi Aspergillus fumigatus, Aspergillus flavus, Alternaria teneis and Fusarium sodani were common allergens. Patients of bronchial asthma had associated allergic rhinitis in 80% cases. Conclusion: Common allergens in patients of nasobronchial allergy were identified. The data may prove useful in of allergen avoidance and immunotherapy in these patients.
Lalani, Aly-Khan A; Bossé, Dominick; McGregor, Bradley A; Choueiri, Toni K
Immunotherapy has historic and contemporary presence in prostate, urothelial (UC), and renal cell (RCC) carcinomas. However, robust data on utility and generalizability of these treatments in older patients are lacking. To systematically evaluate evidence regarding the efficacy and safety of immunotherapy in elderly patients with prostate cancer, UC, or RCC. PubMed/Medline, Embase, Web of Knowledge, and Cochrane Library databases were searched up to October 2017 and according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. A narrative review of studies was performed. Twenty-one reports were included regarding prostate cancer (four studies), UC (eight), and RCC (nine). In prostate cancer, sipuleucel-T improves survival (median age >70 yr) and similar results were seen in the PROSTVAC phase 2 trial. Ipilimumab has not improved survival independent of age; data for programmed cell death 1 inhibition is evolving. In metastatic UC, ≥50% of patients enrolled in pivotal checkpoint inhibitor studies were aged ≥65 yr. Three studies reported similar objective response rates (ORRs) in patients aged <65 versus ≥65 yr, whereas one study reported comparable ORRs in patients <80 versus ≥80 yr. In metastatic RCC, cytokine studies showed no efficacy difference by age; one study reported more ≥grade 3 toxicity in patients aged ≥65 yr. One vaccine-based study suggests that older age was associated with shorter survival. The benefit of nivolumab in second-line therapy was more apparent for patients aged 65-<75 yr than for those aged ≥75 yr. Across tumor subtypes, immunotherapy was well tolerated with minimal data stratifying toxicity by age. Contemporary immunotherapy has informed practice in genitourinary malignancies independent of patient age. Trial reporting of outcomes by age will be important to understand the generalizability of ongoing investigations for elderly patients. With the growing use of immunotherapy in genitourinary
Jarolim, E; Matthiesen, F; Skov, P S
Patients allergic to grass pollen were hyposensitized with two major allergenic components or whole extract of timothy grass pollen. Specific IgE, IgG1, and IgG4 formed during immunotherapy were analyzed by immunoblotting. Similar antibody-binding patterns were observed in both patient groups....... Inhibition experiments using allergenic components isolated by preparative sodium dodecyl sulphate-polyacrylamide gel electrophoresis indicated that all antigenic components of timothy grass pollen detected in immunoblot dispose of private and cross-reactive determinants for binding of human IgE. The worse...
Luoto, Susanne; Lambert, Wietske; Blomqvist, Anna; Emanuelsson, Cecilia
During production of sugar beet (Beta vulgaris) seeds in greenhouses, workers frequently develop allergic symptoms. The aim of this study was to identify and characterize possible allergens in sugar beet pollen. Sera from individuals at a local sugar beet seed producing company, having positive SPT and specific IgE to sugar beet pollen extract, were used for immunoblotting. Proteins in sugar beet pollen extracts were separated by 1- and 2-dimensional electrophoresis, and IgE-reactive proteins analyzed by liquid chromatography tandem mass spectrometry. A 14 kDa protein was identified as an allergen, since IgE-binding was inhibited by the well-characterized allergen Che a 2, profilin, from the related species Chenopodium album. The presence of 17 kDa and 14 kDa protein homologues to both the allergens Che a 1 and Che a 2 were detected in an extract from sugar beet pollen, and partial amino acid sequences were determined, using inclusion lists for tandem mass spectrometry based on homologous sequences. Two occupational allergens were identified in sugar beet pollen showing sequence similarity with Chenopodium allergens. Sequence data were obtained by mass spectrometry (70 and 25%, respectively for Beta v 1 and Beta v 2), and can be used for cloning and recombinant expression of the allergens. As for treatment of Chenopodium pollinosis, immunotherapy with sugar beet pollen extracts may be feasible.
Full Text Available Abstract Background During production of sugar beet (Beta vulgaris seeds in greenhouses, workers frequently develop allergic symptoms. The aim of this study was to identify and characterize possible allergens in sugar beet pollen. Methods Sera from individuals at a local sugar beet seed producing company, having positive SPT and specific IgE to sugar beet pollen extract, were used for immunoblotting. Proteins in sugar beet pollen extracts were separated by 1- and 2-dimensional electrophoresis, and IgE-reactive proteins analyzed by liquid chromatography tandem mass spectrometry. Results A 14 kDa protein was identified as an allergen, since IgE-binding was inhibited by the well-characterized allergen Che a 2, profilin, from the related species Chenopodium album. The presence of 17 kDa and 14 kDa protein homologues to both the allergens Che a 1 and Che a 2 were detected in an extract from sugar beet pollen, and partial amino acid sequences were determined, using inclusion lists for tandem mass spectrometry based on homologous sequences. Conclusion Two occupational allergens were identified in sugar beet pollen showing sequence similarity with Chenopodium allergens. Sequence data were obtained by mass spectrometry (70 and 25%, respectively for Beta v 1 and Beta v 2, and can be used for cloning and recombinant expression of the allergens. As for treatment of Chenopodium pollinosis, immunotherapy with sugar beet pollen extracts may be feasible.
Ohashi-Doi, Katsuyo; Kito, Hirokazu; Du, Weibin; Nakazawa, Hiroshi; Ipsen, Henrik; Gudmann, Pernille; Lund, Kaare
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.
Durham, S R; Varney, V A; Gaga, M; Jacobson, M R; Varga, E M; Frew, A J; Kay, A B
Allergen injection immunotherapy is effective for summer hay fever and reduces cutaneous sensitivity to grass pollen. We have addressed whether this effect of immunotherapy may be due to a decrease in mast cell numbers in the skin. Total mast cells and mast cell subtypes in the dermis were measured by dual immunocytochemistry in 40 adult patients who had received either 'active' grass pollen immunotherapy or placebo injections for 9 months in a double-blind clinical trial. Clinical improvement in hay fever was accompanied by a greater than 10-fold reduction in the immediate cutaneous response to grass pollen (P = 0. 0002) and a sevenfold decrease in mast cell numbers in the skin (P = 0.0001). The number of mast cells after immunotherapy correlated with the clinical response in terms of seasonal symptoms (r = 0.61, P = 0.001) and rescue medication use (r = 0.75, P = 0.0001). Specific double immunostaining showed that the majority of mast cells (greater than 60%) were tryptase/chymase-positive (MCTC) and the remainder tryptase-only (MCT) cells. Following immunotherapy both subtypes were equally reduced. One mechanism by which immunotherapy may act is to reduce mast cell numbers with a consequent reduction in immediate allergic sensitivity.
Martins, Luís Miguel Lourenço; Marques, Andreia Grilo; Pereira, Luísa Maria Dotti Silva; Goicoa, Ana; Semião-Santos, Saul José; Bento, Ofélia Pereira
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.
Hansen, Kirsten Skamstrup; Khinchi, Marianne Søndergaard; Skov, Per Stahl
Conflicting results concerning the effect of specific pollen immunotherapy (SIT) on allergy to plant foods have been reported. The aim of this study was to investigate the effect of SIT using a birch pollen extract on food allergy with focus on allergy to apple. Seventy-four birch pollen......-allergic patients were included in a double-blind, double-dummy, and placebo-controlled comparison of sublingual-swallow (SLIT) and subcutaneous (SCIT) administration of a birch pollen extract. Sixty-nine percent of these patients reported allergy to apple. The clinical reactivity to apple was evaluated by open....... Therefore, oral allergy syndrome (OAS) to apple should not be considered as a main criterion for selecting patients for birch pollen immunotherapy at present....
Chest injury commonly leads to subcutaneous emphysema of the chest, neck and face. It is usually non-life threatening. Massive subcutaneous emphysema may occur and very rarely may spread to involve the scrotal sac and subcutaneous tissue planes of the penis to cause pneumoscrotopenis. This case report presents ...
Full Text Available Bronchogenic cysts occur due to the anomalous development of the primitive tracheobronchial tree early in fetal life. They are usually present in middle mediastinum. Rarely, they have been found in other locations. We describe two patients with subcutaneous bronchogenic cysts located over manubrium sterni with special emphasis on the difficulties in pre-operative diagnosis. The two boys were managed by complete excision of the cysts. The children are well on follow-up.
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
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.
Poulsen, Lars K.; Hansen, T K; Nørgaard, A
Allergens from fish and egg belong to some of the most frequent causes of food allergic reactions reported in the literature. Egg allergens have been described in both white and yolk, and the egg white proteins ovomucoid, ovalbumin, ovotransferrin and lysozyme have been adopted in the allergen...... nomenclature as Gal d1-d4. The most reported allergen from egg yolk seems to be alpha-livitin. In fish, the dominating allergen is the homologues of Gad c1 from cod, formerly described as protein M. A close cross-reactivity exists within different species of fish between this calcium-binding protein family...
Full Text Available Most cancer patients are treated with some combination of surgery, radiation, and chemotherapy. Despite recent advances in local therapy with curative intent, chemotherapeutic treatments for metastatic disease often remain unsatisfying due to severe side effects and incomplete long-term remission. Therefore, the evaluation of novel therapeutic options is of great interest. Conventional, along with newer treatment strategies target the immune system that suppresses genitourinary (GU malignancies. Metastatic renal cell carcinoma and non-muscle-invasive bladder caner represent the most immune-responsive types of all human cancer. This review examines the rationale and emerging evidence supporting the anticancer activity of immunotherapy, against GU malignancies.
Lin, Yuan, E-mail: email@example.com [Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); UCLA Head and Neck Cancer Program, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Sharma, Sherven [Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, 37-131 CHS, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Veterans’ Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073 (United States); John, Maie St. [Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); UCLA Head and Neck Cancer Program, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States); Clinical and Translational Science Institute, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095 (United States)
Cancer, a major health problem, affects 12 million people worldwide every year. With surgery and chemo-radiation the long term survival rate for the majority of cancer patients is dismal. Thus novel treatments are urgently needed. Immunotherapy, the harnessing of the immune system to destroy cancer cells is an attractive option with potential for long term anti-tumor benefit. Cytokines are biological response modifiers that stimulate anti-tumor immune responses. In this review, we discuss the anti-tumor efficacy of the chemotactic cytokine CCL21 and its pre-clinical and clinical application in cancer.
Cashew nut allergy can be a severe food allergy of which the prevalence appears to be increasing. The aim of this thesis was a comprehensive molecular and serological characterisation of the cashew nut allergens Ana o 1, 2 and 3 for improved diagnosis and characterisation of patient populations.
Full Text Available Allergic and photo-allergic contact dermatitis, and immunologic contact urticaria are potential immune-mediated adverse effects from cosmetics. Fragrance components and preservatives are certainly the most frequently observed allergens; however, all ingredients must be considered when investigating for contact allergy.
Verhoeckx, K.C.M.; Vissers, Y.M.; Baumert, J.L.; Faludi, R.; Feys, M.; Flanagan, S.; Herouet-Guicheney, C.; Holzhauser, T.; Shimojo, R.; Bolt, N. van der; Wichers, H.; Kimber, I.
Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat
Verhoeckx, K.; Vissers, Y.; Baumert, J.L.; Faludi, R.; Fleys, M.; Flanagan, S.; Herouet-Guicheney, C.; Holzhauser, T.; Shimojo, R.; Bolt, van der Nieke; Wichers, H.J.; Kimber, I.
Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed.
In this review the impact of processing (heat and
Science Teacher, 2005
Researchers at National Jewish Medical and Research Center have demonstrated that dilute bleach not only kills common household mold, but may also neutralize the mold allergens that cause most mold-related health complaints. The study, published in the Journal of Allergy and Clinical Immunology, is the first to test the effect on allergic…
Burton, M D; Papalia, L; Eusebius, N P; O'Hehir, R E; Rolland, J M
Knowledge of dominant T cell epitopes of major allergens recognized by allergic individuals is required to improve efficacy and safety of allergen immunotherapy. Rye grass pollen (RGP) is the most important source of seasonal aeroallergens in temperate climates and Lol p 1 and Lol p 5 are the two major IgE-reactive allergens. This study aimed to characterize the T cell response to these allergens using a large panel of RGP-sensitive individuals. Short-term RGP-specific T cell lines (TCL) were generated from 38 RGP-sensitive subjects and stimulated with Lol p 1 and/or Lol p 5 allergens and synthetic 20-mer peptides. Proliferative responses were determined by 3H-thymidine uptake and IL-5 and IFN-gamma in culture supernatants analysed by ELISA. Of 17 subjects tested for reactivity to both allergens 16 (94%) responded to Lol p 1 and/or Lol p 5, establishing these as major T cell-reactive allergens. Sites of T cell reactivity were spread throughout the allergen molecules but regions of high reactivity were found. For Lol p 1 these spanned residues 19-38, 109-128, 154-173, 190-209, and for Lol p 5 37-56, 100-119, 145-164, 154-173, 190-209, 217-236 and 226-245. IL-5 and IFN-gamma were produced by T cells cultured with proliferation-inducing peptides. T cell responses to RGP major allergens have been extensively characterized, providing fundamental information for developing T cell-targeted immunotherapy for RGP allergy.
Ngiow, Shin Foong; Loi, Sherene; Thomas, David; Smyth, Mark J
Immunotherapy is now evolving into a major therapeutic option for cancer patients. Such clinical advances also promote massive interest in the search for novel immunotherapy targets, and to understand the mechanism of action of current drugs. It is projected that a series of novel immunotherapy agents will be developed and assessed for their therapeutic activity. In light of this, in vivo experimental mouse models that recapitulate human malignancies serve as valuable tools to validate the efficacy and safety profile of immunotherapy agents, before their transition into clinical trials. In this review, we will discuss the major classes of experimental mouse models of cancer commonly used for immunotherapy assessment and provide examples to guide the selection of appropriate models. We present some new data concerning the utility of a carcinogen-induced tumor model for comparing immunotherapies and combining immunotherapy with chemotherapy. We will also highlight some recent advances in experimental modeling of human malignancies in mice that are leading towards personalized therapy in patients. © 2016 Elsevier Inc. All rights reserved.
Priscila Ferreira de Sousa Moreira
Full Text Available Grass pollen, in particular from Lolium multiflorum is a major allergen source in temperate climate zones of Southern Brazil. The IgE sensitization profile of Brazilian grass pollen allergic patients to individual allergen molecules has not been analyzed yet.To analyze the IgE sensitization profile of a Brazilian grass pollen allergic population using individual allergen molecules.We analyzed sera from 78 grass pollen allergic patients for the presence of IgE antibodies specific for 103 purified micro-arrayed natural and recombinant allergens by chip technology. IgE-ELISA inhibition experiments with Lolium multiflorum, Phleum pratense extracts and a recombinant fusion protein consisting of Phl p 1, Phl p 2, Phl p 5 and Phl p 6 were performed to investigate cross-reactivities.Within the Brazilian grass pollen allergic patients, the most frequently recognized allergens were Phl p 1 (95%, Phl p 5 (82%, Phl p 2 (76% followed by Phl p 4 (64%, Phl p 6 (45%, Phl p 11 (18% and Phl p 12 (18%. Most patients were sensitized only to grass pollen allergens but not to allergens from other sources. A high degree of IgE cross-reactivity between Phleum pratense, Lolium multiflorum and the recombinant timothy grass fusion protein was found.Component-resolved analysis of sera from Brazilian grass pollen allergic patients reveals an IgE recognition profile compatible with a typical Pooideae sensitization. The high degree of cross-reactivity between Phleum pratense and Lolium multiflorum allergens suggests that diagnosis and immunotherapy can be achieved with timothy grass pollen allergens in the studied population.
Wagner, I; Geh, K J; Hubert, M; Winter, G; Weber, K; Classen, J; Klinger, C; Mueller, R S
Cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) are a promising new immunotherapeutic treatment option for canine atopic dermatitis (AD). The aim of this uncontrolled pilot study was to evaluate clinical and immunological effects of gelatine nanoparticle (GNP)-bound CpG ODN (CpG GNP) on atopic dogs. Eighteen dogs with AD were treated for 8 weeks (group 1, n=8) or 18 weeks (group 2, n=10). Before inclusion and after 2 weeks, 4 weeks, 6 weeks (group 1+2), 8 weeks, 12 weeks and 16 weeks (group 2) 75 µg CpG ODN/dog (bound to 1.5 mg GNP) were injected subcutaneously. Pruritus was evaluated daily by the owner. Lesions were evaluated and serum concentrations and mRNA expressions of interferon-γ, tumour necrosis factor-α, transforming growth factor-β, interleukin (IL) 10 and IL-4 (only mRNA expression) were determined at inclusion and after 8 weeks (group 1+2) and 18 weeks (group 2). Lesions and pruritus improved significantly from baseline to week 8. Mean improvements from baseline to week 18 were 23 per cent and 44 per cent for lesions and pruritus, respectively, an improvement of ≥50 per cent was seen in six out of nine and three out of six dogs, respectively. IL-4 mRNA expression decreased significantly. The results of this study show a clinical improvement of canine AD with CpG GNP comparable to allergen immunotherapy. Controlled studies are needed to confirm these findings. British Veterinary Association.
Bøgh, Katrine Lindholm; Madsen, Charlotte Bernhard
Food allergy is a major health problem in the Western countries, affecting 3-8% of the population. What makes a dietary protein a food allergen has not yet been established, though several characteristics have been proposed to be shared by the food allergens. One of the features believed...... potential exist. Resistance to digestion is therefore a test parameter included in the safety assessment of the allergenic potential of novel proteins in genetically modified foods. In recent years, the association between resistance to digestion and allergenic potential has been challenged. When reviewing...... existing data from digestibility studies on known food allergens, it becomes evident that food allergens do not necessarily resist digestion. However, the choice of assay conditions, the method used for detection of residual intact protein as well as fragments hereof greatly influences the outcome. Studies...
Full Text Available Oliver Fuge,1 Nikhil Vasdev,1 Paula Allchorne,2 James SA Green2 1Department of Urology, Lister Hospital, Stevenage, UK; 2Department of Urology, Bartshealth NHS Trust, Whipps Cross Rd, London, UK Abstract: It is nearly 40 years since Bacillus Calmette–Guérin (BCG was first used as an immunotherapy to treat superficial bladder cancer. Despite its limitations, to date it has not been surpassed by any other treatment. As a better understanding of its mechanism of action and the clinical response to it have evolved, some of the questions around optimal dosing and treatment protocols have been answered. However, its potential for toxicity and failure to produce the desired clinical effect in a significant cohort of patients presents an ongoing challenge to clinicians and researchers alike. This review summarizes the evidence behind the established mechanism of action of BCG in bladder cancer, highlighting the extensive array of immune molecules that have been implicated in its action. The clinical aspects of BCG are discussed, including its role in reducing recurrence and progression, the optimal treatment regime, toxicity and, in light of new evidence, whether or not there is a superior BCG strain. The problems of toxicity and non-responders to BCG have led to development of new techniques aimed at addressing these pitfalls. The progress made in the laboratory has led to the identification of novel targets for the development of new immunotherapies. This includes the potential augmentation of BCG with various immune factors through to techniques avoiding the use of BCG altogether; for example, using interferon-activated mononuclear cells, BCG cell wall, or BCG cell wall skeleton. The potential role of gene, virus, or photodynamic therapy as an alternative to BCG is also reviewed. Recent interest in the immune check point system has led to the development of monoclonal antibodies against proteins involved in this pathway. Early findings suggest
Full Text Available 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.
Victor E.S. Cunha
Full Text Available House dust mite antigens have been used for decades to diagnose allergic diseases in humans and animals. The objective of this study was to identify allergens in commercial Dermatophagoides farinae and Blomia tropicalis extracts by immunoblotting using sera from allergic dogs and anti-dog IgE conjugate. The analysis of antigens present in the D. farinae extract (FDA Allergenic using sera from 10 dogs allergic to D. farinae showed that eight sera recognized a band of approximately 102 kDa, eight recognized two bands of 52 to 76 kDa, five recognized one band of approximately 76 kDa, four recognized one band of 31 to 38 kDa, and two recognized one band of 12 to 17 kDa. Immunoblot assays of the B. tropicalis extract (FDA Allergenic using sera from 10 animals allergic to B. tropicalis showed that five sera recognized two bands of 52 to 76 kDa. These results demonstrate the importance of the two house dust mite species for the pathogenesis of canine atopic dermatitis in Brazil. In addition, the results indicate which allergens should be present in allergenic extracts used for diagnosis and allergen-specific immunotherapy.
Manjiri R. Naniwadekar
Full Text Available Subcutaneous phycomycosis is a rare entity. We hereby report a case of subcutaneous phycomycosis in 18 months old female child who presented with a painless, non-tender swelling on the thigh. Skin biopsy showed eosinophilic granuloma lying deep in the subcutaneous tissue, with sparse hyphae. Culture on Sabouraud's dextrose agar showed characteristic colonies. Patient was started on oral potassium iodide. The swelling was completely resolved after one month of treatment.
Full Text Available This article presents trends in the frequency of cosmetics as causal factors of allergic contact dermatitis during a 26-year period in 14,911 patients patch-tested between 1990 and 2014, and discusses the cosmetic allergens identified during the last six years (2010–2015 in 603 patients out of 3105 tested. The data were retrieved from, and evaluated with, a patient database developed in-house. The results show the increasing importance of cosmetic allergies, up to 25% of the patients tested during the last five-year period. As expected, fragrance materials, preservatives, and hair dyes were the most frequent culprits, but a great variety of other allergenic ingredients were involved as well. This underlines the need of additional and extensive patch testing with the patient’s products used and their ingredients.
Borodina, Irina; Jensen, B. M.; Søndergaard, Ib
Saccharomyces cerevisiae preserve their native allergenic properties and whether the yeast native surface glycoproteins interfere with IgE binding. We chose to use the major allergens from the common wasp Vespula vulgaris venom: phospholipase A1, hyaluronidase and antigen 5 as the model. Results: The proteins...... their enzymatic activities. Phospholipase A1 severely inhibited the growth of the yeast cells. Antigen 5 - expressing yeast cells bound IgE antibodies from wasp venom allergic patient sera but not from control sera as demonstrated by FACS. Moreover, antigen 5 - expressing yeast cells were capable of mediating....... The non-modified S. cerevisiae cells did not cause any unspecific reaction in FACS or histamine release assay despite the expression of high-mannose oligosaccharides. In perspective the yeast surface display may be used for allergen discovery from cDNA libraries and possibly for sublingual immunotherapy...
Three new studies have identified intestinal bacteria that appear to influence the response to checkpoint inhibitors. This Cancer Currents blog post explains how the researchers think their findings could be used to improve patients’ responses to these immunotherapy drugs.
This collaborative grant is developing 3D models of both mouse and human biology to investigate aspects of therapeutic vaccination in order to answer key questions relevant to human cancer immunotherapy.
Boye, Joyce I; Godefroy, Samuel Benrejeb
.... Starting with an introduction to food allergens, the book follows with sections on food allergen management during production and processing, guidelines for the processing of specific allergen-free...
Full Text Available The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT, structural WAT (sWAT and fibrous WAT (fWAT. dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical. In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for
In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....
1 AWARD NUMBER: W81XWH-14-1-0587 TITLE: Novel Combinatorial Immunotherapy for Melanoma PRINCIPAL INVESTIGATOR: Li Wang CONTRACTING...Novel Combinatorial Immunotherapy for Melanoma 5b. GRANT NUMBER W81XWH-14-1-0587 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Li...recognizing melanoma antigens, we have confirmed the synergistic activation of T cells in response to combinatorial therapy. These results form the
The term 'immunotherapy' refers to treating diseases by inducing, enhancing or suppressing immune responses. As allergy is an excessive, detrimental immune reaction to otherwise harmless environmental substances, immunotherapy of allergic disease is aimed at the induction of tolerance toward sensitizing antigens. This article focuses on the historical developments, present state and future outlook for immunotherapy with haptens as a therapeutic modality for allergic contact dermatitis. Inspired by the effectiveness of immunotherapy in respiratory allergies, attempts were undertaken at curing allergic contact dermatitis by means of controlled administration of the sensitizing haptens. Animal and human experiments confirmed that tolerance to haptens can be induced most effectively when the induction of tolerance precedes attempted sensitization. In real life, however, therapy is sought by people who are already sensitized and an effective reversal of hypersensitivity seems more difficult to achieve. Decades of research on Rhus hypersensitivity led to a conclusion that immunotherapy can suppress Rhus dermatitis, however, only to a limited degree, for a short period of time, and at a high risk of side effects, which makes this method therapeutically unprofitable. Methodological problems with most available studies of immunotherapy of contact allergy to nickel make any definite conclusions impossible at this stage.
Full Text Available Shellfish are a source of food allergens, and their consumption is the cause of severe allergic reactions in humans. Tropomyosins, a family of muscle proteins, have been identified as the major allergens in shellfish and mollusks species. Nevertheless, few experimentally determined three-dimensional structures are available in the Protein Data Base (PDB. In this study, 3D models of several homologous of tropomyosins present in marine shellfish and mollusk species (Chaf 1, Met e1, Hom a1, Per v1, and Pen a1 were constructed, validated, and their immunoglobulin E binding epitopes were identified using bioinformatics tools. All protein models for these allergens consisted of long alpha-helices. Chaf 1, Met e1, and Hom a1 had six conserved regions with sequence similarities to known epitopes, whereas Per v1 and Pen a1 contained only one. Lipophilic potentials of identified epitopes revealed a high propensity of hydrophobic amino acids in the immunoglobulin E binding site. This information could be useful to design tropomyosin-specific immunotherapy for sea food allergies.
Kitzmüller, Claudia; Kalser, Julia; Mutschlechner, Sonja; Hauser, Michael; Zlabinger, Gerhard J; Ferreira, Fatima; Bohle, Barbara
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.
Full Text Available Background Synthetic peptides, representing CD4+ T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils. Methods and Findings In this study we address the mechanism of action of peptide immunotherapy (PIT in cat-allergic, asthmatic patients. Cell-division-tracking dyes, cell-mixing experiments, surface phenotyping, and cytokine measurements were used to investigate immunomodulation in peripheral blood mononuclear cells (PBMCs after therapy. Proliferative responses of PBMCs to allergen extract were significantly reduced after PIT. This was associated with modified cytokine profiles generally characterised by an increase in interleukin-10 and a decrease in interleukin-5 production. CD4+ cells isolated after PIT were able to actively suppress allergen-specific proliferative responses of pretreatment CD4neg PBMCs in co-culture experiments. PIT was associated with a significant increase in surface expression of CD5 on both CD4+ and CD8+ PBMCs. Conclusion This study provides evidence for the induction of a population of CD4+ T cells with suppressor/regulatory activity following PIT. Furthermore, up-regulation of cell surface levels of CD5 may contribute to reduced reactivity to allergen.
Full Text Available Common ragweed (Ambrosia atremisiifolia is one of the most frequent causes of pollen-induced allergic reactions both in humans and dogs. It has not been defined yet, what is the major allergen(s to which most dogs allergic to ragweed show a positive result on intradermal skin test (IDST. In the present study sensitization to Ambrosia artemisiifolia pollen allergens in dogs with atopic dermatitis was examined with both in vivo and in vitro tests, including IDST and serum allergen specific IgE test. Detection of specific-IgE antibodies against ragweed allergens by immunoblotting in the sera of allergic dogs was optimized, as well. Dogs that were positive, as judged by IDST reactions to ragweed pollen allergens, also had alergen specific IgE antibodies in their sera. Results indicate that major allergens of A. artemisifolia pollen in dogs are Amb a 1 and Amb a 2. Further characterization of ragweed allergens is needed before they could potentially be used in intradermal testing or allergen immunotherapy in affected dogs. Also, we evaluated new Favrots diagnostic criteria for canine atopic dermatitis in dogs allergic to Ambrosia atremisiifolia pollen. It might be concluded that proposed criteria are of great assistance for seting up suspected diagnosis of canine atopic dermatitis, after ruling out other pruritic dermatoses. [Projekat Ministarstva nauke Republike Srbije, br. 172024
Full Text Available BACKGROUND: The goals of treating patients with cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. Therefore, stimulating immune reactions to tumors can be an attractive therapeutic and prevention strategy. CONTENT: During immune surveillance, the host provides defense against foreign antigens, while ensuring it limits activation against self antigens. By targeting surface antigens expressed on tumor cells, monoclonal antibodies have demonstrated efficacy as cancer therapeutics. Recent successful antibody-based strategies have focused on enhancing antitumor immune responses by targeting immune cells, irrespective of tumor antigens. The use of antibodies to block pathways inhibiting the endogenous immune response to cancer, known as checkpoint blockade therapy, has stirred up a great deal of excitement among scientists, physicians, and patients alike. Clinical trials evaluating the safety and efficacy of antibodies that block the T cell inhibitory molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA-4 and programmed cell death 1 (PD-1 have reported success in treating subsets of patients. Adoptive cell transfer (ACT is a highly personalized cancer therapy that involve administration to the cancer-bearing host of immune cells with direct anticancer activity. In addition, the ability to genetically engineer lymphocytes to express conventional T cell receptors or chimeric antigen receptors has further extended the successful application of ACT for cancer treatment. SUMMARY: For cancer treatment, 2011 marked the beginning of a new era. The underlying basis of cancer immunotherapy is to activate a patient’s own T cells so that they can kill their tumors. Reports of amazing recoveries abound, where patients remain cancer-free many years after receiving the therapy. The idea of harnessing immune cells to fight cancer is
Stumvoll, Sabine; Westritschnig, Kerstin; Lidholm, Jonas; Spitzauer, Susanne; Colombo, Paolo; Duro, Giovanni; Kraft, Dietrich; Geraci, Domenico; Valenta, Rudolf
The weed Parietaria judaica is one of the most important pollen allergen sources in the Mediterranean area. We sought to identify P judaica pollen allergen, which might be used to serologically distinguish genuine Parietaria sensitization and cross-reactivity to allergens from other weed species (eg, mugwort and ragweed). The allergen profile of P judaica IgE-reactive sera from weed pollen-sensitized allergic individuals from the Mediterranean region (n = 36) with high Parietaria pollen exposure and from weed pollen-allergic patients with little or no Parietaria exposure (Austria, n = 42; Scandinavia, n = 8; United States, n = 19) was established by CAP FEIA measurements and by IgE immunoblot inhibition experiments with recombinant allergens. The majority (83%) of the Mediterranean weed pollen-allergic patients mounted high IgE antibody levels (mean specific IgE, 20.89 kUA/L) against recombinant (r) Par j 2, whereas only 7% of the non-Mediterranean weed-allergic patients showed low IgE reactivity to rPar j 2 (mean specific IgE, 1.03 kUA/L). The cytoskeletal protein profilin and a 2-EF-hand calcium-binding allergen were identified as cross-reactive Parietaria allergens, which were recognized preferentially by Parietaria -positive, non-Mediterranean weed pollen-allergic patients. rPar j 2 might be used as a diagnostic marker allergen to identify weed pollen-allergic patients who are genuinely sensitized against Parietaria pollen and thus would be particularly suited for specific immunotherapy with Parietaria pollen extract.
Bordas-Le Floch, Véronique; Le Mignon, Maxime; Bouley, Julien; Groeme, Rachel; Jain, Karine; Baron-Bodo, Véronique; Nony, Emmanuel; Mascarell, Laurent; Moingeon, Philippe
Allergy to short ragweed (Ambrosia artemisiifolia) pollen is a serious and expanding health problem in North America and Europe. Whereas only 10 short ragweed pollen allergens are officially recorded, patterns of IgE reactivity observed in ragweed allergic patients suggest that other allergens contribute to allergenicity. The objective of the present study was to identify novel allergens following extensive characterization of the transcriptome and proteome of short ragweed pollen. Following a Proteomics-Informed-by-Transcriptomics approach, a comprehensive transcriptomic data set was built up from RNA-seq analysis of short ragweed pollen. Mass spectrometry-based proteomic analyses and IgE reactivity profiling after high resolution 2D-gel electrophoresis were then combined to identify novel allergens. Short ragweed pollen transcripts were assembled after deep RNA sequencing and used to inform proteomic analyses, thus leading to the identification of 573 proteins in the short ragweed pollen. Patterns of IgE reactivity of individual sera from 22 allergic patients were assessed using an aqueous short ragweed pollen extract resolved over 2D-gels. Combined with information derived from the annotated pollen proteome, those analyses revealed the presence of multiple unreported IgE reactive proteins, including new Amb a 1 and Amb a 3 isoallergens as well as 7 novel candidate allergens reacting with IgEs from 20-70% of patients. The latter encompass members of the carbonic anhydrase, enolase, galactose oxidase, GDP dissociation inhibitor, pathogenesis related-17, polygalacturonase and UDP-glucose pyrophosphorylase families. We extended the list of allergens identified in short ragweed pollen. These findings have implications for both diagnosis and allergen immunotherapy purposes.
Véronique Bordas-Le Floch
Full Text Available Allergy to short ragweed (Ambrosia artemisiifolia pollen is a serious and expanding health problem in North America and Europe. Whereas only 10 short ragweed pollen allergens are officially recorded, patterns of IgE reactivity observed in ragweed allergic patients suggest that other allergens contribute to allergenicity. The objective of the present study was to identify novel allergens following extensive characterization of the transcriptome and proteome of short ragweed pollen.Following a Proteomics-Informed-by-Transcriptomics approach, a comprehensive transcriptomic data set was built up from RNA-seq analysis of short ragweed pollen. Mass spectrometry-based proteomic analyses and IgE reactivity profiling after high resolution 2D-gel electrophoresis were then combined to identify novel allergens.Short ragweed pollen transcripts were assembled after deep RNA sequencing and used to inform proteomic analyses, thus leading to the identification of 573 proteins in the short ragweed pollen. Patterns of IgE reactivity of individual sera from 22 allergic patients were assessed using an aqueous short ragweed pollen extract resolved over 2D-gels. Combined with information derived from the annotated pollen proteome, those analyses revealed the presence of multiple unreported IgE reactive proteins, including new Amb a 1 and Amb a 3 isoallergens as well as 7 novel candidate allergens reacting with IgEs from 20-70% of patients. The latter encompass members of the carbonic anhydrase, enolase, galactose oxidase, GDP dissociation inhibitor, pathogenesis related-17, polygalacturonase and UDP-glucose pyrophosphorylase families.We extended the list of allergens identified in short ragweed pollen. These findings have implications for both diagnosis and allergen immunotherapy purposes.
Dummer, R; Hoeller, C.; Gruter, I.P.; Michielin, O.
Talimogene laherparepvec is a first-in-class intralesional oncolytic immunotherapy. In a recent Phase III trial (OPTiM), talimogene laherparepvec significantly improved durable response rate compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall response rate was also higher in the talimogene laherparepvec arm, and the greatest efficacy was demonstrated in patients with earlier-stage (IIIB, IIIC, or IVM1a) melanoma. Talimogene laherparepvec was well tole...
Full Text Available We report a rare case of transformation of non-small cell lung cancer (NSCLC to small cell lung cancer (SCLC, without epidermal growth factor receptor (EGFR gene mutation, during immunotherapy treatment with nivolumab. A 75-year-old man was referred to our hospital following the observation of a 64 mm mass in a chest computed tomography (CT scan. A transbronchial biopsy of the mass identified the pathological presence of poorly differentiated NSCLC, with no histological signs of SCLC. No mutations were identified in the EGFR gene. A clinical diagnosis of NSCLC (cT3N3M1a, stage IV was made following a positron emission tomography (PET–CT scan and enhanced brain magnetic resonance imaging. Docetaxel and bevacizumab were selected as the first-line chemotherapy regimen; however, after two cycles, the patient developed a gastrointestinal perforation, and discontinuation of cytotoxic chemotherapy was recommended. Owing to gradual disease progression, immunotherapy with nivolumab was selected as the second-line regimen. During the immunotherapy, the tumor continued to progress and some subcutaneous tumors emerged. Biopsy of a subcutaneous tumor revealed SCLC, with positive immunostaining for cluster of differentiation 56, synaptophysin, and thyroid transcription factor-1. Serum tumor markers of SCLC were also elevated. Based on these results, we concluded that in this case NSCLC had transformed to SCLC during immunotherapy with nivolumab.
Suphioglu, C; Blaher, B; Rolland, J M; McCluskey, J; Schäppi, G; Kenrick, J; Singh, M B; Knox, R B
Grass pollen, especially of rye-grass (Lolium perenne). represents an important cause of type I allergy. Identification of IgE-binding (allergenic) epitopes of major grass pollen allergens is essential for understanding the molecular basis of interaction between allergens and human IgE antibodies and therefore facilitates the devising of safer and more effective diagnostic and immunotherapy reagents. The aim of this study was to identify the allergenic epitopes of Lol p 5, a major allergen of rye-grass pollen, immunodissect these epitopes further so that the amino acid residues critical for antibody binding can be determined and investigate the conservation and nature of these epitopes within the context of the natural grass pollen allergens. Peptides, 12-13 amino acid residues long and overlapping each other by 4 amino acid residues, based on the entire deduced amino acid sequence of the coding region of Lol p 5, were synthesised and assayed for IgE-binding. Two strong IgE-binding epitopes (Lol p 5 (49-60) and (265-276), referred to as peptides 7 and 34, respectively) were identified. These epitopes were further resolved by truncated peptides and amino acid replacement studies and the amino acid residues critical for IgE-binding determined (Lol p 5 (49-60) residue Lys57 and (265-276) residue Lys275). Sequences of these epitopes were conserved in related allergens and may form the conserved allergenic domains responsible for the cross-reactivity observed between pollen allergens of taxonomically related grasses. Furthermore, due to its strong IgE-reactivity, synthetic peptide Lol p 5 (265-276) was used to affinity-purify specific IgE antibodies which recognised proteins of other clinically important grass pollens. further indicating presence of allergenic cross-reactivity at the level of allergenic epitope. Moreover, Lol p 5 (265 276) demonstrated a strong capacity to inhibit IgE-binding to natural rye-grass pollen proteins highlighting the antibody accessibility
Loveren H van; LPI
Certain foods lead may to allergic responses in certain individuals. Main allergenic foods are Crustacea (shrimp, lobster, crab), egg, fish, milk, peanuts, soybeans, tree nuts, and wheat, and allergens are always proteins. A wide array of symptoms can result from food allergy (gastrointestinal,
Yun, Yeon Sook; Chung, H. Y.; Yi, S. Y.; Kim, K. W.; Kim, B. K.; Chung, I. S.; Park, J. Y
To increase the curative rate of cancer patients, we developed ideal biological response modifier from medicinal plants: Ginsan, KC68IId-8, KC-8Ala, KG-30. Ginsan activated natural killer cell activity of spleen cells more than 5.4 times than lentinan, 1.4 times than picibanil. Radioprotective activity of Ginsan is stronger than WR2721, glucan, and selenium. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of MOPC tumor cells was augmented by treatment with IL-10 antisense oligonucleotide and by transfection with VEGF sense-, antisense gene. The immunogenicity of A20 tumor cells was also augmented by transfection with B7.1 gene. The immunosuppression of gamma-irradiation was due to the reduction of Th1 sytokine gene expression through STAT pathway. These research will devote to develop new cancer immunotherapy and to reduce side effect of cancer radiotherapy and chemotherapy.
Vermani, Maansi; Vijayan, Vannan Kandi; Agarwal, Mahendra Kumar
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.
Levetin, Estelle; Horner, W Elliott; Scott, James A
The Kingdom Fungi contains diverse eukaryotic organisms including yeasts, molds, mushrooms, bracket fungi, plant rusts, smuts, and puffballs. Fungi have a complex metabolism that differs from animals and plants. They secrete enzymes into their surroundings and absorb the breakdown products of enzyme action. Some of these enzymes are well-known allergens. The phylogenetic relationships among fungi were unclear until recently because classification was based on the sexual state morphology. Fungi lacking an obvious sexual stage were assigned to the artificial, now-obsolete category, "Deuteromycetes" or "Fungi Imperfecti." During the last 20 years, DNA sequencing has resolved 8 fungal phyla, 3 of which contain most genera associated with important aeroallergens: Zygomycota, Ascomycota, and Basidiomycota. Advances in fungal classification have required name changes for some familiar taxa. Because of regulatory constraints, many fungal allergen extracts retain obsolete names. A major benefit from this reorganization is that specific immunoglobulin E (IgE) levels in individuals sensitized to fungi appear to closely match fungal phylogenetic relationships. This close relationship between molecular fungal systematics and IgE sensitization provides an opportunity to systematically look at cross-reactivity and permits representatives from each taxon to serve as a proxy for IgE to the group. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Shukla, Sourabh; Steinmetz, Nicole F
Founded on the growing insight into the complex cancer-immune system interactions, adjuvant immunotherapies are rapidly emerging and being adapted for the treatment of various human malignancies. Immune checkpoint inhibitors, for example, have already shown clinical success. Nevertheless, many approaches are not optimized, require frequent administration, are associated with systemic toxicities and only show modest efficacy as monotherapies. Nanotechnology can potentially enhance the efficacy of such immunotherapies by improving the delivery, retention and release of immunostimulatory agents and biologicals in targeted cell populations and tissues. This review presents the current status and emerging trends in such nanotechnology-based cancer immunotherapies including the role of nanoparticles as carriers of immunomodulators, nanoparticles-based cancer vaccines, and depots for sustained immunostimulation. Also highlighted are key translational challenges and opportunities in this rapidly growing field. © 2016 by the Society for Experimental Biology and Medicine.
Full Text Available To prove clinical benefits of cancer vaccine is currently difficult, except for one phase III trial has documented improved overall survival with the vaccine, Sipuleucel‑T, although induction of anti-tumor immune responses through cancer vaccine is theoretically promising and would be straightforward. In contrast, immune checkpoint blockade with anti-CTLA4 mAb and anti-PD‑1 mAb has demonstrated clear evidence of objective responses including improved overall survival and tumor shrinkage, driving renewed enthusiasm for cancer immunotherapy in multiple cancer types. In addition, there is a promising novel cancer immunotherapy, CAR therapy—a personalized treatment that involves genetically modifying a patient’s T- cells to make them target tumor cells. We are now facing new era of cancer immunotherapy.
Asturias, J A; Ferrer, A; Arilla, M C; Andreu, C; Madariaga, B; Martínez, A
The physicochemical modification of allergen vaccines provides a chance for administering higher doses in a shorter period of time. We sought to assess the safety and immunological changes of using a biologically standardized and modified Parietaria judaica pollen extract in accelerated schedules. Two accelerated schedules were tested in 45 P. judaica-allergic patients: 20 patients reached the maximum dose after two visits using two different concentrations and 25 patients reached the maximum dose after only one visit with two injections of the maximum concentration vial. The tolerance was assessed by recording all side effects related with immunotherapy. Specific antibody levels against native extract and rPar j 2 allergen were evaluated at the beginning and the end of the study. Allergenic potency determined by enzyme allergosorbent test (EAST) inhibition and skin prick test showed that modified P. judaica pollen had a 99.9% less allergenicity than native extract. After 650 doses administered, two clinically irrelevant local reactions (diameter<0 x 5 cm) and no systemic reactions were registered. Significant increases in allergen-specific IgG4 and IgG against P. judaica extract and rPar j 2 and significant decrease of specific IgE against Par j 2 were observed. The modified extract of P. judaica is safe to treat sensitive patients, even at accelerated regimens, and induces significant immunological changes.
Groeme, Rachel; Airouche, Sabi; Kopečný, David; Jaekel, Judith; Savko, Martin; Berjont, Nathalie; Bussieres, Laetitia; Le Mignon, Maxime; Jagic, Franck; Zieglmayer, Petra; Baron-Bodo, Véronique; Bordas-Le Floch, Véronique; Mascarell, Laurent; Briozzo, Pierre; Moingeon, Philippe
Allergy to the short ragweed (Ambrosia artemisiifolia) pollen is a major health problem. The ragweed allergen repertoire has been recently expanded with the identification of Amb a 11, a new major allergen belonging to the cysteine protease family. To better characterize Amb a 11, a recombinant proform of the molecule with a preserved active site was produced in Escherichia coli, refolded, and processed in vitro into a mature enzyme. The enzymatic activity is revealed by maturation following an autocatalytic processing resulting in the cleavage of both N- and C-terminal propeptides. The 2.05-Å resolution crystal structure of pro-Amb a 11 shows an overall typical C1A cysteine protease fold with a network of molecular interactions between the N-terminal propeptide and the catalytic triad of the enzyme. The allergenicity of Amb a 11 was confirmed in a murine sensitization model, resulting in airway inflammation, production of serum IgEs, and induction of Th2 immune responses. Of note, inflammatory responses were higher with the mature form, demonstrating that the cysteine protease activity critically contributes to the allergenicity of the molecule. Collectively, our results clearly demonstrate that Amb a 11 is a bona fide cysteine protease exhibiting a strong allergenicity. As such, it should be considered as an important molecule for diagnosis and immunotherapy of ragweed pollen allergy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
McEnery-Stonelake, Melissa; Silvestri, Dianne L
Excipients in various formulations of active drugs occasionally include known contact allergens. Their ingestion may trigger dermatitis or cause it to become widespread or refractory to therapy. The aim of this study was to investigate the prevalence of common contact allergens among the excipients of oral antihistamines available in this country. We gathered the complete ingredient lists of 2119 different preparations of 12 oral antihistamines from the National Library of Medicine data bank and entered them into an electronic database for analysis. More than half the formulations (55.0%) contained at least 1 member of the 10 allergen families assessed. Most brompheniramine and doxepin preparations included potentially allergenic excipients, whereas fexofenadine was most often free of them. Sorbitan group members, azo dyes, and propylene glycol were the allergens found most frequently in the antihistamines, each present in over 25% of the products. Elixirs, liquids, solutions, suspensions, and syrups were more likely than nonchewable caplets, capsules, and tablets to contain the allergens tabulated (100% vs 39.3%, respectively). Chewable pills frequently contained azo dyes. Ingestion of antihistamines could precipitate a systemic contact dermatitis in a patient sensitized to an allergen present as an excipient in the medicine.
Gawlik, Radoslaw; Glück, Joanna; Jawor, Barbara; Rogala, Barbara
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.
Radulovic, Suzana; Jacobson, Mikila R; Durham, Stephen R; Nouri-Aria, Kayhan T
Regulatory T (Treg) cells play an important role in controlling allergic inflammation. The transcription factor Foxp3 regulates the development and function of natural and adaptive CD4(+)CD25(+) Treg cells. We sought to examine the effect of grass pollen injection immunotherapy on the numbers of Foxp3(+)CD4(+) and Foxp3(+)CD25(+) T cells in and out of season and their expression of IL-10 in the nasal mucosa of patients with hay fever. Nasal biopsy specimens were obtained from untreated patients with hay fever, participants with grass pollen allergy who had received 2 years of immunotherapy, and healthy control subjects. Dual-immunofluorescence microscopy was used to enumerate and colocalize Foxp3 expression to CD4(+) and CD25(+) T cells in the nasal mucosa. Triple staining was performed to colocalize Foxp3(+) cells to CD3(+)CD25(+) and CD3(+) IL-10-expressing cells. At peak season, numbers of Foxp3(+)CD25(+) (P = .02) and Foxp3(+)CD4(+) (P = .03) cells were significantly increased in the nasal mucosa of immunotherapy-treated patients compared with numbers before treatment. Foxp3(+)CD25(+) (P = .03) and Foxp3(+)CD4(+) (P = .04) cells were also greater in immunotherapy-treated patients out of season compared with those in untreated patients with hay fever. Within the immunotherapy-treated group, 20% of CD3(+)CD25(+) cells expressed Foxp3, and 18% of Foxp3(+)CD3(+) cells were IL-10 positive. The presence of local Foxp3(+)CD25(+)CD3(+) cells in the nasal mucosa, their increased numbers after immunotherapy, and their association with clinical efficacy and suppression of seasonal allergic inflammation support a putative role for Treg cells in the induction of allergen-specific tolerance in human subjects.
Dimitrov, Ivan; Naneva, Lyudmila; Doytchinova, Irini; Bangov, Ivan
Allergenicity, like antigenicity and immunogenicity, is a property encoded linearly and non-linearly, and therefore the alignment-based approaches are not able to identify this property unambiguously. A novel alignment-free descriptor-based fingerprint approach is presented here and applied to identify allergens and non-allergens. The approach was implemented into a four step algorithm. Initially, the protein sequences are described by amino acid principal properties as hydrophobicity, size, relative abundance, helix and β-strand forming propensities. Then, the generated strings of different length are converted into vectors with equal length by auto- and cross-covariance (ACC). The vectors were transformed into binary fingerprints and compared in terms of Tanimoto coefficient. The approach was applied to a set of 2427 known allergens and 2427 non-allergens and identified correctly 88% of them with Matthews correlation coefficient of 0.759. The descriptor fingerprint approach presented here is universal. It could be applied for any classification problem in computational biology. The set of E-descriptors is able to capture the main structural and physicochemical properties of amino acids building the proteins. The ACC transformation overcomes the main problem in the alignment-based comparative studies arising from the different length of the aligned protein sequences. The conversion of protein ACC values into binary descriptor fingerprints allows similarity search and classification. The algorithm described in the present study was implemented in a specially designed Web site, named AllergenFP (FP stands for FingerPrint). AllergenFP is written in Python, with GIU in HTML. It is freely accessible at http://ddg-pharmfac.net/Allergen FP. firstname.lastname@example.org or email@example.com.
Poulsen Lars K
Full Text Available Abstract Background Yeast surface display is a technique, where the proteins of interest are expressed as fusions with yeast surface proteins and thus remain attached to the yeast cell wall after expression. Our purpose was to study whether allergens expressed on the cell surface of baker's yeast Saccharomyces cerevisiae preserve their native allergenic properties and whether the yeast native surface glycoproteins interfere with IgE binding. We chose to use the major allergens from the common wasp Vespula vulgaris venom: phospholipase A1, hyaluronidase and antigen 5 as the model. Results The proteins were expressed on the surface as fusions with a-agglutinin complex protein AGA2. The expression was confirmed by fluorescent cytometry (FACS after staining the cells with antibody against a C-tag attached to the C-terminal end of the allergens. Phospholipase A1 and hyaluronidase retained their enzymatic activities. Phospholipase A1 severely inhibited the growth of the yeast cells. Antigen 5 - expressing yeast cells bound IgE antibodies from wasp venom allergic patient sera but not from control sera as demonstrated by FACS. Moreover, antigen 5 - expressing yeast cells were capable of mediating allergen-specific histamine release from human basophils. Conclusions All the three major wasp venom allergens were expressed on the yeast surface. A high-level expression, which was observed only for antigen 5, was needed for detection of IgE binding by FACS and for induction of histamine release. The non-modified S. cerevisiae cells did not cause any unspecific reaction in FACS or histamine release assay despite the expression of high-mannose oligosaccharides. In perspective the yeast surface display may be used for allergen discovery from cDNA libraries and possibly for sublingual immunotherapy as the cells can serve as good adjuvant and can be produced in large amounts at a low price.
Fukuda, Ken; Ishida, Waka; Harada, Yosuke; Wakasa, Yuhya; Takagi, Hidenori; Takaiwa, Fumio; Fukushima, Atsuki
To determine whether oral immunotherapy with transgenic rice seeds expressing hypoallergenic modified antigens suppresses cedar pollen-induced allergic conjunctivitis by eliciting immune tolerance in mice. BALB/c mice were fed once a day for 20 days with 220 mg of transgenic rice expressing modified Japanese cedar pollen allergens Cry j 1 and Cry j 2 or with non-transgenic rice seeds as a control. They were then sensitised with two intraperitoneal injections of Japanese cedar pollen in alum before challenge twice with pollen in eye drops. Twenty-four hours after the second challenge, the conjunctiva, spleen, and blood were isolated for histological analysis, cytokine production assays, and measurement of serum immunoglobulin E concentrations, respectively. The numbers of eosinophils and total inflammatory cells in the conjunctiva were significantly lower in mice fed the transgenic rice than in those fed non-transgenic rice. The clinical score evaluated at 15 min after antigen challenge was also significantly lower in mice fed the transgenic rice than in those fed non-transgenic rice. The serum concentrations of both total and allergen-specific immunoglobulin E were also significantly lower in mice fed the transgenic rice. Oral vaccination with transgenic rice resulted in significant down-regulation of the allergen-induced production of interleukin (IL)-2, IL-4, IL-5, IL-12p70, interferon-γ, and IL-17A by splenocytes. Oral immunotherapy with transgenic rice expressing modified Japanese cedar pollen allergens suppressed pollen-induced experimental allergic conjunctivitis in mice by eliciting immune tolerance. This novel prophylactic approach is potentially safe and effective for allergen-specific oral immunotherapy in allergic conjunctivitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Xie, Lisheng; Jiang, Yinzhu; Li, Qi
To observe the role of the dust mites drops sublingual immunotherapy(SLIT) in pediatric allergic rhiriitis caused by dust mites and compare its efficacy between monosensitized and polysensitized children. A total of 77 pediatric allergic rhinitis patients received Dermatophagoides farina extracts sublingual immunotherapy for 2 years were enrolled as desensitization group and were allocated into monosensitized group (41 cases) and polysensitized group (36 cases) according to the number of coexisting allergens. Meanwhile another 33 allergic rhinitis children treated by pharmacotherapy during the period were collected as control group. The total symptom scores (TNSS), total medication scores (TMS) and visual analogue scale(VAS) were assessed at the beginning, six months, 1 year and 2 years of the treatment. SPSS 13. 0 software was used to analyze the data. the score of TNSS and VAS in desensitization was slightly higher than the control after six months treatment, but without difference at l year and 2 years; the score of TMS had significantly improved in desensitization compared with the corresponding points in control. All the parameters in monosensitized group were equivalent with polysensitizend group, except the score of TMS was slightly lower than the polysensitizend group at six months. Dust mite drops sublingual immunotherapy is effective for the allergic rhinitis children caused by mites. And it has similar immunotherapy efficacy between monosensitized and polysensitized children.
Enker, W.E.; Jacobitz, J.L.; Craft, K.; Wissler, R.W.
One hundred forty-four Wistar-Furth rats in 12 therapeutic groups have been studied in a long-term comparison of the effectiveness of nonspecific immunotherapy with MER (methanol extraction residue) vs active-specific immunotherapy with neuraminidase-modified tumor cells. Six months after surgical adjuvant immunotherapy a 100% improvement in survival was achieved with MER immunotherapy compared to untreated control animals. In addition, the use of MER enhanced the value of active-specific immunotherapy where both modalities were combined in sequence. The predicted value of MER-BCG (Bacillus Calmette-Guerin) for the immunotherapy of solid tumors was borne out by these results suggesting that present ongoing clinical trials of MER as adjuvant therapy for large bowel cancer should prove to be successful if properly controlled. The pattern of survival in these experiments suggests that surgical adjuvant immunotherapy is cytostatic rather than cytocidal, and implies the need for long-term, repeated immunizations.
Full Text Available Getahun Abate,1 Daniel F Hoft1,2 1Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, 2Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO, USA Abstract: Tuberculosis (TB is still a major global health problem. A third of the world's population is infected with Mycobacterium tuberculosis. Only ~10% of infected individuals develop TB but there are 9 million TB cases with 1.5 million deaths annually. The standard prophylactic treatment regimens for latent TB infection take 3–9 months, and new cases of TB require at least 6 months of treatment with multiple drugs. The management of latent TB infection and TB has become more challenging because of the spread of multidrug-resistant and extremely drug-resistant TB. Intensified efforts to find new TB drugs and immunotherapies are needed. Immunotherapies could modulate the immune system in patients with latent TB infection or active disease, enabling better control of M. tuberculosis replication. This review describes several types of potential immunotherapies with a focus on those which have been tested in humans. Keywords: tuberculosis, HDT, immunotherapy, treatment
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
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
Kransdorf, M.J. [Saint Mary`s Hospital, Richmond, VA (United States). Dept. of Radiol.]|[Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States); Murphey, M.D. [Department of Radiologic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)]|[Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States)]|[Department of Radiology, School of Medicine, University of Maryland, Baltimore, Maryland (United States); Temple, H.T. [Department of Orthopedic Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia (United States)]|[Department of Orthopedic Pathology, Armed Forces Institute of Pathology, Washington, DC (United States)
Objective. Granuloma annulare is an uncommon benign inflammatory dermatosis characterized by the formation of dermal papules with a tendency to form rings. There are several clinically distinct forms. The subcutaneous form is the most frequently encountered by radiologists, with the lesion presenting as a superficial mass. There are only a few scattered reports of the imaging appearance of this entity in the literature. We report the radiologic appearance of five cases of subcutaneous granuloma annulare. Design and patients. The radiologic images of five patients (three male, two female) with subcutaneous granuloma annulare were retrospectively studied. Mean patient age was 6.4 years (range, 2-13 years). The lesions occurred in the lower leg (two), foot, forearm, and hand. MR images were available for all lesions, gadolinium-enhanced imaging in three cases, radiographs in four, and bone scintigraphy in one. Results. Radiographs showed unmineralized nodular masses localized to the subcutaneous adipose tissue. The size range, in greatest dimension on imaging studies, was 1-4 cm. MR images show a mass with relatively decreased signal intensity on all pulse sequences, with variable but generally relatively well defined margins. There was extensive diffuse enhancement following gadolinium administration. Conclusion. The radiologic appearance of subcutaneous granuloma annulare is characteristic, typically demonstrating a nodular soft-tissue mass involving the subcutaneous adipose tissue. MR images show a mass with relatively decreased signal intensity on all pulse sequences and variable but generally well defined margins. There is extensive diffuse enhancement following gadolinium administration. Radiographs show a soft-tissue mass or soft-tissue swelling without evidence of bone involvement or mineralization. This radiologic appearance in a young individual is highly suggestive of subcutaneous granuloma annulare. (orig.) With 3 figs., 17 refs.
Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto- Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD).
Pfaar, Oliver; Bachert, Claus; Bufe, Albrecht; Buhl, Roland; Ebner, Christof; Eng, Peter; Friedrichs, Frank; Fuchs, Thomas; Hamelmann, Eckard; Hartwig-Bade, Doris; Hering, Thomas; Huttegger, Isidor; Jung, Kirsten; Klimek, Ludger; Kopp, Matthias Volkmar; Merk, Hans; Rabe, Uta; Saloga, Joachim; Schmid-Grendelmeier, Peter; Schuster, Antje; Schwerk, Nicolaus; Sitter, Helmut; Umpfenbach, Ulrich; Wedi, Bettina; Wöhrl, Stefan; Worm, Margitta; Kleine-Tebbe, Jörg; Kaul, Susanne; Schwalfenberg, Anja
The present guideline (S2k) on allergen-specific immunotherapy (AIT) was established by the German, Austrian and Swiss professional associations for allergy in consensus with the scientific specialist societies and professional associations in the fields of otolaryngology, dermatology and venereology, pediatric and adolescent medicine, pneumology as well as a German patient organization (German Allergy and Asthma Association; Deutscher Allergie- und Asthmabund, DAAB) according to the criteria of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). AIT is a therapy with disease-modifying effects. By administering allergen extracts, specific blocking antibodies, toler-ance-inducing cells and mediators are activated. These prevent further exacerbation of the allergen-triggered immune response, block the specific immune response and attenuate the inflammatory response in tissue. Products for SCIT or SLIT cannot be compared at present due to their heterogeneous composition, nor can allergen concentrations given by different manufacturers be compared meaningfully due to the varying methods used to measure their active ingredients. Non-modified allergens are used for SCIT in the form of aqueous or physically adsorbed (depot) extracts, as well as chemically modified allergens (allergoids) as depot extracts. Allergen extracts for SLIT are used in the form of aqueous solutions or tablets. The clinical efficacy of AIT is measured using various scores as primary and secondary study endpoints. The EMA stipulates combined symptom and medication scores as primary endpoint. A harmonization of clinical endpoints, e. g., by using the combined symptom and medication scores (CSMS) recommended by the EAACI, is desirable in the future in order to permit the comparison of results from different studies. The current CONSORT recommendations from the ARIA/GA2LEN group specify standards for the
Wilson, D R; Nouri-Aria, K T; Walker, S M; Pajno, G B; O'Brien, F; Jacobson, M R; Mackay, I S; Durham, S R
Tissue eosinophilia and infiltration by T(H)2-type T cells are characteristic features of allergic rhinitis both after allergen challenge and during natural allergen exposure. Specific immunotherapy inhibits allergen-induced nasal eosinophilia. We sought to assess, in the context of a randomized trial, the relationships between symptomatic improvement after immunotherapy and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season. Nasal biopsy specimens were taken from 37 adults with severe summer hay fever at baseline (out of season) and at peak season after 2 years of treatment with a depot grass pollen extract or placebo. Biopsy specimens were processed for immunohistochemistry by using mAbs against eosinophils (EG2), T cells (CD3), and IL-2 receptor-positive cells (CD25), as well as for in situ hybridization by using a sulfur 35-labeled antisense riboprobe directed against IL-5. Immunotherapy significantly reduced symptoms (49%, P =.01) and medication requirements (80%, P =.007) compared with placebo. There was a 400% increase (P =.004) in eosinophils during the pollen season in placebo-treated patients, which was inhibited in the immunotherapy group (20% increase, P =.04 between groups). Seasonal increases were also observed for CD25(+) cells (P =.002), CD3(+) cells (P =.02), and IL-5 mRNA-expressing cells (P =.03) in the placebo group but not in the immunotherapy group. A significant correlation was observed between eosinophils and IL-5 expression (r = 0.5, P pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season.
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.
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
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.
Sookrung, Nitat; Chaicumpa, Wanpen
Among cockroaches (CR) that live in people's homes, two species, i.e., German CR (Blattella germanica) and American CR (Periplaneta americana) predominate in temperate and tropical areas, respectively. CR is an important source of inhalant indoor allergens that sensitize atopic subjects to (localized) type I hypersensitivity or atopy including allergic rhinitis and atopic asthma. In Thailand the predominant CR species is P. americana. CR allergens are found throughout CR infested houses; the number found in kitchens correlates with the degree of CR infestation while sensitization and reactivation of the allergic morbidity are likely to occur in the living room and bedroom. Levels of the CR allergens in homes of CR allergic Thais, measured by using locally made quantification test kits, revealed that the highest levels occur in dust samples collected from the wooden houses of urban slums and in the cool and dry season. CR allergens are proteins that may be derived from any anatomical part of the insect at any developmental stage. The allergens may be also from CR secretions, excretions, body washes or frass. The proteins may be the insect structural proteins, enzymes or hormones. They may exist as dimers/multimers and/or in different isoforms. Exposure to CR allergens in infancy leads to allergic morbidity later in life. Clinical symptoms of CR allergy are usually more severe and prolonged than those caused by other indoor allergens. The mechanisms of acute and chronic airway inflammation and airway hyper-responsiveness (AHR) have been addressed including specific IgE- and non-IgE-mediated mechanisms, i.e., role of protease-activated receptor-2 (PAR2). Participation of various allergen activated-CD4+ T cells of different sublineages, i.e., Th2, Th17, Th22, Th9, Th25, Tregs/Th3 as well as invariant NKT cells, in asthma pathogenesis have been mentioned. The diagnosis of CR allergy and the allergy intervention by CR population control are also discussed.
Crameri, R; Garbani, M; Rhyner, C; Huitema, C
Allergic diseases are considered the epidemics of the twentieth century estimated to affect more than 30% of the population in industrialized countries with a still increasing incidence. During the past two decades, the application of molecular biology allowed cloning, production and characterization of hundreds of recombinant allergens. In turn, knowledge about molecular, chemical and biologically relevant allergens contributed to increase our understanding of the mechanisms underlying IgE-mediated type I hypersensitivity reactions. It has been largely demonstrated that fungi are potent sources of allergenic molecules covering a vast variety of molecular structures including enzymes, toxins, cell wall components and phylogenetically highly conserved cross-reactive proteins. Despite the large knowledge accumulated and the compelling evidence for an involvement of fungal allergens in the pathophysiology of allergic diseases, fungi as a prominent source of allergens are still largely neglected in basic research as well as in clinical practice. This review aims to highlight the impact of fungal allergens with focus on asthma and atopic dermatitis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
of secreted, full length and immunologically active allergen. The L. lactis expression system can support recombinant allergen material for immunotherapy and component resolved allergen diagnostics.
Balaji, R; Parasuramalu, B G; Chandregowda, B V; Gangaboraiah
Conventional immunotherapy for allergy with 3-5 years of treatment period has poor compliance. Ultra-rush sublingual immunotherapy with a shorter period of treatment can have better compliance. There are very few studies on ultra-rush sublingual immunotherapy all over the world. (1) To determine allergen sensitivity among allergic rhinitis patients. (2) To assess safety, tolerability and clinical efficacy of ultra-rush sublingual immunotherapy. The present study was conducted in Allergy clinic, KIMS Hospital & Research Centre, Bangalore, India from January 2010 to June 2011. After obtaining Institutional Ethics Committee approval, 40 allergic rhinitis patients (according to ARIA guidelines) in the 18-60 years age group who were positive for aeroallergens in skin prick test were recruited for ultra-rush sublingual immunotherapy (20min initial phase and 4-month maintenance phase) and followed for 8 months with symptom and treatment diary. Out of 40 patients, the majority, 36 (90.00%) patients were sensitive to house dust mites. Six patients had seven immediate adverse reactions and seven patients had eight delayed adverse reactions. All subsided without medication or with symptomatic oral medications. All patients tolerated ultra-rush SLIT and there was significant decrease in both symptom-score and treatment received in these patients. Ultra-rush SLIT regimen has excellent safety, tolerability and clinical efficacy among allergic rhinitis patients. Copyright © 2012 SEICAP. Published by Elsevier Espana. All rights reserved.
Potiwat, Rutcharin; Sitcharungsi, Raweerat
Hypersensitivity reactions caused by ant stings are increasingly recognized as an important cause of death by anaphylaxis. Only some species of ants ( e.g. Solenopsis spp., Myrmecia spp., and Pachycondyla spp.) cause allergic reactions. Ant species are identified by evaluating the morphologic structures of worker ants or by molecular techniques. Ant venom contains substances, including acids and alkaloids, that cause toxic reactions, and those from Solenopsis invicta or the imported fire ant have been widely studied. Piperidine alkaloids and low protein contents can cause local reactions (sterile pustules) and systemic reactions (anaphylaxis). Imported fire ant venoms are cross-reactive; for example, the Sol i 1 allergen from S. invicta has cross-reactivity with yellow jacket phospholipase. The Sol i 3 allergen is a member of the antigen 5 family that has amino acid sequence identity with vespid antigen 5. The clinical presentations of ant hypersensitivity are categorized into immediate and delayed reactions: immediate reactions, such as small local reactions, large local reactions, and systemic reactions, occur within 1-4 hours after the ant stings, whereas delayed reactions, such as serum sickness and vasculitis, usually occur more than 4 hours after the stings. Tools for the diagnosis of ant hypersensitivity are skin testing, serum specific IgE, and sting challenge tests. Management of ant hypersensitivity can be divided into immediate (epinephrine, corticosteroids), symptomatic (antihistamines, bronchodilators), supportive (fluid resuscitation, oxygen therapy), and preventive (re-sting avoidance and immunotherapy) treatments.
Perica, Karlo; De León Medero, Andrés; Durai, Malarvizhi; Chiu, Yen Ling; Bieler, Joan Glick; Sibener, Leah; Niemöller, Michaela; Assenmacher, Mario; Richter, Anne; Edidin, Michael; Oelke, Mathias; Schneck, Jonathan
Artificial antigen presenting cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for both adoptive and active immunotherapy. Thus far, aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to micron-sized beads. Nanoscale platforms have different trafficking and biophysical interaction properties and may allow development of new immunotherapeutic strategies. We therefore manufactured aAPC based on two types of nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles (50-100 nm in diameter) and avidin-coated quantum dot nanocrystals (~30 nm). Nanoscale aAPC induced antigen-specific T cell proliferation from mouse splenocytes and human peripheral blood T cells. When injected in vivo, both iron-dextran particles and quantum dot nanocrystals enhanced tumor rejection in a subcutaneous mouse melanoma model. This is the first description of nanoscale aAPC that induce antigen-specific T cell proliferation in vitro and lead to effective T cell stimulation and inhibition of tumor growth in vivo. Artifical antigen presenting cells could revolutionize the field of cancer-directed immunotherapy. This team of investigators have manufactured two types of nanoscale particle platform-based aAPCs and demonstrates that both iron-dextran particles and quantum dot nanocrystals enhance tumor rejection in a melanoma model, providing the first description of nanoscale aAPCs that lead to effective T cell stimulation and inhibition of tumor growth. © 2013.
Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A
Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.
Bayless, Heather; Schneider, Susan
Although patients diagnosed with melanoma that is confined to the skin have a five-year survival rate of 98%, this number drops to 16% with widely metastatic disease. Melanoma rates have been steadily increasing since the 1970s, but cytotoxic chemotherapy generally prolongs survival by about four months. Nivolumab is an effective immunotherapy agent. This article discusses the use of nivolumab for metastatic melanoma. Clinical trial and early postmarketing data were reviewed. In clinical trials, patients with advanced melanoma experienced partial sustained responses to nivolumab, a new targeted immunotherapy agent, for more than one year. Nivolumab helps the immune system mobilize lymphocytes that have been inactivated by melanoma cells, enhancing the body's ability to recognize the cancer as abnormal. Compared to conventional chemotherapy, nivolumab has been shown to greatly improve survival in widespread, inoperable malignant melanoma. Oncology nurses will administer, monitor, and educate patients about nivolumab.
Jul 9, 2013 ... E-mail: firstname.lastname@example.org. Conflict of interest: None declared. SUMMARY. Basidiobolomycosis is an uncommon chronic deep fungal infection in which gradually enlarging granulomas form, usually in the subcutaneous fat tissues of the limbs, chest or trunk of immunocompetent hosts, primarily children.
Sep 8, 2012 ... department with a history of increasing difficulty with breathing and ... ward and commenced on intravenous antibiotics and high flow oxygen. He made remarkable improvement with complete resolution of subcutaneous emphysema on the 4th day ... the left lateral decubitus position.18 Our patient met most.
Full Text Available A case of subcutaneous phycomycosis occurring in a 2 ½ year old child is reported for its rarity, clinical interest and paucity of literature. The condition failed to resolve with conventional antimycotics but improved with the administration of concomitant pyrexial therapy.
Sep 8, 2012 ... to trauma or pathological disease state3, with gastroin- testinal and respiratory diseases most commonly impli- cated.4,5. The respiratory disease commonly associated with pneu- momediastinum and subcutaneous cervical emphysema is bronchial asthma.6 Pneumonia, though a very com- mon childhood ...
Ellebaek, Eva; Andersen, Mads Hald; Svane, Inge Marie
Although no immunotherapeutic treatment is approved for colorectal cancer (CRC) patients, promising results from clinical trials suggest that several immunotherapeutic strategies may prove efficacious and applicable to this group of patients. This review describes the immunogenicity of CRC...... and presents the most interesting strategies investigated so far: cancer vaccination including antigen-defined vaccination and dendritic cell vaccination, chemo-immunotherapy, and adoptive cell transfer. Future treatment options as well as the possibility of combining existing therapies will be discussed along...
Dharmadhikari, Neal; Mehnert, Janice M; Kaufman, Howard L
Melanoma is a type of skin cancer arising from melanocytes and is increasing in incidence. Although complete surgical excision of early stage lesions may be curative, metastatic melanoma continues to be a major therapeutic challenge. Advances in understanding the molecular pathways that promote tumorigenesis and the interactions between melanoma cells and the immune system have resulted in the approval of several newly targeted agents and immunotherapy strategies for the treatment of advanced disease. Oncolytic virus immunotherapy is a new approach that uses native or attenuated live viruses to selectively kill melanoma cells and induce systemic tumor-specific immune responses. A variety of viruses are now in clinical development with the attenuated oncolytic herpesvirus encoding granulocyte-macrophage colony stimulating factor, known as talimogene laherparepvec, recently demonstrating an improvement in durable response rate in patients with advanced melanoma compared with granulocyte-macrophage colony stimulating factor alone. A major advantage of talimogene laherparepvec and related agents is the limited toxicity and ability to use each individual tumor as a source of antigen to generate a highly specific antitumor immune response. These agents are easily administered in the out-patient setting and may be a reasonable option for patients with limited metastatic tumor burden, those with a good performance status and without extensive prior treatment, and in those who cannot tolerate more difficult therapeutic regimens. Further investigation into the impact on overall survival as monotherapy and combination of oncolytic virus immunotherapy with other forms of immunotherapy merit high priority for further clinical application of these novel agents for the treatment of melanoma and perhaps other cancers as well.
Jeong, Kyoung Yong
Arthropods are important in human health, which can transmit pathogens to humans, parasitize, or produce important allergens. Allergy prevalence becomes higher in Korea recently as well as other developed countries in contrast to a decrease of infectious diseases. Allergic diseases caused by household arthropods have increased dramatically during the last few decades since human beings spend more their time for indoor activities in modernized life style. Household arthropods are one of the most common causes of allergic diseases. Biological characterization of household arthropods and researches on their allergens will provide better understanding of the pathogenesis of allergic diseases and suggest new therapeutic ways. Therefore, studies on arthropods of allergenic importance can be considered one of the major research areas in medical arthropodology and parasitology. Here, the biology of several household arthropods, including house dust mites and cockroaches, the 2 most well known arthropods living indoor together with humans worldwide, and characteristics of their allergens, especially the research activities on these allergens performed in Korea, are summarized. PMID:19885330
Sainio, E L; Engström, K; Henriks-Eckerman, M L; Kanerva, L
It has been known since the 1940s that nail polishes contain allergenic ingredients. The aim of this study was to clarify whether the nail polishes on the market today contain significant amounts of allergens, and what the solvents are. The following ingredients were determined: toluene, toluene sulfonamide formaldehyde resins, free formaldehyde, acrylates, methacrylates and certain organic solvents. The study comprised 20 brands and 42 samples. All the nail polishes analysed contained allergenic toluene sulfonamide formaldehyde resins (TSFR), in concentrations from 0.08 to 11.0%. The concentration of total formaldehyde varied from 0.02% to 0.5%. The more TSFR a nail polish contained, the higher was its formaldehyde content. Probably not only TSFR-allergic but also formaldehyde-allergic persons may get dermatitis from many of the nail polishes studied. The concentrations of acrylates and methacrylates were so small that they are of practical significance only to those previously sensitized to acrylates. Of the organic solvents, toluene was still widely used, whereas xylene was found in only 1 product. The nail polishes on the market today are not safe for all consumers. However, according to the regulations of the European Union, the packaging labeling of all cosmetic products must be supplied with a list of ingredients from the beginning of 1998. This will help the consumer to avoid allergenic products. A better alternative could, however, be to substitute the most allergenic ingredients with substances possessing minor allergy potency.
Full Text Available 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.
Donald W Cockcroft
Full Text Available The allergen challenge has evolved, in less than 150 years, from a crude tool used to document the etiology of allergen-induced disease to a well-controlled tool used today to investigate the pathophysiology and pharmacotherapy of asthma. Highlights of the authors’ involvement with the allergen challenge include confirmation of the immunoglobulin E-dependence of the late asthmatic response, importance of (nonallergic airway hyper-responsiveness as a determinant of the airway response to allergen, identification of allergen-induced increase in airway hyper-responsiveness, documentation of beta2-agonist-induced increase in airway response to allergen (including eosinophilic inflammation, advances in understanding the pathophysiology and kinetics of allergen-induced airway responses, and development of a muticentre clinical trial group devoted to using the allergen challenge for investigating promising new therapeutic strategies for asthma.
Castro, Antonio Jesús; de Dios Alché, Juan; Cuevas, Julián; Romero, Pedro José; Alché, Víctor; Rodríguez-García, María Isabel
Commercial olive pollen from uncertain cultivar origin is the common material used for clinical and biological studies. We aimed to assess the putative heterogeneity of olive cultivars with regard to the presence of the major pollen allergen Ole e 1 and to determine whether these differences have clinical relevance. The Ole e 1 content of several cultivars was determined by immunoblotting and ultrastructural immunocytochemistry and compared to that of a commercially available olive pollen extract designed for diagnosis. Reverse transcription-polymerase chain reaction analysis of Ole e 1 transcripts was also performed. Crude protein extracts were used to carry out skin prick tests (SPTs) on 30 allergic patients in order to evaluate the clinical importance of such differences. Ole e 1 was present in all cultivars, although significant quantitative differences were detected. Ole e 1 transcripts positively correlated with the amount of the allergen. Significant variations in the average reactivity of allergic patients to SPTs were observed depending on the cultivar considered. The presence of the Ole e 1 allergen in all the cultivars suggests that this allergen may play an essential biological role. The expression of the allergen is controlled at the transcriptional level. The significant differences in the Ole e 1 content are likely responsible for the different average reactivity exhibited by patients to the cultivars studied, although the role of other allergens cannot be excluded. Our results suggest that the use of the commercial pollen mixtures currently available may lead to mistakes in allergy diagnosis and to limited success in immunotherapy. Therefore, further standardization is strongly recommended. Copyright 2003 S. Karger AG, Basel
Twaroch, T. E.; Focke, M.; Fleischmann, K.; Balic, N.; Lupinek, C.; Blatt, K.; Ferrara, R.; Mari, A.; Ebner, C.; Valent, P.; Spitzauer, S.; Swoboda, I.; Valenta, R.
Background The mould Alternaria alternata is a major elicitor of allergic asthma. Diagnosis and specific immunotherapy (SIT) of Alternaria allergy are often limited by the insufficient quality of natural mould extracts. Objective To investigate whether recombinant Alt a 1 can be used for reliable diagnosis of Alternaria alternata allergy and to develop a safe, non-allergenic vaccine for SIT of Alternaria allergy. Methods The qualitative sensitization profile of 80 Alternaria-allergic patients from Austria and Italy was investigated using an allergen micro-array and the amount of Alternaria-specific IgE directed to rAlt a 1 was quantified by ImmunoCAP measurements. Peptides spanning regions of predicted high surface accessibility of Alt a 1 were synthesized and tested for IgE reactivity and allergenic activity, using sera and basophils from allergic patients. Carrier-bound peptides were studied for their ability to induce IgG antibodies in rabbits which recognize Alt a 1 and inhibit allergic patients’ IgE reactivity to Alt a 1. Results rAlt a 1 allowed diagnosis of Alternaria allergy in all tested patients, bound the vast majority (i.e. >95%) of Alternaria-specific IgE and elicited basophil activation already at a concentration of 0.1 ng/mL. Four non-allergenic peptides were synthesized which, after coupling to the carrier protein keyhole limpet hemocyanin, induced Alt a 1-specific IgG and inhibited allergic patients’ IgE binding to Alt a 1. Conclusions and clinical relevance rAlt a 1 is a highly allergenic molecule allowing sensitive diagnosis of Alternaria allergy. Carrier-bound non-allergenic Alt a 1 peptides are candidates for safe SIT of Alternaria allergy. PMID:22909168
Full Text Available Allergic reactions can be considered as maladaptive IgE immune responses towards environmental antigens. Intriguingly, these mechanisms are observed to be very similar to those implicated in the acquisition of an important degree of immunity against metazoan parasites (helminths and arthropods in mammalian hosts. Based on the hypothesis that IgE-mediated immune responses evolved in mammals to provide extra protection against metazoan parasites rather than to cause allergy, we predict that the environmental allergens will share key properties with the metazoan parasite antigens that are specifically targeted by IgE in infected human populations. We seek to test this prediction by examining if significant similarity exists between molecular features of allergens and helminth proteins that induce an IgE response in the human host. By employing various computational approaches, 2712 unique protein molecules that are known IgE antigens were searched against a dataset of proteins from helminths and parasitic arthropods, resulting in a comprehensive list of 2445 parasite proteins that show significant similarity through sequence and structure with allergenic proteins. Nearly half of these parasite proteins from 31 species fall within the 10 most abundant allergenic protein domain families (EF-hand, Tropomyosin, CAP, Profilin, Lipocalin, Trypsin-like serine protease, Cupin, BetV1, Expansin and Prolamin. We identified epitopic-like regions in 206 parasite proteins and present the first example of a plant protein (BetV1 that is the commonest allergen in pollen in a worm, and confirming it as the target of IgE in schistosomiasis infected humans. The identification of significant similarity, inclusive of the epitopic regions, between allergens and helminth proteins against which IgE is an observed marker of protective immunity explains the 'off-target' effects of the IgE-mediated immune system in allergy. All these findings can impact the discovery and
Tao, Ai-lin; He, Shao-heng
To clone the pollen allergen genes in Humulus scandens (Lour) Merr (LvCao in Chinese) and short ragweed (Ambrosia artemisiifolia L) for recombinant allergen production and immunotherapy. The allergen genes were selectively amplified in the weed pollen cDNA pool by using a special PCR profile, with the primers designed by a modeling procedure. Following truncated gene cloning and confirmation of the pollen source, unknown 3'cDNA ends were identified by using the 3'-RACE method. The gene function conferred by the full-length coding region was evaluated by a homologue search in the GenBank database. Recombinant proteins expressed in Escherichia coli pET-44 RosettaBlue cells were subsequently characterized by N-terminal end sequencing, IgE binding, and cross-reactivity. Three full-length cDNAs were obtained in each weed. Multiple alignment analysis revealed that the deduced amino acid sequences were 83% identical to each other and 56%-90% identical to panallergen profilins from other species. Five recombinant proteins were abundantly expressed in non-fusion forms and were confirmed by using the N-terminal end sequence identity. Sera from patients who were allergic to A artemisiifolia reacted not only with rAmb a 8(D03) derived from A artemisiifolia, but also with recombinant protein rHum s 1(LCM9) derived from H scandens, which confirmed the allergenicity and cross-reactivity of the recombinant proteins from the 2 sources. Comparison of the degenerate primers used for truncated gene cloning with the full-length cDNA demonstrated that alternative nucleotide degeneracy occurred. This study demonstrates a useful method for cloning homologous allergen genes across different species, particularly for little-studied species. The recombinant allergens obtained might be useful for the immunotherapeutic treatment of H scandens and/or A artemisiifolia pollen allergies.
Jonsdottir, S; Svansson, V; Stefansdottir, S B; Mäntylä, E; Marti, E; Torsteinsdottir, S
Insect bite hypersensitivity is an immunoglobulin (Ig)E-mediated dermatitis of horses initiated by bites of midges of the genus Culicoides. Culicoides spp. are not indigenous to Iceland and the prevalence of insect bite hypersensitivity is much higher in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. Immunotherapy is therefore needed. The aim of the study was to express an allergen from Culicoides in barley grain and investigate whether an immune response could be obtained in healthy Icelandic horses by oral treatment with transgenic barley expressing the allergen. In vivo experiment. The allergen was expressed in barley grain with the Orfeus technique. A device was developed to treat horses orally with barley flour. Four Icelandic horses were treated with transgenic barley and 3 with control barley, in total 500 g in 7 feedings. Serum and saliva samples were collected for measuring specific antibodies. The allergen Cul n 2, a hyaluronidase originating from the salivary gland of Culicoides nubeculosus, was expressed in barley. Horses treated with the transgenic barley mounted a Cul n 2 specific IgG1 and IgG4/7 response in serum and saliva. The serum response was significantly different between the transgenic and control barley treated horses for both subclasses and the saliva response for IgG1. The induced serum antibodies bound to the corresponding allergen from Culicoides obsoletus, rCul o 2 and were able to partially block binding of Cul n 2 as well as Cul o 2 specific IgE from insect bite hypersensitivity affected horses. Small number of horses. This study shows that specific antibody response can be induced in horses not exposed to Culicoides, using oral treatment with transgenic barley expressing an allergen. Further studies will determine whether this approach is a useful alternative for prevention and treatment of equine insect bite hypersensitivity. © 2016 EVJ Ltd.
Full Text Available Background: The prevalence of allergic diseases has risen in the last decades. The objective of this study was to determine the common allergens in children via the skin prick test. Methods: This cross-sectional study recruited 313 allergic children (4 months to 18 years old referred to the Asthma and Allergy Clinic of Children’s Medical Center in Tehran. A questionnaire containing demographic data and patient history was completed. The Skin Prick Test (SPT was selected according to the patients’ history of food and/or aeroallergen sensitivity. Results: Patients (62.4% male, 37.6% female with symptoms of asthma (n=141, 57.1%, allergic rhinitis (n=50, 20.4%, atopic dermatitis (n=29, 11.7%, and urticaria (n=20, 8.1% were studied. Positive skin prick test to at least one allergen was 58.1%. The most prevalent allergens were tree mix (26%, Alternaria alternata (26%, weed mix (23.6%, Dermatophagoides farinae (22.9%, Dermatophagoides pteronyssinus (22.9%, milk (21.7%, eggs (20%, and wheat flour (18.3%. Also, common allergens in the patients with different symptoms of allergic disorders were as follows: asthma (tree mix, weed mix, and Dermatophagoides farinae; allergic rhinitis (Dermatophagoides farinae, tree mix, and Dermatophagoides pteronyssinus; and atopic dermatitis (Alternaria alternata, Dermatophagoides pteronyssinus, and cockroaches. Conclusion: Identifying allergens in each area is necessary and has an important role in the diagnosis and management of allergic disorders and possibility of performing immunotherapy. In this study, the most common aeroallergens were tree mix, Alternaria alternata, and weed mix and also the most common food allergens were milk, eggs, and wheat. Considering these data, appropriate preventive strategies can decrease the cost and morbidity of therapeutic actions.
Bondì, Maria Luisa; Montana, Giovanna; Craparo, Emanuela Fabiola; Di Gesù, Roberto; Giammona, Gaetano; Bonura, Angela; Colombo, Paolo
Parietaria pollen is one of the major causes of allergic reaction in southern Europe, affecting about 30% of all allergic patients in this area. Specific immunotherapy is the only treatment able to modify the natural outcome of the disease by restoring a normal immunity against allergens. The preparation of allergen-solid lipid nanoparticles as delivery vehicles for therapeutic proteins, P. judaica major allergen Par j 2, was investigated. The Par j 2 allergen was expressed in a large amount in Escherichia coli and purified to homogeneity. Its immunological properties were studied by western blotting and enzyme-linked immunosorbent assay inhibition. Solid lipid nanoparticles were obtained by water-in-oil-in-water multiple emulsion method and characterized in terms of mean size and surface charge. These systems (approximately 250 nm diameter and negative surface charge) incorporated recombinant Par j 2 with 40% or greater efficiency. Moreover, the endotoxin level and anaphylactic activity of the empty solid lipid nanoparticles and recombinant Par j 2-loaded solid lipid nanoparticles were evaluated by looking at the overexpression of CD203c marker on human basophils. These results demonstrate that recombinant Par j 2-nanoparticles could be proposed as safe compositions for the development of new therapeutic dosage forms to cure allergic reactions.
Ciprandi, Giorgio; De Amici, Mara; Tosca, Mariangela; Marseglia, Gianluigi
Allergic rhinitis (AR) is characterized by inflammation sustained by dysregulated immune response. T-regulatory cells are involved in AR pathogenesis, mainly producing IL-10 and transforming growth factor (TGF)-beta. Indeed, there is a functional and allergen-specific defect of T-regulatory cells in AR. However, there are no data about the influence of allergen exposure on TGF-beta serum levels. Therefore, the aim of this preliminary study was to evaluate TGF-beta serum levels in patients with seasonal AR. Patients were evaluated either outside the pollen season and after 1 preseasonal sublingual immunotherapy (SLIT) course (38 subjects) or during the pollen season (57 subjects). All patients were allergic to Parietaria and/or grasses alone. TGF-beta was measured by a commercially available kit. Symptoms, drug use and eosinophils were evaluated.Serum allergen-specific IgG and IgA levels were also measured by the ELISA method. TGF-beta serum levels were significantly lower in patients evaluated outside the pollen season in comparison with the other 2 situations. SLIT induced the significantly highest TGF-beta serum levels. There was a significant negative relationship between TGF-beta and eosinophils in patients after SLIT. IgG and IgA levels were higher in SLIT-treated patients. This preliminary study provides evidence that TGF-beta serum levels are significantly dependent on allergen exposure. Copyright 2009 S. Karger AG, Basel.
Burton, Bronwen R; Britton, Graham J; Fang, Hai; Verhagen, Johan; Smithers, Ben; Sabatos-Peyton, Catherine A; Carney, Laura J; Gough, Julian; Strobel, Stephan; Wraith, David C
Antigen-specific immunotherapy combats autoimmunity or allergy by reinstating immunological tolerance to target antigens without compromising immune function. Optimization of dosing strategy is critical for effective modulation of pathogenic CD4(+) T-cell activity. Here we report that dose escalation is imperative for safe, subcutaneous delivery of the high self-antigen doses required for effective tolerance induction and elicits anergic, interleukin (IL)-10-secreting regulatory CD4(+) T cells. Analysis of the CD4(+) T-cell transcriptome, at consecutive stages of escalating dose immunotherapy, reveals progressive suppression of transcripts positively regulating inflammatory effector function and repression of cell cycle pathways. We identify transcription factors, c-Maf and NFIL3, and negative co-stimulatory molecules, LAG-3, TIGIT, PD-1 and TIM-3, which characterize this regulatory CD4(+) T-cell population and whose expression correlates with the immunoregulatory cytokine IL-10. These results provide a rationale for dose escalation in T-cell-directed immunotherapy and reveal novel immunological and transcriptional signatures as surrogate markers of successful immunotherapy.
Full Text Available Fish is a common trigger of severe, food-allergic reactions. Only a limited number of proteins induce specific IgE-mediated immune reactions. The major fish allergens are the parvalbumins. They are members of the calcium-binding EF-hand protein family characterized by a conserved protein structure. They represent highly cross-reactive allergens for patients with specific IgE to conserved epitopes. These patients might experience clinical reactions with various fish species. On the other hand, some individuals have IgE antibodies directed against unique, species-specific parvalbumin epitopes, and these patients show clinical symptoms only with certain fish species. Furthermore, different parvalbumin isoforms and isoallergens are present in the same fish and might display variable allergenicity. This was shown for salmon homologs, where only a single parvalbumin (beta-1 isoform was identified as allergen in specific patients. In addition to the parvalbumins, several other fish proteins, enolases, aldolases and fish gelatin, seem to be important allergens.New clinical and molecular insights advanced the knowledge and understanding of fish allergy in the last years. These findings will be useful for the advancement of the IgE-based diagnosis but also for the management of fish allergies consisting of advice and treatment of fish-allergic patients.
Bożek, Andrzej; Kołodziejczyk, Krzysztof
Specific allergen immunotherapy to Hymenoptera venom (VIT) is a basic treatment for patients allergic to Hymenoptera venom. The aim of the study was to evaluate the safety of an ultra-rush regimen compared with the rush and conventional protocols. In 31 patients with an allergy to bee venom and 82 with an allergy to wasp venom, the allergic adverse reactions during VIT were monitored. Patients were selected based on the criteria established by EAACI (European Academy of Allergy and Clinical Immunology) recommendations. Adverse reactions during the ultra-rush immunotherapy were measured, documented and classified according to the criteria of Mueller. Ultra-rush, rush or conventional protocols of the initial phase VIT using the Venomenhal vaccine (Hal Allergy, Leiden, Netherlands) were conducted. Six (13.7%) patients on the ultra-rush regimen, 5 (14.3%) patients on the rush regimen and 9 (26.5%) on conventional VIT experienced an allergic reaction. There were no associations between the adverse allergic reactions and the following factors: gender, total IgE and allergen-specific IgE to wasp or bee venom before the VIT and cardiological drugs that were used. We found that the ultra-rush protocol (similar to the rush protocol) using the Venomenhal vaccine is safer than the conventional protocol.
Chen, David Lk; Cohen, Joel L; Green, Jeremy B
Mesotherapy is an intradermal or subcutaneous injection of therapeutic agents to induce local effects, and was pioneered in Europe during the 1950s. For the past 2 decades, there has been significant interest in the use of mesotherapy for minimally invasive local fat contouring. Based on the theorized lipolytic effects of the agent phosphatidylcholine, initial attempts involved its injection into subcutaneous tissue. With further studies, however, it became apparent that the activity attributed to phosphatidylcholine mesotherapy was due to the adipolytic effects of deoxycholate, a detergent used to solubilize phosphatidylcholine. Since then, clinical trials have surfaced that demonstrate the efficacy of a proprietary formulation of deoxycholate for local fat contouring. Current trials on mesotherapy with salmeterol, a b-adrenergic agonist and lipolysis stimulator, are underway-with promising preliminary results as well. ©2015 Frontline Medical Communications.
Gonda, Shaun J; Li, Ruizong
The introduction of totally implantable subcutaneous devices in the early 1980s provided patients with secure, reliable venous access and also gave them the ability to move more freely and have a more normal lifestyle with these devices in place. The most common totally implantable device used today is the subcutaneous port. These ports consist of an injection port connected to a catheter. Ports provide a number of advantages compared with other venous catheters; the most important is the reduced risk of infection. These devices have significantly lower rates of infection than nontunneled and tunneled catheters. Additional advantages include less frequent irrigation and minimal home care, and they are less prone to environmental or cutaneous contamination when not being accessed. This article will focus on the placement of these ports. Copyright © 2011 Elsevier Inc. All rights reserved.
Spontaneous subcutaneous accumulations of air in the soft parts of the thorax during an asthmatic crisis (status asthmaticus) are rarely seen. The pathomechanism of the phenomenon, which may lead to the formation of an emphysema of the soft parts via the pneumomediastinum, is discussed, and the possible complications which must be taken into account are pointed out. The value of radiological examination of the thorax in children suffering from asthma bronchiale, is explained briefly. (orig.).
Sener, R. Nuri [Department of Radiology, Ege University Hospital, Bornova, Izmir (Turkey)
A unique case of idiopathic diffuse lipomatosis is reported. The patient was an 11-year-old boy with diffuse lipomatosis in the epidural space, paraspinal muscles, and thoracolumbar subcutaneous regions. Epidural lipomatosis involved the entire thoracolumbar spine and was associated with filar thickening and lipoma. In addition, paraspinal muscles, especially the erector spinae group, had diffuse fatty infiltration. The ultimate clinical effect of this fatty tissue was urinary dysfunction, radicular pain and hypoesthesia in both legs and difficulty walking. (orig.)
Larenas-Linnemann, Désirée E S; Gupta, Payel; Mithani, Sima; Ponda, Punita
Practical issues dealing with the administration of allergen immunotherapy (AIT) by European and US allergists are not well known. Several concerns are only partially covered by guidelines. To survey AIT practice patterns among worldwide members of the American Academy of Allergy, Asthma and Immunology (AAAAI). A web-based survey was conducted among AAAAI members on dosing, dose adjustment after missed doses, and duration of AIT. A total of 1,201 replies (24.7% response rate of which 10% of responses were from non-US and non-Canada members). A total of 57% to 65% of the US-Canadian dosing falls within the recommended Practice Parameter ranges (9.4%-19% too low). Dose adjustment after missed doses is based on time elapsed since the last administered dose by 77% of US-Canadian and 58% of non-US-Canadian allergists. Doses are reduced when a patient comes in more than 14 days for 5 weeks after the last administration and initial dosing restarted after more than 30 days for 12 weeks since last administration during the build-up or maintenance stage. After missing 1 to 3 doses, the dosing schedules were mostly followed (build-up phase: repeat last dose, reduce by 1 dose, reduce by 2doses; maintenance phase: reduce by 1 dose, reduce by 2 doses, reduce by 3 doses). AIT is prescribed for a median of 3 years by non-US-Canadian allergists but for a median of 5 years by 75% of US-Canadian allergists. Main reasons for continuing beyond 5 years were "after stopping, symptoms reappeared" or "patient afraid to relapse." Many patients receive less than recommended doses. Two areas in which to plan further research are establishment of an optimal dose-adjustment plan for missed applications and exploration of the maximum appropriate duration of immunotherapy. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Immunotherapy has been established as a groundbreaking approach to treat cancer. It involves modulation of the host’s immune response to fight cancer. This is achieved by either enhancing tumor-specific T cell responses or inhibition of the tumor-induced immune suppression. Immunotherapy, however
Ciprandi, G; Cadario, G; Valle, C; Ridolo, E; Verini, M; Di Gioacchino, M; Minelli, M; Gangemi, S; Sillano, V; Colangelo, C; Pravettoni, V; Pellegrino, R; Borrelli, P; Fiorina, A; Carosso, A; Gasparini, A; Riario-Sforza, G G; Incorvaia, C; Puccinelli, P; Scurati, S; Frati, F
Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients. To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis. We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer). The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P < .01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44. This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.
Mills, E N; Jenkins, J; Marigheto, N; Belton, P S; Gunning, A P; Morris, V J
The cupin family comprises a family of proteins possessing a common beta-barrel structure that is thought to have originated in a prokaryotic ancestor. This structural motif is found as a single domain in fungal spherulins, fern sporulins and the germins/oxalate oxidase proteins of plants, while the globular storage proteins of plants, called legumins (11 S) and euvicilins (7 S), are two-domain cupins. The 11 S globulins are hexameric heteroligomeric proteins of M (r) approximately 360000, with each subunit comprising an acidic 30000-40000- M (r) polypeptide that is disulphide-linked to a 20000- M (r) basic polypeptide. A number of cupins have been identified as major plant food allergens, including the 7 S globulins of soybean (beta-conglycinin), peanut (conarachin; Ara h 1), walnut (Jug r 2) and lentil, and the 11 S globulins of peanut (arachin; Ara h 3), soybean (glycinin) and possibly also coconut and walnut. Other members of the cupin superfamily have not been identified as allergens, with the exception of one germin (germination-specific protein) from pepper. Cupins are generally very stable proteins. A summary of our current knowledge of allergenic seed storage globulins will be presented, together with an overview of cupin structure and stability properties, as illustrated by the allergenic soya globulins, glycinin and beta-conglycinin.
Naylor, Mark; Li, Xiaosong; Hode, Tomas; Alleruzzo, Lu; Raker, Joseph; Lam, Siu Kit; Zhou, Feifan; Chen, Wei
Immunologically oriented therapy (immunotherapy) has arguably proved to be the most effective method for treating advanced melanoma, the prototypical chemotherapy-resistant solid tumor. The efficacy and benefit of immunotherapy for other tumors, including those that are at least partly responsive to chemotherapy, is less well established. Breast cancer, one of the most common of the solid tumors in humans, is partially responsive to traditional chemotherapy. We believe that breast cancer patients, like melanoma patients, will benefit from the application of immunotherapy techniques. Here we review the different forms of laser immunotherapy (LIT), a key type of immunologically oriented therapy, discuss its use in melanoma and in breast cancer, and discuss its potentially pivotal role in the immunotherapy armamentarium.
Bonura, A; Corinti, S; Artale, A; Di Felice, G; Amoroso, S; Melis, M; Geraci, D; Colombo, P
Allergy is an immunological disorder affecting about 25% of the population living in the industrialized countries. Specific immunotherapy is the only treatment with a long-lasting relief of allergic symptoms and able to reduce the risk of developing new allergic sensitizations and inhibiting the development of clinical asthma in children treated for allergic rhinitis. By means of DNA recombinant technology, we were able to design a head to tail dimer expressing disulphide bond variants of the major allergen of the Parietaria pollen. IgE binding activity was studied by Western blot, ELISA inhibition assays and the skin prick test. T cell recognition was studied by peripheral blood mononuclear cell proliferation. The immunogenicity of the hybrid was studied in a mouse model of sensitization. In vitro and in vivo analysis showed that the disruption of specific cysteine residues in both allergens caused a strong reduction in IgE binding activity of the PjEDcys hybrid. In addition,we were able to show that a reduction in the IgE epitope content profoundly reduced the anaphylactic activity of the hybrid (from 100 to 1,000 times less than wild-type allergens) without interfering with the T cell recognition. Sera from BALB/c mice immunized with the hybrid were able to bind the natural Parietaria allergens and to inhibit the binding of human IgE to wild-type Par j 1 and Par j 2 allergens up to 90%. Our results demonstrate that hybrid-expressing disulphide bond variants of the major allergens of the Parietaria pollen displayed reduced allergenicity and maintained T cell reactivity for induction of protective antibodies.
Sørensen, Anja Elaine; Johnsen, Claus R; Dalgaard, Louise Torp
Background: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing...... of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4...... with pollen extract in vitro and immune factors were evaluated. Results: During SIT, the main changes in the peripheral blood were an increase in CXCR3+CD4+CD25+CD127low/- Tregs and a decrease in CCR4+CD4+CD25+CD127low/- Tregs, an increase in allergen-specific IgG4, and a decrease in sHLA-G during the first...
Gato, M; Liechtenstein, T; Blanco-Luquín, I; Zudaire, M I; Kochan, G; Escors, D
Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are still first line treatments. Even so, there is a quantity of experimental evidence demonstrating that cancer cells are immunogenic. However, the effective activation of anti-cancer T cell responses closely depends on an efficient antigen presentation carried out by professional antigen presenting cells such as DC. Although there are a number of strategies to strengthen antigen presentation by DC, anti-cancer immunotherapy is not as effective as we would expect according to preclinical data accumulated in recent decades. We do not aim to make an exhaustive review of DC immunotherapy here, which is an extensive research subject already dealt with in many specialised reviews. Instead, we present the experimental approaches undertaken by our group over the last decade, by modifying DC to improve their anti-tumour capacities.
Fuchimoto, S; Orita, K
Metastasis is one of the great characteristics of malignant tumors. On the basis of our data, we reported here the immunotherapy for hematogenous metastasis. A randomized controlled study of preoperative transendoscopic intratumoral injection of BRM into gastro-intestinal cancer, which was performed in our Department, revealed a decreasing tendency of distant metastases in lymph node for the injection group, suggesting the disappearance of micro-metastasis due to the injection, namely, systemic immuno-enhancement due to the local effect, leading to diminution of hematogenous metastasis. Next, a mixture of natural human TNF-alpha (nHuTNF-alpha) and natural human IFn-alpha(nHuIFN-alpha), the so-called OH-1, was described. The results of a clinical study dealing with the antitumor effect on advanced and recurrent malignant tumors made it clear that all of the effective results (72 cases) such as CR and PR were obtained by an administration schedule with a maintenance dose of more than 200 X 10(4)U; rate of efficacy was 19.4% (4 cases of CR, 10 of PR and 4 of MR). By disease, breast cancer, renal cancer and liver cancer evidenced the most remarkable effects. Examination of the antitumor effect by metastatic organ revealed the effectiveness on hematogenous metastasic tumor of lung, bone and liver, though dependent upon underlying diseases. Finally, being based on our in vitro and in vivo results, we discussed the role of these immunotherapies for metastatic tumors.
Bakker, Emyr; Guazzelli, Alice; Ashtiani, Firozeh; Demonacos, Constantinos; Krstic-Demonacos, Marija; Mutti, Luciano
Mesothelioma is a rare type of cancer that is strongly tied to asbestos exposure. Despite application of different modalities such as chemotherapy, radiotherapy and surgery, patient prognosis remains very poor and therapies are ineffective. Much research currently focuses on the application of novel approaches such as immunotherapy towards this disease. Areas covered: The types, stages and aetiology of mesothelioma are detailed, followed by a discussion of the current treatment options such as radiotherapy, surgery, and chemotherapy. A description of innate and adaptive immunity and the principles and justification of immunotherapy is also included. Clinical trials for different immunotherapeutic modalities are described, and lastly the article closes with an expert commentary and five-year view, the former of which is summarised below. Expert commentary: Current efforts for novel mesothelioma therapies have been limited by attempting to apply treatments from other cancers, an approach which is not based on a solid understanding of mesothelioma biology. In our view, the influence of the hostile, hypoxic microenvironment and the gene expression and metabolic changes that resultantly occur should be characterised to improve therapies. Lastly, clinical trials should focus on overall survival rather than surrogate endpoints to avoid bias and inaccurate reflections of treatment effects.
Sheehan, William J.; Phipatanakul, Wanda
Purpose of review The aim of the present review is to discuss updates on research regarding the relationship between indoor allergen exposure and childhood asthma with a focus on clinical effects, locations of exposure, and novel treatments. Recent findings Recent data continue to demonstrate that early life sensitization to indoor allergens is a predictor of asthma development later in life. Furthermore, avoidance of exposure to these allergens continues to be important especially given that the vast majority of children with asthma are sensitized to at least one indoor allergen. New research suggests that mouse allergen, more so than cockroach allergen, may be the most relevant urban allergen. Recent evidence reminds us that children are exposed to clinically important levels of indoor allergens in locations away from their home, such as schools and daycare centers. Exposure to increased levels of indoor mold in childhood has been associated with asthma development and exacerbation of current asthma; however, emerging evidence suggests that early exposure to higher fungal diversity may actually be protective for asthma development. Novel treatments have been developed that target TH2 pathways thus decreasing asthmatic responses to allergens. These therapies show promise for the treatment of severe allergic asthma refractory to avoidance strategies and standard therapies. Summary Understanding the relationship between indoor allergens and asthma outcomes is a constantly evolving study of timing, location, and amount of exposure. PMID:27653703
Cvitanović, S; Zekan, L; Capkun, V; Marusić, M
The effects of specific hyposensitization in 40 patients with Parietaria officinalis-sensitive seasonal rhinoconjunctivitis were studied during three years of treatment. The patients were treated with subcutaneous injections of a new, partially purified, characterized and standardized pollen extract of P. officinalis allergen (alum-absorbed depot preparation). Treatment was applied from November to mid March and it was clinically assessed during the plant flowering season (mid March to end of June). Laboratory tests were performed yearly when beginning and ending treatment. Serum concentrations of P. officinalis pollen allergen-specific IgE antibodies decreased (first year: from 18.7 +/- 7.7 to 17.9 +/- 7.6 PRU/ml; second year: from 16.3 +/- 7.1 to 14.1 +/- 6.6 PRU/ml; third year: from 12.3 +/- 5.6 to 10.9 +/- 5.6 PRU/ml) and those of specific IgG increased (first year: from 15.3 +/- 13.2 to 21.7 +/- 14.0%; second year: from 28.5 +/- 13.0 to 36.3 +/- 15.9%; third year: from 29.9 +/- 14.1 to 38.9 +/- 16.8%) during the treatment. Histamine release from peripheral blood leukocytes challenged in vitro with the allergen decreased during the three years of the treatment (first year: from 42.3 +/- 13.0 to 33.1 +/- 10.8%; second year: from 31.9 +/- 11.9 to 19.1 +/- 8.5%; third year: from 19.4 +/- 4.6 to 14.3 +/- 4.6%), whereas the size of skin test reaction and the percentage of eosinophils among white blood cells remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Wang, Shuyi; Takahashi, Hideyuki; Kajiura, Hiroyuki; Kawakatsu, Taiji; Fujiyama, Kazuhito; Takaiwa, Fumio
A versatile hypoallergenic allergen derivative against multiple allergens is an ideal tolerogen for allergen-specific immunotherapy. Such a tolerogen should exhibit high efficacy, without side effects, when administered at high doses and should be applicable to several allergens. Tree pollen chimera 7 (TPC7), a hypoallergenic Bet v 1 tolerogen against birch pollen allergy, was previously selected by DNA shuffling of 14 types of Fagales tree pollen allergens. In this study, transgenic rice seed accumulating TPC7 was generated as an oral vaccine against birch pollen allergy by expressing this protein as a secretory protein using the N-terminal signal peptide and the C-terminal KDEL tag under the control of an endosperm-specific glutelin promoter. The highest level of TPC7 accumulation was approximately 207 µg grain(-1). Recombinant TPC7 is a glycoprotein with high mannose-type N-glycan, but without β1,2-xylose or α1,3-fucose, suggesting that TPC7 is retained in the endoplasmic reticulum (ER). TPC7 is deposited as a novel, giant spherical ER-derived protein body, >20 µm in diameter, which is referred to as the TPC7 body. Removal of the KDEL retention signal or mutation of a cysteine residue resulted in an alteration of TPC7 body morphology, and deletion of the signal peptide prevented the accumulation of TPC7 in rice seeds. Therefore, the novel TPC7 bodies may have formed aggregates within the ER lumen, primarily due to the intrinsic physicochemical properties of the protein.
Burton, Oliver T; Tamayo, Jaciel M; Stranks, Amanda J; Koleoglou, Kyle J; Oettgen, Hans C
Patients with food allergy produce high-titer IgE antibodies that bind to mast cells through FcεRI and trigger immediate hypersensitivity reactions on antigen encounter. Food-specific IgG antibodies arise in the setting of naturally resolving food allergy and accompany the acquisition of food allergen unresponsiveness in oral immunotherapy. In this study we sought to delineate the effects of IgG and its inhibitory Fc receptor, FcγRIIb, on both de novo allergen sensitization in naive animals and on established immune responses in the setting of pre-existing food allergy. Allergen-specific IgG was administered to mice undergoing sensitization and desensitization to the model food allergen ovalbumin. Cellular and molecular mechanisms were interrogated by using mast cell- and FcγRIIb-deficient mice. The requirement for FcγRII in IgG-mediated inhibition of human mast cells was investigated by using a neutralizing antibody. Administration of specific IgG to food allergy-prone IL4raF709 mice during initial food exposure prevented the development of IgE antibodies, TH2 responses, and anaphylactic responses on challenge. When given as an adjunct to oral desensitization in mice with established IgE-mediated hypersensitivity, IgG facilitated tolerance restoration, favoring expansion of forkhead box protein 3-positive regulatory T cells along with suppression of existing TH2 and IgE responses. IgG and FcγRIIb suppress adaptive allergic responses through effects on mast cell function. These findings suggest that allergen-specific IgG antibodies can act to induce and sustain immunologic tolerance to foods. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Drew, Alexander C; Davies, Janet M; Dang, Thanh D; Rolland, Jennifer M; O'Hehir, Robyn E
Group 1 grass pollen allergens are glycoproteins of the β-expansin family. They are a predominant component of pollen and are potent allergens with a high frequency of serum IgE reactivity in grass pollen-allergic patients. Bahia grass is distinct from temperate grasses and has a prolonged pollination period and wide distribution in warmer climates. Here we describe the purification of the group 1 pollen allergen, Pas n 1, from Bahia grass (Paspalum notatum), an important subtropical aeroallergen source. Pas n 1 was purified from an aqueous Bahia grass pollen extract by ammonium sulphate precipitation, hydrophobic interaction and size exclusion chromatography, and assessed by one- and two-dimensional gel electrophoresis, immunoblotting and ELISA. Pas n 1 was purified to a single 29-kDa protein band containing two dominant isoforms detected by an allergen-specific monoclonal antibody and serum IgE of a Bahia grass pollen-allergic donor. The frequency of serum IgE reactivity with purified Pas n 1 in 51 Bahia grass pollen-allergic patients was 90.6%. Serum IgE reactivity with purified Pas n 1 was highly correlated with serum IgE reactivity with Bahia grass pollen extract and recombinant Pas n 1 (r = 0.821 and 0.913, respectively). Pas n 1 is a major allergen reactive at high frequency with serum IgE of Bahia grass pollen-allergic patients. Purified natural Pas n 1 has utility for improved specific diagnosis and immunotherapy for Bahia grass pollen allergy. Copyright © 2010 S. Karger AG, Basel.
Full Text Available Leiomyosarcomas of the penis are rare, with only 29 reported cases to date. We record the case of a patient who presented with a 2-year history of a seemingly indolent penile skin lesion. On histopathology of the local resection, a diagnosis of subcutaneous leiomyosarcoma was made. Specifically, leiomyosarcoma of the penile frenulum has not been clearly reported previously. The patient underwent a further excision to ensure an adequate resection margin and has had no disease recurrence at subsequent follow-up. Our case was of a lesion that, although clinically benign, was malignant and this possibility should be borne in mind when assessing patients.
Eggermont, Alexander M. M.; Janetzki, Sylvia; Hodi, F. Stephen; Ibrahim, Ramy; Anderson, Aparna; Humphrey, Rachel; Blumenstein, Brent; Wolchok, Jedd
Unlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan–Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. PMID:20826737
Cardoso, Thyago Hermylly Santana; Pirovani, Carlos Priminho; Micheli, Fabienne; Noronha, Fátima Soares Motta; Alves, Andréa Catão; Faria, Ana Maria Caetano; da Silva Gesteira, Abelmon
Background The pathogenesis related protein PR10 (TcPR-10), obtained from the Theobroma cacao-Moniliophthora perniciosa interaction library, presents antifungal activity against M. perniciosa and acts in vitro as a ribonuclease. However, despite its biotechnological potential, the TcPR-10 has the P-loop motif similar to those of some allergenic proteins such as Bet v 1 (Betula verrucosa) and Pru av 1 (Prunus avium). The insertion of mutations in this motif can produce proteins with reduced allergenic power. The objective of the present work was to evaluate the allergenic potential of the wild type and mutant recombinant TcPR-10 using bioinformatics tools and immunological assays. Methodology/Principal Findings Mutant substitutions (T10P, I30V, H45S) were inserted in the TcPR-10 gene by site-directed mutagenesis, cloned into pET28a and expressed in Escherichia coli BL21(DE3) cells. Changes in molecular surface caused by the mutant substitutions was evaluated by comparative protein modeling using the three-dimensional structure of the major cherry allergen, Pru av 1 as a template. The immunological assays were carried out in 8–12 week old female BALB/c mice. The mice were sensitized with the proteins (wild type and mutants) via subcutaneous and challenged intranasal for induction of allergic airway inflammation. Conclusions/Significance We showed that the wild TcPR-10 protein has allergenic potential, whereas the insertion of mutations produced proteins with reduced capacity of IgE production and cellular infiltration in the lungs. On the other hand, in vitro assays show that the TcPR-10 mutants still present antifungal and ribonuclease activity against M. perniciosa RNA. In conclusion, the mutant proteins present less allergenic potential than the wild TcPR-10, without the loss of interesting biotechnological properties. PMID:22768037
Sara Pereira Menezes
Full Text Available BACKGROUND: The pathogenesis related protein PR10 (TcPR-10, obtained from the Theobroma cacao-Moniliophthora perniciosa interaction library, presents antifungal activity against M. perniciosa and acts in vitro as a ribonuclease. However, despite its biotechnological potential, the TcPR-10 has the P-loop motif similar to those of some allergenic proteins such as Bet v 1 (Betula verrucosa and Pru av 1 (Prunus avium. The insertion of mutations in this motif can produce proteins with reduced allergenic power. The objective of the present work was to evaluate the allergenic potential of the wild type and mutant recombinant TcPR-10 using bioinformatics tools and immunological assays. METHODOLOGY/PRINCIPAL FINDINGS: Mutant substitutions (T10P, I30V, H45S were inserted in the TcPR-10 gene by site-directed mutagenesis, cloned into pET28a and expressed in Escherichia coli BL21(DE3 cells. Changes in molecular surface caused by the mutant substitutions was evaluated by comparative protein modeling using the three-dimensional structure of the major cherry allergen, Pru av 1 as a template. The immunological assays were carried out in 8-12 week old female BALB/c mice. The mice were sensitized with the proteins (wild type and mutants via subcutaneous and challenged intranasal for induction of allergic airway inflammation. CONCLUSIONS/SIGNIFICANCE: We showed that the wild TcPR-10 protein has allergenic potential, whereas the insertion of mutations produced proteins with reduced capacity of IgE production and cellular infiltration in the lungs. On the other hand, in vitro assays show that the TcPR-10 mutants still present antifungal and ribonuclease activity against M. perniciosa RNA. In conclusion, the mutant proteins present less allergenic potential than the wild TcPR-10, without the loss of interesting biotechnological properties.
Moon, Sung Mo; Lee, Sang Min; Kang, Haeyoun; Choi, Hye Jeong
Abstract Subcutaneous bronchogenic cysts have been described rarely, particularly among adolescents. Only a few reports have described the ultrasonographic features of bronchogenic cysts, characterizing them as nonspecific cystic masses with or without internal echogenic foci or debris. Therefore, it is hard to differentiate subcutaneous bronchogenic cysts from other subcutaneous cystic tumors ultrasonographically. We report a case of presternal subcutaneous bronchogenic cyst in an 18-year-old man with unusual ultrasonographic findings. Ultrasonography revealed a small, oval, cystic mass containing a well-circumscribed, heterogeneously hypoechoic, egg-shaped lesion in the dependent portion of the mass within the subcutaneous fat layer overlying the sternum. Surgical excision was performed, and the cystic mass was diagnosed as a bronchogenic cyst. On pathological examination, the internal, heterogeneously hypoechoic, ball-like lesion was found to be mucous material within the cyst. To our knowledge, this is the first reported case of a presternal subcutaneous bronchogenic cyst presenting with a ball-like lesion inside of the cyst. This unusual ultrasonographic feature can be a clue to the diagnosis of subcutaneous bronchogenic cyst. In conclusion, if an anechoic cyst containing an internal, well-circumscribed, hypoechoic ball-like lesion is seen in the presternal subcutaneous fat layer, subcutaneous bronchogenic cyst should be considered in the differential diagnosis of subcutaneous cystic masses. PMID:28151916
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with poor outcome. Novel radical radiation techniques using intensity modulated radiation therapy (IMRT) have become an important component of therapy in mesothelioma. Immunotherapy also provides new therapeutic options. However, how best to integrate immunotherapy with standard therapy such as radiation, chemotherapy and surgery remains unknown. A change of paradigm from adjuvant normofractionation to induction accelerated hypofractionated hemithoracic radiation could provide a platform to combine immunotherapy due to the potential benefit of short course high dose radiation on the immune system. Immunotherapy can also be combined with chemotherapy. Although chemotherapy is generally considered immunosuppressive, some chemotherapeutic agents do induce cell death that can be immunogenic and stimulate a specific immune response against the tumor. Immunotherapy could also be used in between cycles of chemotherapy to limit tumor cell repopulation and optimize the results of both treatments. The integration of immunotherapy into a multimodality approach is opening new avenue of treatment for mesothelioma. PMID:28713677
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Bolhaar Suzanne THP
indicates the involvement of qualitative as well as quantitative factors in allergenicity and warrants further research in the relative importance of quantitative and qualitative aspects of Mal d 1 gene expression on allergenicity. Results from this study have implications for medical diagnostics, immunotherapy, clinical research and breeding schemes for new hypo-allergenic cultivars.
Bøgh, Katrine Lindholm
potential exist. Resistance to digestion is for this reason a test parameter included in the safety assessment of the allergenic potential of novel proteins in genetically modified foods. The association between resistance to digestion and allergenic potential has though been challenged in recent years...... the immune system in one direction, other mixtures of peptides may guide the immune system in another direction. Together these results demonstrate that several characteristics of digestion products from food allergens may collectively contribute the allergenic potential, where more than just peptide sizes......Food allergy is a major health problem in the Western countries, affecting 3-8% of the population. What makes a dietary protein a food allergen has not yet been established, though several characteristics have been proposed to be shared by food allergens. One of the features believed...
Shamji, M H; Ljørring, C; Francis, J N; Calderon, M A; Larché, M; Kimber, I; Frew, A J; Ipsen, H; Lund, K; Würtzen, P A; Durham, S R
Induction of allergen-specific IgG(4) antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG(4) antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen-specific IgG(4) titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG-associated inhibitory activity such as inhibition of IgE-allergen interactions (IgE-blocking factor) and inhibition of CD23-dependent IgE-facilitated allergen binding (IgE-FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response. In an 8-month dose-response randomized double-blind placebo-controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100,000 SQ-U, 10,000 SQ-U or placebo injections. Serum specimens were collected before treatment, after up-dosing, during the peak season and at the end of the study. Allergen-specific IgG(4) titres and IgG-associated inhibitory activity were evaluated. A time- and dose-dependent increase in serum inhibitory activity for both the IgE-blocking factor and IgE-FAB was observed, which paralleled increases in grass pollen-specific IgG(4) antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom-rescue medication scores (IgE-FAB: r = -0.25, P = 0.0002; IgE-blocking factor: r = -0.28, P < 0.0001), whereas this was not observed for immunoreactive IgG(4) levels (r = -0.11, P = 0.12). Functional assays of inhibitory IgG(4) and IgE-blocking factor may be more useful surrogates of clinical response than IgG(4). Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation. © 2011 John Wiley & Sons A/S.
Carpentier, E; Roméo, B; El Samad, Y; Geslin-Lichtenberger, L; Maingourd, Y; Tourneux, P
Infectious endocarditis in children requires prolonged antibiotic therapy. In adults, antibiotics administrated subcutaneously such as teicoplanin are an alternative to intravenous treatment. We report the use of subcutaneous teicoplanin, after an initial antibiotic treatment administrated intravenously, for 2 children treated for infectious endocarditis following an initial cardiac surgery. Serum concentrations of teicoplanin were within the target range after the adaptation in the teicoplanin subcutaneous dosages. The treatment was effective for both cases. No specific side effects related to the treatment were reported. Subcutaneous administration could be used for prolonged antibiotic therapy for the treatment of infectious endocarditis in children, after an initial intravenous treatment. Variability of the bioavailability of antibiotics administrated subcutaneously requires regular testing. Prospective, randomized trials comparing intravenous and subcutaneous administration of teicoplanin should be conducted to assess the efficacy and safety of this treatment. Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Mou, Dan-Lei; Jia, Zhan-Sheng; Bai, Xue-Fan
Exosomes are small membrane-bound vesicles that are secreted by a multitude of eukaryocytes as a consequence of fusion of multivesicular bodies with the plasma membrane. Exosomes can play critical roles in different physiological processes depending on their origins. Exosomes secreted from professional antigen-presenting cells are enriched in MHC class I and II complexes, costimulatory molecules, hsp 70 and hsp 90 chaperones, therefore exosomes, like Trojan horse, are of importance of immunoregulation in vivo and in vitro. The review will present current trends of research on the fundamental properties, production and purification of exosomes, and will focus on their implementation in cancer and virus immunotherapy as a novel cell-free peptide-based vaccine.
Schadendorf, D; Algarra, S M; Bastholt, L
vaccines based on dendritic cells and peptides is driven by advances in understanding antigen presentation and processing, and by new techniques of vaccine preparation, stabilisation and delivery. Several agents that have shown promising activity in metastatic melanoma including IL-21 and monoclonal......Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated...... with significant toxicity and poor efficacy that does not improve overall survival of 96% of patients. Many studies with allogeneic and autologous vaccines have demonstrated no clinical benefit, and some randomised trials even showed a detrimental effect in the vaccine arm. The ongoing effort to develop melanoma...
Wang, Cai-xia; Huang, Jian-fang; Xiang, Jun-jian; Sun, Yi-fan; Lv, Si; Guo, Jie
To identify sarcoplasmic calcium-binding protein (SCP) as a minor shrimp allergen by mass spectrometry, and to analyze the immune cross-reactivity among crustacean SCPs. The M(r); 21 000 allergen from Litopenaeus vannamei was identified by MALDI-TOF/TOF-MS. BLAST and ClustalW were used to compare amino acid sequence identity of the allergen among crustaceans. The puritifed M(r); 21 000 allergen was injected subcutaneously in mice to produce the specific polyclonal antibodies to analyze immune cross-reactivity of the allergen with proteins from 8 other species of crustaceans by Western blotting. The M(r); 21 000 shrimp allergen was identified as SCP. Sequence comparison revealed that SCP had 81%-100% amino acid identity among crustaceans. Western blotting showed that the proteins with M(r); about 21 000, corresponding to SCP from Metapenaeus ensis, Penaeus monodon, Oratosquilla oratoria, Macrobrachium rosenbergii, Procambarus clarkii, Portunus pelagicus, Charybdis feriatus, Eriocheir sinensis were recognized by polyclonal antibodies against SCP of Litopenaeus vannamei. SCP is a minor shrimp allergen, and SCPs have a high sequence homology and strong immune cross-reactivity among crustaceans, which can be used as detective, diagnostic and safe immunotherapeutic agents for subjects with shrimp allergy.
Andersen, Klaus Ejner; Rastogi, S C; Carlsen, L
The Allergen Bank was established to give dermatologists easy access to special test materials in order to make early diagnoses of special cases of allergic contact dermatitis. The Allergen Bank comprises a computer system to register several hundred contact allergens in appropriate patch test co...
Zandvoort. M.M.J. van
When do you label food products as having been possibly cross contaminated by allergens? TNO can help you to develop a quantitative risk management guidance for food allergens, based on a unique method that quantifies the risk of food allergen traces in products and validated data on thresholds.
Boxtel, van E.L.; Broek, van den L.A.M.; Koppelman, S.J.; Gruppen, H.
Legumin proteins Ara h 3 from peanuts and glycinin from soybeans are increasingly described as important allergens. The stability of an allergen's IgE binding capacity towards heating and digestion is considered an important characteristic for food allergens. We investigated the effects of heating
Ott, Douglas E.
Background: Subcutaneous emphysema and gas extravasation outside of the peritoneal cavity during laparoscopy has consequences. Knowledge of the circumstances that increase the potential for subcutaneous emphysema is necessary for safe laparoscopy. Methods: A literature review and a PubMed search are the basis for this review. Conclusions: The known risk factors leading to subcutaneous emphysema during laparoscopy are multiple attempts at abdominal entry, improper cannula placement, loose fitt...
This clinical trial is testing standard therapy (surgery, radiation and temozolomide) plus immunotherapy with pembrolizumab with or without a cancer treatment vaccine for patients with newly diagnosed glioblastoma, a common and deadly type of brain tumor.
Researchers have identified a “genetic signature” in the tumors of patients with advanced melanoma who responded to a form of immunotherapy called checkpoint blockade. The results could be the basis for a test that identifies likely responders.
Coosemans, An; Tuyaerts, Sandra; Vanderstraeten, Anke; Vergote, Ignace; Amant, Frédéric; Van Gool, Stefaan W
Uterine cancer is the most common pelvic gynecological malignancy. Uterine sarcomas and relapsed uterine carcinomas have limited treatment options. The search for new therapies is urgent. Dendritic cell (DC) immunotherapy holds much promise, though has been poorly explored in uterine cancer. This commentary gives an insight in existing DC immunotherapy studies in uterine cancer and summarizes the possibilities and the importance of the loading of tumor antigens onto DC and their subsequent maturation. However, the sole application of DC immunotherapy to target uterine cancer will be insufficient because of tumor-induced immunosuppression, which will hamper the establishment of an effective anti-tumor immune response. The authors give an overview on the limited existing immunosuppressive data and propose a novel approach on DC immunotherapy in uterine cancer.
Takagi, Hidenori; Hirose, Sakiko; Yasuda, Hiroshi; Takaiwa, Fumio
Transgenic rice seeds, which express a hybrid peptide comprising seven predominant human T cell epitopes (7Crp) derived from Japanese cedar pollen allergens, have been shown to function as an effective edible vaccine for the control of pollen allergen-induced responses. In this study, we characterized biochemical properties of transgenic seeds expressing the 7Crp peptide. The levels of chemical compositions, such as carbohydrate, protein, lipid, amino acid, fatty acid, mineral, and vitamin, were substantially equivalent between transgenic 7Crp and its nontransgenic counterpart seeds. The contents of three major allergenic proteins in transgenic seeds were not enhanced by expression of the 7Crp peptide when compared with those of nontransgenic seeds. The 7Crp peptide expressed in seeds was susceptible to simulated gastric/intestinal fluids. N-Glycosylation was not observed in the 7Crp peptide sequence. These results indicate that transgenic 7Crp seeds are substantially equivalent to nontransgenic parental seeds except for the presence of the 7Crp peptide. Food safety assessment; transgenic rice seed; edible vaccine; peptide-based immunotherapy; Japanese cedar pollinosis.
Velpurisiva, Praveena; Gad, Aniket; Piel, Brandon; Jadia, Rahul; Rai, Prakash
Cancer immunotherapy is a rapidly evolving and paradigm shifting treatment modality that adds a strong tool to the collective cancer treatment arsenal. It can be effective even for late stage diagnoses and has already received clinical approval. Tumors are known to not only avoid immune surveillance but also exploit the immune system to continue local tumor growth and metastasis. Because of this, most immunotherapies, particularly those directed against solid cancers, have thus far only benefited a small minority of patients. Early clinical substantiation lends weight to the claim that cancer immunotherapies, which are adaptive and enduring treatment methods, generate much more sustained and robust anticancer effects when they are effectively formulated in nanoparticles or scaffolds than when they are administered as free drugs. Engineering cancer immunotherapies using nanomaterials is, therefore, a very promising area worthy of further consideration and investigation. This review focuses on the recent advances in cancer immunoengineering using nanoparticles for enhancing the therapeutic efficacy of a diverse range of immunotherapies. The delivery of immunostimulatory agents to antitumor immune cells, such as dendritic or antigen presenting cells, may be a far more efficient tactic to eradicate tumors than delivery of conventional chemotherapeutic and cytotoxic drugs to cancer cells. In addition to its immense therapeutic potential, immunoengineering using nanoparticles also provides a valuable tool for unearthing and understanding the basics of tumor biology. Recent research using nanoparticles for cancer immunotherapy has demonstrated the advantage of physicochemical manipulation in improving the delivery of immunostimulatory agents. In vivo studies have tested a range of particle sizes, mostly less than 300 nm, and particles with both positive and negative zeta potentials for various applications. Material composition and surface modifications have been shown to
Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571
Agrawal, Neena Stephanie; Miller, Rickey; Lal, Richa; Mahanti, Harshini; Dixon-Mah, Yaenette N.; Decandio, Michele L.; Vandergrift, W Alex; Varma, Abhay K.; Patel, Sunil J.; Banik, Naren L.; Lindhorst, Scott M.; Giglio, Pierre; Das, Arabinda
Glioblastoma is a form of brain tumor with a very high morbidity and mortality. Despite decades of research, the best treatments currently in clinical practice only extend survival by a number of months. A promising alternative to conventional treatment for glioblastomas is immunotherapy. Although proposed over a century ago, the field of cancer immunotherapy has historically struggled to translate it into effective clinical treatments. Better understanding is needed of the various regulatory...
Fox Bernard A
Full Text Available Abstract Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC, convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendation