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Background: Over 100 million people worldwide suffer from birch pollen allergy. Bet v 1 has been identified as the major birch pollen allergen. However, the molecular mechanisms of birch allergic sensitization, including the roles of Bet v 1 and other components of the birch pollen extract, remain incompletely understood. Here, we examined how known birch pollen–derived molecules influence the endolysosomal processing of Bet v 1, thereby shaping its allergenicity. Methods: We analyzed the biochemical and immunological interaction of ligands with Bet v 1. We then investigated the proteolytic processing of Bet v 1 by endosomal extracts in the presence and absence of ligands, followed by a detailed kinetic analysis of Bet v 1 processing by individual endolysosomal proteases as well as the T‐cell epitope presentation in BMDCs. Results: We identified E1 phytoprostanes as novel Bet v 1 ligands. Pollen‐derived ligands enhanced the proteolytic resistance of Bet v 1, affecting degradation kinetics and preferential cleavage sites of the endolysosomal proteases cathepsin S and legumain. E1 phytoprostanes exhibited a dual role by stabilizing Bet v 1 and inhibiting cathepsin protease activity. Conclusion: Bet v 1 can serve as a transporter of pollen‐derived, bioactive compounds. When carried to the endolysosome, such compounds can modulate the proteolytic activity, including its processing by cysteine cathepsins. We unveil a paradigm shift from an allergen‐centered view to a more systemic view that includes the host endolysosomal enzymes. [ABSTRACT FROM AUTHOR]

Abstract: Background: The galactose‐α‐1,3‐galactose (α‐Gal) epitope is involved in red meat allergy. As α‐Gal is structurally similar to the blood group B‐antigen, we explored the relationship between the immune responses to α‐Gal‐ and the B‐antigen in red meat‐allergic patients compared to healthy A/O or B blood donors. Methods: Sera from 51 red meat‐allergic patients IgE‐positive to α‐Gal and 102 healthy blood donors (51 blood group A/O; 51 blood group B) were included. α‐Gal‐ and B‐antigen‐specific IgE (ImmunoCAP) and IgG/IgG1‐4 (ELISA) responses were determined. Basophil activation tests were performed. Results: Fifteen healthy donors were IgE positive to α‐Gal, of which 3 had blood group B. The allergic patients had significantly higher α‐Gal IgE levels compared to the healthy donors. The majority of the allergic patients, but none of the healthy donors, had IgE against the B‐antigen. Inhibition studies revealed cross‐reactivity between α‐Gal and the B‐antigen. The biological activity of the B‐antigen was confirmed by basophil activation tests. Anti‐α‐Gal IgG1 and IgG4 levels were significantly higher in the patients compared to the healthy donors. Moreover, the IgG response to the B‐antigen was comparable between the allergic patients and healthy A/O donors. Conclusion: Red meat‐allergic patients showed significantly higher α‐Gal IgE, IgG1, and IgG4 levels, reflecting a Th2 response, compared to healthy blood donors. Blood group B donors had significantly reduced antibody responses to α‐Gal, due to similarities with the B‐antigen, resulting in a lower risk of sensitization to α‐Gal and development of red meat allergy. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim of this study was to investigate the prevalence of epidemiologic and physician‐diagnosed pollen‐induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence. Methods: A multistage, clustered and proportionately stratified random sampling with a field interviewer‐administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count. Results: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05). Conclusion: Pollen‐induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions. [ABSTRACT FROM AUTHOR]

Background Ragweed pollen represents a major allergy risk factor. Ragweed extracts contain five different isoforms of the major allergen Amb a 1. However, the immunological characteristics of Amb a 1 isoforms are not fully investigated. Here, we compared the physicochemical and immunological properties of three most important Amb a 1 isoforms. Methods After purification, the isoforms were physicochemically characterized, tested for antibody binding and induction of human T-cell proliferative responses. Their immunological properties were further evaluated in vitro and in vivo in a mouse model. Results Amb a 1 isoforms exhibited distinct patterns of IgE binding and immunogenicity. Compared to Amb a 1.02 or 03 isoforms, Amb a 1.01 showed higher IgE-binding activity. Isoforms 01 and 03 were the most potent stimulators of patients' T cells. In a mouse model of immunization, Amb a 1.01 induced higher levels of IgG and IgE antibodies when compared to isoforms 02 and 03. Interestingly, ragweed-sensitized patients also displayed an IgG response to Amb a 1 isoforms. However, unlike therapy-induced antibodies, sensitization-induced IgG did not show IgE-blocking activity. Conclusion The present study showed that naturally occurring isoforms of Amb a 1 possess different immunogenic and sensitizing properties. These findings should be considered when selecting sequences for molecule-based diagnosis and therapy for ragweed allergy. Due to its high IgE-binding activity, isoform Amb a 1.01 should be included in diagnostic tests. In contrast, due to their limited B- and T-cell cross-reactivity patterns, a combination of different isoforms might be a more attractive strategy for ragweed immunotherapy. [ABSTRACT FROM AUTHOR]

The Poaceae family comprises over 12 000 wind-pollinated species, which release large amounts of pollen into the atmosphere. Poaceae pollen is currently regarded as the leading airborne biological pollutant and the chief cause of pollen allergy worldwide. Sensitization rates vary by country, and those variations are reviewed here. Grass pollen allergens are grouped according to their protein structure and function. In Poaceae, although species belonging to different subfamilies are characterized by distinct allergen subsets, there is a considerable degree of cross-reactivity between many species. Cross-reactivity between grass pollen protein and fresh fruit pan-allergens is associated with the appearance of food allergies. The additional influence of urban pollution may prompt a more severe immunological response. The timing and the intensity of the pollen season are governed by species genetics, but plant phenology is also influenced by climate; as a result, climate changes may affect airborne pollen concentrations. This article reviews the findings of worldwide research which has highlighted the major impact of climate change on plant phenology and also on the prevalence and severity of allergic disease. [ABSTRACT FROM AUTHOR]

Food allergies are believed to be on the rise, and currently, management relies on the avoidance of the food. Hen's egg allergy is after cow's milk allergy the most common food allergy; eggs are used in many food products and thus difficult to avoid. A technological process using a combination of enzymatic hydrolysis and heat treatment was designed to produce modified hen's egg with reduced allergenic potential. Biochemical ( SDS- PAGE, Size exclusion chromatography and LC- MS/ MS) and immunological ( ELISA, immunoblot, RBL-assays, animal model) analysis showed a clear decrease in intact proteins as well as a strong decrease of allergenicity. In a clinical study, 22 of the 24 patients with a confirmed egg allergy who underwent a double-blind food challenge with the hydrolysed egg remained completely free of symptoms. Hydrolysed egg products may be beneficial as low-allergenic foods for egg-allergic patients to extent their diet. [ABSTRACT FROM AUTHOR]

Pollen is routinely monitored, but it is unknown whether pollen counts represent allergen exposure. We therefore simultaneously determined olive pollen and Ole e 1 in ambient air in Córdoba, Spain, and Évora, Portugal, using Hirst-type traps for pollen and high-volume cascade impactors for allergen. Pollen from different days released 12-fold different amounts of Ole e 1 per pollen (both locations P < 0.001). Average allergen release from pollen (pollen potency) was much higher in Córdoba (3.9 pg Ole e 1/pollen) than in Évora (0.8 pg Ole e 1/pollen, P = 0.004). Indeed, yearly olive pollen counts in Córdoba were 2.4 times higher than in Évora, but Ole e 1 concentrations were 7.6 times higher. When modeling the origin of the pollen, >40% of Ole e 1 exposure in Évora was explained by high-potency pollen originating from the south of Spain. Thus, olive pollen can vary substantially in allergen release, even though they are morphologically identical. [ABSTRACT FROM AUTHOR]

Background Recombinant allergens offer a tool for improving specific immunotherapy ( SIT). Objective To find the optimal dose of a new hypoallergenic folding variant of recombinant Bet v 1 (rBet v 1-FV) as SIT for patients with birch pollen allergy. Methods Before SIT, thirty-seven adult patients were exposed for eight hours in an environmental exposure chamber ( EEC) to birch pollen at an average concentration of 3500 ± 500 grains/m3, then randomized to four maintenance dose groups of rBet v 1-FV and one placebo group: 20 μg ( n = 7), 80 μg ( n = 8), 160 μg ( n = 7), 320 μg ( n = 8), and placebo ( n = 7). Patients were treated for 10 weeks with weekly injections and then re-exposed in the EEC. The optimal dose for SIT was assessed using efficacy results from the EEC, IgG responses, and tolerability. Results Thirty-six patients were evaluable for efficacy assessment. The total symptom score significantly decreased in all active groups compared with placebo (−18.8% for placebo patients; −71.9%, P = 0.0022 for 20 μg; −75.6%, P = 0.0007 for 80 μg; −81.8%, P = 0.0009 for 160 μg; −78.3%, P = 0.0003 for 320 μg). IgG1 increased significantly in all active groups compared to placebo. All four active doses were well tolerated, no serious adverse event occurred; two Grade II reactions, according to EAACI classification, were observed, one in each of the 160- and 320-μg groups. Conclusions Considering efficacy, immunological response, and tolerability, a maintenance dose of 80 μg of rBet v 1-FV appears to be the ideal dose for allergen immunotherapy in birch pollen allergic patients. [ABSTRACT FROM AUTHOR]

Background Patients allergic to pollen have been known to become more symptomatic during pollen season compared with the nonpollen season. However, there are few studies regarding whether higher exposure to pollen might increase the prevalence of allergic diseases. Methods An ecological analysis was conducted to evaluate whether pollen exposure is associated with the prevalence of allergic diseases in schoolchildren. Pollen count data of Japanese cedar ( Cryptomeria japonica) and Japanese cypress ( Chamaecyparis obtusa), which are the major pollen allergens in Japan, were obtained from each prefecture. The prevalence of allergic diseases in schoolchildren in each prefecture was based on a nationwide cross-sectional survey using the International Study of Asthma and Allergies in Childhood questionnaire. Results After omitting three prefectures where pollen data were not available, data of 44 prefectures were analysed. The prevalence of allergic rhinoconjunctivitis in children aged 6-7 years was positively associated with both cedar and cypress pollen counts ( P = 0.01, both), whereas the prevalence of allergic rhinoconjunctivitis in children aged 13-14 years was positively associated with only cypress pollen counts ( P = 0.003). Furthermore, the prevalence of asthma was positively associated with cedar pollen counts in 6- to 7-year-old children ( P = 0.003) but not cypress pollen counts in either age group. Conclusions There are ecological associations between pollen counts and the prevalence of allergic diseases in Japanese schoolchildren. Further studies are needed to determine whether the difference between the effects of cedar and cypress pollens is attributable to pollen counts or allergenicity. [ABSTRACT FROM AUTHOR]

Background CRTH2 mediates activation of Th2 cells, eosinophils and basophils in response to prostaglandin D2. The CRTH2 antagonist OC000459 has previously been demonstrated to reduce airway inflammation and improve lung function in moderate persistent asthma. The objective of the present study was to determine the involvement of CRTH2 in promoting nasal and ocular symptoms in allergic subjects exposed to grass pollen. Methods A single centre, randomised, double-blind, placebo-controlled, two-way crossover study was conducted in 35 male subjects allergic to grass pollen comparing OC000459 200 mg bid with placebo for 8 days. Subjects were exposed to grass pollen (≥1400 grains/m3) for 6 h on the 2nd and 8th days of treatment and assessed for nasal symptoms, ocular symptoms, other symptoms, nasal secretion weight and rhinomanometry over the 6-h period. After a washout period of 3 weeks, subjects were switched to the alternative treatment for a further 8 days. The trial was registered on the clinical trials.gov database (Identifier NCT01448902). Results During the first treatment period, treatment with OC000459 significantly reduced both nasal and ocular symptoms in allergic subjects compared with placebo after challenge with grass pollen. A significant effect was observed on the 2nd day of dosing which was increased on the 8th day of dosing. The therapeutic effects of OC000459 persisted into the second treatment period despite a 3-week washout phase. The safety profile of OC000459 was similar to that of placebo. Conclusion Treatment with OC000459 was well tolerated and led to a significant and persistent reduction in the symptoms of rhinoconjunctivitis. [ABSTRACT FROM AUTHOR]

To cite this article: Smole U, Wagner S, Balazs N, Radauer C, Bublin M, Allmaier G, Hoffmann-Sommergruber K, Breiteneder H. Bet v 1 and its homologous food allergen Api g 1 stimulate dendritic cells from birch pollen-allergic individuals to induce different Th-cell polarization. Allergy 2010; 65: 1388-1396. Background: Bet v 1 is the most relevant sensitizing protein for birch pollen (BP)-allergic individuals. Its homologues from plant foods are mainly involved in allergic reactions caused by IgE cross reactivity. We aimed to evaluate the polarizing effect of dendritic cells (DCs) pulsed with Bet v 1, Mal d 1, Api g 1 or Dau c 1 on Th-cell responses. Methods: Immature DCs were generated from peripheral blood monocytes of BP-allergic and healthy donors by culture with GM-CSF and IL-4 and subsequently pulsed with allergens in combination with maturation factors. Cell surface markers were analysed by FACS. Mature DCs were co-cultured with autologous Th cells and T-cell proliferation and cytokine profiles were determined. Results: In co-culture, mature allergen-pulsed DCs induced autologous Th cells of BP-allergic donors to proliferate significantly more than those of healthy individuals. Exposure of DCs from BP-allergic donors to Bet v 1 resulted in a robust Th2 skewing with significantly higher quantities of IL-5 and elevated IL-13 compared to maturation factors. In contrast, Api g 1-primed DCs from BP allergics significantly enhanced the production of the Th1 cytokine IFN-γ and significantly down-regulated IL-13 compared to maturation factors. In healthy donors, no significant cytokine production could be detected. Conclusion: Bet v 1 in contrast to homologous food allergens seems to possess distinct molecular features that enable it to condition DCs from BP-allergic donors to induce allergen-specific T-cell proliferation and Th2 polarization. [ABSTRACT FROM AUTHOR]

To cite this article: Patiwael JA, Jong NW, Burdorf A, Groot H, Gerth van Wijk R. Occupational allergy to bell pepper pollen in greenhouses in the Netherlands, an 8-year follow-up study. Allergy 2010; 65: 1423-1429. Background: Pollen from bell pepper plants cultivated in greenhouses are known to cause occupational allergic disease. A cross-sectional study among 472 bell pepper employees in 1999 estimated prevalences for sensitization to bell pepper pollen of 28% and for work-related allergic symptoms of 54%. There is scarce information on the incidence of work-related allergy and its risk factors. Aims of the present study were to estimate the cumulative incidence of work-related symptoms and sensitization to bell pepper pollen, and to determine risk factors for the onset of these symptoms and sensitization. Methods: Bell pepper employees who participated in a cross-sectional survey in 1999 were asked to take part in a follow-up study in 2007. Information on demographic characteristics, job characteristics and allergic symptoms was gathered by means of a questionnaire. Furthermore, skin tests were performed with a.o. bell pepper pollen. Results: In total, 280 of 472 employees were available for questionnaires and in 250 employees allergy tests were performed. During the 8-year follow-up, the cumulative incidence of sensitization to bell pepper pollen was 9% and of work-related rhinitis 19%. Atopy [odds ratio (OR) 5.60] and smoking (OR 3.53) were significantly associated with development of rhinitis. The cumulative incidence of work-related asthma symptoms was 8%. Again atopy (OR 5.03) and smoking (OR 11.85) were significant risk factors. Conclusion: Cumulative incidences for sensitization to bell pepper pollen, work-related rhinitis and asthma symptoms were 9%, 19% and 8%, respectively. Atopy and smoking are risk factors for developing work-related symptoms among workers in bell pepper horticulture. [ABSTRACT FROM AUTHOR]

To cite this article: Calderon M, Mösges R, Hellmich M, Demoly P. Towards evidence-based medicine in specific grass pollen immunotherapy. Allergy 2010; 65: 420–434. When initiating grass pollen immunotherapy for seasonal allergic rhinoconjunctivitis, specialist physicians in many European countries must choose between modalities of differing pharmaceutical and regulatory status. We applied an evidence-based medicine (EBM) approach to commercially available subcutaneous and sublingual Gramineae grass pollen immunotherapies (SCIT and SLIT) by evaluating study design, populations, pollen seasons, treatment doses and durations, efficacy, quality of life, safety and compliance. After searching MEDLINE, Embase and the Cochrane Library up until January 2009, we identified 33 randomized, double-blind, placebo-controlled trials (including seven paediatric trials) with a total of 440 specific immunotherapy (SIT)-treated subjects in seven trials (0 paediatric) for SCIT with natural pollen extracts, 168 in three trials (0 paediatric) for SCIT with allergoids, 906 in 16 trials (five paediatric) for natural extract SLIT drops, 41 in two trials (one paediatric) for allergoid SLIT tablets and 1605 in five trials (two paediatric) for natural extract SLIT tablets. Trial design and quality varied significantly within and between SIT modalities. The multinational, rigorous trials of natural extract SLIT tablets correspond to a high level of evidence in adult and paediatric populations. The limited amount of published data on allergoids prevented us from judging the level of evidence for this modality. [ABSTRACT FROM AUTHOR]

Background: Wheat is a potent allergen source and can cause baker’s asthma, food and pollen allergy. The aim of the study was to develop an allergen micro-array for differential diagnosis of baker’s asthma, wheat-induced food allergy and grass pollen allergy. Methods: We analysed the immunoglobulin-E reactivity profiles of patients suffering from baker’s asthma, wheat-induced food allergy and grass pollen allergy to micro-arrayed recombinant wheat flour allergens and grass pollen allergens and compared these results with clinical results and diagnostic tests based on crude wheat flour, wheat pollen and grass pollen allergen extracts. Results: We identified recombinant wheat flour allergens, which are specifically recognized by patients suffering from baker’s asthma, but not from patients with food allergy to wheat or pollen allergy. rPhl p 1 and rPhl p 5 were identified as marker allergens specific for grass pollen allergy. They can be used to replace grass pollen extracts for allergy diagnosis and to identify grass pollen allergic patients among patients suffering from baker’s asthma and wheat-induced food allergy. Profilin was identified as a cross-reactive allergen recognized by patients suffering from baker’s asthma, food and pollen allergy. Conclusions: Our results indicate that it will be possible to design serological tests based on micro-arrayed recombinant wheat seed and grass pollen allergens for the discrimination of baker’s asthma, wheat-induced food allergy and grass pollen allergy. [ABSTRACT FROM AUTHOR]

Background: There is evidence of an allergy protective effect in children raised on farm. It has been assumed that microbial exposure may confer this protection. However in farm, little attention has been given to the pollen level and to concomitant microbiological exposure, and indoor pollen concentrations have never been precisely quantified. Methods: The kinetics of pollen in dairy farms have been studied in a pilot study ( n = 9), and exposure in a sub-sample of the ongoing European birth cohort PASTURE ( n = 106). Measurements of viable microorganisms and pollen were performed in air samples. To identify factors that modulate the pollen concentration multivariate regression analyses were run. Results: Indoor pollen (95% of Poaceae fragments and grains) were significantly higher in winter than in summer ( P = 0.001) and ranged between 858 to 11 265 counts/m3 during feeding in winter, thus exceeding typical outdoor levels during the pollen season. Geometric mean in French farms was significantly higher than in German and Swiss farms (7 534, 992 and 1 079 count/m3, respectively). The presence of a ventilation system and loose housing systems significantly reduced indoor pollen levels. This pollen concentration rise after feeding was accompanied by an increase in fungal and actinomycetal levels, whereas the concentration of bacteria was not associated with feeding. Conclusions: Farmers and their children who attend cowsheds during the feeding sessions are exposed perennially to high pollen concentrations. It might be speculated that the combined permanent exposure to microbes from livestock and grass pollen may initiate tolerance in children living on a farm. [ABSTRACT FROM AUTHOR]

Background: Assessing the allergenicity and toxicity of genetically modified (GM) crops is essential before they become a regular part of our food supply. The present study aimed to assess the allergenicity of Brassica juncea (mustard) expressing choline oxidase ( codA) gene from Arthrobacter globiformis that provides resistance against abiotic stresses. Methods: SDAP, Farrp, and Swiss-Prot databases were used to study allergenicity of choline oxidase. Digestibility of choline oxidase was assessed in simulated gastric fluid (SGF). Specific immunoglobulin E (IgE) reactivity of native and GM mustard was compared by using enzyme-linked immunosorbent assay (ELISA) and skin tests in respiratory-allergic patients. Allergenicity of GM and native mustard proteins was compared in Balb/c mice. Results: Choline oxidase showed no significant homology with allergenic proteins in SDAP and Farrp databases. Cross-reactive epitope search showed a stretch similar to Hev b 6 having some antigenic properties. Purified choline oxidase showed complete degradation with SGF. Skin prick test of native and GM mustard extract on respiratory allergic patients showed significant correlation ( P < 0.05). ELISA with 96 patients’ sera showed comparable IgE reactivity. Balb/c mice immunized with native and GM mustard proteins showed low IgE response. Presensitized mice on intravenous challenge with Brassica extract showed no anaphylactic symptoms unlike ovalbumin (OVA) sensitization that showed anaphylactic reaction in mice. Lung histology of OVA-sensitized mice showed narrowing of airway and large eosinophilic infiltration, whereas native and GM Brassica extract showed normal airway. Conclusion: Genetically modified mustard with the codA gene possessed allergenicity similar to that of native mustard and no enhancement of IgE binding was observed due to genetic manipulation. [ABSTRACT FROM AUTHOR]

Background: Fish is one of the most frequent causes of immunoglobulin E (IgE)-mediated food allergy. Although the fish dark muscle is often ingested with the white muscle, no information about its allergenicity and allergens is available. Methods: Heated extracts were prepared from both white and dark muscles of five species of fish and examined for reactivity with IgE in fish-allergic patients by enzyme-linked immunosorbent assay (ELISA) and for allergens by immunoblotting. Cloning of cDNAs encoding parvalbumins was performed by rapid amplification cDNA ends. Parvalbumin contents in both white and dark muscles were determined by ELISA using antiserum against mackerel parvalbumin. Results: Patient sera were less reactive to the heated extract from the dark muscle than to that from the white muscle. A prominent IgE-reactive protein of 12 kDa, which was detected in both white and dark muscles, was identified as parvalbumin. Molecular cloning experiments revealed that the same parvalbumin molecule is contained in both white and dark muscles of either horse mackerel or Pacific mackerel. Parvalbumin contents were four to eight times lower in the dark muscle than in the white muscle. Conclusions: The fish dark muscle is less allergenic than the white muscle, because the same allergen molecule (parvalbumin) is contained at much lower levels in the dark muscle than in the white muscle. Thus, the dark muscle is less implicated in fish allergy than the white muscle. [ABSTRACT FROM AUTHOR]

Background: Although allergen-specific IgE content in serum can be determined immunochemically, little is known about the relationship between this parameter and the strength of the degranulation response upon allergen triggering. Objectives: Analyse the degranulation capacity of immunochemically defined purified and serum IgE after challenge with anti-IgE or allergen using a rat mast cell line (RBL) transfected with the α -chain of the human high-affinity IgE receptor (Fcℇ RI). Methods: Purified IgE specific for 4-hydroxy-3nitrophenylacetyl, purified IgE of unknown specificity, and sera from allergic patients sensitive to Dermatophagoides pteronyssinus and Dactylis glomerata were assessed. Degranulation was measured by a β -hexosaminidase release assay after anti-IgE or allergen-specific challenge. Results: For purified monoclonal IgE a significant correlation (r = 0.97) was found between the proportion of bound allergen-specific IgE and the strength of the degranulation response. In contrast, no correlation (r = 0.27) was detected after sensitization with serum IgE. Conclusion: Our studies demonstrate that mast cell activation mediated through IgE from allergic patients is a result of complex relationships that are not only dependent on allergen-specific IgE content but also relate to the capacity to efficiently sensitize and trigger the signalling responses that lead to degranulation. [ABSTRACT FROM AUTHOR]

Background: As the incidence of allergy to different compounds increases in society, the need to understand and characterize specific IgE responses becomes obvious. Different cell culture systems have been evaluated for their ability to support such IgE secretion. Methods: One system employed human peripheral lymphocytes (PBL) from normal donors stimulated with anti-CD3 activated T cells with or without the presence of allergens like benzylpenicillin (BP) and Phlenum pratense (PP). Secretion of IgE was analyzed in ELISA and compared to the IgG response to the nonallergenic antigen tetanus toxoid (TT). Another system employed stimulation of T and B cells with a heterotope, consisting of a T helper cell epitope derived from TT, and a B cell allergen epitope derived from BP. The specific IgE secretion was compared, using lymphocytes from normal as well as BP-allergic donors. Results: Anti-CD3 stimulated T cells supported BP-specific IgE secretion in six of 11 normal donors. This response was inhibited in four donors and enhanced in two donors by the addition of the BP-allergen to the culture. In contrast, addition of the protein allergen (PP) or antigen (TT) to the same culture system inhibited both IgE and IgG synthesis in all experiments. Cells from the majority (10/16) of the BP-allergic donors failed to produce BP-specific IgE in vitro , when cultured in the presence of allergen. Conclusions: An allergen specific immune response is readily generated in vitro . The differential response against benzylpenicillin between different donor categories most probably reflects the level of pre-exposure to this allergen in vivo . [ABSTRACT FROM AUTHOR]

The cross-reactivity of IgE antibodies is of interest for various reasons, three of which are discussed. Firstly, from the clinical view, it is important to know the patterns of cross-reactivity, because they often (but not always) reflect the pattern of clinical sensitivities. We discuss the cross-reactivities associated with sensitization to pollen and vegetable foods: PR-10 (Bet v 1-related), profilin, the cross-reactive carbohydrate determinant (CCD), the recently described isoflavone reductase, and the (still elusive) mugwort allergen that is associated with celery anaphylaxis; cross-reactivities between allergens from invertebrates, particularly tropomyosin, paramyosin, and glutathione S-transferase (GST); and latex-associated cross-reactivities. Clustering cross-reactive allergens may simplify diagnostic procedures and therapeutic regimens. Secondly, IgE cross-reactivity is of interest for its immunologic basis, particularly in relation to the regulation of allergic sensitization: are IgE antibodies to allergens more often cross-reactive than IgG antibodies to “normal” antigens? If so, why? For this discussion, it is relevant to compare not only the structural relation between the two allergens in question, but also the relatedness to the human equivalent (if any) and how the latter influences the immune repertoire. Thirdly, prediction of IgE cross-reactivity is of interest in relation to allergic reactivity to novel foods. Cross-reactivity is a property defined by individual antibodies to individual allergens. Quantitative information (including relative affinity) is required on cross-reactivity in the allergic population and with specific allergens (rather than with whole extracts). Such information is still scarce, but with the increasing availability of purified (usually recombinant) allergens, such quantitative information will soon start to accumulate. It is expected that similarity in short stretches of the linear amino-acid sequence is unlikely to result in relevant cross-reactivity between two proteins unless there is similarity in the protein fold. [ABSTRACT FROM AUTHOR]

This paper is a review concerning the way in which heat treatment can modify the allergenicity of food proteins. Any food protein may be allergenic if it can be absorbed intact, or as substantial fragments, through the gut mucosa and then evoke an immune (allergic) response. The intrinsic properties of the protein, the overall composition of the food, and the past processing history (especially thermal processing) all have an effect on the allergic potential. When a protein is denatured by heat, most of the original tertiary structure is lost, so that many of the sites recognized by antibodies on the native molecule are destroyed. There are many examples of allergenicity being reduced, but not eliminated, by heating. But heat-denatured proteins can also present new antigenic sites, uncovered by the unfolding process or created by new chemical reactions with other molecules present in the food (e.g., β-lactoglobulin associating with α-lactalbumin in milk). We have found that heat-denatured β-lactoglobulin has at least one new epitope, not found in the native state. Therefore, thermal processing can be part of a procedure for making hypoallergenic food, but will rarely be sufficient on its own. Increased understanding will help in evaluating novel proteins and processes. [ABSTRACT FROM AUTHOR]

The objective of this study was to analyze both the allergenicity and immunogenicity of cow's milk proteins. To this end, 80 milk-atopic patients were selected on the basis of the presence of cow's milk-specific IgE antibodies in serum and compatible clinical history. Fifteen patients allergic to other allergens and 10 nonatopic subjects were studied as controls. The specificity of serum IgG and IgE antibodies was determined by immunoblotting, employing both cow's milk and milk components, i.e., α- and β-casein, β-lactoglobulin. and α-lactalbumin separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The experiments showed that casein-specific IgE antibodies were present in all (80/80) sera examined: 10/80 showed reactivity to β-lactoglobulin. and 5/80 showed reactivity to α-lactalbumin. None of the 25 negative control sera analyzed showed the presence of specific IgE antibodies against milk proteins. These results were similar to those corresponding to the detection, by the radioallergosorbent test, of IgE antibodies against the milk components coupled to paper disks. All sera from milk-atopic patients also showed IgE reactivity against a high-molecular-mass fraction that hardly enters the gel. This fraction, after separation by gel filtration and treatment with β-mercaptoethanol and urea, was shown by SDS -PAGE analysis to be formed by casein monomers. All sera analyzed by immunoblotting reacted against the components corresponding to casein monomers. Inhibition of immunoblotting by adsorption with different milk components confirmed that those high-molecular-mass aggregates are formed by casein components. The results presented here strongly suggest that casein is the major allergenic component of cow's milk. [ABSTRACT FROM AUTHOR]

High birch pollen antigenic activities in outdoor air samples were found in all particle sizes studied (>7.2, 2.4-7.2,. <2.4 μm and molecular size class, with an ELISA modification), Sampling was done with a low-volume, size-selective bioaerosol sampler (SSBAS) simulating the human respiratory tract in both volume and fractionation; Airborne birch pollen counts for comparisons. were obtained from a Bukard trap. No correlations were obtained between antigen concentrations in any particle size fraction and airborne pollen counts. The meteorologic factors studied differed clearly. Like wise the effect of meteorologic factors differed among the three study periods (period 1, 4 weeks before the peak pollen season, period IL during the season; and period III, 4 weeks after the season). During the peak pollen period, temperature and relative humidity were the most important meteorologic factors Before the season, large and very small particles predominated medium- sized parties being totally absent, The largest size class studied (containing all intact pollen grains) clearly reacted to . changes in meteorologic factors: for smaller size classes these factors were found to be less important, a fact which may make the forecasting of antigen concentrations in the air on the basis of meteorologic data impossible. [ABSTRACT FROM AUTHOR]

We report the sustained efficacy of the SQ-standardized grass allergy immunotherapy tablet Grazax® (Phleum pratense 75 000 SQ-T/2,800 BAU, ALK, Denmark) from a 5-year randomized, double-blind, placebo-controlled phase III trial. Adults with moderate-to-severe grass pollen allergy inadequately controlled by symptomatic medications were followed for 2 years after the completion of 3 years of treatment. The active group demonstrated a 31% reduction in median rhinoconjunctivitis symptom score over the season compared with placebo. Individual symptom scores favoured active treatment. Combined symptom and medication scores demonstrated a 33% reduction in medians with active treatment. Persistent clinical efficacy was accompanied by prolonged increases in allergen-specific IgG4 antibodies and IgEblocking factor, confirming clinical and immunological tolerance for at least 2 years after the treatment completion. No safety issues were identified during follow-up. [ABSTRACT FROM AUTHOR]

The use of specific immunotherapy (SIT) for allergic disorders has recently been extended by introduction of a convenient, tablet-based, disease-modifying vaccine against grass pollen allergy. Allergy immunotherapy tablet (AIT) programmes targeting house dust mite and other allergies are currently in late-phase development. Next-generation allergy vaccines can have optimised potency and onset of action without compromising safety or convenience. Key to achieving these objectives is a combination of evidence-based mode-of-action studies and biomarker-centric translational research approaches. This will rely on using biobank and bioinformatics resources for multi-omic characterisations of the ‘immunome’ of allergic disease. Other important areas are ongoing paediatric trials and long-term studies in adults for further defining the potential role of SIT in allergic disease and primary prevention of asthma. Finally, combining cellular- and serological-based assays, and developments in targeted delivery platforms and component-resolved diagnostics will lead to increased ability to stratify patients, with more personalised diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The article offers information on the first report on thunderstorm-related asthma due to olive tree pollen sensitization in the Mediterranean Region. It states that the report describes 20 cases of patients who had severe asthmatic symptoms after a violent thunderstorm in Puglia, Italy on May 27-28, 2010. It mentions that all the patients were sensitized with olive aeroallergen pollens which were released due to the thunderstorm.

Allergy specific immunotherapy may alter the natural course of allergic disease. Thus, it is of significant importance, particularly in paediatric populations. Four studies using the grass allergy immunotherapy tablet (AIT) for allergic rhinoconjunctivitis in children showed good clinical outcomes and good safety profiles. Allergic rhinoconjunctivitis often precedes asthma, and treatment with specific immunotherapy has the potential to reduce the development of asthma in children suffering from rhinoconjunctivitis. Since Grazax® AIT has been shown to induce disease modification the prevention of asthma might be hypothesised. The GAP (Grazax® Asthma Prevention) trial is investigating the asthma preventive effect of standardised grass AIT in grass allergic children with rhinoconjunctivitis without asthma. The trial is a 5-year, multicentre, multinational, randomised, double-blind, placebo-controlled, prospective trial for children aged 5–12 years. In a few years, the results will show if grass AIT with Grazax® can prevent the development of asthma in children suffering from allergic rhinoconjunctivitis. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to clone and characterize allergen For t 2 from the biting midge Forcipomya taiwana. The study constructed a ZAPII complimentary DNA (cDNA) from the mRNA of the biting midge. It says that skin prick test and enzyme-linked-immunosorbent serologic assay (ELISA) found the immunoglobulin E (IgE) reactivity of For t 2. The results showed that For t 2 binds with serum IgE, as well as induces the inflammatory chemokine production from skin fibroblast.