Allergens In Products Research Articles

Genentech, Inc. v. Immunex Rhode Island Corp. United States Court of Appeals of the Federal Circuit, 2020 964 F.3d 1109

Genentech, Inc. v. Immunex Rhode Island Corp. United States Court of Appeals of the Federal Circuit, 2020 964 F.3d 1109

New guidance on the regulation of allergen products: key aspects and outcomes.

Key aspects and outcomes from the recently published guidance on the regulation of allergen products are summarized. A new regulatory guideline has been published to enhance harmonized national approaches on the regulation of allergen products and thereby strengthen the availability of high-quality products across the European Union (EU). As the guideline was developed, critical aspects for allergen products regulation were identified and are discussed in the document, including recommendations on the regulatory procedures to be applied for diagnostics, allergen immunotherapy products and named-patient products. The new guidance is expected to provide clarifications on and support harmonization of the regulation of allergen products in the EU.

Recombinant Allergens in Immunotherapy of Asthma

Asthma is a chronic inflammatory disorder caused by T-cell-mediated inflammation within airways. The prevalence of allergic diseases is rapidly increasing so that knowing allergens (characterization and types) and strategies for asthma management, prevention and treatment are very important. The most strategy is the production of recombinant allergens. Many of the problems associated with using natural allergenic products for allergy diagnosis and treatment can be overcome with the use of genetically engineered recombinant allergens. Various recombinant allergens are now emerging as strong candidates for allergen-specific immunotherapy. Extrinsic asthma (a type of asthma) may respond to immunotherapy such as using recombinant allergens. These exciting novel therapies provide not only the promise of new therapies for asthma but also valuable tools for the investigation of asthma mechanisms. This review describes strategies for asthma management, prevention and treatment, and especially recombinant allergens and also recent progresses in the molecular biology of recombinant allergens and then advantage and disadvantage of these allergens are explained. There are many methods for producing allergens such as extraction of serum, Ro/SS-A anti-Ro/SS-A system, Using the Solid-Phase Immunoadsorption system and finally recombinant technology for producing recombinant allergens. Recombinant allergens can express in many systems such as bacteria, yeast, insect cells, animal cells, and transgenic plant. We describe recombinant allergens produced in these systems. The obtained results hold promise that recombinant allergen–based immunotherapy will improve current immunotherapy practice and may open possibilities for new treatment strategies and possibly even for prophylactic vaccination.

Assessing the composition, diversity, and allergenic risk of street trees in Qingyang District of Chengdu City

The growing evidences suggest an association between street green space and health in cities. Pollen released by street trees has a considerable adverse impact on human health. This study aims to analyze the characteristics and assess the seasonally allergenic risk of street trees in Qingyang District, Chengdu City. There are 495 streets in Qingyang District, which have been divided into five categories according to their width. Fifty-seven species were identified, belonging to 46 taxa, and 28 botanical families in these streets. However, no significant differences in average diameter at breast height (DBH), tree height, and crown width of street trees were found among the five defined street categories. Both the street trees per capita (0.06) and the number of tree species are significantly higher than that in many Chinese cities. The Shannon's diversity index (SHDI) of street categories are clearly different, ranging from 0.94 to 3.84. Street category 5 (community street) has the highest tree density, area ratio, and SHDI of all street categories. In addition, Chengdu City is exposed to high allergenic risk of street trees. The index of urban green zone allergenicity (IUGZA) ranged from a minimum of 0.1002 for category 1 (urban expressway) to a maximum of 1.0391 for category 5, which indicates that the IUGZA value of different urban green spaces can exceed the upper limit (1.00). A increasing trend of the IUGZA values is observed with decreasing street width. The highest allergic risk of street trees is observed in spring, followed by summer. Ginkgo biloba shows a highly contribute to the IUGZA value for all street categories. Pearson’s correlation analysis identified area ratio and tree density, as crucial factors that affect the IUGZA. No correlation was observed between IUGZA scores and species richness (i.e., SHDI and the total number of species). A series of greening strategies have been proposed to minimize the volume of allergen production for the well-being of inhabitants in Chengdu City.

Characteristics of Asian Mosquito Saliva Allergens for Specific Diagnoses and Effective Therapies.

An allergic reaction to mosquitoes can result in severe or abnormal local or systemic reactions such as anaphylaxis, angioedema, and general urticarial or wheezing. The aim of this review is to provide information on mosquito saliva allergens that can support the production of highly specific recombinant saliva allergens. In particular, candidate allergens of mosquitoes that are well suited to the ecology of mosquitoes that occur mainly in East Asia will be identified and introduced. By doing so, the diagnosis and treatment of patients with severe sensitivity to mosquito allergy will be improved by predicting the characteristics of East Asian mosquito allergy, presenting the future direction of production of recombinant allergens, and understanding the difference between East and West.

Morphology and quantification of fungal growth in residential dust and carpets

Mold growth indoors is associated with negative human health effects, and this growth is limited by moisture availability. Dust deposited in carpet is an important source of human exposure due to potential elevated resuspension compared to hard floors. However, we need an improved understanding of fungal growth in dust and carpet to better estimate human exposure. The goal of this study was to compare fungal growth quantity and morphology in residential carpet under different environmental conditions, including equilibrium relative humidity (ERH) (50%, 85%, 90%, 95%, 100%), carpet fiber material (nylon, olefin, wool) and presence/absence of dust. We analyzed incubated carpet and dust samples from three Ohio homes for total fungal DNA, fungal allergen Alt a 1, and fungal morphology. Dust presence and elevated ERH (≥85%) were the most important variables that increased fungal growth. Elevated ERH increased mean fungal DNA concentration (P < 0.0001), for instance by approximately 1000 times at 100% compared to 50% ERH after two weeks. Microscopy also revealed more fungal growth at higher ERH. Fungal concentrations were up to 100 times higher in samples containing house dust compared to no dust. For fiber type, olefin had the least total fungal growth, and nylon had the most total fungi and A. alternata growth in unaltered dust. Increased ERH conditions were associated with increased Alt a 1 allergen concentration. The results of this study demonstrate that ERH, presence/absence of house dust, and carpet fiber type influence fungal growth and allergen production in residential carpet, which has implications for human exposure.

Is allergy immunotherapy with birch sufficient to treat patients allergic to pollen of tree species of the birch homologous group?

Pollen from various Fagales tree species prolongs the season and makes tree pollen allergy a major health problem. Despite involving the same causative allergens, allergy immunotherapy (AIT) treatment habits differ significantly across different geographical regions. Diagnosis and treatment with AIT in patients allergic to tree pollen were discussed by a group of German medical experts who give practical recommendations based on the available data. Regulatory perspective: According to current guidelines on allergen products, birch pollen are the representative allergen source of the birch homologous group including several Fagales trees based on sequence and structural similarity of their allergen proteins. Immunological perspective: A high level of IgE cross-reactivity towards allergens from the birch homologous group has been observed in basic research and clinical trials. Clinical perspective: Clinical trial data show that the efficacy of birch pollen AIT is not only related to birch pollen allergy but extends to pollen from other trees, especially alder, hazel and oak. In order to optimize diagnosis and treatment of tree pollen allergy, the experts recommend to focus diagnosis and respective treatment with AIT primarily to birch as the representative allergen of the Fagales tree homologous group, but further diagnostics may be needed for some patients to determine adequate treatment.

Allergen content in mouse allergenic samples and products is more complex than a single Mus m 1 value

Mus m 1 is a group of >21 polymorphic major urinary proteins (MUPs) and the specificity of available Mus m 1 immunoassays to any of these MUPs is unknown. In order to improve the diagnostic and therapeutic potency of commercial mouse allergen extracts, we need improved methods to characterize mouse allergens and the immune responses to them. We applied the following analytical methods to commercial extracts, urine from laboratory and wild mice, and environmental samples from homes of Baltimore asthma patients: isoelectric focusing, two-dimensional electrophoresis (2D-PAGE), liquid chromatography, immunostaining, mass spectrometry, and multiple reactions monitoring (MRM). By 2D-PAGE with immunostaining, MUPs are the major IgE-binding proteins (90-95%) in urine, but albumin is more abundant in commercial extracts. MUPs have complex migration patterns on 2D-PAGE, attributable to sequence polymorphisms and posttranslational modifications. For example, we identified at least 14 distinct MUP3-variants with variable glycosylation states. Using MRM, we determined that MUPs with >97% sequence similarity constitute 85-90% of the total MUPs in both commercial extracts and urine. Environmental dust samples, from bed, bedroom, and kitchen, contained MUP profiles consistent with those found in commercial extracts. Commercial extracts are highly variable, with up to 30-fold differences in specific MUP content. Using a full array of proteomic and mass spectrometric tools, we can assess the allergen content of commercial mouse allergen extracts and compare it to allergens in mouse urine and environmental dust samples. These tools will help guide further research, characterization, and standardization of mouse allergenic products.

Fungal allergen production in floor dust: The effects of relative humidity, house dust, and carpet fiber material

Fungal allergen production in floor dust: The effects of relative humidity, house dust, and carpet fiber material

Identification of LincRNA from Dermatophagoides farinae (Acari: Pyroglyphidae) for Potential Allergen-Related Targets.

Long noncoding RNAs (lncRNAs), especially their important subclass of long intergenic noncoding RNAs (lincRNAs), have been identified in some insects. They play important roles in the regulation of biological processes, such as immune response or cell differentiation and as possible evolutionary precursors for protein coding genes. House dust mites (HDMs) are recognized as allergenic mites because allergens are found in their feces and bodies. Dermatophagoides farinae is one of the most important pyroglyphid mites because of its abundance in the household. To determine if lincRNAs can regulate allergen presentation in HDMs, we analyzed RNA-seq data for HDMs. We identified 11 lincRNAs that are related to mRNAs coding for allergens in HDMs. Using qRT-PCR, we amplified 10 lincRNAs and their putative target allergen-encoding mRNAs, confirming expression of these lincRNAs and allergen genes. The results suggest that lincRNAs might be involved in the regulation of allergen production in HDMs and might represent potential acaricidal candidates to inhibit mite allergen production.

Маркировка продуктов и пищевая анафилаксия у детей. Где точки пересечения?

Anaphylaxis is an acute life-threatening condition affecting several body systems. It might have a rapid onset and lead to a lethal outcome. The major provoking factors for the development of anaphylactic reactions in childhood are food allergens. High hypersensitivity to one food allergen can make it difficult for a family to find a substitution for an allergenic product. Food-induced anaphylactic reaction to quite a number of food allergens is a serious problem for both the physician and the family of an allergic child necessitating organization of appropriate and safe nutrition. In real life, the standard recommendation for the patient – to strictly follow the rules of the elimination diet with exclusion of the causative allergen and all cross-reactive allergens – often becomes unrealizable. There is a serious risk of developing new allergic reactions due to accidental intake of the triggering allergens because of incorrect food labelling by manufacturers. The objective of the work is to present a clinical case report that demonstrates the importance of performing allergy component testing (ImmunoCAP ISAC-112,) for identification of the full spectrum of allergens with subsequent assessment of allergenic molecules as triggering allergens and shows serious difficulties in the elaboration of recommendations on a personalised diet that should be adequate and safe for a child with a history of recurrent episodes of food-induced anaphylaxis. Key words: children, life-threatening reactions, allergy component testing, food labelling, food-induced anaphylaxis, food allergens

Manufacturing and quality assessment of allergenic extracts for immunotherapy: state of the art

The recent developments in the manufacturing and quality assessment of allergenic extracts in Europe are summarized. Quality assessment has always been a fundamental part of allergen product evaluation. New analytical methods have been reported that fill currently existing gaps in the characterization of commonly used allergen products. New types of products require innovative considerations and concepts for their assessment. Advanced standardization efforts aim at increasing reliability and comparability of analytical tools applied for allergen product characterization. In consequence, regulatory requirements are updated in line with such developments. Current demands on the quality of allergen products ensure production of well characterized products of consistent quality. While experience with manufacturing processes and successful product characterization approaches increase, accompanying and continuous re-evaluation of underlying quality control and assessment concepts is being performed.

Elemental Ratios Link Environmental Change and Human Health

Humans have fundamentally altered the cycling of multiple elements on a global scale. These changes impact the structure and function of terrestrial and aquatic ecosystems, with many implications for human health. Most prior studies linking biogeochemical changes to human health have evaluated the effects of single elements in isolation. However, the biological impact of shifts in the concentration of a single element often depend on its relative balance with other elements. This balance among multiple elements is the focus of ecological stoichiometry, which highlights the importance of elemental ratios in biological function across all systems and scales of organization. Consequently, ecological stoichiometry is a promising framework to inform research on the links between global changes to elemental cycles and human health. We synthesize evidence that elemental ratios link global change with human health through biological processes occurring at two scales: in the environment (natural ecosystems and food systems) and within the human body. Elemental ratios in the environment impact the key ecosystem processes of productivity and biodiversity, both of which contribute to the production of food, toxins, allergens, and parasites. Elemental ratios in diet impact processes within the human body, including the function and interactions of the immune system, parasites, and the non-pathogenic microbiome. Collectively, these stoichiometric effects contribute to a wide range of non-infectious and infectious diseases. By describing stoichiometric mechanisms linking global change, ecological processes, and human health, we hope to inspire future empirical and theoretical research on this theme.

Dynamics of the microbial community during growth of the house dust mite Dermatophagoides farinae in culture.

The variation in house dust mite microbial communities is important because various microorganisms modulate the production of allergens by their mite hosts and/or contaminate immunotherapeutic extracts. Temporal changes in mite microbiomes and the mite culture environment occurring at different stages of mite culture development are particularly understudied in this system. Here, we analyzed the dynamics of microbial communities during the culture growth of Dermatophagoides farinae. Changes in microbiomes were related to three key variables: the mite population density, microbial microcosm respiration and concentration of guanine (the mite nitrogenous waste metabolite). Mite populations exhibited the following phases: exponential growth, plateau and exponential decline. The intracellular bacterium Cardinium and the yeast Saccharomyces cerevisiae prevailed in the internal mite microbiomes, and the bacterium Lactobacillus fermentum was prevalent in the mite diet. The reduction in the mite population size during the late phases of culture development was related to the changes in their microbial profiles: the intracellular bacterium Cardinium was replaced by Staphylococcus, Oceanobacillus and Virgibacillus, and S. cerevisiae was replaced by the antagonistic fungi Aspergillus penicillioides and Candida. Increases in the guanine content were positively correlated with increases in the Staphylococcus and A. penicillioides profiles in the culture environment. Our results show that the mite microbiome exhibits strong, dynamic alterations in its profiles across different mite culture growth stages.

Development of ELISA Method for Detecting Crustacean Major Allergen Tropomyosin in Processed Food Samples

Crustacean aquatic products were recognized as allergenic food source and tropomyosin (TM) was identified as putative major allergen. At present, the most effective way to control allergenic incidence was avoidance of causative dietary source. This study reports the development of sandwich ELISA for effective detection of TM in suspected food sources by pairing two TM-specific polyclonal antibodies obtained from different species. The LOD was identified as 6.8 ng mL−1, with high specificity to the TM of shrimp and crab. No cross-reactivity was observed with the TM of fish, poultry, and mammalian. The mean recoveries in food matrices were range from 87.96 to 118.77%, by both intra- and inter-assay systems with coefficients of variation of < 10% and < 25%, respectively. The sandwich ELISA can be effectively applied for detection of TM in commercial products available in the market. It facilitates the allergen labeling and management for allergenic crustacean food products by both manufacturing and regulatory agencies.

Aberrant endosperm formation caused by reduced production of major allergen proteins in a rice flo2 mutant that confers low-protein accumulation in grains.

Rice flo2 mutation produces grains showing a reduced amount of storage proteins. Using Nipponbare and the flo2 mutant, we created rice transformants that showed defective production of major allergen proteins RA14 and RA33 (14-16 kDa and 33 kDa allergen proteins, respectively) by RNAi introduction. The knock-down transformant generated using Nipponbare showed greatly reduced accumulation of both allergen proteins, normal growth, and production of a sufficient amount of normal-shaped seeds. F1 seeds were obtained by crossing between the transformants containing RNAi genes to RA14 and RA33, and showed decreased accumulation of both proteins. However, a peculiar phenotype was observed in the flo2 transformants that lacked accumulation of RA14 or RA33. They showed significantly reduced fertility. A wrinkled grain feature was found on the transformant lacking accumulation of RA14. F1 seeds obtained by crossing these transformants showed significantly lower fertility. F2 seeds showed decreases in both allergen proteins but morphological abnormality with small and severely wrinkled features. These results indicated that it is hard to obtain any transformant lacking accumulation of these allergen proteins using the flo2 mutant, whereas a knock-down transformant of both allergen protein genes was obtained when a wild-type Nipponbare was used as a host. These facts strongly suggest that RA14 and RA33 have some roles in rice seeds.

Editorial introductions

Editorial introductions

Diversity and complexity of mouse allergens in allergenic products assessed with an immuno-allergomic approach

Diversity and complexity of mouse allergens in allergenic products assessed with an immuno-allergomic approach

House Dust Mite Allergy Under Changing Environments.

Environmental variations induced by industrialization and climate change partially explain the increase in prevalence and severity of allergic disease. One possible mechanism is the increase in allergen production leading to more exposure and sensitization in susceptible individuals. House dust mites (HDMs) are important sources of allergens inducing asthma and rhinitis, and experimentally they have been demonstrated to be very sensitive to microenvironment modifications; therefore, global or regional changes in temperature, humidity, air pollution or other environmental conditions could modify natural HDM growth, survival and allergen production. There is evidence that sensitization to HDMs has increased in some regions of the world, especially in the subtropical and tropical areas; however, the relationship of this increase with environmental changes is not so clear as has reported for pollen allergens. In this review, we address this point and explore the effects of current and predicted environmental changes on HDM growth, survival and allergen production, which could lead to immunoglobulin E (IgE) sensitization and allergic disease prevalence. We also assess the role of adjuvants of IgE responses, such as air pollution and helminth infections, and discuss the genetic and epigenetic aspects that could influence the adaptive process of humans to drastic and relatively recent environmental changes we are experiencing.

Lower allergen levels in hypoallergenic Curly Horses? A comparison among breeds by measurements of horse allergens in hair and air samples.

BackgroundExposure to horses can cause severe allergic reactions in sensitized individuals. The breed, American Bashkir Curly Horse is categorized as hypoallergenic, primarily due to reports of allergic patients experiencing fewer symptoms while handling this special breed. The possible reasons for this phenomenon could be lower allergen production and/or reduced allergen release into the air because of increased sebum content in their skin and hair compared to other breeds. Therefore, the aim of the current study was to compare different horse breeds in relation to allergen content in hair and airborne dust samples.MethodsIn total, 224 hair samples from 32 different horse breeds were investigated. Personal nasal filters were used to collect airborne dust during the grooming of 20 Curly Horses and 20 Quarter Horses. Quantitative analysis of all samples was performed using two newly developed immunoassays for the detection of horse dander (HD) antigens and the major allergen Equ c 1 and the commercial assay for Equ c 4. Results were analyzed using multiple linear regression models for hair samples and the Mann Whitney U test for airborne samples.ResultsHorse antigen and allergen levels differed up to four orders of magnitude between individual animals. Despite enormous variability, levels of HD antigen, Equ c 1 and Equ c 4 in hair were significantly related to the breed and gender combined with the castration status of male animals. Curly Horses had significantly higher concentrations of all three tested parameters compared to the majority of the investigated breeds (medians: 11800 μg/g for HD antigen, 2400 μg/g for Equ c 1, and 258 kU/g for Equ c 4). Tinker Horses, Icelandic Horses and Shetland Ponies were associated with approximately 7-fold reduced levels of HD antigen and Equ c 1, and up to 25-fold reduced levels of Equ c 4 compared to Curly Horses. Compared to mares, stallions displayed increased concentrations of HD antigens, Equ c 1 and Equ c 4 by a factor 2.2, 3.5 and 6.7, respectively. No difference was observed between mares and geldings. No differences in airborne allergen concentrations collected with personal nasal filters during grooming were found between Curly and Quarter Horses.ConclusionBreed and castration status had a significant influence on the antigen and allergen levels of horse hair. However, these differences were smaller than the wide variability observed among individual horses. Compared to other breeds, Curly Horses were not associated with lower allergen levels in hair and in air samples collected during grooming. Our approach provides no molecular explanation why Curly Horses are considered to be hypoallergenic.