Alternaria as an Inducer of Allergic Sensitization

Alternaria alternata is a saprophytic mold whose spores are disseminated in warm dry air, the typical weather of the Mediterranean climate region (from 30° to 45°), with a peak during the late summer and early autumn. Alternaria spores are known to be biological contaminants and a potent source of aeroallergens. One consequence of human exposure to Alternaria is an increased risk of developing asthma, with Alt a 1 as its main elicitor and a marker of primary sensitization. Although the action mechanism needs further investigation, a key role of the epithelium in cytokine production, TLR-activated alveolar macrophages and innate lymphoid cells in the adaptive response was demonstrated. Furthermore, sensitization to A. alternata seems to be a trigger for the development of co-sensitization to other allergen sources and may act as an exacerbator of symptoms and an elicitor of food allergies. The prevalence of A. alternata allergy is increasing and has led to expanding research on the role of this fungal species in the induction of IgE-mediated respiratory diseases. Indeed, recent research has allowed new perspectives to be considered in the assessment of exposure and diagnosis of fungi-induced allergies, although more studies are needed for the standardization of immunotherapy formulations.

Sensitisation To Imbrasia Belina (Mopane Worm) and Other Local Allergens in Rural Gwanda District of Zimbabwe

Background The prevalence of allergic diseases is increasing in Zimbabwe and the data relate to local as well as exotic allergen sources. As entomophagy, the practice of eating insects, is a recognised source of local allergens, we sought to measure the prevalence of and risk factors for sensitisation to Imbrasia belina (mopane worm), a popular edible insect. This was investigated alongside other locally relevant allergens in a rural community in Gwanda district, south of Zimbabwe. Methods A cross sectional study was conducted among 496 adults and children aged 10 years and above in Gwanda district, a mopane worm harvesting area in Zimbabwe. Data on individual characteristics, mopane worm exposure factors, sensitivity to commercial allergen extracts (Stallergenes, France) and in-house extracts of mopane worm (Imbrasia belina) and mopane leaves (Colophospermum mopane) were collected at a local clinic. Data were analysed using Stata version 13 software. Results The prevalence of sensitisation to at least one allergen was 31.17% (n = 144). The prevalence of atopy was higher in adults (33.33%) than in children (23.53%) (p = 0.059). The commonest inhalant allergen sources were mopane worm (14.29%), Tyrophagus putrescentiae (14.29%), mopane leaves (13.42%), Alternaria alternata (6.49%) and Dermatophagoides pteronyssinus (6.49%). Polysensitisation was demonstrated in the study population and of the 108 participants who were sensitised to two or more allergens, 66 (61%) were women. Sensitisation to mopane worm and mopane leaves often clustered with Tyrophagus putrescentiae amongst adults. Adjusted logistic regression analyses between mopane worm sensitisation and self-reported exposure variables showed that sensitisation was more likely amongst mopane worm harvesters (OR = 1.92, 95%CI = 0.77–4.79), those who cooked or roasted mopane worms during harvesting (OR = 2.69, 95%CI = 0.78–9.31) and harvesting without personal protective equipment (PPE) (OR = 2.12, 95%CI = 0.83–5.44) compared to non-harvesters. Conclusion Atopic sensitization was common in this mopane worm harvesting community in Gwanda district of Zimbabwe. There was frequent co-sensitisation of mopane worm and mopane leaves with Tyrophagus putrescentiae in children and adults. It is important to determine the clinical relevance of our findings, particularly relating to mopane worm sensitisation.

Analysis of Cross-Reactivity and Allergic Symptoms of 19 Allergens: Results from NHANES 2005–2006

<b><i>Introduction:</i></b> We explored the cross-reactivity among 19 common allergen sources and evaluated the influence of serum IgE concentrations and the number of sensitized allergens on the incidence of allergic symptoms. <b><i>Methods:</i></b> We conducted this cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2005–2006 which is a program of studies designed to assess the health and nutritional status of adults and children in the USA. After excluding participants with missing data from the allergen IgE test, allergy questionnaire, and respiratory health questionnaire, a total of 7,224 participants aged 6 years and older were included, as children younger than 6 years old did not complete all 19 allergen-specific IgE tests. Spearman correlation analysis was used to analyze the cross-reactivity between allergen sources. An independent sample Kruskal-Wallis test was performed to investigate the relationship between the serum-specific IgE levels of 19 allergens and the incidence of allergic symptoms. <b><i>Results:</i></b> The cross-reactivity between <i>D. farinae</i> and <i>D. pteronyssinus</i> was the strongest (ρ = 0.88), and cross-reactivity of cross-species was universal. With the increase in serum-specific IgE levels of <i>D. farinae</i>, <i>D. pteronyssinus</i>, oak, and birch, the incidence of sneezing increased (<i>p</i> &#x3c; 0.05). With the increase in serum-specific IgE levels of cats, dogs, peanuts, <i>Aspergillus</i>, and <i>Alternaria</i>, the incidence of wheezing increased (<i>p</i> &#x3c; 0.05). The incidence of rash was positively correlated with serum-specific IgE levels of <i>D. farinae</i>, <i>D. pteronyssinus</i>, shrimp, and peanut (<i>p</i> &#x3c; 0.05). The incidence of wheezing continued to increase with an increase in sensitized allergens. When participants were sensitized to &#x3c;10 allergens, the incidence of sneezing continued to increase as the number of sensitized allergens increased, whereas the incidence of rash did not have a clear association with the number of sensitized allergens. <b><i>Conclusion:</i></b> Species that are biologically close are more likely to have antigen cross-reactivity, while cross-reactivity among different species is common. Different allergens tend to cause different allergic symptoms. Different allergic sites in the body have inconsistent responses to the number of sensitized allergens.

The Molecular Allergen Recognition Profile in China as Basis for Allergen-Specific Immunotherapy

Approximately 30% of the world population suffers from immunoglobulin-E (IgE)-mediated allergy. IgE-mediated allergy affects the respiratory tract, the skin and the gastrointestinal tract and may lead to life-threatening acute systemic manifestations such as anaphylactic shock. The symptoms of allergy are mediated by IgE-recognition of causative allergen molecules from different allergen sources. Today, molecular allergy diagnosis allows determining the disease-causing allergens to develop allergen-specific concepts for prevention and treatment of allergy. Allergen-specific preventive and therapeutic strategies include allergen avoidance, vaccination, and tolerance induction. The implementation of these preventive and therapeutic strategies requires a detailed knowledge of the relevant allergen molecules affecting a given population. China is the world´s most populous country with around 1.4 billion inhabitants and an estimated number of more than 400 million allergic patients. Research in allergy in China has dramatically increased in the last decade. We summarize in this review article what is known about the dominating allergen sources and allergen molecules in China and what further investigations could be performed to draw a molecular map of IgE sensitization for China as a basis for the implementation of systematic and rational allergen-specific preventive and therapeutic strategies to combat allergic diseases in this country.

Mosquitoes: Important Sources of Allergens in the Tropics

There are more than 3,000 mosquito species. Aedes aegypti, Ae. communis, and C. quinquefasciatus are, among others, three of the most important mosquito allergen sources in the tropics, western, and industrialized countries. Several individuals are sensitized to mosquito allergens, but the epidemiological data indicates that the frequency of sensitization markedly differs depending on the geographical region. Additionally, the geographical localization of mosquito species has been affected by global warming and some mosquito species have invaded areas where they were not previously found, at the same time as other species have been displaced. This phenomenon has repercussions in the pathogenesis and the accuracy of the diagnosis of mosquito allergy. Allergic individuals are sensitized to mosquito allergens from two origins: saliva and body allergens. Exposure to saliva allergens occurs during mosquito bite and induces cutaneous allergic reactions. Experimental and clinical data suggest that body allergens mediate different manifestations of allergic reactions such as asthma and rhinitis. The most studied mosquito species is Ae. aegypti, from which four and five allergens of the saliva and body, respectively, have been reported. Many characterized allergens are homologs to arthropod-derived allergens, which cause strong cross-reactivity at the humoral and cellular level. The generalized use of whole body Ae. communis or C. quinquefasciatus extracts complicates the diagnosis of mosquito allergy because they have low concentration of saliva allergens and may result in poor diagnosis of the affected population when other species are the primary sensitizer. This review article discusses the current knowledge about mosquito allergy, allergens, cross-reactivity, and proposals of component resolved approaches based on mixtures of purified recombinant allergens to replace saliva-based or whole-body extracts, in order to perform an accurate diagnosis of allergy induced by mosquito allergen exposure.

Serum allergen-specific IGE to common aeroallergens among allergic rhinitis patients in Egypt

Background Allergic rhinitis is the most prevalent allergic disease, and the prevalence and sensitization patterns differ among countries. Identifying the most common inhalant allergen in each region plays a key role in the diagnosis and management of allergic rhinitis. There are no data available about the most prevalent aeroallergen among allergic rhinitis patients in Egypt. The aim of this study is to evaluate the prevalence of positive serum allergen-specific IGE to common inhalant allergens among allergic rhinitis patients in Egypt. A cross-sectional study was conducted on 354 allergic rhinitis patients, serum allergen-specific IGE was measured by using the Immuno CAP system to 16 common regional aeroallergens including (pollens, mite, molds, animal dander, and cockroach). Results The overall rate of sensitization to any allergen was 74.6%. Dermatophagoides pteronyssinus, birch pollens, and Dermatophagoides farina were the most prevalent allergens (29.7%, 23.7%, and 18.6%), respectively. Cladosporuim molds were the least prevalent individual allergens (1.7%). Conclusion Our data suggest that Dermatophagoides pteronyssinus and birch pollens were the predominant allergen sources among allergic rhinitis patient in Egypt.

Inhibition of Both Cyclooxygenase-1 and -2 Promotes Epicutaneous Th2 and Th17 Sensitization and Allergic Airway Inflammation on Subsequent Airway Exposure to Protease Allergen in Mice

<b><i>Introduction:</i></b> Epicutaneous (e.c.) allergen exposure is an important route of sensitization toward allergic diseases in the atopic march. Allergen sources such as house dust mites contain proteases that involve in the pathogenesis of allergy. Prostanoids produced via pathways downstream of cyclooxygenases (COXs) regulate immune responses. Here, we demonstrate effects of COX inhibition with nonsteroidal anti-inflammatory drugs (NSAIDs) on e.c. sensitization to protease allergen and subsequent airway inflammation in mice. <b><i>Methods:</i></b> Mice were treated with NSAIDs during e.c. sensitization to a model protease allergen, papain, and/or subsequent intranasal challenge with low-dose papain. Serum antibodies, cytokine production in antigen-restimulated skin or bronchial draining lymph node (DLN) cells, and airway inflammation were analyzed. <b><i>Results:</i></b> In e.c. sensitization, treatment with a nonspecific COX inhibitor, indomethacin, promoted serum total and papain-specific IgE response and Th2 and Th17 cytokine production in skin DLN cells. After intranasal challenge, treatment with indomethacin promoted allergic airway inflammation and Th2 and Th17 cytokine production in bronchial DLN cells, which depended modestly or largely on COX inhibition during e.c. sensitization or intranasal challenge, respectively. Co-treatment with COX-1-selective and COX-2-selective inhibitors promoted the skin and bronchial DLN cell Th cytokine responses and airway inflammation more efficiently than treatment with either selective inhibitor. <b><i>Conclusion:</i></b> The results suggest that the overall effects of COX downstream prostanoids are suppressive for development and expansion of not only Th2 but also, unexpectedly, Th17 upon exposure to protease allergens via skin or airways and allergic airway inflammation.

Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses

The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.

Effects of Extraction Buffer on the Solubility and Immunoreactivity of the Pacific Oyster Allergens

Despite recent technological advances, novel allergenic protein discovery is limited by their low abundance, often due to specific physical characteristics restricting their recovery during the extraction process from various allergen sources. In this study, eight different extraction buffers were compared for their ability to recover proteins from Pacific oyster (Crassostrea gigas). The protein composition was investigated using high resolution mass spectrometry. The antibody IgE-reactivity of each extract was determined using a pool of serum from five shellfish-allergic patients. Most of the investigated buffers showed good capacity to extract proteins from the Pacific oyster. In general, a higher concentration of proteins was recovered using high salt buffers or high pH buffers, subsequently revealing more IgE-reactive bands on immunoblotting. In contrast, low pH buffers resulted in a poor protein recovery and reduced IgE-reactivity. Discovery of additional IgE-reactive proteins in high salt buffers or high pH buffers was associated with an increase in allergen abundance in the extracts. In conclusion, increasing the ionic strength and pH of the buffer improves the solubility of allergenic proteins during the extraction process for oyster tissue. This strategy could also be applied for other difficult-to-extract allergen sources, thereby yielding an improved allergen panel for increased diagnostic efficiency.

Novel Allergen Discovery through Comprehensive De Novo Transcriptomic Analyses of Five Shrimp Species

Shellfish allergy affects 2% of the world’s population and persists for life in most patients. The diagnosis of shellfish allergy, in particular shrimp, is challenging due to the similarity of allergenic proteins from other invertebrates. Despite the clinical importance of immunological cross-reactivity among shellfish species and between allergenic invertebrates such as dust mites, the underlying molecular basis is not well understood. Here we mine the complete transcriptome of five frequently consumed shrimp species to identify and compare allergens with all known allergen sources. The transcriptomes were assembled de novo, using Trinity, from raw RNA-Seq data of the whiteleg shrimp (Litopenaeus vannamei), black tiger shrimp (Penaeus monodon), banana shrimp (Fenneropenaeus merguiensis), king shrimp (Melicertus latisulcatus), and endeavour shrimp (Metapenaeus endeavouri). BLAST searching using the two major allergen databases, WHO/IUIS Allergen Nomenclature and AllergenOnline, successfully identified all seven known crustacean allergens. The analyses revealed up to 39 unreported allergens in the different shrimp species, including heat shock protein (HSP), alpha-tubulin, chymotrypsin, cyclophilin, beta-enolase, aldolase A, and glyceraldehyde-3-phosphate dehydrogenase (G3PD). Multiple sequence alignment (Clustal Omega) demonstrated high homology with allergens from other invertebrates including mites and cockroaches. This first transcriptomic analyses of allergens in a major food source provides a valuable resource for investigating shellfish allergens, comparing invertebrate allergens and future development of improved diagnostics for food allergy.