Relevant Allergens Research Articles

Optimization of the allergen classification of the International Classification Of Diseases, 11th Revision (ICD-11)

Accurate diagnosis of triggers or causative allergens is essential for appropriate risk assessment, providing correct advice to patients with allergy and their caregivers and personalized treatment. However, allergens have never been represented in the World Health Organization International Classification of Diseases (ICD). In this article, we present the process of selection of allergens to better fit the ICD, 11th Revision (ICD-11) structure and the outcomes of this process. The Logical Observation Identifiers Names and Codes database, containing 1444 allergens, was used as the basis for the selection process. Two independent experts were responsible for the first selection of the allergens according to specific technical criteria. The second step of the selection process was based on real-life relevance of the allergens according to the frequency of requests regarding each of them. We selected 1109 allergens (76.8%) from all 1444 present in the Logical Observation Identifiers Names and Codes database, with considerable agreement between experts (Cohen κ= 8.6). After assessment of real-life data, 297 additional relevant allergens worldwide were selected and grouped as plants (36.4%), drugs (32.6%), animal proteins (21%), mold and other microorganisms (1.5%), occupational allergens (0.4%), and miscellaneous allergens (0.5%). The stepwise approach allowed us to select the most relevant allergens in practice, which is the first step to building a classification of allergens for the WHO ICD-11. Aligned with the achievement in the construction of the pioneer section addressed to the allergic and hypersensitivity conditions in the ICD-11, the introduction of a classification for allergens can be considered timely and much needed in clinical practice.

CD4+ T cells inhibit the generation of CD8+ epidermal-resident memory T cells directed against clinically relevant contact allergens.

CD8+ epidermal-resident memory T (TRM ) cells play central roles in local flare-up responses to experimental contact allergens by inducing massive influx of neutrophils to the epidermis upon allergen challenge. Whether similar immunopathogenic mechanisms are involved in the responses to clinically relevant contact allergens is unknown. The immune response to cinnamal, ρ-phenylenediamine (PPD) and methylisothiazolinone (MI) was studied in a well-established mouse model for allergic contact dermatitis that includes formation of TRM cells by ELISA, flow cytometry, fluorescence microscopy analyses and cell depletion protocols. We show that the formation of CD4+ and CD8+ epidermal TRM cells and the inflammatory response are highly allergen-dependent. However, the magnitude of the flare-up responses correlated with the number of epidermal CD8+ TRM cells, CXCL1/CXCL2 release and recruitment of neutrophils to the epidermis. Finally, depletion of CD4+ T cells strongly enhanced the number of epidermal CD8+ TRM cells, the flare-up response and the epidermal infiltration of neutrophils for all allergens. As the first, this study demonstrates that clinically relevant contact allergens have the ability to generate pathogenic, epidermal CD8+ TRM cells that recruit neutrophils following re-exposure to the allergen, but that this normally is counteracted by the simultaneous induction of anti-inflammatory CD4+ T cells.

Perspectives on Non-IgE-Mediated Gastrointestinal Food Allergy in Pediatrics: A Review of Current Evidence and Guidelines.

Food allergy is an immune-mediated disease that can result in considerable morbidity and even mortality, with a significant negative impact on patients' quality of life. It is characterized by allergic symptoms that can occur shortly after a relevant food allergen ingestion, or can be delayed or chronic, which make it more difficult for diagnosis. The symptoms of this disease can range from mild to severe, and rarely can cause anaphylaxis, a life-threatening allergic reaction. The prevalence of non-immunoglobulin E (IgE)-mediated food allergy is poorly established outside of cow's milk allergy, with an adjusted incidence ranging between 0.13% and 0.72%. Several disorders are classified as non-immunoglobulin E (IgE)-mediated food allergies that predominantly affect the gastrointestinal tract including food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), food protein-induced allergic enteropathy (FPE), and food protein-induced dysmotility disorders (GORD and constipation). Eosinophilic esophagitis (EoE) is listed in this group, even though it considered by some authorities to be mixed reaction with both IgE and cell-mediated immune response to be involved in the reaction. The most common types of non-IgE-mediated food allergy are food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). These disorders typically present in infancy and are often triggered by cow's milk protein. Patients with FPIES present with profuse emesis and dehydration, while FPIAP patients present with hematochezia in otherwise healthy infants. Since there are no specific confirmatory non-invasive diagnostic laboratory tests, the diagnosis is usually made clinically when typical symptoms improve upon the removal of the culprit food. Food reintroduction should be attempted, when possible, with documentation of symptoms of relapse to confirm the diagnosis. The management includes dietary avoidance, supportive treatment in the case of accidental exposure, and nutritional counseling. This review focuses on the clinical manifestations, epidemiology, management, and recent guidelines of the most common non-IgE-mediated food hypersensitivity disorders (FPIES, FPIAP, and FPE).

Patch Testing of Thai Children with Eczema

Objective: To detect contact allergy rate and common allergens in Thai children presented with eczema. Materials and Methods: A total of 124 children, aged 1-15 years, were patch tested using a pediatric screening series of 16 allergens and relevant additional allergens. Data on clinical presentation, atopic history and test results were collected. Results: Contact allergy was found in 51 of 124 children (41.1%) presented with all forms of eczema. The common allergens were lanolin alcohol (8.9%), cocamidopropyl betaine (8.1%), nickel sulfate (7.3%), fragrance mix I (5.6%), formaldehyde (5.6%), thimerosal (5.6%), fragrance mix II (4.8%), cobalt chloride (4.0%), methylchloroisothiazolinone/methylisothiazolinone (2.4%), methylisothiazolinone (2.4%) and thiuram mix (2.4%). Nineteen of 50 atopic dermatitis patients (38%) showed positive patch test reactions. Conclusion: Allergic contact dermatitis is common in children. Both atopic and non-atopic patients can develop contact dermatitis. Patch testing should be performed in children presented with eczema regardless of contact dermatitis history.

Proteomics-based approach for detailing allergenic profile of cannabis chemotypes

Allergic sensitization to cannabis is difficult to establish owing to lack of standardized diagnostic approaches. Using proteomics-based approach, we examined if distinct varieties of cannabis plant contain relevant allergens of cannabis.

Occupational contact allergy: The European perspective-Analysis of patch test data from ESSCA between 2011 and 2020.

Occupational skin diseases have led the occupational disease statistics in Europe for many years. Especially occupational allergic contact dermatitis is associated with a poor prognosis and low healing rates leading to an enormous burden for the affected individual and for society. To present the sensitization frequencies to the most relevant allergens of the European baseline series in patients with occupational contact dermatitis (OCD) and to compare sensitization profiles of different occupations. The data of 16 022 patients considered having OCD after patch testing within the European Surveillance System on Contact Allergies (ESSCA) network between January 2011 and December 2020 were evaluated. Patients (n= 46 652) in whom an occupational causation was refuted served as comparison group. The highest percentages of OCD were found among patients working in agriculture, fishery and related workers, metal industry, chemical industry, followed by building and construction industry, health care, food and service industry. Sensitizations to rubber chemicals (thiurams, carbamates, benzothiazoles) and epoxy resins were associated with at least a doubled risk of OCD. After a decline from 2014 onwards, the risks to acquire an occupation-related sensitization to methyl(chloro)isothiazolinone (MCI/MI) and especially to methylisothiazolinone (MI) seem to increase again. Sensitization rates to formaldehyde were stable, and to methyldibromo glutaronitrile (MDBGN) slightly decreasing over time. Among allergens in the European Baseline Series, occupational relevance is most frequently attributed to rubber accelerators, epoxy resins and preservatives.

Identification of carboxymethyl (CM)-binding proteins derived from Lolium multiflorum pollen extract and antibody reactivity in Brazilian allergic patients.

Lolium multiflorum grass is the major pollen allergen source in the southern region of Brazil, but most of its allergens remain poorly characterized. The aim of this study was to investigate antibody reactivity to L. multiflorum crude and carboxymethyl-ligand extracts in allergic patients and healthy individuals. Ion exchange carboxymethyl (CM) chromatography (CM-Sepharose) was used to isolate proteins (S2) from L. multiflorum crude extract (S1), which were assessed by SDS-PAGE. S1- and S2-specific IgE and IgG4 levels were measured by ELISA using sera from 55 atopic and 16 non-atopic subjects. Reactive polypeptide bands in S1 and S2 were detected by immunoblotting, and the most prominent bands in S2 were analyzed by mass spectrometry (MS-MS). Similar IgE and IgG4 levels were observed to both S1 (IgE median absorbance: 1.22; IgG4 median absorbance: 0.68) and S2 (IgE median absorbance: 1.26; IgG4 median absorbance: 0.85) in atopic subjects. S1 and S2 had positive correlations for IgE and IgG4 (IgE: r=0.9567; IgG4: r=0.9229; P<0.0001) levels. Homology between S1 and S2 was confirmed by IgE (84%) and IgG4 (83%) inhibition. Immunoblotting revealed that the 29-32 kDa band was recognized by 100% of atopic subjects in both S1 and S2. MS-MS analysis identified similarity profile to groups 1 and 5 grass allergens. This study revealed that carboxymethyl-ligand fraction played an important role for pollen allergy diagnosis by containing clinically relevant allergens and constituted a promising candidate for allergen-specific immunotherapy.

Allergen immunotherapy in the polyallergic adolescent

Allergen immunotherapy is the only disease-modifying treatment option for allergic rhinitis, with adherence being its major limitation. We report a case of an adolescent with rhinitis, proven allergy to multiple non-homologous pollens, and troublesome symptoms despite maximal symptomatic therapy during the late spring and early summer months. Allergen immunotherapy to the most clinically relevant allergen was initiated under the supervision of a pediatrician. Shortly before her second year of treatment, she transferred to adult care and maintained a high degree of adherence and a favourable response to immunotherapy. In conclusion, allergen immunotherapy is effective in polyallergic adolescents with good adherence.

Prevalence and trend of allergen sensitization in patients with cheilitis referred for patch testing, North American Contact Dermatitis Group data, 2001-2018.

An updated understanding of allergic contact cheilitis is needed. To characterize clinical characteristics and allergen relevance in patients with cheilitis referred for patch testing. Retrospective analysis of 43 772 patients patch tested with the North American Contact Dermatitis Group (NACDG) screening series from 2001 to 2018. Overall, 2094 patients (4.8%) had lips as one of three sites of dermatitis, 1583 (3.6%) had lips as the primary site and 1167 (2.7%) had lips as the sole site of dermatitis. Prevalences of cheilitis at any, primary, and sole sites significantly increased throughout the study cycle from 2001-2002 (2.7%, 2.2% and 1.7%) to 2017-2018 (7.8%, 5.2% and 3.7%). Approximately 60% of patients with any, a primary, or a sole site of cheilitis had one or more positive allergic patch-test reactions compared to 65% of those without cheilitis. Patients with cheilitis who were referred for patch testing had high rates of positive and relevant allergens. More than one in four patients with any, primary, or sole cheilitis had a positive reaction to non-NACDG screening allergens (28.0%, 26.8%, 31.1% vs. 21.6%) compared to patients without cheilitis, emphasizing the need for expanded patch test series in cheilitis.

Rhinitis symptom in patients with self-reported allergic rhinitis is influenced by sensitization pattern: A cross-sectional study of China.

Allergic rhinitis (AR) is characterized by distinct clinical heterogeneity and allergic sensitization patterns. We aimed to quantify rhinitis symptoms in patients with self-reported allergic rhinitis according to the potential sensitization patterns for relevant allergens in China. We used latent class analysis (LCA; a subset of structural equation modeling) to independently cluster patients into different patterns of atopic sensitization in an unsupervised manner, based on specific immunoglobulin E tests. AR symptom severity was assessed by the visual analogue scale. We evaluated the association between the severity of AR and the allergen sensitization patterns. LCA revealed four phenotypes of atopic sensitization among 967 patients with self-report AR. We labeled latent classes as: Class 1, weed pollens and indoor sensitization (n = 74 [7.7%]); Class 2, weed pollen with low indoor sensitization (n = 275 [28.4%]); Class 3, low or no sensitization (n = 350 [36.2%]); and Class 4, house dust mite-dominated sensitization (n = 268 [27.7%]). AR was more severe in Class 2 compared to the other 3 classes, indicating that upper respiratory symptoms are more severe among patients with isolated seasonal rhinitis. We have identified four sensitization patterns in patients with self-reported AR, which were associated with different clinical symptoms and comorbidities.

Novel peanut-specific human IgE monoclonal antibodies enable screens for inhibitors of the effector phase in food allergy.

Background10% of US residents have food allergies, including 2% with peanut allergy. Mast cell mediators released during the allergy effector phase drive allergic reactions. Therefore, targeting sensitized mast cells may prevent food allergy symptoms.ObjectiveWe used novel, human, allergen-specific, IgE monoclonal antibodies (mAbs) created using human hybridoma techniques to design an in vitro system to evaluate potential therapeutics targeting sensitized effector cells.MethodsTwo human IgE mAbs specific for peanut, generated through human hybridoma techniques, were used to sensitize rat basophilic leukemia (RBL) SX-38 cells expressing the human IgE receptor (FcϵRI). Beta-hexosaminidase release (a marker of degranulation), cytokine production, and phosphorylation of signal transduction proteins downstream of FcϵRI were measured after stimulation with peanut. Degranulation was also measured after engaging inhibitory receptors CD300a and Siglec-8.ResultsPeanut-specific human IgE mAbs bound FcϵRI, triggering degranulation after stimulation with peanut in RBL SX-38 cells. Sensitized RBL SX-38 cells stimulated with peanut increased levels of phosphorylated SYK and ERK, signal transduction proteins downstream of FcϵRI. Engaging inhibitory cell surface receptors CD300a or Siglec-8 blunted peanut-specific activation.ConclusionAllergen-specific human IgE mAbs, expressed from human hybridomas and specific for a clinically relevant food allergen, passively sensitize allergy effector cells central to the in vitro models of the effector phase of food allergy. Peanut reproducibly activates and induces degranulation of RBL SX-38 cells sensitized with peanut-specific human IgE mAbs. This system provides a unique screening tool to assess the efficacy of therapeutics that target allergy effector cells and inhibit food allergen-induced effector cell activation.

Allergens from house dust and storage mites

SummaryHouse dust mites are among the most important allergy triggers worldwide. While mites of the genus Dermatophagoides occur almost worldwide, the tropical mite Blomia tropicalis and storage mites are only of importance for certain areas or groups of people. The most important allergens of Dermatophagoides pteronyssinus are Der p 1, Der p 2, and Der p 23 with immunoglobulin E (IgE)-binding frequencies of more than 70% and high allergenic activity. Also of importance are Der p 5, Der p 7, and Der p 21, which have IgE-binding frequencies of about 30%. According to the current state of knowledge, these six allergens are the allergens of clinical relevance which are also required for diagnosis and immunotherapy with individual components.

A Retrospective Review of Late Delayed Positive Patch Testing Greater Than Day 8 at Mayo Clinic From 2001 to 2020.

Patch tests are read between days 5 and 7, because most hypersensitivity reactions occur within 7 days. Later reactions can occur after day 8, which may be missed. The aim of the study was to review all late delayed positive (LDP) reactions that have occurred after day 8 at Mayo Clinic from 2001 to 2020. Mayo Clinic records were reviewed for patients who had patch test readings performed at greater than day 8. Late delayed positive reactions were defined as any patch tests that were initially negative from days 4 to 7 yet became positive after day 8. Two hundred seventy-four patients developed 439 LDPs to 89 allergens. Fourteen allergens had LDPs in at least 2% of patients: gold (gold sodium thiosulfate-3 concentrations, gold chloride, potassium dicyanoaurate), cobalt (cobalt sulfate, cobalt chloride hexahydrate), beryllium, palladium, acrylates (2-hydroxypropyl methacrylate, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate), dodecyl gallate, and gentamycin. Late delayed positive reactions to gold allergens were the most frequent reactions. Up to 90% of relevant gold allergen LDPs were positive by day 15. Positive patch test readings after day 8 are uncommon, but allergens most likely to be positive are metals (gold, cobalt, palladium, beryllium), acrylates, dodecyl gallate, and gentamycin. Gold allergens showed the highest LDP rates and relevance, with most reactions occurring by day 15.

The ketone body β-hydroxybutyrate mitigates ILC2-driven airway inflammation by regulating mast cell function.

Ketone bodies are increasingly understood to have regulatory effects on immune cell function, with β-hydroxybutyrate (BHB) exerting a predominantly anti-inflammatory response. Dietary strategies to increase endogenous ketone body availability such as the ketogenic diet (KD) have recently been shown to alleviate inflammation of the respiratory tract. However, the role of BHB has not been addressed. Here, we observe that BHB suppresses group 2 innate lymphoid cell (ILC2)-mediated airway inflammation. Central to this are mast cells, which support ILC2 proliferation through interleukin-2 (IL-2). Suppression of the mast cell/IL-2 axis by BHB attenuates ILC2 proliferation and the ensuing type 2 cytokine response and immunopathology. Mechanistically, BHB directly inhibits mast cell function in part through GPR109A activation. Similar effects are achieved with either the KD or 1,3-butanediol. Our data reveal the protective role of BHB in ILC2-driven airway inflammation, which underscores the potential therapeutic value of ketone body supplementation for the management of asthma.

Reconsider the Art of Allergen Immunotherapy

This symposium took place during the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress, held in Prague, Czechia, in July 2022. Stephanie Dramburg, Medical Doctor at Charité Universitätsmedizin, Berlin, Germany, explained that the traditional diagnostic work-up for allergic rhinoconjunctivitis (AR) comprises retrospective clinical history and allergen exposure assessment, extract-based diagnostics, component-resolved diagnostics (CRD), which enables markers of genuine sensitisation to be distinguished from markers of cross-reactivity, and confirmation of clinical relevance. She highlighted that molecular IgE assessment supports the diagnostic work-up and personalised risk assessment in complex cases and that confirmation of clinical relevance of IgE results is key. Furthermore, broadening of a serum IgE response is indicative of ‘molecular spreading’. Dramburg considered that digital technologies have the potential to enhance medical decisions at the point-of-care via targeted patient information, guideline- and evidence-based clinical knowledge, and prospectively collected patient- and sensor-generated data. Marek Jutel, Medical Professor at Wroclaw Medical University, Poland, and the ALL-MED Medical Research Institute, Wroclaw, Poland, described that patients with allergies show different clinical pictures due to differing sensitisation profiles assessed at the molecular level. He noted that patients with allergies react differently to different allergen doses and allergen immunotherapy (AIT) preparations, and minor/intermediate allergens are necessary, in addition to major allergens, for optimal clinical efficacy. Jutel described that allergens that are decisive for AIT efficacy are defined in grass pollen but are not yet determined for other allergen sources such as birch and house dust mite (HDM). Petra Zieglmayer, Medical Professor at Karl Landsteiner University, Krems, Austria, and Head of Vienna Challenge Chamber, Austria, discussed that patients with allergies show complex molecular sensitisation profiles and that extract preparations from different manufacturers vary in terms of allergen composition, with major and intermediate allergens not always detectable. She clarified that optimal efficacy of AIT may only be expected from preparations containing all relevant allergen components in sufficient amounts. Zieglmayer proposed that the target should be to find a match between the patient molecular sensitisation profile and the allergen preparation and that this can be achieved.

Reconsider the Art of Allergen Immunotherapy

This symposium took place during the European Academy of Allergy and Clinical Immunology (EAACI) Hybrid Congress, held in Prague, Czechia, in July 2022. Stephanie Dramburg, Medical Doctor at Charité Universitätsmedizin, Berlin, Germany, explained that the traditional diagnostic work-up for allergic rhinoconjunctivitis (AR) comprises retrospective clinical history and allergen exposure assessment, extract-based diagnostics, component-resolved diagnostics (CRD), which enables markers of genuine sensitisation to be distinguished from markers of cross-reactivity, and confirmation of clinical relevance. She highlighted that molecular IgE assessment supports the diagnostic work-up and personalised risk assessment in complex cases and that confirmation of clinical relevance of IgE results is key. Furthermore, broadening of a serum IgE response is indicative of ‘molecular spreading’. Dramburg considered that digital technologies have the potential to enhance medical decisions at the point-of-care via targeted patient information, guideline- and evidence-based clinical knowledge, and prospectively collected patient- and sensor-generated data. Marek Jutel, Medical Professor at Wroclaw Medical University, Poland, and the ALL-MED Medical Research Institute, Wroclaw, Poland, described that patients with allergies show different clinical pictures due to differing sensitisation profiles assessed at the molecular level. He noted that patients with allergies react differently to different allergen doses and allergen immunotherapy (AIT) preparations, and minor/intermediate allergens are necessary, in addition to major allergens, for optimal clinical efficacy. Jutel described that allergens that are decisive for AIT efficacy are defined in grass pollen but are not yet determined for other allergen sources such as birch and house dust mite (HDM). Petra Zieglmayer, Medical Professor at Karl Landsteiner University, Krems, Austria, and Head of Vienna Challenge Chamber, Austria, discussed that patients with allergies show complex molecular sensitisation profiles and that extract preparations from different manufacturers vary in terms of allergen composition, with major and intermediate allergens not always detectable. She clarified that optimal efficacy of AIT may only be expected from preparations containing all relevant allergen components in sufficient amounts. Zieglmayer proposed that the target should be to find a match between the patient molecular sensitisation profile and the allergen preparation and that this can be achieved.

Food allergy testing in atopic dermatitis

Food allergy and food-related worsening of dermatitis can occur in patients with atopic dermatitis (AD). We reviewed the relationship of AD with food allergen hypersensitivity and the risks and benefits of food allergen testing and avoidance in patients with AD. Skin prick testing and specific immunoglobulin E to aeroallergens may identify patients with immediate hypersensitivity. Atopy patch tests may detect non–immunoglobulin E–mediated reactions but are not standardized or routinely used. Younger children with more severe AD in whom the optimal management failed may have food-triggered AD. Egg, milk, and peanut account for most food allergens. Elimination of relevant food allergens should improve AD but must be guided by appropriate allergy testing and establishing clinical relevance. Serum immunoglobulin E panels for food allergens are discouraged in the primary care setting because of their difficulty of interpretation. Empiric avoidance of foods is entirely discouraged in AD because of their risk of causing nutritional issues, food allergy, and other problems.

Hand and foot dermatitis in patients referred for patch testing: Analysis of North American Contact Dermatitis Group Data, 2001-2018

Dermatitis localized to hands (HD), feet (FD), or both hands and feet (HFD) has multiple etiologies, including atopic dermatitis, irritant contact dermatitis, and allergic contact dermatitis. Unfortunately, little is known about clinical differences between patients with HD, FD, and HFD. To characterize differences in demographics, etiology, and patch testing results among patients presenting with HD, FD, or HFD referred for patch testing. A retrospective analysis of patients patch tested by the North American Contact Dermatitis Group between 2001 and 2018. Of 43,677 patients who were patch tested, 22.8% had HD, 2.9% had FD, and 3.7% had HFD. Allergic and currently relevant patch test reactions to ≥1 North American Contact Dermatitis Group screening allergen occurred in similar proportions in all 3 study groups. However, HD (18.0%) had higher proportions of occupationally relevant reactions than HFD (8.9%) or FD (4.0%). Nickel and fragrance mix I were in the top 5 currently relevant allergens for HD, FD, and HFD. Other top allergens, as well as allergen sources, differed between HD, FD, and HFD. No data on HD or FD morphology or distribution. HD, FD, and HFD have several differences with respect to patient characteristics, etiologies, and clinically relevant allergens.

Mammalian derived lipocalin and secretoglobin respiratory allergens strongly bind ligands with potentially immune modulating properties.

Allergens from furry animals frequently cause sensitization and respiratory allergic diseases. Most relevant mammalian respiratory allergens belong either to the protein family of lipocalins or secretoglobins. Their mechanism of sensitization remains largely unresolved. Mammalian lipocalin and secretoglobin allergens are associated with a function in chemical communication that involves abundant secretion into the environment, high stability and the ability to transport small volatile compounds. These properties are likely to contribute concomitantly to their allergenic potential. In this study, we aim to further elucidate the physiological function of lipocalin and secretoglobin allergens and link it to their sensitizing capacity, by analyzing their ligand-binding characteristics. We produced eight major mammalian respiratory allergens from four pet species in E.coli and compared their ligand-binding affinities to forty-nine ligands of different chemical classes by using a fluorescence-quenching assay. Furthermore, we solved the crystal-structure of the major guinea pig allergen Cav p 1, a typical lipocalin. Recombinant lipocalin and secretoglobin allergens are of high thermal stability with melting temperatures ranging from 65 to 90°C and strongly bind ligands with dissociation constants in the low micromolar range, particularly fatty acids, fatty alcohols and the terpene alcohol farnesol, that are associated with potential semiochemical and/or immune-modulating functions. Through the systematic screening of respiratory mammalian lipocalin and secretoglobin allergens with a large panel of potential ligands, we observed that total amino acid composition, as well as cavity shape and volume direct affinities to ligands of different chemical classes. Therefore, we were able to categorize lipocalin allergens over their ligand-binding profile into three sub-groups of a lipocalin clade that is associated with functions in chemical communication, thus strengthening the function of major mammalian respiratory allergens as semiochemical carriers. The promiscuous binding capability of hydrophobic ligands from environmental sources warrants further investigation regarding their impact on a molecule's allergenicity.

A Pragmatic Primary Practice Approach to Using Specific IgE in Allergy Testing in Asthma Diagnosis, Management, and Referral

Asthma afflicts an estimated 339 million people globally and is associated with ill health, disability, and early death. Strong risk factors for developing asthma are genetic predisposition and environmental exposure to inhaled substances that may provoke allergic reactions. Asthma guidelines recommend identifying causal or trigger allergens with specific IgE (sIgE) testing after a diagnosis of asthma has been made. Allergy testing with sIgE targets subpopulations of patients considered at high risk, such as those with frequent exacerbations, emergency visits or hospitalizations, or uncontrolled symptoms. Specific recommendations apply to preschool children, school-age children, patients with persistent or difficult-to-control asthma, patients needing oral corticosteroids or high-dose inhaled steroids, patients seeking understanding and guidance about their disease, and candidates for advanced therapies (biologics, allergen immunotherapy). Allergen skin testing is common in specialized settings but less available in primary care. Blood tests for total and sIgE are accessible and yield quantifiable results for tested allergens, useful for detecting sensitization. Results are interpreted in the context of the patient’s clinical presentation, age, and relevant allergen exposures. Incorporating sIgE testing into asthma management adds objective information to identify specific allergies and can guide personalized treatment plans, which reinforce patient-doctor communication. Test results can also be used to predict exacerbations and response to therapies. Additional diagnostic information can be gleaned from (i) eosinophil count ≥300 μL, which significantly increases the odds of having exacerbations, and emerging eosinophil biomarkers (eg, eosinophil-derived neurotoxin), which can be measured in plasma or serum samples, and (ii) fractional exhaled nitric oxide (FeNO), with values ≥25 ppb regarded as the cutoff for diagnosis, evaluating inhaled corticosteroid response, and of probable response to anti-IgE, anti-IL4 and anti-IL5 receptor biologics. Referral to asthma/allergy specialists is warranted when the initial diagnosis is uncertain, and when asthma symptoms, impairment, or exacerbations are repeated or severe.