Relevant Allergens Research Articles

Molecular Profiles of Sensitization to Non-Specific Lipid Transfer Proteins in Lithuania: Single Center Experience.

Non-specific Lipid Transfer proteins (nsLTPs) are relevant allergens of several pollens and plant foods. Sensitization to nsLTPs is not typical in our region. Still, it has become an increasingly common cause of IgE-mediated food allergies and food-induced anaphylaxis in Northern Europe in recent decades. No in-depth studies describe the prevalence of sensitization of molecular components to nsLTPs in Lithuania. This study aimed to determine the sensitization profile of atopic patients at the Immunology and Allergy Department of Kauno Klinikos to the components of nsLTPs, using molecular allergen component analysis. Sixty Lithuanian adults with symptoms of allergic rhinitis and/or allergic asthma and/or food allergies were included into the study. Specific immunoglobulin E (IgE) levels were measured using two in vitro techniques: allergen extract and molecular component analysis. Results showed that 25% of subjects were sensitized to nsLTP-containing allergen sources, mostly to Zea m 14, Mal d 3, Vit v 1, and Art v 3. The median amount of total IgE was higher in nsLTP-sensitized patients than in nsLTP-nonsensitized patients. Based on Cohen's Kappa and McNemar tests, the results of allergen extract and component analysis tests do not always agree, especially when we determine the sensitization to allergen sources containing nsLTPs. Molecular allergen component analysis could be the first choice in determining detailed sensitization to nsLTPs in patients who experienced anaphylaxis of unknown origin.

Investigation of the diagnostic accuracy of basophil activation test for allergic phenotypes of rhinitis.

Basophil activation test (BAT) might be an alternative to nasal allergen challenge (NAC) to identify the allergic etiology in rhinitis patients. Here, we investigate the diagnostic performance of BAT for allergic phenotypes of rhinitis. Rhinitis patients and healthy controls were subjected to NAC with Dermatophagoides pteronyssinus (DP), Alternaria alternata (AA), grass (GP) and olive (OP) pollens. Rhinitis subjects also underwent skin prick test (SPT) with relevant allergens. Patients were classified into allergic rhinitis (AR, positive NAC and SPT), local allergic rhinitis (LAR, positive NAC and negative SPT), dual allergic rhinitis (DAR, defined as AR for ≥1 allergen and LAR for ≥1 allergen), and non-allergic rhinitis (NAR, negative NAC and SPT) phenotypes. BAT with DP, AA, GP and OP was conducted in study individuals and compared with NAC results. A total of 47 AR, 31 DAR, 26 LAR, 12 NAR and 21 control subjects were recruited. The best positivity cut-offs of BAT for DP-, AA-, GP- and OP-driven allergy (all phenotypes) were a %CD63 cells of 8.650, 14.250, 26.200, and 12.780, respectively (AUC 0.851, 0.701, 0.887, and 0.921, respectively). Sensitivity, specificity, negative and positive predictive values of BAT (all phenotypes) ranged 43.5%(AA)-83.3%(OP), 88.9%(GP)-100%(AA), 87%(GP)-100%(AA), and 61.1%(DP)-80.0%(pollens), respectively. BAT identified 79%-100% of SPT-positive allergies (AR and DAR), and 25%-75% of SPT-negative allergies (LAR and DAR), while ≤10% of NAR/HC subjects tested positive. BAT positivity correlated with rhinitis severity in LAR patients (p = 0.018), and associated with conjunctivitis (p = 0.015) in allergic subjects. BAT can replace NAC for AR confirmation, and limit the number of NAC required for LAR and DAR diagnosis. BAT can demonstrate sIgE in SPT-negative allergies.

Cannabis sativa as a clinically relevant nsLTP allergen in the Mediterranean region: a case series exemplifying different possible routes of sensitization.

Cannabis is the most widely used drug worldwide sought for recreational and medicinal purposes. Cannabis allergy was first described 50 years ago but has become more frequently reported over the past decade due to a larger industrial and domestic cultivation, and an evolving legal status. However, it remains an infrequent cause of allergy in the Mediterranean European countries. We describe three clinical cases with primary sensitization to cannabis characterized by anaphylactic reactions. We hypothesize that in all three case reports, sensitization to Can s 3 nsLTP played a crucial role in the development of anaphylaxis, either directly following ingestion of hemp-containing food, or even indirectly through primary sensitization via involuntary exposure or occupation exposure to cannabis sativa.

Component-resolved diagnostics of fruit and vegetable allergy: precise identification and individualized treatment strategies

Vegetable and fruit allergies are common types of food allergies worldwide, most of them are triggered by primary sensitization to pollen. Most allergens in vegetables and fruits belong to a few cross-reactive proteins such as PR-10 proteins, profilins, and nsLTPs. The presence of these allergens in various plants can lead to widespread cross-reactive allergic responses. Component-resolved diagnostics (CRD) can improve diagnostic accuracy by precisely identifying specific allergenic proteins, aiding physicians in making more accurate treatment and management decisions, and reducing unnecessary food avoidance. This article, based on the "Molecular Allergology User's Guide 2.0 (MAUG 2.0)" issued by the European Academy of Allergy and Clinical Immunology (EAACI), analyzes the primary mechanisms, relevant allergens, and diagnostic and clinical management strategies for vegetable and fruit allergies. By detailing and analyzing these allergenic components, this article may help the healthcare professionals to deep the understandings of vegetable and fruit allergies, offer new perspectives and practical guideline for the research and treatment of these allergies, and promot the development of precise diagnostics and personalized treatment strategies.

Neglected but Clinically Relevant Allergens in Korea.

Allergy diagnostics and immunotherapeutics in Asia heavily rely on imported products from Western countries, raising concerns about the accuracy and efficacy of these products for the management of Asian allergy patients. Recent advancements in allergen research have led to the identification and characterization of novel allergens from indigenous Korean species. While some allergens share homology with well-known allergens, others lack counterparts in imported allergen extracts. Classifying regional allergens in Asia into three categories based on their cross-reactivity with imported allergens offers valuable insights. Highly cross-reactive allergens, such as oak allergens Que m 1 from Quercus mongolica and Que ac 1 from Q. acutissima, can be effectively substituted with the imported allergens. Allergens with partial cross-reactivity, like the Asian needle ant allergen Pac c 3 (Antigen 5), permit limited diagnostic value by the currently available products. Unique allergens, including the Japanese hop allergen Hum j 6 (pectin methylesterase inhibitor) and the silkworm pupa allergen Bomb m 4 (30kDa hemolymph lipoprotein) lack alternatives in the available product list. Greater attention is needed, particularly for species listed as ecologically invasive in Western regions. Additionally, allergens from domestic fruits and vegetables causing pollen food allergy syndrome require characterization for the development of improved diagnostics.

Supplemental Patch Testing Identifies Allergens Missed by Standard Screening Series.

Background: Supplemental patch testing is an adjunct to standard patch test screening series. Objective: To determine the demographics, characteristics, frequency, relevance, and interpretation of patch test reactions for supplemental patch testing. Methods: Retrospective study of patients tested 2017-2020 with North American Contact Dermatitis Group (NACDG) and supplemental screening series (Supplemental Series A [SSA], Supplemental Series B [SSB]). Demographics, characteristics, reaction strengths, relevance, and final interpretation were recorded. Results: Cohort included 791 patients; 73.5% female, 68.6% age >40 years. 74.1% were White, 15.2% Black, 5.7% Asian, and 1.5% Hispanic. The most common Dermatitis sites were scattered/generalized (27.2%), face (24.0%), and hands (23.5%). For 2017-2018 and 2019-2020, respectively, 82% (318/388) and 78.4% (316/403) had ≥1 "allergic" reaction. In addition, 13.5% (52/385) and 11.7% (47/403) had SSA reactions, and 38.1% (115/302) and 31.5% (101/321) had SSB reactions. In the 87 (2017-2018) and 99 (2019-2020) patients with negative NACDG testing, 17 (19.5%) and 12 (12.1%) had supplemental reactions. Of the 34 supplemental allergens with reaction frequency ≥1%, 58.8% (20/34) are not part of the American Contact Dermatitis Society 90 (2020) or NACDG 2021-2022 screening series. The highest frequency allergens from this group were dodecyl and octyl gallate, cinnamic alcohol, phenyl salicylate, hexahydro-1,3,5-tris-(2-hydroxyethyl) triazine, and abitol. Conclusions: Supplemental patch testing identifies additional relevant allergens in patients with suspected allergic contact Dermatitis.

Characterization of Pediatric Patch Testing: A Retrospective Review, 2020-2023.

Background: Recent evidence shows similar rates of allergic contact Dermatitis® (ACD) among children and adults despite children accounting for less than 10% of patch testing subjects. With a need for in-depth analyses of pediatric ACD, we herein characterize a pediatric cohort at a large North American patch testing center. Methods: A retrospective chart review was conducted for 135 patients ages 1-17 years who underwent patch testing from July 2020 from August 2023. Data were stratified by age 1-5, 6-11, and 12-17 years. Significance-Prevalence Index Numbers (SPIN) were calculated. Results: A total of 86% were sensitized, 40% had a relevant reaction, and positivity rates were equal between males and females. Top allergens by SPIN differed with age, but overall were linalool hydroperoxides (SPIN = 11.01), propylene glycol (10.30), limonene hydroperoxides (10.27), fragrance mix I (5.62), and lanolin (4.90). In total, 14% of the top allergens were not represented on the North American Contact Dermatitis® Group standard series. Of those tested to personal products, 45% had positive reactions and 72% of which were relevant. Conclusions: Emulsifiers and fragrances were the most relevant allergen categories, with the impact of emulsifiers not previously reported. ACD may affect males and females equally in this population. Supplemental allergens and personal products tested "as-is" contribute to conclusive pediatric patch testing.

Occupational Contact Dermatitis in Construction Workers: A Retrospective Analysis of the North American Contact Dermatitis Group Data, 2001-2020.

Background: Construction workers (CWs) are at risk for occupational contact dermatitis (CD) owing to workplace exposures. Objective: Determine the prevalence of occupational allergic CD and characterize common occupational allergens in CWs referred for patch testing in the United States and Canada. Methods: Retrospective cross-sectional analysis of patients patch tested by the North American Contact Dermatitis Group from 2001 to 2020. Results: Of 47,843 patch-tested patients, 681 (1.4%) were CWs. Compared with non-CWs, CWs were more likely to be male (91.0% vs 30.9%) have occupational skin disease (36.9% vs 11.4%) and have hand involvement (37.2% vs 22.5%) (all P < 0.0001). Of 681 CWs, 60.1% (411) had clinically relevant positive patch test reactions, and nearly 1/3 of CWs (128) had occupationally relevant reactions. Most common occupationally relevant allergens were potassium dichromate 0.25% pet. (30.5%, 39/128), bisphenol A epoxy resin 1% pet. (28.1%, 36/128), carba mix 3% pet. (14.8%, 19/128), cobalt (ii) chloride hexahydrate 1% pet. (14.1%, 18/128), and thiuram mix 1% pet. (14.1%, 18/128). Top sources of occupationally relevant allergens were cement/concrete/mortar (20.4%, 46/225), gloves (15.1%, 34/225), and coatings (paint/lacquer/shellac/varnish/stains) (9.8%, 22/225). Conclusions: Occupational CD in North American CWs is common. In this group, frequently identified etiological sources of occupational allergic CD included metals, epoxy resin, and rubber.

Heterogenous Induction of Blocking Antibodies against Ragweed Allergen Molecules by Allergen Extract-Based Immunotherapy Vaccines.

Currently, allergen-specific immunotherapy (AIT) for ragweed allergy is still based on natural allergen extracts. This study aimed to analyse the ability of four commercially available AIT vaccines (CLUSTOID, TYRO-SIT, POLLINEX Quattro Plus and Diater Depot) regarding their ability to induce IgG antibodies against ragweed pollen allergens in rabbits. Accordingly, the IgG reactivity of AIT-induced rabbit sera was tested for ten different ragweed pollen allergens (Amb a 1, 3, 4, 5, 6, 8, 9, 10, 11 and 12) by an ELISA. Furthermore, the ability of rabbit AIT-specific sera to block allergic patients' IgE binding to relevant ragweed allergens (Amb a 1, 4, 6, 8 and 11) and to inhibit allergen-induced basophil activation was evaluated by an IgE inhibition ELISA and a mediator release assay. Only two AIT vaccines (Diater Depot > CLUSTOID) induced relevant IgG antibody levels to the major ragweed allergen Amb a 1. The IgG responses induced by the AIT vaccines against the other ragweed allergens were low and highly heterogeneous. Interestingly, the kinetics of IgG responses were different among the AIT vaccines and even within one AIT vaccine (Diater Depot) for Amb a 1 (long-lasting) versus Amb a 8 and Amb a 11 (short-lived). This could be due to variations in allergen contents, the immunogenicity of the allergens, and different immunization protocols. The IgE inhibition experiments showed that rabbit AIT-specific sera containing high allergen-specific IgG levels were able to inhibit patients' IgE binding and prevent the mediator release with Diater Depot. The high levels of allergen-specific IgG levels were associated with their ability to prevent the recognition of allergens by patients' IgE and allergen-induced basophil activation, indicating that the measurement of allergen-induced IgG could be a useful surrogate marker for the immunological efficacy of vaccines. Accordingly, the results of our study may be helpful for the selection of personalized AIT vaccination strategies for ragweed-allergic patients.

Novel strategies for predicting allergenicity: development of a ranking method and screening tools to assess the allergy risk of innovative proteins

Abstract To protect individuals who already have or are at risk of developing immune‐mediated adverse reactions to food, novel foods and genetically modified organisms (GMOs) undergo an allergenicity risk assessment. There are shortcomings in this process that could be improved through use of well‐defined clinically relevant allergen molecules with different allergenic potential. The objective of this project was to develop novel strategies for predicting allergenicity of innovative/novel proteins that address this issue. We undertook a systematic review of allergen molecules in foods listed on Annex II of the Food Information for Consumers Regulation together with additional foods known to cause IgE‐mediated food allergies in at least one European region with a prevalence of 0.5%. Around 750 in‐scope papers were quality assessed to allow clinical relevance of allergen molecules to be ranked. The best characterised clinically relevant allergens were identified in peanut, hazelnut, cow's milk, fish and crustacean shellfish with data lacking for allergens from foods such as pecan, Macadamia, lupin and melon. Furthermore, an assessment of in silico tools allergenicity prediction found that, whilst many were able to correctly predict allergenicity, none were able to provide an output that could be linked to the clinical relevance. Building on these outcomes an approach for allergenicity risk assessment has been developed that brings together elements of exposure assessment, combining in silico, in vitro, and in vivo methods. Tools for assessment of risks of cross‐reactive allergies are more mature and only require refinement to improve the outputs to inform the allergenicity risk assessment process. However, as mechanisms underlying development of food allergy are not fully elucidated, and remain a matter of ongoing research, prediction of de novo sensitisation is uncertain.

Bronchom assuages airway hyperresponsiveness in house dust mite-induced mouse model of allergic asthma and moderates goblet cell metaplasia, sub-epithelial fibrosis along with changes in Th2 cytokines and chemokines.

Asthma is a common obstructive airway disease with an inflammatory etiology. The main unmet need in the management of asthma is inadequate adherence to pharmacotherapy, leading to a poorly-controlled disease state, necessitating the development of novel therapies. Bronchom is a calcio-herbal formulation, which is purported to treat chronic asthma. The objective of the current study was to examine the in-vivo efficacy of Bronchom in mouse model of allergic asthma. Ultra high performance liquid chromatography was utilized to analyze the phytocompounds in Bronchom. Further, the in-vivo efficacy of Bronchom was evaluated in House dust mite (HDM)-induced allergic asthma in mice. Mice were challenged with aerosolized methacholine to assess airway hyperresponsiveness. Subsequently, inflammatory cell influx was evaluated in bronchoalveolar lavage fluid (BALF) followed by lung histology, wherein airway remodeling features were studied. Simultaneously, the levels of Th2 cytokines and chemokines in the BALF was also evaluated. Additionally, the mRNA expression of pro-inflammatory and Th2 cytokines was also assessed in the lung along with the oxidative stress markers. Phytocompounds present in Bronchom included, gallic acid, protocatechuic acid, methyl gallate, rosmarinic acid, glycyrrhizin, eugenol, 6-gingerol and piperine. Bronchom effectively suppressed HDM-induced airway hyperresponsiveness along with the influx of leukocytes in the BALF. Additionally, Bronchom reduced the infiltration of inflammatory cells in the lung and it also ameliorated goblet cell metaplasia, sub-epithelial fibrosis and increase in α-smooth muscle actin. Bronchom decreased Th2 cytokines (IL-4 and IL-5) and chemokines (Eotaxin and IP-10) in the BALF. Likewise, it could also suppress the mRNA expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-6 and IL-33), and IL-13. Moreover, Bronchom restored the HDM-induced diminution of endogenous anti-oxidants (GSH and SOD) and the increase in pro-oxidants (GSSG and MDA). Furthermore, Bronchom could also decrease the nitrosative stress by lowering the observed increase in nitrite levels. Taken together, the results of the present study data convincingly demonstrate that Bronchom exhibits pharmacological effects in an animal model of allergic asthma. Bronchom mitigated airway hyperresponsiveness, inflammation and airway remodeling evoked by a clinically relevant allergen and accordingly it possesses therapeutic potential for the treatment of asthma.

Structural and Immunological Features of PR-10 Allergens: Focusing on the Major Alder Pollen Allergen Aln g 1.

Today, allergies have become a serious problem. PR-10 proteins are clinically relevant allergens that have the ability to bind hydrophobic ligands, which can significantly increase their allergenicity potential. It has been recently shown that not only the birch pollen allergen Bet v 1 but also the alder pollen allergen Aln g 1, might act as a true sensitizer of the immune system. The current investigation is aimed at the further study of the allergenic and structural features of Aln g 1. By using qPCR, we showed that Aln g 1 was able to upregulate alarmins in epithelial cells, playing an important role in sensitization. With the use of CD-spectroscopy and ELISA assays with the sera of allergic patients, we demonstrated that Aln g 1 did not completely restore its structure after thermal denaturation, which led to a decrease in its IgE-binding capacity. Using site-directed mutagenesis, we revealed that the replacement of two residues (Asp27 and Leu30) in the structure of Aln g 1 led to a decrease in its ability to bind to both IgE from sera of allergic patients and lipid ligands. The obtained data open a prospect for the development of hypoallergenic variants of the major alder allergen Aln g 1 for allergen-specific immunotherapy.

The Contact Sensitivity of Turkish Children and Adolescents to European Baseline Series Allergens between 2013 and 2023.

Increasing the numbers of patch testing in suspected children increases the rate of diagnosis of allergic contact dermatitis and the identification of clinically relevant allergens. The aim of this study was to identify the most frequently observed allergens among Turkish children and adolescents patch-tested in 2013-2023. The patch test results of 160 patients (age ≤18) were analyzed retrospectively. The frequency of contact allergens and distribution of positive results in terms of sex, age group (children and adolescents), and the presence of atopic dermatitis (AD) were identified. Forty-nine patients (30.6%) (34 girls and 15 boys) exhibited positive patch test reactions to a minimum of one allergen, and contact sensitivity was statistically significantly higher in girls (P=0.034). The five most frequent allergens were nickel sulfate (10.6%), MCI/MI (8.1%), cobalt chloride (5.6%), p-phenylenediamine (PPD) (5%), and MI (3.5%). No significant association was observed between patch test positivity and age groups (P>.05). Nickel sulfate sensitivity was significantly higher in girls than in boys (P=.043). A positive reaction was detected in 31.3% of patients with AD and in 33.7% of those without (P>.05), and a statistically significant relationship was observed between contact sensitivity to fragrance allergens and AD (P=.046). Metals and preservatives represent the most frequent allergens in Turkish children and adolescents. Metal sensitivity is expected to decrease as legislation is enforced. Regulatory measures are now required to reduce MI and MCI/MI contact allergy in Turkey.

Are "clean" products safe for children? An analysis of contact allergens in "clean" children's products from a popular retailer.

Considering consumer trends toward the use of "clean" personal care products and increasing recognition of childhood allergic contact dermatitis, we sought to characterize the allergen profile of such children's products. Ingredients of baby washes/shampoos, bubble baths, and moisturizers identified using the "Clean Baby" filter on Target®'s online marketplace were analyzed for relevant pediatric contact allergens. Product compositions declared fragrance in 82% of products, Compositae in 46%, cocamidopropyl betaine in 45%, glucosides in 37%, propylene glycol in 12%, lanolin in 1%, and no allergens in 9%-methylisothiazolinone and formaldehyde were not found. Children are greatly impacted by atopic dermatitis and skin barrier dysfunction, which underscores a need for greater public awareness of sensitizing and irritating ingredients, particularly regarding pediatric personal care products.

Executive Summary of Clinical Practice Guideline on Immunotherapy for Inhalant Allergy.

Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AITis administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2)reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Clinical Practice Guideline: Immunotherapy for Inhalant Allergy.

Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AITis administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm.The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients'symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.

Trends in contact sensitization, results, and implications from a contact dermatitis clinic in Israel.

The baseline series includes common allergens, evolves over time, and differs by location. Our study aims to characterize allergen sensitization trends among the Israeli population during the last two decades, compare our results to American and European registries, as well as to highlight significant allergens in additional series outside the European baseline series (OEBS). We analysed patch test results of 2086 patients from a designated contact dermatitis clinic in Tel Aviv between 2019 and 2022, compared them to European and North American registries and to 2156 patch test results conducted in Israel two decades ago. 38.6% of patients had at least one positive reaction to an allergen in the European baseline series (EBS), nickel sulphate (14.6%), fragrance mix I (4.6%), and Methylchloroisothiazolinone methylisothiazolinone (MCI/MI; 3.7%) were the most common among them. N-Isopropyl N-Phenyl-4-Phenylenediamine (NIPPD; 0%), Propolis (0.1%), Sesquiterpene lactone mix (0.1%), and Budesonide (0.1%) elicited a sensitization frequency significantly lower than the proposed threshold for baseline inclusion. Chi-square test revealed a statistically significant decrease (p < 0.05) in the sensitization frequency of fragrance mix I, Formaldehyde, Potassium dichromate, Neomycin sulphate, Myroxylon pereirae, Sesquiterpene lactone, and NIPPD during the last two decades. The overall sensitization frequency to the majority of allergens was lower in our cohort in comparison to the North American and European registries. MCI/MI and 2-hydroxyethyl methacrylate-2 (HEMA) are common, relevant allergens, with high SPIN (significance and prevalence index number) and should be better regulated by the authorities. While among the EBS, NIPPD, Propolis, Sesquiterpene lactone, and Budesonide usually do not elicit a positive reaction and therefore should be reconsidered in baseline series, among the OEBS, Chloramphenicol, Quaternium 15, Propyl gallate, and Amerchol L101 have elicited high SPIN values and should be vigilantly examined in the suitable clinical scenario. Significantly lower sensitization frequency to propolis raises the possibility of a protective effect due to early oral exposure among the Israeli population.

Defining the cross-reactivity between peanut allergens Ara h 2 and Ara h 6 using monoclonal antibodies.

In peanut allergy, Arachis hypogaea 2 (Ara h 2) and Arachis hypogaea 6 (Ara h 6) are two clinically relevant peanut allergens with known structural and sequence homology and demonstrated cross-reactivity. We have previously utilized X-ray crystallography and epitope binning to define the epitopes on Ara h 2. We aimed to quantitatively characterize the cross-reactivity between Ara h 2 and Ara h 6 on a molecular level using human monoclonal antibodies (mAbs) and structural characterization of allergenic epitopes. We utilized mAbs cloned from Ara h 2 positive single B cells isolated from peanut-allergic, oral immunotherapy-treated patients to quantitatively analyze cross-reactivity between recombinant Ara h 2 (rAra h 2) and Ara h 6 (rAra h 6) proteins using biolayer interferometry and indirect inhibitory ELISA. Molecular dynamics simulations assessed time-dependent motions and interactions in the antibody-antigen complexes. Three epitopes-conformational epitopes 1.1 and 3, and the sequential epitope KRELRNL/KRELMNL-are conserved between Ara h 2 and Ara h 6, while two more conformational and three sequential epitopes are not. Overall, mAb affinity was significantly lower to rAra h 6 than it was to rAra h 2. This difference in affinity was primarily due to increased dissociation of the antibodies from rAra h 6, a phenomenon explained by the higher conformational flexibility of the Ara h 6-antibody complexes in comparison to Ara h 2-antibody complexes. Our results further elucidate the cross-reactivity of peanut 2S albumins on a molecular level and support the clinical immunodominance of Ara h 2.

360° approach to the patient with mite allergy: from scientific evidence to clinical practice.

In the recent years, several important advances have been made in the diagnosis of allergy using molecular techniques. The aetiological diagnosis of allergy using molecular components of allergens allows a more precise definition of the patient's IgE repertoire. Precision medicine is a structural model aimed at personalising healthcare and places the patient at the centre of the specialist's decision-making process. To this end, an accurate characterisation of the external exposome at a molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease, with a view to personalising diagnosis and therapy. It has been proposed a decision algorithm, the Top-Down approach, where the clinical history is set first and is followed by the use of skin tests or specific IgE techniques, which facilitates the clinicians to make decisions. The therapeutic intervention driven by the standard diagnostic approach, but supported by these innovative tools, can lead to a better phenotyping of highly complex patients, and a more appropriate prescription of AIT. To this end, the allergen extracts used for diagnosis require to be of proven quality and contain the most relevant allergens. Likewise, allergen vaccines must gather efficacy, safety, duration, and patient compliance, hence the demand for new vaccines to overcome these drawbacks.

Pediatric Patch Testing at Mayo Clinic Between 2016 and 2020.

Background: Allergic contact Dermatitis (ACD) is a common condition within the pediatric population. Patch testing is an important way to identify relevant allergens. Objective: To provide an update of the common contact allergens seen in children based on patch testing data at our institution from 2016 to 2020. Methods: We performed a retrospective analysis of patch test data from children aged 1-18 years from 2016 to 2020 at Mayo Clinic. Reaction rates were compared to the rates reported by the Pediatric Contact Dermatitis Registry (PCDR). Results: One hundred ninety-two children aged 1-18 were patch tested to various allergens. A total of 15,457 allergens were tested, with 291 positive tests. The top 5 allergens with highest positive reaction rates were hydroperoxides of linalool, hydroperoxides of limonene, methylisothiazolinone, nickel, and cobalt. Seven of the top 38 allergens with the highest reaction rates are not currently included in the Mayo Clinic Pediatric Patch Test Series, and 11 are not currently included in the Pediatric Baseline Series (as developed by the Pediatric Contact Dermatitis Workgroup). Conclusions: Patch testing is a useful tool to diagnose children with ACD. With new products and exposures, there is an opportunity to expand current pediatric patch testing series.