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AbstractObjectiveMethodsResultsConclusionsAsthma is a common chronic condition in children globally. Allergen-specific immunotherapy, such as subcutaneous (SCIT) and sublingual (SLIT) therapies, are promising by increasing allergen tolerance. This meta-analysis compares the efficacy and safety of SLIT and SCIT in pediatric asthma.We searched PubMed, Cochrane Library, and Embase for randomized controlled trials and case–control studies comparing SLIT and SCIT in asthmatic children. Meta-analysis was conducted using random-effects models with calculations via R software version 4.3.2 and RevMan version 5.4. Study quality and bias risk were assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool.The literature search yielded a total of 1787 records, with 7 studies meeting the inclusion criteria after screening and assessments. There was no significant difference in the Total Asthma Symptoms Score between SLIT and SCIT (mean difference −0.05 [95% CI: −0.21; 0.10]). However, asthma improvement rates were higher in the SLIT group (risk ratio 0.77 [95% CI: 0.64; 0.93]). FEV1 improvement showed no significant difference (mean difference −1.60 [95% CI: −6.27; 3.08]). Adverse events were similar between the treatments (risk ratio 0.56 [95% CI: 0.11; 2.82]).SLIT and SCIT were generally similarly effective and safe for treating pediatric asthma. SLIT may be preferred due to its noninvasive administration. More research is needed on long-term effects and tailored treatment approaches. [ABSTRACT FROM AUTHOR]

Introduction: Allergen immunotherapy is the only modifying treatment of the natural course of respiratory allergic diseases; however, the lack of evidence leads to little inconclusive results. Real life studies are on the rise and are becoming a valuable tool to confirm and complement findings from clinical trials. The objective of this study was to evaluate the effectiveness and safety of a depigmented-polymerized undiluted subcutaneous extract of grass and olive pollen, under routine clinical practice conditions. Methods: This was an observational, retrospective, longitudinal, single-center study on the use of a 2-pollen (grass mix and Olea europaea) undiluted subcutaneous extract over at least 3 consecutive years. Data were collected from 76 patients (n = 44 female; median age: 12.5 years old) diagnosed with allergic rhinoconjunctivitis with/without allergic asthma due to sensitization to both grasses and O. europaea. Primary and secondary effectiveness endpoints were symptom severity, concomitant medication, and immunological profile before and after completing the immunotherapy. A 2-year follow-up of patients’ symptoms and medication history after completing the subcutaneous immunotherapy (SCIT) was performed. Results: There was a significant improvement of symptoms and medication consumption after 3 years of SCIT treatment, and a significant decrease in specific IgE levels for grasses and O. europaea was observed after finishing the treatment. Conclusion: Three years treatment of allergic patients using an undiluted mixture of two allergen extracts was shown to be safe and effective for rhinitis and asthma, with efficacy maintained for at least 2 years after finishing SCIT. These results reinforce the importance of real life clinical data in addition to those from clinical trials, helping to individualize allergic treatments. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the knowledge, attitudes, and practices (KAP) of patients with allergic rhinitis towards allergen-specific immunotherapy (AIT). Methods: This cross-sectional study was conducted through a questionnaire survey at The Fourth Affiliated Hospital of Zhejiang University School of Medicine from October 15, 2023, to December 3, 2023. Results: A total of 550 valid questionnaires were included in the analysis. The median scores with interquartile ranges (IQR) for knowledge, attitude, and practice were 17 (11, 23), (possible range: 0– 34); 20 (17, 22), (possible range: 7– 35); and 30 (24, 34), (possible range: 8– 40). Multivariate logistic regression analysis showed that individuals engaging in physical activity 1– 3 times per week (OR = 2.895, 95% CI: [1.745, 4.804], P < 0.001), those participating in physical activity 5– 7 times per week (OR = 3.811, 95% CI: [1.502, 9.671], P = 0.005), and those with higher knowledge scores (OR = 4.485, 95% CI: [2.942, 6.837], P < 0.001) were independently associated with positive practices. The structural equation modeling (SEM) results revealed that knowledge had a significant influence on attitude (β = − 0.354, P = 0.010) and practice (β = 0.618, P = 0.010), and attitude also demonstrated a noteworthy impact on practice (β = − 0.120, P = 0.020). Furthermore, it is worth noting that the indirect effects of knowledge on practice were statistically significant (β = 0.042, P = 0.020). Conclusion: Patients with allergic rhinitis had inadequate knowledge, negative attitudes and proactive practices towards AIT. To improve their understanding and adherence, healthcare providers should prioritize education and interventions aimed at enhancing patient engagement with this treatment option. [ABSTRACT FROM AUTHOR]

Allergic diseases of the respiratory tract (allergic rhinitis and bronchial asthma) are the leading pathology in therapeutic practice. The results of a meta-analysis in the East Asian region showed that the overall prevalence of bronchial asthma and allergic rhinitis with bronchial asthma was 10.17% and 38.97%, respectively. On the territory of Mongolia there are 2883 plant species belonging to 662 genera and 128 families. In this regard, given the climatic and geographical features of Mongolia, the flowering and pollination season is long, which affects the quality of life of patients with allergic diseases. The purpose of the study is to analyze the prevalence and incidence of allergic rhinitis and bronchial asthma in Mongolia and present the experience of treatment with Antipollin.The study was conducted in Ulaanbaatar, Darkhan and Sukhbaatar for 2019-2022. Based on the data obtained, the following statistical indicators were calculated: incidence (cumulative incidence) per 1000 patients, prevalence (prevalence) for specific annual indicators and age groups.The cumulative incidence of allergic rhinitis for the fourth quarter of 2022 was determined to be from 28.9‰ to 43.92‰, the cumulative incidence of bronchial asthma was from 20.16‰ to 37.2‰, while in some age subgroups this figure exceeds 50‰. Determined that for 2022 in Ulaanbaatar – 4.39% and 2.66%, in Darkhan – 2.89% and 2.02%, in Sukhbaatar – 2.91% and 3.72% of patients were diagnosed with allergic rhinitis and bronchial asthma, respectively. In the cities of Ulaanbaatar and Darkhan, the number of patients registered with allergic rhinitis is 1.5 times higher than the number of patients with bronchial asthma, but in the city of Sukhbaatar the opposite trend is observed. The prevalence of bronchial asthma in the city of Sukhbaatar is much higher than in other cities, higher than in the AR, and as the population ages, this indicator only increases in the group 0 – 10 years – the prevalence of bronchial asthma is 12.72‰, which 2 times higher than the figure in Darkhan – 6.9‰ and 1.5 times higher than in Ulaanbaatar – 8.1‰.Taking into account the climatic, geographic, population and epidemiological characteristics of Mongolia, the use of Antipollin for sublingual immunotherapy is the optimal solution that can improve the quality of life of thousands of patients suffering from allergic diseases of the respiratory tract.

Background: Allergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed. Methods: Amurinemodel of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7Hbenzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome. Results: Although AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhRdependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels. Conclusion: This study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT. [ABSTRACT FROM AUTHOR]

Food allergies (FA), a major public health problem recognized by the World Health Organization, affect an estimated 3%-10% of adults and 8% of children worldwide. However, effective treatments for FA are still lacking. Recent advances in glycoimmunology have demonstrated the great potential of sialic acids (SAs) in the treatment of FA. SAs are a group of nine-carbon a-ketoacids usually linked to glycoproteins and glycolipids as terminal glycans. They play an essential role in modulating immune responses and may be an effective target for FA intervention. As exogenous food components, sialylated polysaccharides have anti-FA effects. In contrast, as endogenous components, SAs on immunoglobulin E and immune cell surfaces contribute to the pathogenesis of FA. Given the lack of comprehensive information on the effects of SAs on FA, we reviewed the roles of endogenous and exogenous SAs in the pathogenesis and treatment of FA. In addition, we considered the structure-function relationship of SAs to provide a theoretical basis for the development of SA-based FA treatments. [ABSTRACT FROM AUTHOR]

Background: Allergy represents a major health problem of increasing prevalence worldwide with a high socioeconomic impact. Our knowledge on the molecular mechanisms underlying allergic diseases and their treatments has significantly improved over the last years. The generation of allergen-specific regulatory T cells (Tregs) is crucial in the induction of healthy immune responses to allergens, preventing the development and worsening of allergic diseases. Summary: In the last decades, intensive research has focused on the study of the molecular mechanisms involved in Treg development and Treg-mediated suppression. These mechanisms are essential for the induction of sustained tolerance by allergen-specific immunotherapy (AIT) after treatment discontinuation. Compelling experimental evidence demonstrated altered suppressive capacity of Tregs in patients suffering from allergic rhinitis, allergic asthma, food allergy, or atopic dermatitis, as well as the restoration of their numbers and functionality after successful AIT. Key Message: The better understanding of the molecular mechanisms involved in Treg generation during allergen tolerance induction might well contribute to the development of novel strategies for the prevention and treatment of allergic diseases. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionThis meta-analysis aimed to evaluate the effectiveness and adverse effects of specific immunotherapy (SIT) in the management of respiratory allergens, including allergic asthma, rhinitis, and related disorders, based on a review of current literature up to November 8, 2022.We conducted a search of databases, including PubMed, Embase, Cochrane, and Web of Science, to identify relevant randomized controlled trials (RCTs) assessing respiratory allergy-specific immunotherapy. We employed the Consolidated Standards of Reporting Trials (CONSORT) Statement to select RCTs that adhered to rigorous reporting standards. Specifically, we focused on double-blind placebo-controlled (DBPC) trials and open studies involving both adults and children, considering factors such as dosage, inclusion criteria, allergens, and primary outcome measurements.A total of 25 meta-analyses were included in this study. Among them, 14 evaluated sublingual-specific allergen immunotherapy (SLIT), 4 assessed subcutaneous allergen immunotherapy (SCIT), 4 explored both sublingual and subcutaneous immunotherapy, and 3 investigated intralymphatic immunotherapy. The outcomes of these meta-analyses indicated a reduction in medication scores in 20 cases and a decrease in symptom scores in 23 cases. Additionally, six studies reported on changes in IgE levels, seven studies focused on IgG4, four studies examined FEV1 (forced expiratory volume in 1 s), and eight studies reported on symptom and medication scores. Furthermore, 11 studies reported on differences in adverse reactions.The results of our meta-analysis suggest that specific immunotherapy, while associated with some adverse effects, effectively reduces the symptoms of asthma and rhinitis. Therefore, we recommend its use in the treatment of respiratory allergies. [ABSTRACT FROM AUTHOR]

Background: IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome. Methods: We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding sites of Bet v 1 and the cross‐reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB‐PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB‐PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB‐PreS and birch pollen extract‐based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA. Results: IgE‐binding experiments and basophil activation test revealed the hypoallergenic nature of AB‐PreS. AB‐PreS induced lower T‐cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB‐PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract‐based vaccines. Additionally, immunization with AB‐PreS induced HBV‐specific antibodies potentially protecting from infection with HBV. Conclusion: The recombinant AB‐PreS‐based vaccine is hypoallergenic and superior over currently registered allergen extract‐based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals. [ABSTRACT FROM AUTHOR]

Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) is the only disease-modifying treatment with the potential to re-establish clinical tolerance towards the corresponding allergen(s). However, conventional AIT has certain drawbacks, including long treatment durations, the risk of inducing allergic side effects, and the fact that allergens by themselves have a rather low immunogenicity. To improve AIT, adjuvants can be a powerful tool not only to increase the immunogenicity of co-applied allergens but also to induce the desired immune activation, such as promoting allergen-specific Th1- or regulatory responses. This review summarizes the knowledge on adjuvants currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants that have been studied in recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan) and TLR-ligands (flagellin and CpG-ODN). The investigated adjuvants show distinct properties, such as prolonging allergen release at the injection site, inducing allergen-specific IgG production while also reducing IgE levels, as well as promoting differentiation and activation of different immune cells. In the future, better understanding of the immunological mechanisms underlying the effects of these adjuvants in clinical settings may help us to improve AIT. [ABSTRACT FROM AUTHOR]

Food allergy is a growing public health issue among children and adults that can lead to life-threatening anaphylaxis following allergen exposure. The criterion standard for disease management includes food avoidance and emergency epinephrine administration because current allergen-specific immunotherapy treatments are limited by adverse events and unsustained desensitization. A promising approach to remedy these shortcomings is the use of nanoparticle-based therapies that disrupt disease-driving immune mechanisms and induce more sustained tolerogenic immune pathways. The pathophysiology of food allergy includes multifaceted interactions between effector immune cells, including lymphocytes, antigen-presenting cells, mast cells, and basophils, mainly characterized by a T H 2 cell response. Regulatory T cells, T H 1 cell responses, and suppression of other major allergic effector cells have been found to be major drivers of beneficial outcomes in these nanoparticle therapies. Engineered nanoparticle formulations that have shown efficacy at reducing allergic responses and revealed new mechanisms of tolerance include polymeric-, lipid-, and emulsion-based nanotherapeutics. This review highlights the recent engineering design of these nanoparticles, the mechanisms induced by them, and their future potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Allergens originated from Salsola kali (Russian thistle) pollen grains are one of the most important sources of aeroallergens causing pollinosis in desert and semi-desert regions. T-cell epitope-based vaccines (TEV) are more effective among different therapeutic approaches developed to alleviate allergic diseases. The physicochemical properties, and B as well as T cell epitopes of Sal k 1 (a major allergen of S. kali) were predicted using immunoinformatic tools. A TEV was constructed using the linkers EAAAK, GPGPG and the most suitable CD4+ T cell epitopes. RS04 adjuvant was added as a TLR4 agonist to the amino (N) and carboxyl (C) terminus of the TEV protein. The secondary and tertiary structures, solubility, allergenicity, toxicity, stability, physicochemical properties, docking with immune receptors, BLASTp against the human and microbiota proteomes, and in silico cloning of the designed TEV were assessed using immunoinformatic analyses. Two CD4+ T cell epitopes of Sal k1 that had high affinity with different alleles of MHC-II were selected and used in the TEV. The molecular docking of the TEV with HLADRB1, and TLR4 showed TEV strong interactions and stable binding pose to these receptors. Moreover, the codon optimized TEV sequence was cloned between NcoI and XhoI restriction sites of pET-28a(+) expression plasmid. The designed TEV can be used as a promising candidate in allergen-specific immunotherapy against S. kali. Nonetheless, effectiveness of this vaccine should be validated through immunological bioassays. [ABSTRACT FROM AUTHOR]

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Objective: Analyze feelings about allergen-specific immunotherapy on Twitter using the VADER model VADER (Valence Aware Dictionary and sEntiment Reasoner) model. Methods: tweets related to specific allergen immunotherapy were obtained through the Twitter Application Programming Interface (API). The keywords "allergy shot" were used between January 1, 2012, and December 31, 2022. The data was processed by removing URLs, usernames, hashtags, multiple spaces, and duplicate tweets. Subsequently, a sentiment analysis was performed using the VADER model. Results: A total of 34,711 tweets were retrieved, of which 1928 were eliminated. Of the remaining 32,783 tweets, 32.41% expressed a negative sentiment, 31.11% expressed a neutral sentiment, and 36.47% expressed a positive sentiment, with an average polarity of 0.02751 (neutral) over the 11-year period. Conclusions: The average polarity of tweets about allergen-specific immunotherapy is neutral over the 11 years analyzed. There was an annual increase in the average polarity over the years, with 2017, 2018, and 2022 having positive polarity averages. Additionally, the number of tweets decreased over time. [ABSTRACT FROM AUTHOR]

Background: Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms remain unclear, AIT has been shown to reduce basophil activation (BA) against nontarget allergens. Objectives: The aim of this study was to assess immunological changes in Dermatophagoides farinae (Der f) after Japanese cedar pollen (JCP)-based subcutaneous immunotherapy (SCIT) monotherapy. Method: The data of 16 patients (age: 6–37 years) with JCP-induced allergic rhinitis who were sensitive to Der f (serum Der f-specific immunoglobulin E [IgE] level >0.34 kUA/L) and received JCP-based SCIT for 5 years were reviewed retrospectively. BA by Der f and JCP extracts and serum-specific IgE and immunoglobulin G4 (IgG4) levels against these allergens were evaluated before and after completing 5 years of JCP-based SCIT monotherapy. Results: The areas under the dose-response curves of BA by Der f and JCP extracts were significantly reduced (p = 0.02 and p = 0.002, respectively). JCP-specific IgE levels decreased and JCP-specific IgG4 levels increased significantly (p < 0.001 for both), whereas Der f-specific IgE and IgG4 levels did not change significantly. Conclusions: JCP-based SCIT monotherapy reduced Der f-specific BA. These findings suggest that JCP-based SCIT has the potential to modulate immune response toward nontarget allergens. [ABSTRACT FROM AUTHOR]

Up to 90% of asthmatic patients have comorbid allergic rhinitis (AR). Although appropriate therapy of AR can improve asthma symptoms and management, AR is often underdiagnosed and under-treated in asthmatics. A non-systematic literature research was conducted on AR as a comorbidity and risk factor of asthma. Latest international publications in medical databases, international guidelines, and the Internet were reviewed. Based on the conducted literature research there is proved evidence of the necessity of diagnosis and treatment of AR in patients with asthma because it affects health care utilization. Therefore, it is recommended in national and global guidelines. AR increases the risk of asthma development and contributes to the severity of an existing asthma. Early treatment of AR with drugs as intranasal steroids, antihistamines, leukotriene receptor antagonists, and especially allergen-specific immunotherapy can reduce the risk of asthma development and the concomitant medication use in addition to severity of symptoms in AR and asthma. [ABSTRACT FROM AUTHOR]

BackgroundAllergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed.MethodsA murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome.ResultsAlthough AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels.ConclusionThis study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.

Introduction: Oral immunotherapy (OIT) imposes a burden on parents and their children with food allergies (FAs). We already developed a questionnaire for OIT-related Parental Burden (OIT-PB) scale. However, the previous questionnaire had some problems. This study modified OIT-PB and verified its reliability and validity. Methods: A 20-item draft covering the physical and mental burdens caused by OIT was prepared jointly with multiple allergists. The Food Allergy Quality of Life Questionnaire-Parental Burden (FAQLQ-PB) and Stress Response Scale-18 (SRS-18) were used to verify concurrent validity. A questionnaire survey was administered during treatment to parents of FA children who had started OIT for the first time. An additional OIT-PB survey was performed at one specific institution 1 week after the posttreatment survey. Results: The responses of 64 of the 76 recruited parents were analyzed. Of the 20 questions, 1 item was excluded owing to the floor effect, 1 was excluded because its commonality was less than 0.2, and 2 were excluded because their factor loading values were less than 0.4. Factor analysis was used to classify the OIT-PB into the following 4 subscales: "burden caused by adherence to treatment plan," "anxiety about symptom-induced risk," "burden due to patient's eating behavior," and "anxiety about treatment effect." The Cronbach's α for all 16 items of the OIT-PB was 0.893; Cronbach's α for each subscale was 0.876, 0.898, 0.874, and 0.717. The re-test reliability coefficient was 0.864 (95% confidence interval [CI]: 0.720−0.937, p < 0.001). A significant positive correlation was found between the OIT-PB and FAQLQ-PB (R = 0.610 [95% CI: 0.422−0.747], p < 0.001) and the SRS-18 (R = 0.522 [95% CI: 0.306–0.687], p < 0.001). A significant negative correlation was found between the rate of increase in OIT food intake and the "anxiety about treatment effect" score (R = −0.355 [95% CI: −0.558–0.112], p < 0.001). Parents of children on the hen's egg OIT treatment scored higher on the "burden due to patient's eating behavior" subscale than did parents of children on the milk and wheat OIT treatment. Conclusion: The burden of OIT experienced by parents can be broadly classified into four categories. The modified OIT-PB was able to evaluate them individually and was shown to have reliability and validity. This scale is expected to be useful in the development of OIT that considers not only therapeutic effect but also the burden experienced by FA children and their parents. [ABSTRACT FROM AUTHOR]

Nurse practitioners are likely to encounter pediatric and adult patients with symptoms of food allergy who need an accurate diagnosis, emergency treatment plans, and options for management. The pathophysiology of immunoglobulin E (IgE)-mediated food allergy, current and emerging diagnostics, treatment, and emergency management is briefly reviewed, and promising new and potential future treatment options are discussed. Currently, Food and Drug Administration-approved oral immunotherapy (OIT) treatment for peanut allergy, but clinical trials are underway to explore multiple-allergen OIT and alternate routes for IT such as sublingual and epicutaneous. Treatments that modulate the immune system are also potential treatments for food allergies (FAs), including biologic agents. Omalizumab, an anti-IgE therapy, dupilumab, an interleukin-4Ra receptor monoclonal antibody, and etokimab, an anti–IL-33, are all being studied for the treatment of food allergy. There is hope that these novel therapies for FAs will be a viable option translated to the practice setting in the near future, so that strict avoidance is not the only treatment plan for FAs. Nurse practitioners can support their patients with FAs and their families by keeping abreast of progress in food allergy research and assisting patients to consider novel treatment options, when appropriate, using shared decision making. [ABSTRACT FROM AUTHOR]

Aim: Patients experiencing persistent complaints of moderate-severe allergic rhinoconjunctivitis despite symptomatic treatment are considered candidates for Allergen Specific Immunotherapy (ASIT). The present study aims to assess the effectiveness and safety of ASIT using Gramineae pollen in children afflicted by allergic rhinoconjunctivitis. Materials and Methods: The study involved participants between 5 and 18 years of age who had allergic rhinoconjunctivitis. These participants were divided into two distinct groups. The initial group underwent ASIT, while the other constituted the control group that refrained from it. The control group comprised participants with akin ages and equivalent disease durations. Visual analog scores (VAS), daily symptom scores (dSS), daily medication scores (dMS), and combined symptom and medication scores (CSMS) were assessed at three specific time junctures: Baseline, post the initial year of ASIT, and after the second year of ASIT. Results: The study encompassed 188 children who had been diagnosed with allergic rhinoconjunctivitis. Among these, 94 patients had undergone immunotherapy. Of the total cases, 105 (55.9%) were male, with a median age of 14 years (range: 7-18 years). Among the patients who had received ASIT, there were statistically significant reductions in VAS, dSS, dMS, and CSMS after one and two years of therapy when compared to the baseline values (p<0.001). Upon comparing the group receiving ASIT with the control group after a two-year follow-up, notable reductions were observed in VAS, dSS, dMS, and CSMS (p<0.001). Five patients (5.3%) experienced systemic reactions. Conclusion: The current study demonstrated that ASIT with Gramineae pollen is clinically effective in patients with Graminae pollen-induced allergic rhinoconjunctivitis. [ABSTRACT FROM AUTHOR]

Background: Allergen‐specific immunotherapy (ASIT) is an effective therapy for canine atopic dermatitis (cAD). Intralymphatic immunotherapy (ILIT) is potentially beneficial in decreasing time to clinical effectiveness. Objective: To compare clinical efficacy of six monthly ILIT injections combined with three monthly injections of lokivetmab (LVM) with monthly LVM monotherapy at Day (D)168. To monitor dogs treated with ILIT for an additional six months of subcutaneous immunotherapy (SCIT). Animals: Thirty‐six client‐owned dogs with cAD. Materials and Methods: In this double‐blinded, randomised study, dogs received either six monthly injections of ILIT combined with three monthly LVM injections (ILIT group) or six monthly LVM injections (LVM group). Monthly evaluations with pruritus Visual Analogue Scale (pVAS), Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI‐04) and medication scores (MS) were undertaken. Owners completed a Quality of Life (QoL) questionnaire. Treatment success was predefined as ≥50% reduction in pVAS and CADESI‐04 score ≤ 10. After D168, the ILIT group continued with SCIT until subjective assessment at 12 months. Results: The treatment benchmark at D168 was achieved by 11.1% of the ILIT group and 11.8% of LVM group. A significant decrease in mean pVAS and CADESI scores was observed in both groups (p < 0.001). The ILIT group had a trend towards higher MS compared to LVM. QoL was better in LVM (p = 0.01). At 12 months subjective good‐to‐excellent response in 77.8% of dogs in the ILIT/SCIT group was seen. Conclusion and Clinical Relevance: The efficacy of this ILIT protocol was comparable with LVM monotherapy at six months. When ILIT was continued with SCIT, a favourable response was seen. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to fill the gap in systematic reviews on the efficacy and safety of subcutaneous allergen-specific immunotherapy (AIT) in horses with allergic diseases. The review included horses with respiratory diseases, urticaria, and pruritic dermatitis treated with insect monotherapy or multi-allergen AIT. Beneficial effects were observed with multi-allergen AIT in respiratory diseases, urticaria, and pruritic dermatitis. However, when insect AIT was used solely for pruritic dermatitis, the response was less favorable. Overall, AIT demonstrated safety, with any adverse events generally being self-limiting. The review highlighted the presence of common biases and confounding factors in the included studies, warranting the need for more rigorous research. Allergen-specific immunotherapy (AIT) is the only current intervention that has the ability to modify the immune response toward a tolerogenic state. This study aimed to assess the efficacy and safety of AIT in horses with allergic diseases in a systematic manner. Three databases were searched to identify articles reporting clinical outcomes and adverse events associated with AIT. The articles were evaluated for beneficial responses to AIT, defined as a ≥50% reduction in clinical signs, and clinical remission. Horses with respiratory diseases, urticaria, and pruritic dermatitis receiving insect monotherapy or multi-allergen AIT were included. All adverse events were graded, and analytical and confounding biases were assessed. The results showed that multi-allergen AIT had a beneficial response in 75% of horses with respiratory diseases, 88% with urticaria, and 56% with pruritic dermatitis. However, horses treated solely with insect AIT for pruritic dermatitis had a lower response rate (36%). Self-limiting local reactions were the most common adverse events, with systemic reactions grade II accounting for 11% of reported events. Analytical and confounding biases were identified as major limitations in the available studies. Further research is needed to address these biases and provide stronger evidence on the efficacy and safety of AIT in horses with allergic diseases. [ABSTRACT FROM AUTHOR]

House dust mite (HDM) is the most common allergen exacerbating atopic dermatitis (AD), and allergen‐specific immunotherapy (AIT) using HDM exhibited significant improvements in previous studies. Alopecia can occur as a complication of AD. Alopecia totalis (AT), a severe form of alopecia areata (AA), does not respond well to treatment and the chance of full recovery is less than 10%. For extensive hair loss, topical immunotherapy such as diphenylcyclopropenone (DPCP) is used as the first‐line treatment. However, since DPCP is a kind of contact allergen, it has the potential to exacerbate AD. A 38‐year‐old man with AD and AA visited our clinic with symptoms worsening from 3 months ago. Although taking oral methylprednisolone (8 mg/day) and cyclosporine (100 mg/day) for 3 months, he has lost over 90% of his hair and the Eczema Area and Severity Index (EASI) was 43. Total serum immunoglobulin E (IgE) levels were 4454 kU/L (normal <100 kU/L) and the specific IgE levels for Dermatophagoides pteronyssinus and Dermatophagoides farinae following ImmunoCAP® were 20.8 and 37.4 kU/L, respectively. This patient did not respond well to previous treatment and was reluctant to use long‐term steroids, so subcutaneous AIT using HDM was administered along with oral cyclosporine (100 mg/day). Topical tacrolimus was also applied to the AD lesions throughout the body. To reduce itching, nonsedative antihistamines were used if necessary. Hair loss was almost completely improved 1 year after the AIT initiation and the skin lesions of AD also improved (EASI 2.4). The specific IgE levels for D. pteronyssinus and D. farinae were 3.73 and 7.16 kU/L, respectively. Herein, we report a patient with promising results following AIT for AT with severe AD. In severe alopecic patients with AD refractory to conventional treatment, including immunosuppressants, AIT could be considered as a treatment option. [ABSTRACT FROM AUTHOR]

Purpose of Review: Immunoglobulin A (IgA) mediates immune exclusion of antigens in the gut. Notably, IgA plays also a role in the prevention of IgE-mediated allergies and induction of immune tolerance. The present review addresses the role of IgA in the manifestation of IgE-mediated allergies, including allergen-specific immunotherapy (AIT), the regulation of IgA production, and the mechanism of IgA in immune cell activation. Recent Findings: The majority of studies report an association of IgA with the induction of immune tolerance in IgE-mediated allergies. However, reports on the involvement of humoral and mucosal IgA, IgA subtypes, monomeric and polymeric IgA, and the mechanism of IgA-mediated immune cell activation are confounding. Summary: Effects by IgA are likely mediated by alteration of microbiota, IgE-blocking capacity, or activation of inhibitory signaling pathways. However, the precise mechanism of IgA-regulation, the contribution of serum and/or mucosal IgA, and IgA1/2 subtypes, on the manifestation of IgE-mediated allergies, and the underlying immune modulatory mechanism are still elusive. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy (AIT) was born in 1911 and great progress has been made over the last 110 years, from the invention of subcutaneous and sublingual administration to new strategies. It can be applied in respiratory allergies, such as rhinoconjunctivitis and asthma, with even long-term effects in the use of drugs, symptoms, hospitalizations and prognosis. Many protocols are described in venom allergy, but it is not yet established which is the best and further studies are needed to guide personalized treatment. The use in food allergies is growing, it determines immunological changes in a long-term process, with results that are different between adulthood and pediatric age. Sensitization to allergenic molecules is a gradual process that starts from one or a few molecules, often asymptomatic, to a polymolecular sensitization through a “molecular spreading”. New strategies in AIT have been proposed in recent years, such as the use of adjuvants and modifications of allergens, while biomarkers that allow optimization of treatment with AIT are continually being studied.

Abstract Background Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR. Methods The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment. Results GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1. Conclusion Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR.

Canine atopic dermatitis (cAD) is a genetic, chronic, and recurrent inflammatory and pruritic skin disorder. Allergen-specific immunotherapy (ASIT) is presently recognized as the only clinically effective disease-modifying treatment for allergies. The aim of our study was to analyze the changes in gene expression observed in the peripheral blood nuclear cells of cAD patients subjected to ASIT. Blood samples designated for transcriptomic analyses were collected from AD dogs twice, before and six months after ASIT, and also from healthy dogs. Statistical analysis revealed 521 differentially expressed transcripts, among which 241 transcripts represented genes with well-described functions. Based on the available literature, we chose nine differentially expressed genes (RARRES2, DPP10, SLPI, PLSCR4, MMP9, NTSR1, CBD103, DEFB122, and IL36G) which may be important in the context of the dysregulated immune response observed in cAD patients. The expressions of five out of the nine described genes (DPP10, PLSCR4, NTSR1, DEFB122, and IL36G) changed after the application of ASIT. The expressions of three of these genes returned to the level observed in the healthy control group. The genes listed above need further investigation to determine details of their role in the molecular mechanism of immune tolerance induction in response to allergen-specific immunotherapy. [ABSTRACT FROM AUTHOR]

Shellfish is a leading cause of food allergy and anaphylaxis worldwide. Recent advances in molecular characterization have led to a better understanding of the allergen profile. High sequence homology between shellfish species and between shellfish and house dust mites leads to a high serological cross-reactivity, which does not accurately correlate with clinical cross-reactions. Clinical manifestations are immediate and the predominance of perioral symptoms is a typical feature of shellfish allergy. Diagnosis, as for other food allergies, is based on SPTs and specific IgE, while the gold standard is DBPCFC. Cross-reactivity between shellfish is common and therefore, it is mandatory to avoid all shellfish. New immunotherapeutic strategies based on hypoallergens and other innovative approaches represent the new frontiers for desensitization. [ABSTRACT FROM AUTHOR]

Background: Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR. Methods: The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment. Results: GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1. Conclusion: Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a widespread disease that can be associated with other conditions, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on the history and documentation of sensitization, such as the production of allergen-specific IgE, preferably using molecular diagnostics. Treatments are based on patient education, non-pharmacological and pharmacological remedies, allergen-specific immunotherapy (AIT), and surgery. Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. This review discusses current and emerging management strategies for AR, covering pharmacological and non-pharmacological remedies, AIT, and biologics in selected cases with associated severe asthma. However, AIT presently remains the unique causal treatment for AR. The management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered in the fixed association between intranasal antihistamines and corticosteroids, probiotics and other natural substances, and new formulations (tablets) of AIT. [ABSTRACT FROM AUTHOR]

Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based skin prick test and specific IgE measurement while clinical management consists of food avoidance and as-needed use of adrenaline autoinjector should they develop severe allergic reactions. Such a standard of care is unsatisfactory to both patients and healthcare practitioners. There is a pressing need to introduce more specific diagnostic methods, as well as effective and safe therapies for patients with shellfish allergy. Knowledge gained on the identifications and defining the immuno-molecular features of different shellfish allergens over the past two decades have gradually translated into the design of new diagnostic and treatment options for shellfish allergy. In this review, we will discuss the epidemiology, the molecular identification of shellfish allergens, recent progress in various diagnostic methods, as well as current development in immunotherapeutic approaches including the use of unmodified allergens, hypoallergens, immunoregulatory peptides and DNA vaccines for the prevention and treatment of shellfish allergy. The prospect of a "cure "for shellfish allergy is within reach.

RETRACTED ARTICLEThis article reviews the methodological basic procedures of the allergenic extracts standardization protocols used for the allergen-specific immunotherapy in the world nowadays. The comparative analysis of the normative documents regulating the basic technological stages of allergenic extracts production was carried out. The data concerning the production and quality control of this biological drugs group was generalized. It is shown that the method of tandem mass spectrometry of high resolution combined with high performance liquid chromatography could be advantageously employed in the study area.

At present, there are no effective, non-invasive, and objective indicators to evaluate the efficacy of pediatric house dust mite (HDM)-specific allergen immunotherapy (AIT). A prospective, observational study was performed in children with Dermatophagoides pteronyssinus (Der p) asthma and/or allergic rhinitis (AR). Forty-four patients received subcutaneous Der p-AIT for 2 years, and eleven patients received only symptomatic treatment. The patients needed to finish their questionnaires at each visit. Serum and salivary Der p-specific IgE, IgG4, and IgE-blocking factors (IgE-BFs) were measured at 0, 4, 12, and 24 months during AIT. A correlation between them was also evaluated. Subcutaneous Der p-specific AIT improved the clinical symptoms of children with asthma and/or AR. The Der p-specific IgE-BF significantly increased at 4, 12, and 24 months after AIT treatment. Serum and salivary Der p-specific IgG4 significantly increased with the time of the AIT treatment, and significant correlations between them at different time points were observed (p < 0.05). Furthermore, there were significant correlations (R = 0.31–0.62) between the serum Der p-specific IgE-BF and Der p-specific IgG4 at the baseline, 4, 12, and 24 months after the AIT (p < 0.01). The salivary Der p-specific IgG4 levels also demonstrated a certain correlation with the Der p-specific IgE-BF. Der p-specific AIT is an effective treatment for children with asthma and/or AR. Its effect was associated with increased serum and salivary-specific IgG4 levels, as well as an increased IgE-BF. Non-invasive salivary-specific IgG4 may be useful for monitoring the efficacy of AIT in children. [ABSTRACT FROM AUTHOR]

The allergic march is a progression of naturally occurring symptoms whose nature changes with age. The classic allergic march typically begins in infancy and manifests in the form of atopic dermatitis and food allergy. As immune tolerance develops over time, these conditions may resolve by the age of 3–5 years; however, they may evolve into allergic rhinitis and bronchial asthma. Traditional diagnostic assessments, such as skin prick testing or serum allergen-specific immunoglobulin E (sIgE) level testing, are conducted to introduce effective treatment. Recent years saw the emergence of precision allergy molecular diagnosis (PAMD@), which assesses sIgE against allergenic molecules. This new technology helps more accurately evaluate the patient's allergy profile, which helps create more precise dietary specifications and personalize allergen-specific immunotherapy. This review presents possible predictions regarding the allergic march and the means of controlling it based on PAMD@ results. [ABSTRACT FROM AUTHOR]

A systematic review and narrative synthesis of publications was undertaken to analyze the role of component-resolved diagnosis technology in identifying polysensitization for the provision of allergen-specific immunotherapy to patients with seasonal allergic rhinitis. A search of publications was carried out in electronic databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search helped to identify 568 publications, 12 of which were included in this review. Overall, 3302 patients were enrolled. The major finding was that component-resolved diagnostics change the choice of relevant allergens for allergen-specific immunotherapy in at least 50% of cases. Sensitization to allergen components differs with age, type of disease, and overall disease duration. Patients who had both bronchial asthma and allergic rhinitis were sensitized to a larger number of allergens than patients who had bronchial asthma alone. [ABSTRACT FROM AUTHOR]

Background: Allergen‐specific immunotherapy (AIT) is the only clinical approach that can potentially cure some allergic diseases by inducing immunological tolerance. Dermatophagoides pteronyssinus is considered as the most important source of mite allergens worldwide, with high sensitization rates for the major allergens Der p 1, Der p 2 and Der p 23. The aim of this work is to generate a hypoallergenic hybrid molecule containing T‐cell epitopes from these three major allergens. Methods: The hybrid protein termed Der p 2231 containing T‐cell epitopes was purified by affinity chromatography. The human IgE reactivity was verified by comparing those with the parental allergens. The hybrid was also characterized immunologically through an in vivo mice model. Results: The hybrid rDer p 2231 stimulated in peripheral blood mononuclear cells (PBMCs) isolated from allergic patients with higher levels of IL‐ 2, IL‐10, IL‐15 and IFN‐γ, as well as lower levels of IL‐4, IL‐5, IL‐13, TNF‐α and GM‐CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies that blocked the IgE binding to the parental allergens in the serum of allergic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL‐10 and IFN‐γ and decreased the secretion of IL‐4 and IL‐5, when compared with parental allergens and D. pteronyssinus extract. Conclusions: rDer p 2231 has the potential to be used in AIT in patients co‐sensitized with D. pteronyssinus major allergens, once it was able to reduce IgE production, inducing allergen‐specific blocking antibodies, restoring and balancing Th1/Th2 immune responses, and inducing regulatory T‐cells. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy (AIT) is the only current intervention that has the ability to modify the immune response toward a tolerogenic state. This study aimed to assess the efficacy and safety of AIT in horses with allergic diseases in a systematic manner. Three databases were searched to identify articles reporting clinical outcomes and adverse events associated with AIT. The articles were evaluated for beneficial responses to AIT, defined as a ≥50% reduction in clinical signs, and clinical remission. Horses with respiratory diseases, urticaria, and pruritic dermatitis receiving insect monotherapy or multi-allergen AIT were included. All adverse events were graded, and analytical and confounding biases were assessed. The results showed that multi-allergen AIT had a beneficial response in 75% of horses with respiratory diseases, 88% with urticaria, and 56% with pruritic dermatitis. However, horses treated solely with insect AIT for pruritic dermatitis had a lower response rate (36%). Self-limiting local reactions were the most common adverse events, with systemic reactions grade II accounting for 11% of reported events. Analytical and confounding biases were identified as major limitations in the available studies. Further research is needed to address these biases and provide stronger evidence on the efficacy and safety of AIT in horses with allergic diseases.

Atopic dermatitis (AD) is a common inflammatory skin disease, but current treatments for AD are mostly limited to the alleviation of symptoms and inhibition of inflammation. Allergen‐specific immunotherapy (ASIT) is the only curative approach for allergic diseases and could be a promising way to cure AD. Although ASIT has been gradually applied to patients with AD, there are still few studies on its efficacy evaluation and mechanisms. Based on our previous established AD mouse model by dinitrofluorobenzene and an extract of Dermatophagoides farina, we performed ASIT on this AD model through subcutaneous injection of Dermatophagoides farina extracts to evaluate the efficacy of ASIT and study its underlying mechanisms. Our results showed that ASIT could not only alleviate skin lesions and scratching behaviors of AD mice but also inhibit their Th2‐type immune responses. Furthermore, ASIT could increase the infiltration of monocyte‐derived dendritic cells in skin lesions but attenuated their maturation and production of interleukin 1α and interleukin 12/23 p40. As immature and semi‐mature dendritic cells preferentially induce tolerance, accumulation but inhibition of maturation of monocyte‐derived dendritic cells after ASIT may indicate a novel mechanism of ASIT and a potential therapeutic target for AD. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is an important risk factor for bronchial asthma. Allergen-specific immunotherapy (ASIT) is the gold standard for treatment of allergic rhinitis, conjunctivitis, and asthma. A disadvantage of current ASIT methods is the length of therapy which requires numerous allergen administrations. The success of ASIT is determined by its schedule, which, depending on the vaccine and type of allergy, can be pre-seasonal (before the allergy season begins), combined pre/co-seasonal (during the allergy season) etc. The aim of the present study was to evaluate a vaccine based on recombinant Artemisia vulgaris pollen major Art v 1 protein formulated with ISA-51 adjuvant for therapy of allergic rhinitis and bronchial asthma in Artemisia-sensitized mice in an ultrashort (4 subcutaneous injections at weekly intervals) pre- and co-seasonal ASIT regimen. To simulate co-seasonal ASIT in mice, mice were regularly challenged with intranasal and nebulized Artemisia vulgaris pollen extract at the same time as receiving subcutaneous ASIT. For comparison, we used a previous Art v 1 protein vaccine formulated with SWE adjuvant, which in this study was modified by adding CpG oligonucleotide (Th1-biasing synthetic toll-like receptor 9 agonist), and a commercial vaccine containing a modified Artemisia vulgaris extract with aluminum hydroxide adjuvant. The therapeutic potential of Art v 1 based vaccine formulations with different ASIT regimens was evaluated in high and low (10 times lower) dose regimens. The ISA-51-adjuvanted vaccine formulations were the only ones among those studied in the ultrashort pre- and co-seasonal ASIT regimens to provide significant reduction in both signs of allergic rhinitis and bronchial asthma in sensitized mice (vs. positive control). In the ISA-51 adjuvanted group, immune response polarization toward Th1/Treg was observed in pre-seasonal ASIT, as reflected in a significant decrease in the serum level of total and Art v 1-specific IgE and increased ratios of allergen-specific IgG2a/IgG1 and IFN-γ/IL-4. The high dose SWE-CpG-adjuvanted vaccine had similar efficacy to the ISA-51 adjuvanted groups whereas the commercial vaccine showed significantly less effectiveness. The findings support further preclinical safety studies of the Art v 1-based vaccine formulated with ISA-51 adjuvant. [ABSTRACT FROM AUTHOR]

Background: In vitro immunoglobulin E (IgE) tests can be better standardized if based on molecules rather than extracts. However, singleplex screening tests for respiratory or food allergies are still based on extracts only. Target: To validate a novel singleplex IgE screening test for respiratory allergies, based on a mix of major allergenic molecules Der p 1, Der p 2, Fel d 1, Can f 1, Can f 2, Can f 3, Can f 5, Bet v 1, Phl p 1, and Art v 1 (Molecular SX01, NOVEOS, HYCOR, USA), and requiring only four microliters (μl) of serum. Methods: We examined six subsets of sera from participants of the German Multicenter Allergy Study (MAS) birth cohort enrolling 1314 newborns during 1990: (1) monosensitized (n = 58); (2) polysensitized (n = 24); (3) nonsensitized, with total IgE levels above (n = 24) or (4) below (n = 24) 300 kU/L; (5) sensitized to milk and/or egg but not to airborne allergens (n = 24); and (6) sera of children aged ≤5 years at their earliest IgE monosensitization to airborne allergens (n = 41). Sera were analyzed with the novel molecular SX01 test (NOVEOS) and with three categories of comparators: ImmunoCAP Phadiatop SX01, extracts, and molecules of D. pteronyssinus, cat, dog, grass, and birch. Sensitivity, specificity, positive and negative predictive values were calculated. Quantitative interrelationships were determined using Spearman's rank‐order correlation coefficient and Bland–Altmann plots. Results: The molecular SX01 test predicted the outcome of IgE tests based on molecules, extracts, or Phadiatop in 188 (96.4%), 171 (87.7%), and 171 (87.7%) of the 195 sera, respectively. Accordingly, sensitivity was 93.5%, 89.0%, and 82.4%, whereas specificity was 100%, 97.6%, and 96.1% when compared with molecular, extract, and Phadiatop tests, respectively. Inconsistent outcomes were largely confined to sera with IgE‐Ab levels around the cutoff value of 0.35 kU/L, except for 5/195 (2.5%) sera, containing high levels of IgE to Phl p 5 and/or Alt a 1 only. IgE levels measured by the molecular SX01 test and with IgE tests to molecules, extracts, and Phadiatop were highly correlated (rho 0.90; p <.001), (rho 0.87, p <.001), (rho 0.84, p <.001), respectively. The novel molecular SX01 test detected IgE‐Ab in 27/28 (sensitivity 96.4%) of the sera of preschool children at their earliest IgE sensitization to the same molecules. Discussion Our study validates the prototype of a novel category of IgE test, based on molecular mixes. The test's rather good precision and accuracy in early screening IgE sensitization to airborne allergens in German children may be further improved by adding a few other molecules, such as Phl p 5 and Alt a 1. [ABSTRACT FROM AUTHOR]

Successful treatment of IgE mediated allergies by allergen-specific immunotherapy (AIT) usually correlates with the induction of allergenspecific IgG4. However, it is not clear whether IgG4 prevents the allergic reaction more efficiently than other IgG subclasses. Here we aimed to compare allergen-specific monoclonal IgG1 and IgG4 antibodies in their capacity to inhibit type I allergic reactions by engaging FcγRIIb. We found that IgG1, which is the dominant subclass induced by viruses, binds with a similar affinity to the FcγRIIb as IgG4 and is comparable at blocking human basophil activation from allergic patients; both by neutralizing the allergen as well as engaging the inhibitory receptor FcγRIIb. Hence, the IgG subclass plays a limited role for the protective efficacy of AIT even if IgG4 is considered the best correlate of protection, most likely simply because it is the dominant subclass induced by classical AITs. [ABSTRACT FROM AUTHOR]

Asthma represents one of the biggest global health concerns with increasing prevalence and influence on global health. Several distinct asthma phenotypes have been identified with one of the most common, earliest recognized, and described being the allergic asthma phenotype, in which allergens trigger asthma through mechanisms involving allergen-specific immunoglobulin E (IgE). Allergen-specific immunotherapy (AIT), in the forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has been used for many decades as a tool for reducing IgE-mediated sensitization and controlling symptoms of allergic disease, most commonly for allergic rhinitis, and it remains the only currently available disease modifying therapy in atopic patients. AIT has been studied for use in mild to moderate allergic asthma. While the data are often inconsistent, and utilize a multitude of different methods, antigens, and outcome measures, in general, AIT may have several beneficial effects on asthma disease control, quality of life, and requirement for medication. These benefits are notable when immunotherapy is used as an adjunct to pharmacologic treatment in carefully selected and monitored patients with mild to moderate persistent asthma. Patients with severe asthma are excluded from these trials. Importantly, patients with asthma, and in particular severe asthma, may have a higher rate of systemic adverse reactions to SCIT, including anaphylaxis; however, these events are overall rare. Future research in the area is needed to definitively assess the benefit of SCIT and SLIT for patients with asthma, comparing outcomes with different methods, addressing the role of AIT in severe asthma, significance of multiallergen AIT in allergic asthma, and safety concerns in asthma. [ABSTRACT FROM AUTHOR]

Background: The European Academy of Allergy and Clinical Immunology recommended the Combined Symptom and Medication Score (CSMS) as primary endpoint in clinical trials on allergen‐specific immunotherapy (AIT) in allergic rhinoconjunctivitis. Here, the correlation between the CSMS and the validated standardised Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)), Rhinitis Control Assessment Test (RCAT) and Visual Analogue Scale (VAS) was analysed. Methods: Two prospective, multicentre, non‐interventional studies on tree pollen, grass pollen and house dust mite allergic patients were performed. The first study comprised 167 patients receiving AIT (AIT population), and the second included 56 patients treated with symptomatic medication only (control population). For up to two seasons (pollen)/exposure periods (house dust mites), participants documented their symptoms and medication intake in a CSMS diary, including VAS. In addition, the standardised RQLQ(S) and the RCAT were completed during study visits. Results: Comparison between CSMS and RQLQ(S) revealed a positive correlation in the AIT population (r = 0.426) and in the control population (r = 0.569). For CSMS and RCAT, a negative correlation with r = −0.409 (AIT) and r = −0.547 (control) was shown. Positive correlation between CSMS and VAS was also demonstrated with r = 0.585 (AIT) and r = 0.563 (control). Conclusion: These results support the assumption that the CSMS correlates with quality of life, symptom severity and symptom control on the one hand, while the moderate strength of correlations on the other hand mirrors distinctions of the CSMS compared to the assessments used here. [ABSTRACT FROM AUTHOR]

Background: Molecular antibody reactivity profiles have not yet been studied in depth in patients treated by sublingual house dust mite (HDM) tablet immunotherapy. Humoral immune responses to a large panel of HDM mite allergens were studied using allergen microarray technology in a subset of clinically defined high and low responder patients from a double‐blind placebo‐controlled allergen‐specific immunotherapy (AIT) trial using sublingual 300 IR HDM tablets. Methods: Serum levels of IgE, IgG and IgG4 to 13 Dermatophagoides pteronyssinus molecules were measured at baseline and after 1‐year AIT, using allergen microarrays in 100 subjects exhibiting high or low clinical benefit. Results: Der p 1, Der p 2 and Der p 23 were the most frequently recognized allergens in the study population. Patients with HDM‐related asthma had significantly higher allergen‐specific IgE levels to Der p 1 and Der p 23. No significant difference in the distribution of allergen sensitization pattern was observed between high and low responders. An increase in serum allergen‐specific IgG and IgG4 occurred upon AIT, in particular to allergens Der p 1, Der p 2 and Der p 23 (p < 0.0001). Conclusions: We confirm for our study population that Der p 1‐ and Der p 23‐specific IgE levels are associated with asthma. IgE reactivity profiles were not predicitive of sublingual AIT outcomes, with 300 IR tablets as efficacious in pauci‐ and multi‐sensitized subjects. Our study is the first to demonstrate the induction of IgG and IgG4 specific for the HDM allergens Der p 1, Der p 2 and Der p 23 by sublingual AIT. [ABSTRACT FROM AUTHOR]

Next-generation allergy vaccines refer to allergen-derived attenuated molecules that can boost allergen-blocking IgG response. These IgG antibodies are specifically directed toward the IgE epitope of allergens and interfere in allergen-IgE interaction. Our study is a computational approach to design such vaccines against four widespread pan-allergens families. Pan-allergens display extensive immunological cross-reactivity due to the presence of conserved IgE epitope and T cell epitope. In this study, the vaccine design is based on hapten–carrier concept in which the carrier protein is an immunogenic component providing T cell help. Either PreS protein of hepatitis B or cholera enterotoxin B (CTB) fused with three tetanus toxoid fragments (TTFrC) was used here as the carrier. The hapten components are nonanaphylactic peptides (NAPs) derived from experimentally determined antigenic regions of the allergens. The charged residues of NAPs are selectively modified to obliterate IgE, as well as T cell reaction, and hence, are safe to apply in allergy patients. Various combinations of vaccine constructs (PreS/CTB+TTFrC and NAPs) were designed with intermediate linker motifs. Screening of constructs was performed through a three-step method such as physicochemical parameters, secondary structures, and tertiary structures using various bioinformatic tools. The final construct with best quality and stability was selected for each allergen family. Suitability of these constructs for being expressed in recombinant form was checked at DNA, RNA, and protein level. Presence of putative epitopes inducing tolerogenic interleukin-10 was also predicted for these constructs. The present work led to the design of putative vaccines with immunotherapeutic potential and broad applicability for allergic diseases caused by a wide array of cross-reactive allergens. [ABSTRACT FROM AUTHOR]

Allergen-specific immunotherapy (AIT) involves administering allergen extracts. It is used to desensitize allergic patients. Herbal allergen extracts that are optimum in efficacy and fewest in side effects are still challenging to produce. To overcome these limitations, oral immunotherapy, epicutaneous immunotherapy, intralymphatic immunotherapy, and artificial recombinant allergen preparations have been evaluated. Recombinant allergens have become more popular with the development of molecular diagnostics and therapeutics. Besides food and drug allergens, pollen, fungal spores, and other allergens have been studied. Based on related clinical studies, this comprehensive overview will present the latest perspectives on AIT methods and available allergenic products, as well as discuss the challenges and opportunities for treating allergic disorders. [ABSTRACT FROM AUTHOR]

Transdermal drug delivery systems (TDDSs) overcome the hurdle of an intact skin barrier by penetrating the skin to allow molecules through. These systems reduce side effects associated with conventional hypodermic needles. Here, we introduce novel microneedle (MN) TDDSs that enhance drug delivery by creating micron-sized pores across the skin. Many MN TDDSs designed to deliver a diverse array of therapeutics, including allergen-specific immunotherapy, skin disease treatments, and vaccines, are under pre-clinical and clinical trials. Although epicutaneous approaches are emerging as new options for treating food allergy in many clinical trials, MN TDDSs could provide a more efficient and convenient route to deliver macromolecules. Furthermore, MN TDDSs may allow for safe vaccine delivery without permanent scars. MN TDDSs are a major emerging strategy for delivering novel vaccines and treatments for diseases, including skin diseases, allergic diseases, and so on. [ABSTRACT FROM AUTHOR]