Subcutaneous Immunotherapy of Food Allergy.

PURPOSE OF REVIEW: While there are compelling arguments for developing subcutaneous allergen-specific immunotherapy for alleviation of food allergies, there is a limited number of studies in the public domain. The review seeks to present the approaches taken, to explain the paucity of studies, and to identify new roads for development. RECENT FINDINGS: A literature search revealed clinical trials of immunotherapy of food allergies to fish and peanut, but studies had limited patient numbers, short treatment courses and follow-up periods. Indications, but no clearcut effects, were seen with both classical allergen extracts and hypo-allergenic preparations. A special case is the influence on cross-reactive food allergies, when subcutaneously administered birch-pollen extracts are used for treatment of birch pollen hayfever and/or asthma. Again indications, but no convincing efficacy has been registered. Newer developments include recombinant hypoallergens and DNA-technologies. Subcutaneous immunotherapy for food allergies has not matured to provide clinically relevant treatment opportunities.

Knowledge, Attitudes, and Practices of Patients with Allergic Rhinitis Towards Allergen-Specific Immunotherapy.

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 (ß = -0.354, P = 0.010) and practice (ß = 0.618, P = 0.010), and attitude also demonstrated a noteworthy impact on practice (ß = -0.120, P = 0.020). Furthermore, it is worth noting that the indirect effects of knowledge on practice were statistically significant (ß = 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.

Retrospective, Real Life Study on the Effectiveness and Safety of a Depigmented-Polymerized Subcutaneous Vaccine Containing a Mixture of Grasses and Olea europaea.

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.

Efficacy and safety of subcutaneous and sublingual allergen immunotherapy in the treatment of asthma in children: a systematic review and meta-analysis.

OBJECTIVE: Asthma 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. METHODS: 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. RESULTS: 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]). CONCLUSIONS: 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.

[Molecular allergen IgE tests show neosensitizaions occurring during house dust mite specific immunotherapy].

Objective:Neosensitizations may be occur during the allergen specific immunotherapy（AIT） due to the differences between allergen vaccine's content and a patient's molecular sensitization profile. This study investigates whether AIT with HDM extract changes the sensitization profile, whether de novo sensitization occurs, and the clinical importance of the neosensitization. Methods:Fifty-three patients with HDM allergic rhinitis ,with/without asthma, patients were received one year HDM subcutaneous AIT . Fourteen patients were recruited as control group and received only necessary medications. Serum samples were collected at baseline, 6thmoths and 12thof AIT, respectively. Serum samples were tested specific IgE against Der p, Der p 1/2/3 and Der f, Der f 1/2/3, as well as IgG4 against Der p, Der p 1/2 and Der f, Der f 1/2. VAS were collected at the time-points as well. Results:In AIT group, Der p, Der p 1/3, and Der f 1/3 specific IgE levels were significantly higher after one-year treatment, especially for Der p 3. There were 69.2%（18/26） patients whose Der p 3 specific IgE below 0.35 kU/L at baseline but became positive（>0.35 kU/L） after treatment, that is, neosensitization occurred. All tested allergen specific IgG4 level significantly increased after one year AIT treatment and the VAS declined dramatically. However, for patients with neosensitization and without neosensitization, there were no significantly changes concerning to IgG4 level and VAS. Conclusion:Patients undergoing AIT might have a risk of neosensitization to the allergen components in the vaccines. However, the clinical importance of the neosensitization remains unclear and warrants further studies.

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.

The cytoskeletal protein profilin is an important allergen in saltwort (Salsola kali).

Pollen from Salsola kali, i.e., saltwort, Russian thistle, is a major allergen source in the coastal regions of southern Europe, in Turkey, Central Asia, and Iran. S. kali-allergic patients mainly suffer from hay-fever (i.e., rhinitis and conjunctivitis), asthma, and allergic skin symptoms. The aim of this study was to investigate the importance of individual S. kali allergen molecules. Sal k 1, Sal k 2, Sal k 3, Sal k 4, Sal k 5, and Sal k 6 were expressed in Escherichia coli as recombinant proteins containing a C-terminal hexahistidine tag and purified by nickel affinity chromatography. The purity of the recombinant allergens was analyzed by SDS-PAGE. Their molecular weight was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and their fold and secondary structure were studied by circular dichroism (CD) spectroscopy. Sera from clinically well-characterized S. kali-allergic patients were used for IgE reactivity and basophil activation experiments. S. kali allergen-specific IgE levels and IgE levels specific for the highly IgE cross-reactive profilin and the calcium-binding allergen from timothy grass pollen, Phl p 12 and Phl p 7, respectively, were measured by ImmunoCAP. The allergenic activity of natural S. kali pollen allergens was studied in basophil activation experiments. Recombinant S. kali allergens were folded when studied by CD analysis. The sum of recombinant allergen-specific IgE levels and allergen-extract-specific IgE levels was highly correlated. Sal k 1 and profilin, reactive with IgE from 64% and 49% of patients, respectively, were the most important allergens, whereas the other S. kali allergens were less frequently recognized. Specific IgE levels were highest for profilin. Of note, 37% of patients who were negative for Sal k 1 showed IgE reactivity to Phl p 12, emphasizing the importance of the ubiquitous cytoskeletal actin-binding protein, profilin, for the diagnosis of IgE sensitization in S. kali-allergic patients. rPhl p 12 and rSal k 4 showed equivalent IgE reactivity, and the clinical importance of profilin was underlined by the fact that profilin-monosensitized patients suffered from symptoms of respiratory allergy to saltwort. Accordingly, profilin should be included in the panel of allergen molecules for diagnosis and in molecular allergy vaccines for the treatment and prevention of S. kali allergy.

Activation of the aryl hydrocarbon receptor improves allergen-specific immunotherapy of murine allergic airway inflammation: a novel adjuvant option?

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: A 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. 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 AhR-dependent 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.

Allergen-Encapsulating Nanoparticles Reprogram Pathogenic Allergen-Specific Th2 Cells to Suppress Food Allergy.

Food allergy is a prevalent, potentially deadly disease caused by inadvertent sensitization to benign food antigens. Pathogenic Th2 cells are a major driver for disease, and allergen-specific immunotherapies (AIT) aim to increase the allergen threshold required to elicit severe allergic symptoms. However, the majority of AIT approaches require lengthy treatments and convey transient disease suppression, likely due to insufficient targeting of pathogenic Th2 responses. Here, the ability of allergen-encapsulating nanoparticles to directly suppress pathogenic Th2 responses and reactivity is investigated in a mouse model of food allergy. NPs associate with pro-tolerogenic antigen presenting cells, provoking accumulation of antigen-specific, functionally suppressive regulatory T cells in the small intestine lamina propria. Two intravenous doses of allergen encapsulated in poly(lactide-co-glycolide) nanoparticles (NPs) significantly reduces oral food challenge (OFC)-induced anaphylaxis. Importantly, NP treatment alters the fates of pathogenic allergen-specific Th2 cells, reprogramming these cells toward CD25+FoxP3+ regulatory and CD73+FR4+ anergic phenotypes. NP-mediated reductions in the frequency of effector cells in the gut and mast cell degranulation following OFC are also demonstrated. These studies reveal mechanisms by which an allergen-encapsulating NP therapy and, more broadly, allergen-specific immunotherapies, can rapidly attenuate allergic responses by targeting pathogenic Th2 cells.

[Feeling analysis on allergen immunotherapy on Twitter using an unsupervised machine learning model]. / Análisis de sentimientos acerca de la inmunoterapia con alérgenos en Twitter mediante un modelo de aprendizaje automático no supervisado.

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.

OBJETIVO: Analizar los sentimientos acerca de la inmunoterapia alérgeno-específica en Twitter mediante el modelo VADER (Valence Aware Dictionary and sEntiment Reasoner). MÉTODOS: Se utilizaron tweets relacionados con la inmunoterapia alérgeno-específica obtenidos a través del API (Application Programming Interface) de Twitter. Se incorporaron las palabras clave "allergy shot" en el período comprendido entre el 1 de enero de 2012 y el 31 de diciembre de 2022. Los datos obtenidos fueron procesados, eliminando las URL, nombres de usuarios, hashtags, espacios múltiples y tweets duplicados. Posteriormente, se realizó un análisis de sentimientos utilizando el modelo VADER. RESULTADOS: Se recolectaron 34,711 tweets, de los que se eliminaron 1928. De los 32,783 tweets restantes, se encontró que el 32.41% de los usuarios expresó un sentimiento negativo, el 31.11% un sentimiento neutral y el 36.47% un sentimiento positivo, con una media de polaridad de 0.02751 (neutral) a lo largo de los 11 años. CONCLUSIONES: La polaridad media de los tweets acerca de la inmunoterapia alérgeno-específica es neutral a lo largo de los 11 años analizados. Existe un aumento anual en la polaridad media positiva a lo largo de los años, sobre todo entre 2017, 2018 y 2022. La cantidad de tweets disminuyó con el tiempo.

A meta-analysis investigating the efficacy and safety of allergen-specific immunotherapy in the management of respiratory allergies.

BACKGROUND: This 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Hymenoptera Venom Immunotherapy Meets Factitious Disorder.

Factitious disorder on self is a psychiatric disorder in which individuals fabricate or induce signs or symptoms of a disease. Factitious anaphylaxis, with symptoms suggestive of a life-threatening allergic reaction, is extremely rare. Several cases of factitious disorder reactions during allergen immunotherapy for airborne allergens have been reported. We report the case of a young female patient who presented factitious anaphylaxis during venom immunotherapy to vespid venom extract. Symptoms of stridor, dyspnea, coughing and loss of consciousness were observed during the built-up phase of venom immunotherapy, mimicking allergic reactions to the venom extracts. Diagnosis of factitious disorder prompted the discontinuation of venom immunotherapy.

Comparative study of the commonly used protein quantitation assays on different Hymenoptera venoms: A fundamental aspect of Hymenoptera venom proteome analysis.

Determination of protein concentration in Hymenoptera venoms requires an accurate and reproducible assay as the results will be used to support subsequent proteomic techniques employed in their analyses. However, all protein assay techniques have inherent strengths and weaknesses, demanding their assessment before selecting the most suitable platform for sample analysis. In this study, protein profiles of ant, honeybee, and wasp venoms, and bovine serum albumin (BSA) and hyaluronidase standards were qualitatively assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Their amino acid and protein concentration were quantitatively determined via Amino Acid Analysis (AAA). Amino acid concentration was determined via hydrolysis, derivatization, and chromatographic quantification. Protein concentration was estimated using four different protein concentration assays. The ratios of protein concentration in venom samples to protein standards were calculated, and the accuracy of the protein concentration assays was analysed relative to the concentration determined from AAA. SDS-PAGE analysis showed that BSA contained several protein bands, while hyaluronidase contained a mixture of peptide and protein bands. Ant and honeybee venoms contained a higher proportion of peptide bands, while wasp venom contained more protein bands. As determined by AAA, the ratio of protein concentration in Hymenoptera venoms varied between 1.01 and 1.11 to BSA, and between 0.96 and 1.06 to hyaluronidase. Overall, the Bradford assay was found to be the least accurate and the BCA assay was the most accurate in estimating protein concentration in Hymenoptera venoms. There was no significant advantage in using hyaluronidase as a standard or increasing incubation temperature of BCA assay when analysing Hymenoptera venoms. Diluent solutions containing phenol and human serum albumin interfered with Lowry-based assays.

Novel adjuvants in allergen-specific immunotherapy: where do we stand?

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.

The Role of Regulatory T Cells in Allergic Diseases: Collegium Internationale Allergologicum (CIA) Update 2024.

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.

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.

Designing a T-cell epitope-based vaccine using in silico approaches against the Sal k 1 allergen of Salsola kali plant.

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.

The pharmacotherapeutic management of allergic rhinitis in people with asthma.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

[Insect venom allergies-What will change in times of global change?] / Insektengiftallergien ­ Was wird sich ändern in Zeiten des globalen Wandels?

BACKGROUND: In Germany, honeybees (Apis mellifera) and various Vespula species (wasps) are primarily relevant for hypersensitivity reactions to stings. Hornets (Vespa crabro), bumblebees, paper wasps (Polistes) and yellowjackets (Dolichovespula) less frequently cause sting reactions. OBJECTIVE: What effects do intensive agricultural utilization and climate change have on the living conditions and occurrence of Hymenoptera and what consequences do they have for the diagnostics and treatment of hypersensitivity reactions to Hymenoptera stings. MATERIAL AND METHODS: A literature search was carried out. RESULTS: Honeybees and wild bees are endangered due to introduced diseases, invasive species and pesticides. The aim of widespread beekeeping activity is to protect honeybees, which is why no reduction in stings is to be expected despite increased bee mortality. In Germany, there is evidence of the spread of thermophilic Polistes species (paper wasps) from south to north and the immigration of Vespa velutina nigrithorax (Asian hornet). It is unlikely that these species will lead to a significant increase in sting reactions. Nests of the red fire ant (Solenopsis invicta), which was originally common in South America, were first detected in Sicily in 2022. Red fire ants are aggressive insects with a high potential for adverse sting reactions. CONCLUSION: Invasive insects must be considered as a trigger in the anamnesis and diagnostics. Diagnostics are only available for the detection of Polistes sensitization. Therapeutic allergens can be obtained from other European countries for venom immunotherapy of a Polistes allergy. Due to cross-reactivity, diagnostic and therapeutic allergens from Vespula spp. are used for the diagnosis and treatment of suspected allergies to the Asian hornet.