Allergen immunotherapy (AIT) represents the sole causal and preventive disease-modifying therapy currently available for allergic diseases. However, it must be acknowledged that controlled studies feature inherent results bias due to specific criteria and monitoring during the study. This real-world evidence (RWE) study was therefore designed to analyse data on large longitudinal prescriptions of different types of AIT in order to evaluate the therapeutic effect on the progression and onset of atopic dermatitis (AD).

The analysis was based on IQVIA LRx prescription data for statutorily insured patients in Germany. A total of 122,600 patients were included in the study, and we identified prescriptions of AIT for house dust mites (HDM), grasses (GR) and early flowering trees (EFT) from 2008 to 2017. We compared AIT groups to control groups, which were selected from patients not treated with AIT but with at least 2 prescriptions of symptomatic allergic rhinitis (AR) medication. We measured the impact of AIT treatment on AD using symptomatic AD medication.

The use of all 3 forms of AIT resulted in a significant decrease in the necessity for AD medication when compared to the control group. Moreover, in patients who did not present with AD at the outset of the study, AIT was observed to significantly reduce the likelihood of developing AD at a later stage, in comparison to allergic patients who were not subjected to AIT.

Our results confirm the positive effects of AIT in patients with AD. The findings of this study illustrate the value of RWE studies as a means of further analysis of AIT as a disease modifier, thus providing a complementary perspective to that gained from clinical studies and enhancing the efficacy of AIT in the future.

The safety of aluminium (Al) exposure from medicinal products for subcutaneous allergen immunotherapy (SCIT) is still under debate due to their administration in many doses over years. Especially for children, model-informed risk assessment is urgently needed in the absence of clinical study data.

We applied a physiologically-based toxicokinetic Al model for simulation of Al exposure from various SCIT scenarios in children (5 and 10 years) compared to adults (35 years) in addition to continuous Al exposure from dietary intake.

Simulations of a worst-case Al exposure scenario (five-year SCIT; four-weekly injections; 1.25 mg Al per dose) in children reveal substantial, but subtoxic and transient increases in bone Al content. Predicted increases of Al levels in the brain appear negligible. In both of these storage organs, Al levels predicted at 50 years of age were only marginally affected by the previous SCIT treatment. Two exceptional SCIT scenarios, prolongation of treatment duration to 40 years and parallel treatment with two 1.25 mg Al-containing products, were associated with elevated bone Al levels above the normal adult range and close to a level where potential harm to bone metabolism cannot be excluded.

Simulations support the tolerability of single SCIT treatments in all age groups ≥5 years, also with respect to the long-term Al body burden. The Pharmacopoeial limit of 1.25 mg Al per dose could be seen as a conservative threshold also for the sum of doses from parallel treatments. The decision to prolong therapy with Al-containing SCIT products should be taken under careful consideration of Al accumulation.

Children with IgE-mediated food allergies, particularly milk, are at risk for hampered growth. Limited data is available regarding the benefit of oral immunotherapy (OIT) on growth outcomes.

Evaluate the impact of OIT on growth metrics in this population.

We retrospectively analyzed data from patients [ages 4–15 (females) and 4–16.5 (males) years] who successfully completed OIT. Pre- and post-OIT height-for-age and weight-for-age z-scores (HAZ and WAZ, respectively) were calculated using WHO standards.

Patients (n=458, mean age 8.0 ± 2.7 years) successfully treated for tree-nut (33.4%), peanut (29.7%), milk (17.2%), sesame (14.6%) and egg (4.8%) allergy, were analyzed. Baseline mean HAZ -0.19 ± 1.05 improved to -0.10 ± 1.05 (p<0.001) following OIT (median duration, 19.4 months). This was positively correlated with the mean change in WAZ (r=0.44, p<0.001). Milk, compared to non-milk, allergic patients had lower baseline HAZ (-0.45 ± 0.91 vs -0.14 ± 1.07, p=0.016). Patients beginning OIT before age 6 had the greatest HAZ improvement (0.16 ± 0.42), while those starting after age 12 experienced a decrease (-0.11 ± 0.49). In 113 patients with a median 34-month follow-up, HAZ improved by 0.30 ± 0.73 (p<0.001). This effect was not observed at long-term follow-up in a group of patients who did not achieve successful OIT (n=21). Using a linear regression model, significant predictors of follow-up HAZ were younger age at baseline (B= -0.09, 95% CI [-0.15, -0.03], p=0.002) and lower baseline HAZ (B=0.83, 95% CI [0.69, 0.97], p<0.001).

OIT may enhance long-term growth in allergic children, especially in younger patients and those with a lower baseline HAZ. Effects on their final stature remains to be determined.

Allergic sensitization and viral infections are risk factors for asthma development and progression. Sublingual vaccination with MV130, a whole heat-inactivated polybacterial preparation, protects against viral infections, but its impact on allergic sensitization and asthma development remains unknown. Here we show MV130 prevents house dust mite (HDM)-induced local type 2 immune responses and associated eosinophilic airway inflammation, conferring protection up to 9 weeks after vaccination. MV130 reduces pathophysiological and clinical asthma features in an in vivo experimental mouse model of HDM-induced allergic eosinophilic asthma, restoring normal airway functionality. MV130 impairs allergen-specific IgE sensitization and systemic type 2 inflammation endorsing type 1 and IL-10 responses. In human DCs, MV130 induces a transcriptomic and metabolic reprogramming, and restores non-pathological immune responses to allergens in healthy and asthmatic donors. Additionally, the adoptive transfer of MV130-stimulated BMDCs was sufficient to reproduce the protective features of the vaccine administration in vivo. Collectively, we show MV130 reduces allergic sensitization and eosinophilic asthma. Our findings support the exploration of mucosal interventions aimed at reducing the risk of allergen-induced asthma development.

Specific venom immunotherapy (VIT) in patients with hymenoptera venom allergy (HVA) represents a well-studied approach to reduce the severity of a possible anaphylactic reaction. Currently, data on mechanisms of tolerance induction at the cellular level within the first hours of therapy are lacking. To address this, total and unoccupied high-affinity IgE receptor (FcεRI) numbers per basophil, soluble FcεRI (sFcεRI) and serum tryptase levels were measured before and after the first day of VIT induction in HVA patients. Additionally, basophil activation tests (BATs) were performed at those time points. In the early phase of VIT induction, no significant change in total FcεRI receptor density on basophils was observed, but a significant increase in unoccupied FcεRI was noticeable, predominantly in patients with high total IgE and low baseline unoccupied FcεRI density. No meaningful difference in serum tryptase levels or sFcεRI levels was observed after VIT induction. BATs showed heterogeneous results, often unchanged before and after VIT (in 47% of the cases), sometimes increased (in 40%) and only rarely decreased EC50 sensitivity (in 13%). Changes in the BAT EC50 correlated with FcεRI receptor density changes in basophils. In summary, VIT induction led to an increased ratio of unoccupied-to-total FcεRI without notable tryptase or sFcεRI serum elevation, pointing towards subthreshold cell activation with receptor internalization and recycling. However, the mostly unchanged or even increased basophil sensitivity in EC50 calls for further research to clarify the clinical relevance of these rapid receptor modulations.

Allergic diseases are very broad-ranging conditions and affect the health and comfort of patients in different manners. To date, the only effective treatment is allergen immunotherapy. Unfortunately, apart from observations of drug use or the severity of symptoms, there is no direct method of determining the effectiveness or ineffectiveness of the medical intervention that has been provided. The hope of gaining insight into the adaptive processes occurring in the body during immunotherapy is offered by epigenetics. By observing such areas of biological activity as DNA methylation, modification of histone proteins, or studies of non-coding RNA fragments, physicians will gain reliable tools for determining the effectiveness of the undertaken therapy. They can link the data acquired to the expression levels of specific genes that activate or suppress the immune response, perhaps even before it is initiated. This paper describes the basic epigenetic mechanisms, their known links to specific diseases and therapies, and potential areas for further research.

Food allergies (FAs) are an increasing public health concern, particularly in children. Oral immunotherapy (OIT) is an emerging treatment strategy under clinical investigation for desensitization of children with FA to food allergens. Dysbiosis of the gut microbiota has been implicated in FAs, and various factors influence its composition; however, the impact of OIT on the gut microbiota remains largely unexplored.

This study aimed to identify the changes in diversity of the gut microbiota following OIT in children with FA.

Thirty children with FA (mean age 3.93 years, age range 2.00–14.00) undergoing oral immunotherapy targeting legumes (lentils, peanuts, peas), tree nuts (cashews, hazelnuts, pistachios), animal products (milk, egg), and fish and shellfish (salmon, shrimp), as well as seven non-allergic controls (mean age 2.65 years, age range 0.25–5.00) participated in this study. Fecal samples were collected before and after OIT from children with FA, and once from controls. The gut microbiota was profiled using 16S rRNA sequencing, followed by diversity and differential abundance analyses. Alpha and beta diversities were compared, and differential abundance was assessed.

Beta diversity analysis revealed small but significant differences in microbial composition between children with FA before and after OIT, and between controls and children with FA before OIT. Differential abundance analysis showed that OIT induced a reversion of the abundance levels of Bacteroidota and Verrucomicrobiota toward those observed in controls.

To our knowledge, this is the first study to investigate the impact of OIT on the gut microbiota in children with different FAs for identifying potential microbial biomarkers and convincingly demonstrated their interrelation. These findings may help improve and personalize FA treatment.

Peanut allergy is the most common childhood-onset, persistent food allergy. Peanut oral immunotherapy (OIT) is a potential treatment, but few studies prospectively examine the outcome of peanut OIT in young children using parent-measured doses compared to standard care (peanut avoidance).

To determine the efficacy, safety and tolerability of a pragmatic peanut OIT protocol (parent-measured doses with low maintenance dose) compared to avoidance.

In this unblinded randomised controlled trial (1:1 ratio), children 1–4 years old were assigned to receive peanut OIT (maintenance dose 360 mg) or avoidance for 12 months. The primary outcome was desensitisation, defined as the ability to tolerate at least 600 mg peanut protein during an end-of-treatment oral food challenge (EOT OFC), with secondary outcomes frequency and severity of adverse events, change in quality of life and change in immunological markers of peanut allergy.

A total of 54 children were randomised, with 23/27 in the peanut OIT and 25/27 in the avoidance group undergoing open peanut challenge after 12 months. An eliciting dose of ≥ 600 mg peanut protein was tolerated by 74% (20/27) of OIT compared to 11% (3/27) of avoidance participants. 41% of OIT (11/27) and 7% of avoidance (2/27) participants passed the end-of-treatment challenge. The OIT group reported significantly better quality of life than the avoidance group after 12 months (Food Allergy Quality of Life Questionnaire-Parent Form mean difference -0.5, p = 0.041). There were 79 treatment-related adverse events reported by 21 participants in the OIT group (median 2 per participant, range 0–13).

Peanut OIT using parent-measured doses and a low maintenance dose of 360 mg is effective at inducing desensitisation after 12 months in 1-to-4-year-old children. In this cohort, peanut OIT is associated with improved quality of life compared to avoidance and appears to have an acceptable safety profile.

Cats and dogs are the primary and most common sources of indoor allergens from domestic animals. These allergens are mainly found in saliva, epithelium, and hair and are dispersed in the air as small particles. They are detected in schools and homes even without cats or dogs, transported attached to fomites and people in contact with these animals. Allergy to exotic pets, such as gerbils, guinea pigs, ferrets, iguanas, and others also exists, especially in a day and age when 68% and 38% of families in the United States and Europe, respectively, have a pet in their home. This document is intended to be a tool to aid decision-making by professionals who care for people who suffer from dog, cat, or exotic animal allergies, to establish diagnostic and therapeutic strategies, and to improve the patient's quality of life.

Subcutaneous allergen immunotherapy (SCIT) is recognized as an effective and safe treatment for children and adults suffering from allergic respiratory diseases driven by house dust mites (HDM) in tropical regions.

To assess the clinical effectiveness and safety of SCIT using glutaraldehyde-polymerized allergen extracts of Dermatophagoides pteronyssinus and D. farinae in Colombian pediatric patients.

A retrospective, observational study including 49 children diagnosed with HDM-induced allergic rhinitis, with or without asthma, who were treated with SCIT for 1 year. Primary endpoints were measured using the Combined Symptom and Medication Score (CSMS). Secondary outcomes were asthma medication use and Asthma Control Test (ACT) scores.

Significant improvement in CSMS (median reduction: -0.8; p = 0.015) and ACT scores (median increase: -1.3; p = 0.015) were observed within 3 months; 76% of patients had at least a 20% reduction of the CSMS compared to baseline after 6 months with immunotherapy (IT). Medication use for asthma decreased significantly after 1 year (p = 0.035).

SCIT using polymerized HDM extracts demonstrated to be effective and safe in allergic pediatric populations.