Climate change is imposing a profound effect on health conditions triggered by environmental exposures. Climate change has affected aeroallergens in numerous ways, including: (1) changes in the vegetation microbiomedistribution, (2) increases in C4grasses globally, (3) increased occurrence of acute weather events, (4) increases in ambient temperature that amplify fungal spore concentration and pollen season duration, and (5) increased allergenicityof pollen and fungi due to exposure to higher levels of carbon dioxide, ozone, and diesel exhaust particles. In addition, greenhouse gases and air pollutants disrupt the epithelial barrier, trigger eosinophilicinflammation, and serve as adjuvantsthat stimulate IgE-mediated responses. All of these factors have influenced the prevalence and morbidity of allergic rhinitis, nonallergicrhinitis, and chronic rhinosinusitis. Data regarding changes in aeroallergen exposures due to climate change are lacking, and longitudinal sensitization data are rarely available. Allergists need to adapt diagnostic and treatment strategies to limit aeroallergen and air pollutant exposure and facilitate desensitization. Steps needed to address these challenges include: (1) expanding local measurement of pollen and fungal spores, (2) increasing the intensity of allergen avoidance measures, (3) addressing supply chain issues, and (4) promoting collaboration between allergists, insurance companies, aeroallergen manufacturers, and regulatory agencies

Peanut oral immunotherapy (OIT) has shown effectiveness in achieving desensitization of children; however, evidence in adultsislacking.

This phase II trial evaluated peanut OIT in peanut-allergic adults using real-world peanut products. A Simon's minimaxtwo-stage design, incorporating a stop:gofor futility, was employed. A separate untreated control group was also recruited for comparison of mechanistic parameters. Participants underwent baseline double-blind placebo-control food challenges (DBPCFC) with peanut protein doses of 0.3 to 300 mg. Reacting participants were initiated on daily OIT with 2-weekly updosinguntil reaching a maintenance dose of 1000 mg (four large peanuts). The primary outcome was the proportion of OIT participants who tolerated a cumulative dose of 1.4 g peanut protein during exit DBPCFC (doses provided 0.3-3000 mg).

Twenty-one adults (8 female; mean age 24.2 years [SD 4.9]) were enrolled in the OIT group, with 67% achieving the daily maintenance dose and meeting the primary endpoint. Three withdrew due to adverse reactions, and a further three did not complete the trial for reasons unrelated to OIT. The median tolerated dose increased from 30 mg (equivalent to approximately 1/8th of a peanut) to 3000 mg (12 peanuts) at the exit challenge, representing a 100-fold increase (p < 0.0001). OIT was associated with an improvement in QoLmeasures. Suppression of peanut skin prick test sizes and induction of peanut-specific IgGwere observed in OIT but not in control participants.

Peanut OIT appears to be an efficacious treatment for adults with peanut allergy. Further studies are needed for confirmationand to characterize safety profiles in different adult subgroups.

Most patients with respiratory allergy are polyallergic. Combining different allergen extracts in the same allergen-specific immunotherapy is a common practice. However, it should be justified. To analyze the stability, safety, and immune response of allergen extract mixtures from nonhomologousgroups.

We analyzed 2 depigmented-polymerized mixture extracts (DPmixEs): cat dander grass pollen and Alternariaalternata-grass pollen. The stability of the mixtures was investigated by studying proteolysis and degradation effects. The allergenicityand humoraland cellular immune responses of DPmixEswere also evaluated using various technical approaches, including the Bradford assay, enzyme-linked immunosorbentassay, rabbit immunization, peripheral blood mononuclear cell culture, and flow cytometry. The results were compared with those of individual depigmented-polymerized extracts (DPEs) and native mixture extracts (NmixEs).

The proteolyticactivity of DPmixEswas lower than that of NmixEs. The protein content of DPmixEsremained stable for 18 months, whereas that of NmixEsdecreased significantly during the first month. The allergenicityof DPmixEswas similar to that of DPEs and lower than that of NmixEs. Regarding the immune response, DPmixEsinduced functional specific IgGantibodies in rabbits and blocked sIgEallergenbinding. Moreover, DPmixEsinduced IL-10 secretion in peripheral blood mononuclear cells from polyallergicpatients, improving the Treg/TH2 cell balance.

These findings support the use of DPmixEas a promising formulation for allergen immunotherapy, combining stability, reduced enzymatic activity, and enhanced immunological stimulation, while preserving in vitro safety and efficacy comparable to separated depigmented-polymerized extracts.

Sublingual immunotherapy (SLIT) was recently shown to safely induce desensitization and remission of peanut allergy in 1-to 4-year-old children.

Basophil activation has been shown to be suppressed in allergen-specific immunotherapy. We aimed to evaluate the timing of basophil suppression during peanut SLIT and its impact on clinical outcomes.

Fifty peanut-allergic children were enrolled in a peanut SLIT trial and randomized to active peanut or placebo SLIT for 36 months followed by a three-month avoidance period to evaluate remission. Blood was collected at baseline, 12, 24, 36, and 39 months to measure basophil activation by CD63 and CD203c.

For participants on peanut SLIT, basophil activation based on CD63 expression was significantly reduced by 12 months and continued to decrease throughout peanut SLIT, whereas CD63 activation in participants receiving placebo remained unchanged from 0-36 months. CD203c expression remained unchanged for both peanut SLIT and placebo participants throughout the trial. Actively treated participants who achieved remission had lower CD63 expression at baseline and significant suppression of CD63 expression by 12 months, while treatment failures had higher CD63 expression at baseline and lack of suppression by 12 months. Lower basophil activation in those achieving remission, compared to those that failed treatment, remained present for up to 3 years.

Following peanut SLIT, participants who achieved remission had significantly suppressed basophils by 12 months, compared to unsuccessful participants that were not desensitized, suggesting that early suppression of basophilsmay be indicative of peanut SLIT efficacy.

The variability in the efficacy of allergen-specific immunotherapy (AIT) for nasal symptom control can be attributed to individual differences, to explore the hypothesis of systematic variability in AR symptom alleviation with AIT and to determine whether this variability correlates with AR severity, route of administration, treatment duration, age, or study publication year.

We reviewed randomized controlled trials (RCTs) of AIT for dust mite (DM)-induced AR, extracting data on baseline mean, endpointmean, standard deviation (SD), and participant numbers. A random-slope mixed-effects model (RSMM) was employed to evaluate the differences in variability between the AIT and control groups, as well as to identify potential influencing factors.

There was no significant difference in response variability between the AIT and control groups. The response variability to AIT was not associated with AR severity, route of administration, age, or year of publication. The cohort that underwent 36 months of AIT exhibited a higher degree ofresponse variability compared to the group treated for 6 months.

The present study did not identify systematic variability in individual response to AIT when measured by TNSS alone. More refined outcome measures and more associated factors are needed to explore personalized AIT in the future.

The guideline on allergen-specific immunotherapy of the European Academy of Allergy and Clinical Immunology recommends subcutaneous allergen-specific immunotherapy for the treatment of allergic rhinitis in children and adults with moderate to severe symptoms. The five years cohort study described below was designed in 2020 to demonstrate non-inferiority in terms of safety, tolerability, and efficacy in a paediatric population compared with adult patients treated with microcrystalline tyrosine-adsorbed allergoids for their tree and grass pollen allergy in a perennial setting. Here, we present the preliminary findings from the first year.

The Combined Symptom and Medication Score was chosen as the primary endpoint of this therapy. Secondary endpoints include the Rhinoconjunctivitis Quality of Life Questionnaire, the retrospective Rhinoconjunctivitis score, the Asthma Control Test, and the Rhinitis Control Test, as well as an analysis of adverse drug reactions.

A total number of 320 patients were enrolled into this study, with 129 of these patients in the age group between 5 and 17 years and 191 patients in the adult age group. Mean Combined Symptom and Medication Score values did not differ significantly between minors and adults in the first pollen season after treatment induction. The retrospective score showed a strong and significant reduction in rhinoconjunctivitis and asthma symptoms. Treatment was well tolerated, with more than 80% of patients reporting no adverse drug reactions.

The validity of this study approach of a cohort study has been confirmed by this first interim analysis for the initial course of therapy in the first year.

Mucosal-associated invariant T cells (MAIT) are emerging as important regulators at mucosal surfaces. While these cells have been linked to a Th1-biased immune response and support for B cells, their roles in allergic diseases characterisedby type 2 inflammation remain elusive. The study seeks to characteriseMAIT cells in house dust mite (HDM)-induced allergic rhinitis (AR) and subsequent allergen immunotherapy (AIT), aiming to elucidate their clinical significance in AR and potential to enhance AIT effectiveness.

MAIT cells were assessed in patients with AR and individuals undergoing AIT. The ratio and cytokine-producing capacity of these cells were analysedto explore their correlations with AR progression and their responsiveness to HDM extracts and MAIT cell-specific agonists.

In AR patients, there was an increase in the ratios of circulating MAIT cells and tonsil follicular T helper-like MAIT cells, alongside a decrease in the IFN-γ-producing MAIT cells. AIT restored their IFN-γ producing capacity, which was further boosted by T cell receptor (TCR) activation using MAIT cell-specific agonist-loaded artificial antigen-presenting cells (aAPCs). Synergistic effects of aAPCsand HDM enhance MAIT cell activation and IFN-γ production while reducing HDM-induced IgElevels in PBMC cocultures. Moreover, higher ratios of MAIT cells and IFN-γ-producing MAIT cells correlated with decreased IgEand increased IgG4 and improved clinical outcomes during AIT.

These findings underscore the compromised IFN-γ-producing MAIT cells in AR and their restoration following AIT and TCR stimulation, highlighting the cell's therapeutic potential and predictive value for clinical outcomes in AR and AIT.

IgE-mediated food allergies are common and can be life-threatening, especially for children. With increasingly rapid advances in immunological technologies, including the ability to profile highly complex immune features from small sample volumes, our understanding of the immune mechanisms that underpin the development of food allergies continues to grow. This also extends to the immune mechanisms associated with the outcomes of oral immunotherapy (OIT). This review focuses on studies within the past 5 years related to immune signatures associated with food allergy in childhood, immune responses that determine reaction severities to offending allergens, immune alterations that occur during OIT in children, and immune effects of adjunct therapies including omalizumab, dupilumab, and abrocitinib. We conclude by providing a perspective on current evidence and directions for future research that will enable new prediction and screening tools and facilitate the development of effective curative strategies

Previously, it was reported that droplet SLIT in Japanese cedar pollinosis reduced metachromatic cell and eosinophil counts in nasal swabs along with symptom improvement. In this study, it was confirmed that SLIT using tablets also reduces the number of these cells along with symptom improvement, and examined the time course of these effects.

One hundred twenty-one visits of 57 subjects treated with SLIT occurred in our clinic between January 16 and April 8, 2023 (Jc pollen season). The 57 patients had been receiving SLIT for 0.16 to 7.8 years, and symptoms were assessed using a self-reported questionnaire. Nasal swab cytology was used to compare the reduction in metachromatic cell, eosinophil, and neutrophil numbers with that of 110 non-SLIT subjects. We then investigated the timelines of the decrease in metachromatic cells and eosinophils and their relationship to symptoms.

Subjects who received SLIT had significantly reduced moderate to most severe symptoms compared to non-SLIT subjects over the Jc pollen season. There was symptom improvement for subjects with ≤2 years of SLIT treatment, but more improvement after >2 years of SLIT treatment. Metachromatic cell and eosinophil numbers in nasal swabs of SLIT subjects were significantly lower than in non-SLIT subjects. Moreover, levels of eosinophilia decreased within 2 years of SLIT treatment but further decreased with >2 years of SLIT. Metachromatic cell numbers in subjects with >2 years of SLIT were significantly lower than in non-SLIT subjects. There was no significant difference in neutrophil numbers in nasal swabs between non-SLIT and SLIT subjects.

SLIT administered by tablet was effective in improving symptoms within 2 years, and further improved after 2 years. The eosinophil counts also decreased within 2 years, and further decreased over 2 years. The metachromatic cell count significantly decreased only after 2 years of SLIT treatment.

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