Clinical algorithm for diagnosis and treatment of patients with suspected animal allergy. We recommend a stepwise approach for the interpretation of test results, but sampling for marker allergens and cross-reactive allergens can be done simultaneously. Multiplex analysis is advantageous for a comprehensive assessment. No single measure is fully effective; combined strategies are needed: HEPA vacuuming/air filtration, washing the animal, removing carpets, restricting bedroom access, frequent ventilation, and neutering. Allergen immunotherapy may be considered for a proven animal allergy if symptoms continue despite allergen avoidance. The allergen molecule content (standardization) of the immunotherapy product (extract) should be a key factor in this decision. The accuracy of IgE quantification depends on the analytical sensitivity of the assay used.

Identifying predictive and monitoring biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to investigate the systemic and local levels of immunoglobulins and identify potential biomarkers in house dust mite (HDM) allergic rhinitis (AR) patients who are undergoing subcutaneous immunotherapy (SCIT).

This study enrolled 114 AR patients who completed 1-year SCIT follow-up. High responders and low responders were classified based on >30% improvement in the average total combined score (ATCS). Immunoglobulin levels of HDM and its major components were measured in serum and nasal secretions before and after treatment. Predictive index (Pi) and therapeutic index (Ti) analyses were performed using linear regression to assess the impact of baseline immunoglobulin concentrations and their pre-to-post-treatment changes on symptom alleviation. Receiver operating characteristic (ROC) curve analysis with area under the curve (AUC) quantification was performed to evaluate predictive value for clinical responses.

Positive SCIT response correlated with lower baseline age and higher symptom scores, allergen-specific IgE (sIgE) levels, and sIgE/total IgE (tIgE) ratio. Pi analysis revealed that elevated pre-treatment nasal sIgE levels and higher sIgE/tIgE ratios for Der p, Der f, Der p 1, and Der p 2 distinguished high from low responders. Ti analysis showed that post-treatment decreases in these nasal sIgE levels correlated with improved clinical outcomes. Logistic regression showed baseline sIgE/tIgE ratios for Der p and Der f both in serum and nasal secretions, and Der p 1 and Der p 2 in serum positively correlated with clinical improvement. The sIgE/tIgE ratios of Der p (0.833 vs. 0.758) and Der f (0.813 vs. 0.738) in nasal secretions exhibited higher AUC values compared to serum.

Immunologic indicators in nasal secretions are potential biomarkers for the effective prediction and monitoring of early SCIT responses.

To compare the efficacy and safety of house dust mite (HDM) subcutaneous immunotherapy (SCIT) between monosensitized and polysensitized allergic rhinitis (AR) patients, and evaluate the independent impact of polysensitization on SCIT outcomes.

Large retrospective real-world cohort study.

Tertiary referral center.

AR patients completing a 3-year HDM-SCIT regimen between January 2011 and January 2019 were included. Based on allergen profiles, patients were classified as monosensitized or polysensitized. Propensity score matching balanced baseline characteristics. SCIT efficacy and adverse events were compared before and after matching. Multivariable regression assessed the independent effect of polysensitization on SCIT outcomes.

1584 patients were enrolled (994 monosensitized and 590 polysensitized). Before matching, polysensitized patients exhibited higher baseline symptom scores, older age, longer AR duration, more frequent dose modifications, greater prevalence of family history of allergy, and increased asthma comorbidity. After matching, polysensitized patients showed significantly less symptom improvement and lower overall efficacy at both SCIT 1 and 3 years (P < .05). The incidence of local reactions (LRs) was also significantly higher (P < .05), while systemic reaction rates did not differ. Multivariable regression confirmed polysensitization as an independent risk factor for reduced SCIT efficacy and increased LRs (P < .05).

Polysensitization was linked to reduced SCIT efficacy and a higher risk of LRs. These results underscore the value of allergen profiling and support personalized SCIT strategies and closer monitoring for polysensitized patients.

The gut microbiota plays a crucial role in modulating mucosal immunity and allergic responses, yet its predictive value for sublingual immunotherapy (SLIT) outcomes remains underexplored in Artemisia pollen-induced allergic rhinitis (AR). In this single-center prospective cohort study, 204 adults with Artemisia pollen-induced AR underwent baseline stool collection before initiating standardized SLIT. Gut microbiota was analyzed using 16S rRNA sequencing of the V3-V4 region, with prespecified features including Shannon diversity index, composite abundance of butyrate-producing bacteria (Faecalibacterium, Roseburia, Eubacterium rectale group), and Prevotella-to-Bacteroides (P/B) ratio. Clinical response was defined as ≥30% reduction in combined symptom-medication score (CSMS) during the peak pollen season. We developed three prediction models: Model A (clinical variables only), Model B (clinical variables plus microbiota features), and Model C (parsimonious model via L1 regularization). The response rate was 54.41% (111/204). In multivariable analysis, all three microbiota features independently predicted treatment response: butyrate-producing bacteria (OR = 1.59, q = 0.006), P/B ratio (OR = 1.43, q = 0.020), and Shannon diversity (OR = 1.33, q = 0.046). Model B demonstrated superior discrimination compared to Model A (AUC 0.79 vs 0.71, ΔAUC = 0.08, P = 0.021), with improved calibration (intercept α = -0.03, slope β = 0.98) and significant net reclassification improvement (NRI = 0.36, P = 0.002). Decision curve analysis confirmed greater net benefit across clinically relevant threshold probabilities. The parsimonious Model C maintained good performance (optimism-corrected AUC = 0.78) with 77.48% sensitivity and 72.04% specificity. Baseline gut microbiota characteristics, particularly butyrate-producing bacterial abundance, microbial diversity, and Prevotella/Bacteroides community structure, significantly predict SLIT response in Artemisia pollen-induced AR and provide substantial incremental value over conventional clinical parameters. These findings support the integration of gut microbiota assessment into pretreatment stratification algorithms for allergen immunotherapy.

While allergen-specific immunotherapy (AIT) is recognized as an effective treatment, its efficacy varies widely. However, whether clinical response trajectories to AIT differ among individuals and influence its effectiveness has not been investigated.

This study aimed to characterize real-world clinical response trajectories to three-year AIT (3y-AIT).

We conducted a retrospective multicenter study across 53 centers to identify clinical response trajectories in patients with house dust mite allergic asthma and rhinitis undergoing three-year AIT. The efficacy of AIT was primarily assessed using the Visual Analog Scale (VAS) for allergic symptoms at 4 time points: baseline (before AIT), and at 1, 2, and 3 years of treatment. Clustering analysis based on VAS changes at these time points was used to define response trajectories. Initial analysis was performed using data from 52 centers (Alliance cohort), and validation was conducted using data from a separate center (Guangzhou cohort).

In the Alliance cohort, 4 distinct clinical response trajectories were identified. Cluster 1 showed symptom worsening in the first year, with no improvement by year 3. Cluster 2 exhibited symptom deterioration in the second year, followed by significant recovery and a positive response by year 3. Clusters 3 and 4, characterized by higher and lower baseline symptom severity, respectively, demonstrated marked improvement after 3 years of AIT. In the Guangzhou cohort, a similar pattern of 4 response trajectories was observed: higher baseline symptom severity and family tobacco exposure were key features of Cluster 1 (p 1/year, p < 0.001). Despite these distinct trajectories, first-year effectiveness emerged as an ideal predictor of the 3-year AIT response, with an AUC of 0.75.

This study identified 4 primary treatment response trajectories to 3-year AIT in daily clinical practice, highlighting the heterogeneous nature of AIT responses among individuals. Notably, first-year effectiveness appears to be an ideal predictor of the 3-year AIT outcome.

Lipid transfer protein (LTP) allergy is the leading cause of food allergy and food anaphylaxis in adults in the Mediterranean region. Treatment options include avoidance of the implicated foods and specific sublingual peach immunotherapy (Pru p3 SLIT). This study aims to determine the effectiveness of Pru p3 SLIT in patients with cofactor-induced and noncofactor-induced LTP syndrome, assessing the change in food tolerance before and after treatment.

We conducted a retrospective observational study of 23 patients diagnosed with LTP allergy who were treated with Pru p3 SLIT. To assess food tolerance before and after treatment, all patients underwent an oral challenge with unpeeled peach, as well as other foods to which they were allergic or sensitized.

Fifty-five percent of patients were female, with a mean age of 25.8 years, 39% of whom were under 14 years of age. Thirteen percent were allergic only to pink fruits, 4.3% to nuts, 43.4% to two families, and 39.1% to more than two families of vegetables. Eighty-six percent of the reactions were systemic, including 47% anaphylaxis. After a mean of 2.7 years of treatment, 95.6% of the patients tolerated oral provocation with unpeeled peach and all foods to which they were allergic. However, none of the seven patients with cofactor-induced or cofactor-enhanced allergic reactions to food showed improved tolerance following Pru p3 SLIT.

Pru p3 SLIT can induce clinical remission of LTP food allergy in both adult and pediatric populations. However, it doesn´t resolve cofactor-triggered LTP reactions; therefore, patients with this profile should continue to avoid such triggers.

Micro-RNAs (miRNAs) are short, non-coding RNA molecules regulating genes' expression. Studies published over last years demonstrated that they play an important role in allergic diseases by regulating humoral and cellular immunity, cytokine secretion and epithelium function. Some of them seem potential non-invasive biomarkers facilitating diagnosis of the most common allergic diseases, such as allergic rhinitis (miR-21, miR-126, miR-142-3p, miR-181a, miR-221), asthma (miR-16, miR-21, miR-126, miR-146a, miR-148a, miR-221, miR-223) and atopic dermatitis (miR-24, miR-124, miR-155, miR-191, miR-223, miR-483-5p), or objectively assessing severity of inflammation and endotype of the disease. In spite of the large body of literature available, its scientific value is limited due to the small numbers of study participants, heterogeneity of populations enrolled, and diverse methodology. Some studies have revealed significant changes in miRNAs' profile in the course of allergen immunotherapy. Tolerance induction is associated with processes controlled by miRNAs: enhanced activity of Treg cells and increased production of tolerogenic IL-10 and TGF-β. Thus, miRNAs may be candidates as biomarkers of successful immunotherapy. Finally, they are also possible therapeutic agents or targets of therapies based on antagomirs blocking their activity. However, so far no studies are available that demonstrate efficacy in overcoming delivery barriers, tissue targeting or drugs' safety. As a consequence, despite promising results of in vitro and animal model studies, translation into human therapeutic agents is uncertain.

Allergic rhinitis (AR) is a complex immune-mediated disorder characterized by defective regulatory mechanisms. Emerging evidence suggests that impaired immune tolerance mediated by regulatory B cell (Breg) plays a pivotal role in AR pathogenesis. This study investigates the therapeutic potential of Der p1 allergen-modified dendritic cells (DC) in enhancing Breg-mediated immunotherapy and explores novel mechanisms underlying AR immunomodulation.

Breg and the inflammatory cytokines were detected before and after allergen immunotherapy (AIT) in AR patients. Dust mite gene-derived dendritic cells were used to induce Breg. AR mice were treated with Der p1-DCs, and changes in Breg and related inflammatory indicators, as well as the impact of the IL-10/STAT pathway on DC vaccine treatment, were observed.

Following 6-month AIT, AR patients exhibited significant alleviation of nasal symptoms alongside restored peripheral Breg and Treg. In vitro co-culture of Der p1-DC-induced Bregs with CD4+CD25-T cells revealed that IL-10 blockade markedly increased Th cell. In AR murine models, intraperitoneal Der p1-DC administration suppressed allergic symptoms, upregulated nasal mucosal IL-10 expression, and attenuated STAT3 phosphorylation via IL-10 overexpression.

AIT establishes immune tolerance through Breg-mediated regulatory mechanisms, while Der p1-DCs potently induce Breg differentiation and drive tolerance induction via the IL-10/STAT3 signaling axis.

In southern Europe, allergy to Alternaria alternata (A. alternata) and Olea europaea (O. europaea) pollen are prevalent, significantly contributing to allergic conditions like asthma and rhinitis. This study investigates the effectiveness and safety of immunotherapy in pediatric patients utilizing a glutaraldehyde-polymerized allergen extract mixture of A. alternata and O. europaea.

This real-world, retrospective, observational study included pediatric patients diagnosed with rhinitis with or without asthma, co-sensitized to A. alternata and O. europaea. Patients received immunotherapy with a mixture of individually polymerized allergen extracts of A. alternata and O. europaea, each at a concentration of 10,000 TU/mL. Effectiveness was assessed by comparing rhinitis and asthma severity and medication requirements before and after at least 6 months of treatment. Safety was evaluated by documenting local and systemic adverse reactions.

A total of 49 patients were included, with a median treatment duration of 9 months. Prior to treatment, 84% (41/49) of patients had moderate-severe rhinitis, which significantly decreased to 49% (24/49) post treatment (p=0.001). Asthma severity also improved considerably, with the proportion of patients experiencing intermittent-mild asthma rising from 8% pretreatment to 61% post treatment. The use of medication for both rhinitis and asthma also declined. Out of 424 injections, only two local reactions were reported (0.47%), with no systemic reactions.

Immunotherapy using a mixture of glutaraldehyde-polymerized A. alternata and O. europaea extract is both safe and effective in reducing the severity of rhinitis and asthma in children. This treatment exhibits a high safety profile, with a very low incidence of adverse reactions, making it a promising therapeutic option for pediatric patients with coexisting sensitivities to these common allergens.

Protocols for adjusting allergy injection doses after gaps in therapy, and optimal intervals for maintenance injections, are based on expert opinion only.

To assess (1) incidences of systemic allergic reactions (SRs) to subcutaneous allergen immunotherapy (SCIT), (2) clinical practices that reduce the risk of SRs, (3) SCIT-related infections, and (4) risks associated with interruptions in SCIT.

From 2008 to 2023, members of the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma, & Immunology completed annual surveys of SCIT-related SRs; SCIT-related infections were assessed since 2014. Questions were added in 2020 regarding dose adjustment after gaps in immunotherapy, and maintenance intervals prescribed.

Data were gathered on 84.1 million injection visits and 4.9 million patients (2008-2023). Four new SCIT-related fatalities were confirmed (2018-2023). One contaminated vial, resulting in 2 local skin infections, was identified (2014-2023). Practices reducing to 1 vial lower in patients who were more than 7 weeks late for maintenance vial injections had fewer grade 4 SRs (P = .02). Practices decreasing to the next lower vial in patients who were more than 28 days late during buildup had fewer grade 3 and 4 SRs (P = .03). For the period from 2021 to 2022, there was an increased rate of total (P < .0001), grade 2 (P < .0001), and grade 3 SRs (P = .0005) for practices that used a maintenance injection interval longer than 4 weeks.

Fatal reactions to SCIT still rarely occur. The risk of infections from SCIT is extremely low. Controlled studies are needed to define optimal dose adjustment strategies after gaps in therapy as well as the safest, most efficacious maintenance intervals for aeroallergen SCIT.