Allergen Immunotherapy Research Articles

Mechanism differences in the start time of sublingual immunotherapy in a mouse allergic airway inflammation model

Sublingual immunotherapy (SLIT) has received considerable attention as a method for allergen immunotherapy (AIT). However, the mechanism of SLIT, especially its timing, has not been thoroughly investigated. We evaluated therapeutic and prophylactic SLIT in an allergic airway inflammation model and evaluated their efficacies. Mice were intranasally exposed to Dermatophagoides farinae (Der f) extract and received SLIT before (prophylactic model) and after (therapeutic model) intranasal exposure of Der f. We investigated airway responsiveness, airway inflammation, allergen-specific antibodies, lung histology and single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing were also investigated. SLIT in the therapeutic model was effective; however, the effects of SLIT in the prophylactic model were stronger and immune tolerance was maintained for three months. ScRNA-seq of lung CD4+CD25+ T cells revealed that the expansion of induced T regulatory (iTreg) cells was greater in the prophylactic model than that in the therapeutic model. Additionally, the TCR repertoire of iTregs from the prophylactic model was abundant, sharing many clones with the TCR repertoire of effector T cells. These data suggest that the prophylactic model of AIT is extremely effective and persistent, and may respond to allergen diversity, and provide evidence for the clinical recommendation of preventive AIT.

An International Delphi Consensus on the Management of Pollen–Food-Allergy Syndrome: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee

Pollen-food-allergy syndrome (PFAS) is common among patients with allergic rhinitis. Treatment recommendations for patients with PFAS remain variable. To develop consensus recommendation statements for managing patients with PFAS. An international panel of allergists, researchers, and nutritionists with an interest in PFAS from 25 different institutions across 11 countries convened and a list of statements was written by 3 authors. The RAND/University of California Los Angeles methodology was adopted to establish consensus on the statements. After 2 Delphi rounds, a consensus was reached on 14 statements. The panel agreed that patients with PFAS would benefit from counseling on the nature and basis of PFAS and the rare chance of more severe systemic reactions and their recognition. The panel agreed on avoiding the raw food responsible for the index reaction, but not potentially cross-reactive fruits/vegetables based on the responsible food of the index reaction. Epinephrine autoinjectors should be recommended for patients with PFAS who experienced severe symptoms (beyond the oropharynx) or for patients considered at risk for severe reactions. The panel agreed that the benefit of allergen immunotherapy remains unclear and that PFAS should not be considered the primary indication for such intervention. We developed consensus statements regarding counselling patients about the nature and severity of PFAS, potential risk factors, dietary avoidance, epinephrine autoinjector prescription, and allergen immunotherapy consideration for patients with PFAS.

Efficacy and perceived satisfaction of 3-year SLIT in children with allergic rhinitis and asthma: a pilot study

Background: Despite the presence of robust evidence, there is very limited data on the efficacy of allergen immunotherapy (AIT) for selected patients. Accordingly, we aimed to evaluate the efficacy and perceived satisfaction of a 3-year course of sublingual immunotherapy (SLIT) in a paediatric population with allergic rhinitis and/or asthma. Methods: A pilot, monocentre, retrospective cohort study was performed. One hundred fifty-three children who fulfilled the criteria for allergic rhinitis and asthma and were either mono- or poly-sensitized were enrolled. A standardized questionnaire assessing perceived efficacy, use of rescue medication, disease control, number of exacerbations, quality of life, and perceived satisfaction was administered to each patient. Results: Seventy patients (49 males, 21 females; mean age, 14.3±1.9 years) were included in the final analysis. All 70 patients received SLIT for up to 3 years, with 100% adherence to the treatment throughout the study. Significant improvements in symptoms and quality of life were reported (p<0.01). There was also a significant decrease in disease severity, use of rescue medication, and sleep disturbances (p<0.01). Additionally, a significant improvement in school performance was also recorded (p<0.01). Of the enrolled patients, 60 out of 70 (85.7%) reported being very satisfied, 6 out of 70 (8.57%) were much satisfied, and 4 out of 60 (5.71%) were satisfied. Conclusions: We were the first to demonstrate the efficacy and perceived satisfaction of a 3-year SLIT in a paediatric population, with 100% treatment adherence throughout the study.

Allergen Immunotherapy for a Year Can Effectively Reduce the Risk of Postoperative Recurrence of Adenoid Hypertrophy in Children with Concurrent Allergic Rhinitis (IMPROVEII)

Allergen Immunotherapy for a Year Can Effectively Reduce the Risk of Postoperative Recurrence of Adenoid Hypertrophy in Children with Concurrent Allergic Rhinitis (IMPROVEII)

EAACI guidelines on the management of IgE-mediated food allergy.

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes.

Development of Cashew and Pistachio Ladders through a Food-Processing Approach

Following successful oral immunotherapy (OIT) for peanut allergy using boiled peanuts (BOPI trial), this study investigated the potential of wet-thermal-processing-induced allergen modification, specifically soaking and boiling (1–4 h) to reduce the allergenicity of cashew and pistachio allergens. In addition, this study provides a foundation of understanding for developing safer forms of cashew/pistachio administration for application in OIT by gradual exposure to increasing doses of modified allergens with reduced potency as an “allergen ladder”. An SDS-PAGE analysis and an intrinsic-fluorescence spectroscopy revealed altered tertiary structures of the allergens, leading to their denaturation and even degradation. Notably, the reduction in both allergen-specific polyclonal IgG and human-specific IgE (sIgE) binding correlated with the treatment time, with the most significant decrease observed after 4 h of boiling. In contrast, shorter soaking treatments showed negligible effects on the IgE-binding capacity of these nuts, therefore indicating a further need for optimization. These findings indicate that extended boiling effectively reduced the amounts of the highly potent allergenic component Ana o 3 in cashew and Pis v 1 in pistachio, as confirmed by ELISA using polyclonal anti-Ana o 3 antibodies, and an immunoblot showed decreased IgE epitope binding in cashew and pistachio allergens, which further modified their allergenic profiles. This approach shows promise as a viable method for offering a safer therapeutic option for cashew/pistachio allergy.

Safety and adherence of early oral immunotherapy for peanut allergy in a primary care setting: a retrospective cross-sectional study

BackgroundPeanut allergy is a common food allergy with potentially life-threatening implications. Early oral immunotherapy for peanut allergy (P-EOIT) has been shown to be effective and safe in research and specialty clinic settings. Provision of P-EOIT in primary care would make it available to more patients. We sought to assess the safety of P-EOIT in a primary care setting by documenting the rates of peanut-related allergic reactions leading to emergency department (ED) visits and use of epinephrine. We also examined adherence by assessing the percentage of patients reaching maintenance phase and continuing ingestion after one year of P-EOIT.MethodsThis retrospective study included all patients aged less than 36 months who started P-EOIT at a primary care allergy clinic in New Brunswick, Canada, from 2016 to 2020. The population included patients who (1) had a history of an allergic reaction to peanuts with a positive skin prick test or positive peanut specific IgE level (ps-IgE) or (2) no history of ingestion and a baseline ps-IgE ≥5 kU/L. Patients had biweekly clinic visits with graded increases in peanut protein up to a maintenance dose of 300 mg of peanut protein daily. A blinded retrospective review of paper charts and electronic medical records was conducted along with phone interviews regarding ED visits and epinephrine use.ResultsAll 69 consented patients reached maintenance dose over a median of 29 weeks, and 66 patients (95.7%) were still regularly consuming peanut protein after 1 year of maintenance. One patient had a peanut ingestion-related ED visit requiring epinephrine during the escalation phase of peanut protein dosing (1.4%). During the first year of maintenance phase, no patients had peanut ingestion-related ED visits nor required epinephrine.ConclusionEarly oral immunotherapy for peanut allergy in a primary care setting appears to be safe and our findings suggest that it does not lead to an increased burden of emergency department visits. Our population had high adherence rates, with the majority achieving maintenance dose and staying on this dose for one year.

Improved quality control of allergen products: Assessing the molecular allergen composition by mass spectrometry.

Natural allergen sources contain a variety of allergens, against which allergic subjects have developed individual sensitization profiles. Ideal allergen products for skin prick testing (SPT) and allergen immunotherapy (AIT) should contain the complete set of allergens of the respective allergen sources to cover all sensitization profiles. However, commercially available allergen products were shown to vary regarding their allergen composition. The qualitative allergen composition of different SPT and AIT products produced from pollen of grasses, birch, mugwort and from house dust mites was assessed by a consistent high-resolution liquid chromatography-coupled tandem mass spectrometry method (LC-MS/MS). All major, mid-tier and most minor allergens were detected in each of the investigated three batches of SPT and AIT products, demonstrating the completeness of the allergen composition and a high degree of batch-to-batch consistency. This is the first study using a single consistent high-resolution LC-MS/MS method to provide solid data on the qualitative allergen composition of SPT and AIT products manufactured from various common allergen sources. The applied method showed high reliability in qualitative batch-to-batch consistency testing and can be performed fast and with high throughput. High-resolution LC-MS/MS is applicable for process development and quality control to ensure market availability of allergen products corresponding to the composition of the respective natural allergen sources.

Sensitizations to pollen differ between Central European and Sub-Saharan African atopic dermatitis patients

Summary Background Atopic dermatitis (AD) is often associated with allergic comorbidities, such as allergic asthma or allergic rhinoconjunctivitis (ARC). Sensitizations to pollen can directly impact AD, as patients can experience exacerbation during pollen season. This study aims to gain more insights into the pollen sensitization patterns of AD patients in Central Europe compared with sub-Saharan Africa (SSA). Methods We performed a case–control study involving a total of 90 participants: 20 AD patients and 10 healthy controls (HC) each from Switzerland (CH), Tanzania (TZ), and Madagascar (MD). We collected clinical data and serum samples and performed a multiplex IgE test (ALEX2 Allergy Explorer, MacroArray Diagnostics, Vienna, Austria). Results The prevalence of ARC and asthma in AD patients was similar in all countries (ARC: 60% TZ, 70% CH, 75% MD; asthma: 25% TZ, 30% CH, 20% MD). Total IgE levels were significantly higher in both SSA HC populations compared with the Swiss HC. The analysis of specific IgE levels revealed major differences in sensitization patterns between Africa and Europe, especially regarding grass pollen allergens. Swiss AD patients were sensitized to various grass pollen such as Bahia grass, Bermuda grass, common reed, perennial ryegrass, rye, and timothy grass. However, these allergens were irrelevant in the SSA population: no AD patient or HC subject was sensitized to the tested grass pollen. Conclusion The considerably different sensitization patterns between European and SSA AD patients warrant the development of allergy testing and desensitization therapies tailored to the African setting. Therefore, there is a need to characterize local pollen types and counts.

Effect and mechanism of allergen-specific immunotherapy on small airway dysfunction in children with asthma.

The purpose of this study was to investigate the effectiveness of allergen-specific immunotherapy (AIT) on small airway dysfunction (SAD) and the underlying mechanism with a special focus on basophils. Sixty-five children with mild to moderate asthma who were under regular inhaled corticosteroid (ICS) treatment for more than 1 year but whose FEF75 remained below 65% of the predicted value and had positive results for serum Der p or Der f were enrolled. Children with asthma underwent house dust mite (HDM) subcutaneous immunotherapy (SCIT) treatment for 1 year. Clinical symptoms and lung function were evaluated every 3 months during HDM SCIT treatment. Basophil activation test (BAT) was carried out before and after HDM SCIT treatment. RNA sequencing was performed in isolated basophils from peripheral blood after 6 months of HDM SCIT treatment, followed by GO term and KEGG pathway enrichment analysis between patients with and without HDM SCIT treatment. HDM AIT treatment ameliorated clinical symptoms while concurrently improved lung function parameters, such as FEV1/FVC, FEF75, FEF50 and MMEF (p < .05). It is worth noting that FEF75 values showed a highly significant, gradual and persistent increase (from 49.55 ± 1.27% at baseline to 71.89 ± 2.64% after 1 year of therapy) and 22 of 35 patients no longer had SAD after 1 year of treatment. BAT results revealed that AIT treatment significantly reduced basophil activity to the inhalant allergen mixtures containing HDM in vitro challenge from baseline. GO term and KEGG pathway enrichment analysis of basophils revealed that downregulated genes were mainly involved in immune cell activation, antigen presentation, and Th2 cell differentiation. Our study demonstrated that HDM AIT not only improved SAD related lung function parameters, but also reduced basophil activity. RNA sequencing revealed the inhibition of phagocytosis and the phagosome pathway in basophils which may affect the polarization of Th2 cell differentiation after HDM AIT.

Diagnosis and management of shrimp allergy.

Shrimp allergy, the most common food allergy in the United States, affects up to 2% of the population. Its etiology is multi-factorial with the combination of genetic predisposition and environmental exposures. This review summarizes the latest diagnosis and management strategies for shrimp allergy. Currently, the double-blind, placebo-controlled food challenge is the gold standard for diagnosis. Moreover, mainstream and experimental management strategies include food allergen avoidance, the FDA-approved omalizumab, and oral immunotherapy. Herein, we emphasize the urgent need to develop more effective diagnostic tools and therapies for shrimp allergy.

Protective Effect of Allergen Immunotherapy in Patients With Allergic Rhinitis and Asthma Against COVID-19 Infection: Observational, Nationwide, and Multicenter Study.

Allergic diseases are associated with an increased susceptibility to respiratory tract infections. Although allergen immunotherapy (AIT) alters the course of allergies, there is limited evidence from clinical practice demonstrating its ability to enhance the host defense against pathogens. The aim of this study was to investigate the protective effect of AIT against viral infection in patients with allergic rhinitis (AR) and allergic asthma (AS) based on clinical evidence. A multicenter, questionnaire-based survey was conducted during a tremendous surge in COVID-19 cases between February 10, 2023, and March 15, 2023, in 81 centers across China recruiting healthy volunteers and patients with AR and AS to investigate the clinical outcomes of COVID-19 infection. Of 10,151 participants recruited in the survey, 3654 patients and 2192 healthy volunteers who tested positive for COVID-19 were included in this analysis after screening. Overall, no significant differences in COVID-19 outcomes were observed between patients and healthy volunteers. An additional 451 patients were excluded due to their use of biologics as the sole add-on treatment, leaving 3203 patients in the further analysis. Of them, 1752 were undergoing routine medication treatment (RMT; the RMT group), whereas 1057 and 394 were receiving AIT and a combination of AIT and omalizumab (OMA) as adjunct therapies to RMT, respectively (AIT+RMT and AIT+OMA+RMT groups). The AIT group showed milder COVID-19 symptoms, shorter recovery periods, and a lower likelihood of hospitalization or emergency department visits than the RMT group (all P<.05). After adjusting for confounding factors, including demographic characteristics and COVID-19 vaccination, AIT remained a significant protective factor associated with shorter recovery time (adjusted odds ratio [OR] 0.62, 95% CI 0.52-0.75; adjusted P<.001) and a lower incidence of hospitalization or emergency department visits (adjusted OR 0.73, 95% CI 0.54-0.98; adjusted P=.03). Furthermore, the AIT+OMA+RMT group showed greater protection with a shorter recovery time (adjusted OR 0.51, 95% CI 0.34-0.74; adjusted P<.001) than the AIT+RMT group. Our multicenter observational study provides valuable clinical evidence supporting the protective effect of AIT against COVID-19 infection in patients with AR and AS.

Efficacy and safety of omalizumab combined with allergen immunotherapy in children with moderate to severe allergic asthma.

Omalizumab enables children who are intolerant to AIT to initiate AIT successfully. Combination therapy better improves asthma and rhinitis symptoms, FeNO, and lung function compared to single SCIT or omalizumab treatment. Combination therapy reduces the incidence of adverse reactions during the initial phase of SCIT and enhances its safety.

Probiotics as adjuvants to mitigate adverse reactions and enhance effectiveness in Food Allergy Immunotherapy.

In the past decades, food allergies became increasingly dominant since early childhood, leading to a lower quality of life and to increasing costs addressed by the health care system. Beside standard avoidance of specific allergens and drug treatments following allergen exposure, a great deal of research has lately focused on Food Allergy Allergen Immunotherapy (FA-AIT). SCIT and EPIT (Subcutaneous and Epicutaneous Immunotherapy), OIT (Oral Immunotherapy), and SLIT (Sublingual Immunotherapy) consist in gradual exposure to allergens to desensitize and achieve tolerance once therapy has ended. Although promising, FA-AIT may bring acute local and systemic adverse reactions. To enhance efficacy, safety and convenience of AIT, the quest of potential adjuvants to mitigate the adverse reactions becomes crucial. Immunomodulatory activities, such as that of increasing the regulatory T cells and decreasing the IgE, have been observed in specific probiotics' strains and multiple studies elucidated the role of gut microbiota as a major interplayer among the host and its immune system. In this review, the microbiome modulation is shown as potential AIT adjuvant, nevertheless the need of more clinical studies in the near future is pivotal to assess the efficacy of targeted bacterial therapies and faecal microbiota transplantation.

Equivalence in intradermal reactions to histamine and compound 48/80 in dogs before and after sedation with dexmedetomidine or a 1:20 combination of medetomidine and vatinoxan.

Intradermal allergen testing (IDAT) is commonly used to formulate allergen-specific immunotherapy, a pillar treatment for canine atopic dermatitis. Many sedatives have shown histaminergic or anti-histaminergic effects and thus been deemed unsuitable for IDAT. The goal of this study was to determine whether, in healthy dogs, dexmedetomidine (Dexdomitor) or a 1:20 combination of medetomidine and vatinoxan (Zenalpha) will affect intradermal reactions compared to unsedated dogs. Ten privately owned healthy dogs were enrolled in this equivalence study. Wheal formation was subjectively and objectively assessed in conscious then sedated dogs. Dogs were randomly sedated with either Dexdomitor (dexmedetomidine [0.5 mg/m2]) or Zenalpha (medetomidine [1 mg/m2/vatinoxan] 20 mg/m2) intramuscularly. Once sedated, five 10-fold histamine (100-0.01 μg/mL) and compound 48/80 (200-0.02 μg/mL) dilutions were intradermally injected into the lateral thorax. The study was repeated on the opposite side with the alternative sedation 1 week later. Quality of sedation, cardiorespiratory function and rectal temperature were recorded every 5 min. There was no difference in the median values of the reactions with either sedative when compared to unsedated dogs. Dexdomitor and Zenalpha achieved an equivalence in both subjective and objective scoring systems for all concentrations tested. A faster median time to sedation (10 vs. 18 min, p = 0.013) was seen with Zenalpha compared to Dexdomitor. Although both sedatives depressed the cardiovascular function, such parameters were less affected by Zenalpha than by Dexdomitor (p ≤ 0.001). Owing to the lack of effects on wheal formation, both sedatives are appropriate for sedating dogs undergoing IDAT. Although, such results should be validated in allergic dogs. Zenalpha may induce more rapid and reliable sedation than Dexdomitor.

Breaking the mold: nontraditional approaches to allergen immunotherapy for environmental allergens.

Allergen immunotherapy is a disease-modifying treatment for allergic diseases. The predominant traditional immunotherapy is through subcutaneous administration of allergens to gradually desensitize allergic individuals. While effective, traditional allergen immunotherapy approaches are often lengthy, time consuming for patients and can result in local or systemic adverse reactions. Nontraditional immunotherapies are emerging as promising alternatives, offering potentially more convenient, safe and efficacious treatment options. This review sought to comprehensively examine the safety, efficacy and performance of various nontraditional immunotherapies for environmental allergens. Nontraditional immunotherapy approaches covered in this review include sublingual, local nasal, intralymphatic rush and ultra-rush immunotherapy, allergoid, microbial and anti-IgE immunotherapies. Nontraditional immunotherapies show significant promise in addressing the limitations of traditional subcutaneous immunotherapy. Methods like intralymphatic and rush immunotherapy offer shorter treatment regimens, enhancing patient adherence and convenience. The co-administration of probiotics or monoclonal antibodies, like omalizumab, with AIT appears to improve treatment efficacy and safety. Despite these advancements, further large-scale, long-term studies are needed to establish standardized protocols, dosing and validate long-term effects of these nontraditional immunotherapies. Standardizing outcome measurements across studies is crucial for accurate comparisons of nontraditional immunotherapies prior to widespread clinical adoption of these innovative techniques.

The Immune Regulatory Functions in B Cells Are Restored by CpG to Reduce Experimental Food Allergy.

Dysfunctional immune regulation contributes to the pathogenesis of food allergy (FA). The mechanism behind regulatory B-cell dysfunction is unclear. CpG has immune regulatory functions. The purpose of this study is to use CpG to recover the immune suppressive functions of B cells in mice with FA. An FA mouse model was created using ovalbumin as the specific antigen. Flow cytometry was used to isolate B cells from the intestinal tissues. The immune regulatory functions of B cells were assessed using immunological approaches. The results showed that the FA response was linked to low IL-10 levels in gut lavage fluids of FA mice. FA mouse intestinal B cells produced lower amounts of IL-10 as compared with B cells isolated from naïve control mice. Impaired immune suppressive functions were observed in B cells isolated from the FA mouse intestine. The inducibility of the Il10 expression in naïve B cells of the intestine of FA mice was defective. The induction of Il10 expression in FA B cells could be restored by CpG through regulating the methylation status of the Cmip promoter. CpG promoted the therapeutic efficacy of allergen specific immunotherapy by restoring the induction of IL-10+ B cells in the intestine. The expression of Il10 in B cells of the FA mouse intestine was impaired. Administration of CpG could restore the expression of Il10 in B cells in the intestine and promote immunotherapy for FA.

Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy

Objective One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs). Methods The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed. Results Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups. Conclusion Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans.

6810 Successful Insulin Allergy Desensitization To Humalog During The Second Trimester Of Pregnancy

Abstract Disclosure: J. Noreña: None. S. Seav: None. S. Jiang: None. S. McGhee: None. M. Tan: None. M. Basina: None. Background: Insulin allergy is rare, occurring in only 0.1 to 3% of people with insulin-treated diabetes. During pregnancy, this incidence is even lower due to a relative immunosuppressive state. Currently, there are no standardized insulin allergy desensitization protocols for this specific patient population. Clinical Case: A 39-year-old female (G4P3003) with T2DM and multiple prior medication allergies presented to the antepartum unit in her 17th week of pregnancy due to hyperglycemia and reported insulin allergy to NPH insulin.Patient was initially diagnosed with gestational diabetes during her third pregnancy, requiring NPH insulin which she seemed to tolerate well at the time. She remained medication-free for two years post-delivery but later developed T2DM with an A1c of 6.8%. Metformin and Jardiance, previously prescribed, were discontinued upon confirmation of her current pregnancy. She opted to manage her diabetes through diet and exercise alone, but her A1c rose to 7.0%, prompting the initiation of NPH.Following the first dose of NPH at home, she experienced a localized burning sensation at the injection site associated with facial flushing, followed by a diffuse, pruritic, erythematous rash on her face, chest, abdomen, and bilateral arms. Due to her history of anaphylaxis to other drugs (mainly antibiotics), she was admitted to the hospital for monitoring. Inpatient attempts with lower doses of NPH and then a trial of glargine triggered new rash episodes. Work-up revealed negative insulin antibodies, low IgG, and a normal CBC. She was started on Humalog to cover basal dose administered every 6 hours and additional prandial injections, which she tolerated prior to discharge. One week later, she developed a new local erythematous reaction at the Humalog injection site followed by a generalized rash which led to her readmission.Allergy was consulted and facilitated a successful desensitization protocol to Humalog. The protocol included escalating doses of insulin administered every 30 minutes (0.1u, 0.2u, 0.4u, 0.8u, 1u, 2u, 3u, 3u) to achieve a pre-determined cumulative dose of 10.5 units. Patient tolerated the protocol well and was discharged with q6h Humalog for basal coverage in addition to prandial doses with plan to transition to insulin pump therapy with Humalog soon. Conclusion: This unique case demonstrates how insulin desensitization can be a safe and successful strategy to help achieve insulin tolerance and glycemic control during pregnancy. Election of an insulin, such as Humalog, that can achieve the one-hour post-prandial glucose target during pregnancy and also provide effective basal coverage should be considered as desensitization can only be done with one insulin type at a time. Presentation: 6/2/2024

Allergen Immunotherapy for the Prevention and Treatment of Asthma.

Allergic asthma is the predominant phenotype among asthmatics. Although conventional pharmacotherapy is a central component in the management of asthma, it does not enable control of asthma symptoms in all patients. In recent decades, some uncontrolled asthmatic patients, especially those with allergic asthma, have benefited from biological therapies. However, biologics do not address all the unmet needs left by conventional pharmacotherapy. Furthermore, it is noteworthy that neither conventional pharmacotherapy nor biological therapies have disease-modifying properties. In this context, allergen immunotherapy (AIT) represents an indispensable component of the therapeutic arsenal against allergic asthma, due to its disease-modifying immunological effects. In this review article, funded by an AIT manufacturer, we find clinical trials support AIT as the only treatment option able both to improve allergic asthma symptoms and to prevent the onset and worsening of the condition. For patients with severe asthma or other safety concerns, the combination of AIT and biologics offers very promising new treatment modalities for the management of allergic asthma. Trial Registration: clinicaltrials.gov identifier: NCT06027073.