The Future of Food Allergy Management: Advancements in Therapies.

PURPOSE OF REVIEW: To review current and future treatment options for IgE-mediated food allergy. RECENT FINDINGS: Recent years have seen major developments in both allergen-specific and allergen-non-specific treatment options, with the first FDA-approved peanut oral immunotherapy (OIT) product becoming available in 2020. In addition to OIT, other immunotherapy modalities, biologics, adjunct therapies, and novel therapeutics are under investigation. Food allergy is a potentially life-threatening condition associated with a significant psychosocial impact. Numerous products and protocols are under investigation, with most studies focusing on OIT. A high rate of adverse events, need for frequent office visits, and cost remain challenges with OIT. Further work is needed to unify outcome measures, develop treatment protocols that minimize adverse events, establish demographic and clinical factors that influence candidate selection, and identify patient priorities.

Enhancing quality of life with 3-year course of sublingual immunotherapy for house dust mite-induced allergic rhinitis: An observational prospective study in real-life settings.

PURPOSE: This prospective study aims to provide further supportive evidence by assessing the sustained effectiveness and safety of sublingual immunotherapy (SLIT) using a vaccine containing house dust mite (HDM) extracts in patients diagnosed with allergic rhinitis (AR) with/without conjunctivitis (AR/C). MATERIALS AND METHODS: AR/C patients (n = 111, SLIT group: 57, control group: 54) allergic to HDM were treated with standardized SLIT drops or symptomatic drugs from October to December in 2020. The patients were directed by the investigators to attend annual hospital visits for the assessment of various parameters including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), visual analog scale (VAS), total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total medication score (TMS). During the study period, all participants were mandated to maintain comprehensive records of any adverse events (AEs) on diary cards, which were then communicated to the investigators via telephone. RESULTS: At baseline (2020), TNSS, TOSS, TMS, VAS, and RQLQ scores were comparable between SLIT and control groups (P > 0.05). After one year of treatment (2021), significant reduction in all scores compared to the baseline for both groups (P < 0.001). At the end of the second year of treatment (2022), TNSS and RQLQ score in the SLIT group continued to decrease significantly compared to 2021 (P < 0.05). In the third year (2023), the control group showed a rebound in TNSS, TOSS, TMS, and RQLQ scores, significant differences compared to 2022 or 2021 (P < 0.05). Besides, the SLIT group had significantly lower scores across all domains of RQLQ compared to the control group (P < 0.001). Symptomatic treatment influenced the scores of Nasal Symptoms, Eye Symptoms, Practical Problems, and Emotions domains significantly in 2023 compared to 2021 or 2022 (P < 0.05). Within the SLIT group, no significant differences in TNSS, TMS, VAS, and RQLQ scores were observed between monosensitized and polysensitized patients throughout the three years of treatment (P > 0.05). All AEs were mild to moderate. CONCLUSION: The 3-year course of HDM-SLIT has shown significant therapeutic efficacy and a favorable safety profile in patients with AR/C. Importantly, our study presents initial evidence suggesting that the greater impact of AR/C on quality of life (QoL) may primarily stem from nasal symptoms, eye symptoms, practical issues, and emotional well-being.

Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms.

BACKGROUND: Atopic dermatitis (AD, eczema) is driven by a combination of skin barrier defects, immune dysregulation, and extrinsic stimuli such as allergens, irritants, and microbes. The role of environmental allergens (aeroallergens) in triggering AD remains unclear. OBJECTIVE: We systematically synthesized evidence regarding the benefits and harms of allergen immunotherapy (AIT) for AD. METHODS: As part of the 2022 American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters AD Guideline update, we searched the MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, Global Resource for Eczema Trials, and Web of Science databases from inception to December 2021 for randomized controlled trials comparing subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT), and/or no AIT (placebo or standard care) for guideline panel-defined patient-important outcomes: AD severity, itch, AD-related quality of life (QoL), flares, and adverse events. Raters independently screened, extracted data, and assessed risk of bias in duplicate. We synthesized intervention effects using frequentist and Bayesian random-effects models. The GRADE approach determined the quality of evidence. RESULTS: Twenty-three randomized controlled trials including 1957 adult and pediatric patients sensitized primarily to house dust mite showed that add-on SCIT and SLIT have similar relative and absolute effects and likely result in important improvements in AD severity, defined as a 50% reduction in SCORing Atopic Dermatitis (risk ratio [95% confidence interval] 1.53 [1.31-1.78]; 26% vs 40%, absolute difference 14%) and QoL, defined as an improvement in Dermatology Life Quality Index by 4 points or more (risk ratio [95% confidence interval] 1.44 [1.03-2.01]; 39% vs 56%, absolute difference 17%; both outcomes moderate certainty). Both routes of AIT increased adverse events (risk ratio [95% confidence interval] 1.61 [1.44-1.79]; 66% with SCIT vs 41% with placebo; 13% with SLIT vs 8% with placebo; high certainty). AIT's effect on sleep disturbance and eczema flares was very uncertain. Subgroup and sensitivity analyses were consistent with the main findings. CONCLUSIONS: SCIT and SLIT to aeroallergens, particularly house dust mite, can similarly and importantly improve AD severity and QoL. SCIT increases adverse effects more than SLIT. These findings support a multidisciplinary and shared decision-making approach to optimally managing AD.

Safety of allergen-specific immunotherapy in children.

Allergic respiratory diseases, such as asthma and allergic rhinitis, are global health issues and have had an increasing prevalence in the last decades. Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic rhinitis and asthma, as it has a disease-modifying effect. AIT is generally administered by two routes: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). Local side effects are common, but usually well-tolerated and self-limited. However, systemic side effects are rare, and associated with uncontrolled asthma and bronchial obstruction, or related to errors in administration. Physicians should constantly assess potential risk factors for not only reporting systemic reactions and fatalities but also implementing other therapies to improve AIT safety. This paper highlights recent evidence on local and systemic reactions related to SCIT and SLIT in children.

Eosinophilic gastrointestinal disorders and allergen immunotherapy: Lights and shadows.

Allergic diseases, such as IgE-mediated food allergy, asthma, and allergic rhinitis, are relevant health problems worldwide and show an increasing prevalence. Therapies for food allergies are food avoidance and the prompt administration of intramuscular epinephrine in anaphylaxis occurring after accidental exposure. However, allergen immunotherapy (AIT) is being investigated as a new potential tool for treating severe food allergies. Effective oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) induce desensitization and restore immune tolerance to the causal allergen. While immediate side effects are well known, the long-term effects of food AIT are still underestimated. In this regard, eosinophilic gastrointestinal disorders (EGIDs), mainly eosinophilic esophagitis, have been reported as putative complications of OIT for food allergy and sublingual immunotherapy (SLIT) for allergic asthma and rhinitis. Fortunately, these complications are usually reversible and the patient recovers after AIT discontinuation. This review summarizes current knowledge on the possible causative link between eosinophilic gastrointestinal disorders and AIT, highlighting recent evidence and controversies.

House Dust Mite Related Allergic Rhinitis and REM Sleep Disturbances.

PURPOSE: Sleep disturbances are common in patients with allergic rhinitis (AR). Perennial allergens like house dust mites (HDM) are difficult to avoid and have nocturnal impacts on the respiratory system and Quality of Life (QOL). The Rapid Eye Movement (REM) sleep stage is associated with memory, cognition, dreams, and overall restfulness, which can be impaired in AR patients with Sleep Disordered Breathing (SDB) even when normal all-night apnea-hypopnea (AHI) or respiratory disturbance (RDI) indices are noted on polysomnography (PSG). We hypothesized that AR HDM allergen positive patients would show REM-specific SDB reflected in their objectively elevated REM-RDI values. MATERIALS AND METHODS: This retrospective analysis of 100 patients included 47 with HDM positive allergy testing. All patients underwent PSG testing calculating the RDI during REM. Multivariate logistic regression models evaluated relationships between allergic statuses and sleep parameters while controlling for potential confounders. RESULTS: Compared with allergy negative patients, HDM allergen positive patients were significantly more likely (OR 4.29, 95%CI 1.26-14.62) to have a REM-RDI in the moderate/severe range (≥15 events/h). CONCLUSIONS: Our study highlighted the significance of respiratory allergies to HDM in patients with SDB. We revealed a significant relationship between HDM allergen positivity and SDB characterized by elevated REM-RDI regardless of all-night AHI, RDI, or REM-AHI values. Clinical implications of knowing about disturbed REM and/or HDM allergenicity include better preparation, treatment, outcomes, and QOL for allergic, SDB, and upper airway surgery patients.

Successful of subcutaneous and oral hyposensitizing therapy in 30 patients.

SUMMARY: Background. Pharmacotherapy and immunotherapy are the main treatment modalities for respiratory allergy. The aim of this paper has been to evaluate the efficacy and tolerability of subcutaneous and sublingual immunotherapy in association in allergic patients, and to demonstrate that the patients who have performed a second oral vaccination cycle after 4-5 years from the first subcutaneous treatment, derive benefits that may last for years. This is due to immune system's plasticity. Methods. The study was conducted in 30 allergic patients which had previously executed a full cycle of classical subcutaneous immunotherapy, with a partial remission of symptoms. After 4-5 years, they were subjected to sublingual immunotherapy for the same allergen, improving the results obtained. Results. All the patients reported a decrease or absence of clinical symptoms, a reduction in the use of anti-allergic drugs, and lower values of PRIST and RAST after the treatment. Conclusions. The results of this clinical study confirm the improvement of results when subcutaneous and sublingual immunotherapy are associated.

Utility of component analyses in subjects undergoing sublingual immunotherapy for peanut allergy.

BACKGROUND: Sublingual immunotherapy (SLIT) with peanut changes clinical and immune responses in most peanut-allergic individuals, but the response is highly variable. OBJECTIVE: We sought to examine the component-specific effects of peanut SLIT and determine whether peanut component testing could predict the outcome of a double-blind, placebo-controlled food challenge (DBPCFC) after 12 months of peanut SLIT. METHODS: We included 33 subjects who underwent peanut SLIT with a DBPCFC of 2500 mg of peanut protein performed after 12 months of therapy. Plasma samples from baseline and after 12 months of peanut SLIT were assayed using ImmunoCAP for IgE and IgG4 against whole peanut, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9. RESULTS: Following 12 months of SLIT, 10 subjects (30%) passed the DBPCFC without symptoms and were considered desensitized. Subjects that failed the DBPCFC tolerated a median of 460 mg peanut protein (range: 10-1710 mg). The desensitized group had significantly lower baseline levels of IgE against peanut (median 40.8 vs. 231 kUA /L, P = 0.0082), Ara h 2 (median 17 vs. 113 kUA /L, P = 0.0082), and Ara h 3 (median 0.3 vs. 8.5 kUA /L, P = 0.0396). ROC curves indicated that baseline IgE against peanut and Ara h 2 were equally effective at discriminating between the two groups (AUC = 0.7957, P = 0.007752 for both). CONCLUSION AND CLINICAL RELEVANCE: In this cohort of subjects undergoing SLIT for peanut allergy, lower baseline levels of IgE against Ara h 2, Ara h 3, and peanut were associated with successful desensitization.

Immunotherapy in all aspects.

Allergen immunotherapy is a form of long-term treatment that decreases symptoms for many people with allergic rhinitis, allergic asthma, conjunctivitis (eye allergy) or stinging insect allergy. In this review, we presented the important topics in immunotherapy. The important aspects of immunotherapy are considered to be "Immunological responses to immunotherapy"; "The principal types of immunotherapy"; "Effectiveness"; "Indications"; "Contraindications"; "Allergen immunotherapy in children"; "Safety"; and "Anaphylactic reactions after immunotherapy". The principal types of immunotherapy are subcutaneous immunotherapy (SCIT) and sublingual immunotherapy. Both of them can be used in indicated cases. When using SCIT, physicians must be more careful because of reported rare fatal cases. The risks and benefits of continuing allergen immunotherapy in patients who have experienced severe systemic reactions should be carefully considered.

Efficacy of sublingual immunotherapy for house dust mite allergic rhinitis.

In the present study, we investigated the outcomes of sublingual immunotherapy (SLIT) in house dust mite-induced allergic rhinitis (HDM-AR) patients. In this prospective, multicentric study, 186 patients with AR who had positive skin prick test results for HDMs were included. The patients were administered SLIT using Staloral 300 for 1 year. Evaluation of the patients regarding symptom scores, clinical findings and Rhinitis Quality of Life Questionnaire (RQLQ) scores was performed at baseline, and then at 6 and 12 months of therapy. Our results showed that, for all of the evaluated items (symptom scores, clinical findings and RQLQ scores), 12-month values were significantly lower than those at 6 months and baseline. Similarly, 6-month values were significantly lower than those at baseline. There were no complications in any of our patients. SLIT for HDM-AR is a treatment modality that can be used safely. We obtained better results than expected, and the treatment showed a positive psychological effect; the patients believed that SLIT was the final step of treatment and, which made them feel better.

Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy.

INTRODUCTION: Our prior clinical study assessed the efficacy and safety of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farina drops on patients with allergic rhinitis (AR) while analyzing the characteristics of adverse reactions. This study was conducted to evaluate the immune cell composition alterations in AR patients before and after SLIT, and to comprehensively investigate the role and changes of antigen-specific immune cells associated with treatment efficacy. METHODS: A total of 68 AR patients who completed 12 months of SLIT were included in the study. Before the trial's initiation and after 1 year of SLIT, 10 ml of venous blood was collected. Peripheral blood mononuclear cells were isolated using the Ficoll gradient method. The mRNA transcriptome was analyzed using an Affymetrix microarray. The proportions of 22 immune cell types were calculated via the CIBERSORTx platform. Correlations between each immune cell type and SLIT were analyzed. PI3K-PKB pathway dysregulation were analyzed using quantitative PCR and Western blot. Flow cytometry was utilized to assess the percentages of Th1 and Th2 cells. RESULTS: Mono-sensitized AR patients exhibited marked increases in plasma cells, activated memory T cells, regulatory T cells, and activated dendritic cells, while experiencing decreased neutrophils and resting dendritic cells. In poly-sensitized AR patients, the most notable change was an increase in regulatory T cells, coupled with decreased T follicular helper cells, resting dendritic cells, and activated mast cells. These findings indicated that SLIT reshaped immune cell profiles in AR patients, and, notably, the specific changes differed between mono-sensitized and poly-sensitized individuals. Furthermore, SLIT appeared to shift the immune response towards a Th2 decrease profile in both groups. Importantly, suppression of the PI3K-PKB pathway was evidenced as inhibition of PKB phosphorylation and the decrease of glycogen synthase kinase 3 ß (GSKß) and mammalian target of rapamycin (mTOR) expression after SLIT. CONCLUSION: Our study has demonstrated that SLIT treatment led to distinct changes in immune cell profiles between mono-sensitized and poly-sensitized AR patients. Furthermore, SLIT appeared to reduce a Th2 immune response, highlighting its efficacy in AR treatment. Importantly, the study revealed the suppression of the PI3K-PKB pathway, shedding light on the immunological mechanisms underlying SLIT's effectiveness.

The effect of subcutaneous and sublingual birch pollen immunotherapy on birch pollen-related food allergy: a systematic review.

Background: Birch pollen-related food allergy (BPFA) is the most common type of food allergy in birch-endemic areas such as Western and Central Europe. Currently, there is no treatment available for BPFA. Due to the cross-reactivity between birch pollen and a range of implicated plant foods, birch pollen allergen immunotherapy (AIT) may be effective in the treatment of BPFA. In this study, we systematically evaluate the effectiveness of birch pollen-specific subcutaneous or sublingual immunotherapy in treating BPFA. Methods: A search was performed in the PubMed, Embase, and Cochrane libraries. Studies were independently screened by two reviewers against predefined eligibility criteria. The outcomes of interest were changes in (1) severity of symptoms during food challenge, (2) eliciting dose (ED), and (3) food allergy quality of life (FA-QoL). The validity of the selected articles was assessed using the revised Cochrane risk of bias tool. We focused on studies with the lowest risk of bias and considered studies with a high risk of bias as supportive. Data were descriptively summarized. Results: Ten studies were selected that included 475 patients in total. Seven studies were categorized into "high risk of bias" and three into "moderate risk of bias." The three moderate risk of bias studies, with a total of 98 patients, reported on severity of symptoms during challenge and on the ED. All three studies had a control group. Compared to the control group, improvement in severity of symptoms was observed during challenge in two out of the three studies and on the eliciting dose in one out of three. Only one study investigated the effect of birch pollen AIT on FA-QoL, showing that there was no significant difference between patients receiving subcutaneous immunotherapy or a placebo. Of the seven supportive studies, four had a control group and of those, three showed improvement on both severity of symptoms and ED. None of the supportive studies investigated the effect of the therapy on FA-QoL. Conclusion: This systematic review shows that there is not enough evidence to draw firm conclusions about the effect of AIT on BPFA. Future research is warranted that uses robust clinical studies that include long-term effects, QoL, and multiple BPFA-related foods.

Update on clinical research for food allergy treatment.

The incidence of IgE-mediated food allergy (FA) has continued to increase over the years which places substantial burden on patient health and quality of life. With no cure for this disease, the mainstay of management has been allergen avoidance. However, there have been advancements in FA treatment in recent years with multiple clinical trials utilizing novel and innovative therapeutic strategies. A landmark event came in 2020 with the first drug approval for food allergy with the approval of a product for peanut oral immunotherapy. In addition to oral immunotherapy, different delivery systems of immunotherapy (SLIT, EPIT) are being studied in addition to probiotics, biologic agents - used as monotherapy and as an adjunct, and modified allergens has taken place with the hope to further enhance existing therapeutic options. The hope through these continued developments is for therapies to emerge that will provide a more comprehensive benefit to this patient population.

Omalizumab is effective for a patient with pollen-food allergy syndrome who experienced intractable lip edema.

Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergic reaction caused when patients with pollen allergy ingest food having cross-reactivity with pollen. To date, no effective treatment method for this has been established. Here we report the case of a patient with PFAS who experienced lip edema, causing difficulties in treatment. This report describes the case of a 12-year-old boy with perennial allergic rhinitis since the age of 8 years. After ingesting fresh fruits and raw vegetables at the age of 11 years, he started to experience lip edema repeatedly. Thus, the patient was referred to our department. Based on the results of serum antigen-specific IgE, prick-to-prick, and allergen component tests, he was diagnosed with PFAS. He has been instructed to avoid causative food. Furthermore, the treatment using an antihistamine and antileukotriene receptor antagonist was initiated for pollen allergy. Sublingual immunotherapy (SLIT) for Japanese cedar pollen was initiated because the patient experienced severe nasal allergy symptoms during the dispersal season of this pollen. These treatments alleviated the nasal symptoms; however, the lip edema persisted. Omalizumab administration improved the lip edema. The combination of SLIT and omalizumab may be an effective treatment option for patients with PFAS.

Serum vitamin D3 deficiency can affect the efficacy of sublingual immunotherapy in children with allergic rhinitis: a retrospective cohort study.

Background: Sublingual immunotherapy (SLIT) is effective and convenient for many allergic patients but it is still ineffective for many children with allergic rhinitis (AR). In previous studies, most of the patients with poor efficacy of SLIT used the method of individualized adjustment of drug dosage. Currently, there are few reports on the relationship between serum vitamin D3 level and the efficacy of SLIT. Methods: In this study, 153 patients with AR who received SLIT were selected as the study objects. All patients collected serum for vitamin D3 test before treatment. The clinical characteristics of the patients were collected, and all patients were regularly followed up for at least 6 months. The improvement rates were assessed according to the combined symptom medication score (CSMS). A receiver operating characteristic (ROC) curve was drawn, and the optimal cut-off point was determined according to the Youden index. Univariate and multivariate logistic regression were used to analyze the relationship between serum vitamin D3 and SLIT efficacy. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression. Results: Of 153 AR patients, 101 patients entered the final statistical analysis. According to CSMS, 29.7% of patients in low response (LR) group. The mean vitamin D3 level was (20.42±7.48) ng/mL. The optimal cutoff point for vitamin D3 was 22.25 ng/mL. Univariate logistic regression analysis of SLIT efficacy showed that whether the patient also had a food allergy (P<0.001) or asthma (P=0.011), whether they used acarid products (P=0.002), and whether vitamin D3 is sufficient (P=0.001) were significantly related to the efficacy of SLIT. Multivariate logistic regression analysis showed that after adjusting for whether the patient also had asthma and whether they had used acarid products, whether the patient also had a food allergy (OR: 12.13, 95% CI: 3.57-41.18, P<0.001) and whether vitamin D3 is sufficient (OR: 22.21, 95% CI: 4.04-122.30, P<0.001) were independent factors affecting the efficacy of SLIT. Conclusions: Serum Vitamin D3 deficiency can affect the efficacy of SLIT in children with AR. This study provided a new therapeutic approach for SLIT patients with poor efficacy.

Tolerability and Safety of Sublingual Immunotherapy in Patients with Tree Pollen Allergy in Daily Practice-An Open, Prospective, Non-Interventional Study.

To investigate the tolerability and safety of two sublingual tree pollen extracts approved in 2018, a non-interventional study (NIS) was performed. This NIS was an 8-month observational study conducted at 84 sites throughout Germany. Study participants received either a sublingual liquid allergen extract of birch pollen (SBPE) or a liquid allergen extract consisting of a mixture of birch, hazel, and alder tree pollen (STPE). Data from 432 patients were analyzed for the occurrence of adverse events and patient compliance. At least one local reaction occurred in 69 (22.2%) patients, whereas systemic reactions were only observed in 27 (6.3%) patients. STPE-treated patients developed systemic reactions more frequently than SBPE-treated patients (SBPE: 9 (4.3%) vs. STPE: 18 (8.0%)). Only one patient developed a systemic grade III reaction. Severe systemic grade IV reactions were not observed. A total of 348 (98.6%) of the patients who completed all visits were satisfied or very satisfied with the sublingual immunotherapy (SLIT), and 322 (71%) patients completed all visits. Both investigated products were well tolerated by the patients and demonstrated a good safety profile. AEs were observed less frequently than in the preceding clinical phase III trial, and no new safety concerns were identified.

Safety of Sublingual Immunotherapy: A Secondary Analysis of Post-marketing Adverse Events Reports Using a Japanese Public Database.

Purpose Allergic rhinitis impacts a significant portion of the Japanese population, leading to the rise of sublingual immunotherapy (SLIT) as an alternative treatment. Despite its growing popularity, there is limited safety information. Therefore, this study aimed to consolidate data on its adverse effects in an academic context. Methods We conducted a secondary analysis of adverse events reported in the Pharmaceutical Adverse Events Information Database for three SLIT drugs (Actair®, Cedarcure®, and Miticure®) approved in Japan. A descriptive analysis concerning age, gender, underlying diseases, symptoms, time of onset, and outcomes was performed. Results We identified 98 cases of adverse reactions reported for the SLIT drugs. These cases were mainly from the pediatric to adolescent group (73.7%). Males made up 59.5% of reports. Recovery or improvement was noted in 97.7% of reports. Anaphylactic reactions were the most common adverse event (42.6%), followed by respiratory distress (12.2%). Reactions typically occurred within one week of starting treatment (54.1%). Conclusions Our research illuminated the safety of SLIT drugs in Japan, revealing a favorable profile. It underscores the need for vigilance, particularly among younger patients and during initial doses, emphasizing the importance of proper patient selection and further research to enhance the treatment's efficacy.

Immune response modulation by allergen loaded into mesenchymal stem cell-derived exosomes as an effective carrier through sublingual immunotherapy.

BACKGROUND: Allergen-specific sublingual immunotherapy (SLIT) was considered an interesting needle-free alternative for subcutaneous immunotherapy (SCIT). Mesenchymal stem cell (MSC)-derived exosomes were introduced as potent nanoscale delivery systems with immunomodulatory potentials. The current study investigated the therapeutic efficacy of SLIT using ovalbumin (OVA)-enriched MSC-derived exosomes formulation in a murine model of allergic asthma. MATERIAL AND METHODS: MSCs were harvested from mice adipose tissues. Then, exosomes were isolated, and OVA-loaded exosomes were prepared. Following sensitization, Balb/c mice received therapeutic formulation (10 µg/dose OVA-containing MSC-derived exosomes) twice a week for two months. Serum OVA-specific IgE levels as well as IFN-γ, IL-4, and TGF-ß secretions by cultured splenocytes were measured by ELISA. Also, lung tissue underwent histopathologic analysis, and the numbers of inflammatory cells and eosinophils in nasopharyngeal lavage fluid (NALF) were examined. RESULTS: SLIT using OVA-enriched exosomes significantly reduced IgE levels and IL-4 production, while the secretion of IFN-γ and TGF-ß were significantly elevated. Also, a decrease was observed in the numbers of total cells and eosinophils in the NALF, and lower levels of perivascular and peribronchiolar inflammation and cellular infiltrations were observed in the lung tissue. CONCLUSION: SLIT using OVA-loaded exosomes improved immunomodulatory responses and efficiently alleviated allergic inflammation.

The Combined Effects of Sublingual Immunotherapy and Lactobacillus acidophilus-Producing Extract on Cedar Pollinosis Symptoms.

INTRODUCTION: Sublingual immunotherapy (SLIT), in which standardized cedar pollen extract solution is administered, has been used to treat cedar pollinosis, but SLIT is problematic because it takes a long time to become effective, and some cases are ineffective even after long-term treatment. It has also been reported that lactobacillus acidophilus extract (LEX), a food-derived ingredient, alleviates various allergic symptoms. This study examined the usefulness of LEX as a treatment for cedar pollinosis in comparison with SLIT. We also examined whether the combined use of SLIT and LEX could have an early-onset of therapeutic effect on cedar pollinosis. We also examined the usefulness of LEX as a salvage therapy for patients who failed to respond to SLIT. SUBJECTS AND METHODS: Fifteen patients with cedar pollinosis were divided into three groups. The three groups were: three patients in the standardized cedar pollen extract group (S group), seven patients in the lactobacillus-producing extract group (L group), and five patients in the combination group of standardized cedar pollen extract and lactobacillus-producing extract (SL group). The subjects were treated for three years, corresponding to the three scattering seasons of cedar pollen, and observed according to the evaluation items. The evaluation items were severity score based on examination findings, subjective symptom score (QOL score) based on the Japanese Standard QOL Questionnaire for Allergic Rhinitis (JRQLQ No. 1) questionnaire, nonspecific IgE level measurement by blood test, and cedar pollen-specific IgE level measurement. RESULTS: After three years of observation, there were no significant differences in severity score and nonspecific IgE levels among the three groups, while QOL score decreased significantly between the first and third years of treatment in the L group. Cedar pollen-specific IgE levels in the S and SL groups showed an increase in the first year and a gradual decrease in the second and third years of treatment compared to the pre-treatment period. In group L, no increase was observed in the first year, and a significant decrease was observed in the second and third years during the cedar pollen dispersal period. CONCLUSIONS: The results of severity and quality of life scores indicated that it took three years of treatment for the S and SL groups to show efficacy, while the L group showed improvement in quality of life scores and cedar pollen-specific IgE levels from the first year, suggesting that LEX is useful as a treatment for cedar pollinosis. The efficacy of combination therapy with SLIT and LEX was not clear, but since the effect of LEX was observed from the early stage of treatment, it was thought that the combination therapy with LEX intake from the early stage of treatment may be effective in reducing the incidence of ineffective cases. The combination therapy of SLIT and LEX may also be useful as a salvage therapy.