Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10+ ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1+ but not KLRG1- ILC2 produced IL-10 upon activation with IL-33 and retinoic acid. These cells attenuated Th responses and maintained epithelial cell integrity. IL-10+ KLRG1+ ILC2s were lower in patients with grass-pollen allergy when compared to healthy subjects. In a prospective, double-blind, placebo-controlled trial, we demonstrated that the competence of ILC2 to produce IL-10 was restored in patients who received grass-pollen sublingual immunotherapy. The underpinning mechanisms were associated with the modification of retinol metabolic pathway, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathways in the ILCs. Altogether, our findings underscore the contribution of IL-10+ ILC2s in the disease-modifying effect by allergen immunotherapy.

Tolerability of sublingual versus vestibular allergy immunotherapy tablet administration: A randomized pilot study.

BACKGROUND: Local application site reactions are common with sublingual allergy immunotherapy (AIT)-tablets for the treatment of allergic rhinitis/conjunctivitis (AR/C) and occasionally lead to treatment discontinuation. Because of the lower mast cell density in the vestibular mucosa than the sublingual area, vestibular AIT-tablet administration may result in fewer adverse events (AEs). This pilot study evaluated the tolerability of the vestibular administration route of AIT-tablets compared with the sublingual route in adult subjects with AR/C. METHODS: Adults (n = 164) aged 18-65 years with AR/C treated with daily birch pollen, grass pollen, ragweed pollen or house dust mite AIT in tablet form were randomized 1:1 to vestibular or sublingual administration for 28 days, followed by 28 days of sublingual administration only. The primary endpoint was the severity (mild, moderate, severe) of local treatment-related adverse events (TRAEs) during the first 28 days of treatment. RESULTS: During the first 28 days, the percentage of subjects in the vestibular and sublingual groups reporting mild TRAEs were 55.6% versus 50.6%, respectively; moderate TRAEs were 27.2% versus 30.1%; and severe TRAEs were 12.3% versus 6.0% (p = .16). In the vestibular group, 95.1% of the subjects experienced at least one TRAE during the first period versus 81.9% in the sublingual group (p = .01) and discontinuation rates due to AEs were higher (12.3% vs. 3.6%). CONCLUSION: The frequencies of subjects experiencing severe TRAEs, at least one TRAE, and discontinuations due to AEs at the initiation of AIT-tablets were numerically higher with vestibular administration than sublingual administration. Sublingual administration should remain the standard of care for subjects treated with AIT-tablets for AR/C.

Clinical validation of grass pollen exposure chamber in patients with allergic rhinitis triggered by timothy grass.

BACKGROUND: The fluctuation in concentrations of airborne allergens frequently presents a challenge to assessing the efficacy of allergen immunotherapy (AIT) in 'field' studies. Allergen exposure chambers (AECs) are specialized medical installations developed to expose individuals to allergens at defined and consistent concentrations under a controlled environment. The aim of the study was to validate the provocation test with timothy grass pollen as well as to assess its safety in the AEC in patients with allergic rhinitis. METHODS: In the ALLEC® AEC, varying concentrations of timothy grass pollen were dispersed. Allergic symptoms were measured by total nasal symptom score (TNSS), acoustic rhinometry, peak nasal inspiratory flow (PNIF) and nasal discharge volume. Lung function, assessed through peak expiratory flow rate (PEFR) and forced expiratory volume in the first second (FEV1), was used to evaluate safety. RESULTS: The consistency of the test was proved by the stability of environmental conditions, including temperature, humidity and CO2 levels, as well as constant concentrations of grass pollen at predetermined levels ranging from 1000 to 10,000 particles per cubic meter (p/m3). Allergic individuals developed symptoms at concentrations of 3000 p/m3 and above, across all measured endpoints. Lung function was not affected throughout all the challenges. The reproducibility of symptoms was confirmed throughout the tests. The concentration of 8000 p/m3 together with a challenge duration of 120 min was found to be optimal. CONCLUSION: The study demonstrates that the ALLEC® grass pollen exposure chamber provides a reliable and safe method for inducing repeatable symptoms in patients with allergic rhinitis. This approach can be effectively applied for allergy diagnostics and clinical endpoint determination during AIT.

A randomized, double-blind, placebo-controlled trial with mannan-conjugated birch pollen allergoids.

BACKGROUND: There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan-conjugated birch pollen allergoids for the short-course treatment of birch pollen-induced allergic rhinoconjunctivitis. METHODS: For this prospective, randomized, double-blind, placebo-controlled, dose-finding study, 246 birch pollen-allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan-conjugated birch pollen allergoids at five pre-seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti-allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed. RESULTS: The highest dose of mannan-conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose-dependent manner (3.6- and 4.5-fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to -70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II). CONCLUSION: All doses of mannan-conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation.

Nasal allergen-neutralizing antibodies correlate closely with tolerated intranasal allergen challenge dose following grass pollen subcutaneous immunotherapy in patients with local allergic rhinitis.

BACKGROUND: Local allergic rhinitis (LAR) is defined by chronic nasal symptoms, absence of atopy, positive nasal allergen challenge (NAC) and a good response to subcutaneous allergen immunotherapy (SCIT). We sought to investigate SCIT capacity to induce local and systemic blocking antibodies in LAR patients. METHODS: A RDBPC study of grass SCIT was performed, with participants receiving either SCIT (Group A; n = 10) or placebo (Group B; n = 14) in the first 6 months. Both groups subsequently received SCIT for 12 months at Year 2. Nasal and serum antibodies (IgG4, IgA1 and IgA2) and their inhibitory capacity were measured at multiple timepoints. RESULTS: The allergen concentration tolerated increased significantly at 6 months (Group A; p = .047) and 24 months (Group B; p = .049) compared with baseline and persisted until the end of the study. Induction of serum sIgA1 to Phl p was seen in Groups A and B, albeit the former being induced earlier (1.71-fold, p = .027). A significant induction in sIgG4 to Phl p 1 and 5 was observed in serum of Group A (p = .047 and p = .0039) and sIgA2 to Phl p in Group B (p = .032 and p = .0098) at 18 and 24 months, respectively. Both local and systemic blocking antibodies can inhibit allergen-IgE complexes binding to CD23 on B cells, and this correlated with level of allergen tolerated intra-nasally in Group A (serum; 𝜌 = -.47, p = .0006, nasal; 𝜌 = -.38, p = .0294). CONCLUSIONS: Grass pollen SCIT induced functional systemic blocking antibodies that correlate with the concentration of allergen tolerated following NAC, highlighting their potential as a biomarker of SCIT in LAR.

IL-10-modulated dendritic cells from birch pollen- and hazelnut-allergic patients facilitate Treg-mediated allergen-specific and cross-reactive tolerance.

BACKGROUND: Approximately 70% of individuals allergic to birch pollen (Bet v 1.01 [Bet]) develop a secondary food allergy (e.g., hazelnut: Cor a 1.04 [Cor]), due to allergen cross-reactivity. However, standard immunotherapy for type I allergies often does not improve the food allergy sufficiently. We analyzed the allergen-specific and cross-reactive suppressive capacity of primary human regulatory T cells (Treg) induced by autologous IL-10-modulated dendritic cells (IL-10 DC) in vitro and in vivo. METHODS: CD4+ T cells of patients with birch pollen and associated hazelnut allergies were differentiated into Bet-specific or non-specific induced Treg (iTreg). After Bet- or Cor-specific restimulation the phenotype, proliferation, and suppressive capacity of iTreg subsets were analyzed. iTreg function was further investigated in humanized mouse models of airway and intestinal allergy, generated by engraftment of peripheral blood mononuclear cells from allergic donors into immunodeficient animals. RESULTS: After IL-10 DC priming and allergen-specific restimulation (Bet or Cor), non-specific control iTreg remained anergic, whereas Bet-specific iTreg proliferated extensively and exhibited a regulatory phenotype (enhanced expression of CTLA-4, PD-1, TNFR2, IL-10). Accordingly, activated Bet-specific iTreg displayed a high capacity to suppress Bet- and Cor-induced responder Th2 cell responses in vitro, indicating induction of both allergen-specific (birch) and cross-reactive tolerance (hazelnut). In vivo, the beneficial effect of Bet-specific iTreg was verified in humanized mouse models of allergic airway and intestinal inflammation, resulting in reduced allergen-induced clinical symptoms, and immune responses. CONCLUSION: Human IL-10 DC-induced iTreg facilitate allergen-specific and cross-reactive tolerance. Therefore, they are potential candidates for regulatory cell therapy in allergic and autoimmune diseases.

Decreased Basophil Activation against House Dust Mite after Japanese Cedar Pollen Subcutaneous Immunotherapy: A Retrospective Study.

BACKGROUND: Allergen-specific immunotherapy (AIT), an established treatment for allergic diseases, prevents the development of other allergic manifestations. Although the mechanisms remain unclear, AIT has been shown to reduce basophil activation (BA) against nontarget allergens. OBJECTIVES: The aim of this study was to assess immunological changes in Dermatophagoides farinae (Der f) after Japanese cedar pollen (JCP)-based subcutaneous immunotherapy (SCIT) monotherapy. METHOD: The data of 16 patients (age: 6-37 years) with JCP-induced allergic rhinitis who were sensitive to Der f (serum Der f-specific immunoglobulin E [IgE] level >0.34 kUA/L) and received JCP-based SCIT for 5 years were reviewed retrospectively. BA by Der f and JCP extracts and serum-specific IgE and immunoglobulin G4 (IgG4) levels against these allergens were evaluated before and after completing 5 years of JCP-based SCIT monotherapy. RESULTS: The areas under the dose-response curves of BA by Der f and JCP extracts were significantly reduced (p = 0.02 and p = 0.002, respectively). JCP-specific IgE levels decreased and JCP-specific IgG4 levels increased significantly (p < 0.001 for both), whereas Der f-specific IgE and IgG4 levels did not change significantly. CONCLUSIONS: JCP-based SCIT monotherapy reduced Der f-specific BA. These findings suggest that JCP-based SCIT has the potential to modulate immune response toward nontarget allergens.

Efficacy of a Non-Pharmacological Intervention in Seasonal Allergic Rhinitis Symptoms.

BACKGROUND: Patients suffering from allergic rhinitis seek for several therapeutic symptomatic options, including nonconventional treatments, to control their symptoms. OBJECTIVES: Through the present proof-of-concept study, we prospectively investigated the potential role of Puressentiel® nasal protection spray (SNPA) in patients suffering from cypress pollen allergic rhinitis. METHODS: In 15 adults, we performed two nasal provocation tests, with a cypress pollen extract, with a 15-day interval, with and without previous randomized administration of SNPA, and evaluated a nasal symptom score, the nasal inspiratory peak flow, and the concentration of inflammatory cytokines in the nasal lavage after the procedures. RESULTS: Comparing results in patients challenged with and without the SNPA spray before the nasal challenge, we found a 57% mean decrease in symptoms, and a 62% average difference in inspiratory peak flow, after the use of the spray. CONCLUSIONS: Puressentiel® SNPA is effective in reducing nasal symptoms, as assessed by nasal symptoms score and nasal inspiratory peak flow, and could be a valid natural non-pharmacological option in patients suffering from allergic rhinitis.

Effectiveness of sublingual immunotherapy in pediatric cedar pollinosis: A real-world database study.

BACKGROUND: Pediatric allergic rhinitis (AR), including cedar pollinosis (CP), is increasing in Japan. We investigated the effects of sublingual immunotherapy (SLIT), which has limited studies of its effectiveness in real-world settings, on children with CP. METHODS: This retrospective cohort study used a claim database in 2018-2021. Children aged ≤15 years with CP records in 2019 were eligible and were followed up through 2021. We included 2962 CP children undergoing SLIT and 547 who were not. The medication score was used to evaluate SLIT effectiveness in the cedar pollen dispersal season each year. Adverse events and the occurrence of allergic diseases were also evaluated. RESULTS: Medication score was higher in the SLIT group during the index period but lower in 2021 compared to the non-SLIT group (mean ± standard deviation: 5.17 ± 2.39 and 4.74 ± 2.38 in 2019, 3.13 ± 2.30 and 3.55 ± 2.48 in 2021, respectively). The adjusted mean difference between groups from 2019 to 2021 was -0.62 (95% confidence interval: -0.86 to -0.39, p < .0001), and the medication score was reduced in the SLIT group (risk ratio: 1.2: 1.1 to 1.3). The occurrence of adverse events involving abdominal disorders (adjusted odds ratio [aOR]: 0.64: 0.51 to 0.81), asthma exacerbation (aOR: 0.37: 0.24 to 0.57), and allergic diseases involving hay fever unrelated to CP (aOR: 0.60: 0.45 to 0.80) or asthma (aOR: 0.71: 0.58 to 0.86) was lower in the SLIT group. CONCLUSION: In children with CP, SLIT is effective, well tolerated, and could decrease the occurrence of other allergic diseases.

Tablet allergen immunotherapy: the anaphylaxis issue.

For the first time 15 years ago, tablet allergen immunotherapy (T-AIT) formulations were approved by regulatory agencies for treating allergic rhinitis caused by grass pollen in adults and children aged >5 years. Extensive evidences existed about effectiveness and safety of AIT. However, the safety profile is particularly compelling in children. Generally, T-AIT causes local reactions, mostly in the oral cavity, that are usually mild-to-moderate and often self-resolving. However, systemic allergic reactions are also observed with T-AIT, anaphylaxis representing the most fearsome adverse event, considering that it occurs in subjects treated for allergic rhinitis. Therefore, we conducted a literature search of patients reporting anaphylaxis because of T-AIT. Nine cases of anaphylactic reactions were reported in literature. Notably, no death was reported using T-AIT. This outcome was very important as it underscored the substantial safety of T-AIT. However, T-AIT deserves careful attention, mainly in the pediatric population. In this regard, after the first report of anaphylactic reaction at the first administration of T-AIT, manufacturers recommended that the first dose should be administered in a medical facility in the presence of staff with experience in managing anaphylaxis and the patient should be observed for at least 30 min. Interestingly, reported anaphylactic reactions were due to grass pollen extracts, with no report concerning other allergen extracts. However, it is relevant to note that anaphylactic reactions because of T-AIT are not reported in recent years.

A real-life ImmunoCAT study: impact of molecular diagnosis through ImmunoCAPTM ISAC 112 on immunotherapy prescription in pollen-polysensitized patients in Catalonia, Spain.

BACKGROUND: Molecular diagnosis in allergology helps to identify multiple allergenic molecules simultaneously. The use of purified and/or recombinant allergens increases the accuracy of individual sensitization profiles in allergic patients. OBJECTIVE: To assess the impact of molecular diagnosis through the ImmunoCAPTM ISAC 112 microarray on etiological diagnosis and specific immunotherapy (SIT) prescription. This was compared to the use of conventional diagnoses in pediatric, adolescent, and young adult patients with rhinitis or rhinoconjunctivitis and/or allergic asthma, sensitized to three or more pollen allergens of different botanical species. METHODS: A multicenter, prospective, observational study was conducted in patients aged 3-25 years who received care at the Allergology service of 14 hospitals in Catalonia from 2017 to 2020. Allergology diagnosis was established based on the patient's clinical assessment and the results of the skin prick test and specific immunoglobulin E assays. Subsequently, molecular diagnosis was conducted using ImmunoCAPTM ISAC® 112 to recombinant and/or purified allergen components. RESULTS: A total of 109 patients were included; 35 (32.1%) were pediatric patients and 74 (67.9%) were adolescents or young adults (mean age: 18 years), with 58.0% being females. A change of 51.0% was observed in SIT prescription following molecular etiological diagnosis by means of a multi-parameter microarray. CONCLUSIONS: Molecular diagnosis by means of multi-parameter tests increases the accuracy of etiological diagnosis and helps to define an accurate composition of SIT.

Real-World Study of Ragweed Sublingual Immunotherapy in Hungary.

BACKGROUND: Ragweed (Ambrosia elatior) has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest. OBJECTIVE: This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen. METHODS: We retrospectively reviewed the clinical records of 57 patients during the 2015 and 2016 ragweed pollen seasons. Patients were divided into two groups: Group 1 (n = 29), who had not received immunotherapy, and Group 2 (n = 28), who had previously undergone immunotherapy with another sublingual preparation. All patients were treated with Oraltek® ragweed for 4-6 months, initiating 2-4 months before the pollen season and rest of the period was 2 months of the 2016 pollen season. Symptom score (SS), medication score (MS), and combined symptom and medication score (CSMS) were evaluated intra- and intergroup. RESULTS: Pollen counts were consistent between 2015 and 2016. All patients showed significant improvement in SS, MS, and CSMS, with a large effect size (>0.8). Group 2 had significantly lower SS and CSMS in 2015 because of prior immunotherapy. By 2016, both groups exhibited marked improvements, with Group 1 showing a 75% improvement in CSMS. No local or systemic reactions were recorded, indicating a high safety profile. CONCLUSIONS: Ragweed SLIT significantly improved symptoms and reduced use of medication in patients allergic to ragweed pollen. The treatment was effective even in patients with previous immunotherapy, with a high benefit-risk ratio demonstrated by the absence of adverse reactions. These findings support the use of Oraltek SLIT for managing ragweed pollen allergy.

Pollen effects in a changing climate: Ragweed pollen exposure and sleepiness in immunotherapy patients of a Southeastern Michigan allergy clinic.

Allergic rhino-conjunctivitis (AR) is a globally relevant health disorder characterized by sneezing, rhinorrhea and sleep disturbance. Ragweed (Ambrosia artemisiifolia) is a plant common to North America and an important allergen. Coarse methods of measuring airborne pollen counts are used to predict seasonal allergy symptoms. This research used a longitudinal study design with a novel, model-based raster of predicted pollen counts to test associations with self-reported symptoms of AR collected from patients receiving immunotherapy for pollen allergies at an allergy clinic. Researchers visited a clinic six times over three weeks. Immunotherapy patients were asked to fill out a brief intake survey on allergic and symptomatic profiles, daytime sleepiness, housing quality, and demographics. Participants responded to a daily, emailed survey on sleepiness and asthma symptoms for 21 days. Using the date and location of responses, ragweed pollen counts were extracted from a prognostic, model based raster (25km pixels). Lag associations of pollen counts with sleepiness were tested using a logistic regression model , adjusted for housing and demographic characteristics, in a distributed lag non-linear model (DLNM) framework. 49 people participated in the study. 26 (52%) were female. The mean age was 37.9 years. Asthma/allergy symptoms were not associated with ragweed pollen but sleepiness was highest two days after exposure (Estimate: 0.33 [0.04,0.62]). Subjects traveled widely during the study period. Intense exposures to ragweed pollen may be associated with daytime sleepiness within small exposure windows. Model-based predicted pollen counts could be used to study health impacts of pollen in people with disease severe enough to receive immunotherapy. Daytime sleepiness can affect productivity and injury risk, and pollen season length and allergenicity may be increasing with climate change. Thus our results may have important implications for population health.

Local nasal immunotherapy with birch pollen-galactomannan conjugate-containing ointment in mice and humans.

BACKGROUND: Allergen immunotherapy (AIT) is the only disease-modifying treatment for immunoglobulin (Ig) E-mediated allergy. Owing to the high prevalence and early onset of hay fever and pollen-food allergy syndrome (PFAS), a safer and simpler treatment method than conventional AIT is needed. To develop a local nasal immunotherapy using an ointment containing hypoallergenic pollen and assess its efficacy in mice and healthy humans. METHODS: Hypoallergenicity was achieved by combining pollen and galactomannan through the Maillard reaction to create birch pollen-galactomannan conjugate (BP-GMC). The binding of galactomannan to Bet v 1 was confirmed using electrophoresis and Western blotting (WB). Binding of specific IgE antibodies to BP-GMC was verified using enzyme-linked immunosorbent assay (ELISA) and basophil activation test (BAT). The localization of BP-GMC absorption was confirmed using a BALB/c mouse model. BP-GMC mixed with white petrolatum was intranasally administered to 10 healthy individuals (active drugs, 8; placebo, 2) for 14 days. RESULTS: In electrophoresis and WB, no 17-kDa band was observed. In ELISA and BAT, BP-GMC did not react to specific IgE but was bound to IgA and IgG. In the mouse model, BP-GMC was detected in nasopharyngeal-associated lymphoid tissues. In the active drug group, the salivary-specific IgA level significantly increased on day 15 (p = 0.0299), while the serum-specific IgG level significantly increased on day 85 (p = 0.0006). CONCLUSIONS: The BP-GMC ointment rapidly produced antagonistic antibodies against IgE; it is safe and easy to use and might serve as a therapeutic antigen for hay fever and PFAS.

From the genesis to the present: The evolution of sublingual immunotherapy for cedar pollinosis.

In 2004, we started the initial attempt to evaluate the efficacy of SLIT for Japanese cedar pollinosis (JCP) using Japanese cedar (JC) pollen extract solution through a multicenter, placebo-controlled, double-blind comparative study. Based on its success in demonstrating the substantial efficacy of SLIT, we next conducted a larger-scale study by administering JC pollen to all JCP patients recruited. It was because of aiming to ascertain the effectiveness and safety of SLIT and its underlying mechanisms by comparing high- and non-responder patients. Despite limitations posed by liquid medication, significant effectiveness and safety demonstrated by the 2-year treatment served as the foundation for launching the first SLIT medicine for JCP, in 2014. Furthermore, in addition to the clearer Th1/Th2-imbalanced property in the high-responders, the possible involvement of bitter taste receptors in CD4+ T cells, apoptosis pathways in CD4+ T cells and basophils, and inducing a mast cell degranulation inhibitory molecule in the effect of SLIT was demonstrated. To solve the limitations posed by liquid medication, clinical trials evaluating JC pollen sublingual tablets started in 2014. Due to the minimal side effects, ease of administration, and convenient storage, the sublingual tablet medicine was launched in 2018. Giving the ongoing rise in demand for SLIT and considering that more than 1% of JCP patients are currently undergoing SLIT, the practical use of this treatment for multiple allergens is becoming increasingly important.

[Expert consensus on the diagnosis and management of pollen-food allergy syndrome].

Pollen-food allergy syndrome (PFAS) is a unique type of food allergy that specifically affects individuals with pollen allergy. In recent years, pollen allergy is increasingly and shows younger tendency. PFAS has also become a topic of interest in China. The characteristics of PFAS vary across regions and show obviously heterogeneity due to different pollen sensitization profile. Currently, diagnostic methods for PFAS in China are limited, which may lead to underdiagnosed and underrecognized of this syndrome, there are currently no accessible diagnostic criteria and procedures for clinical use. Unlike primary food allergy, the management of PFAS need a combined strategy which involves managing both pollen allergy and food allergy. Therefore, its management is particularly complex and varies among doctors in clinical practice. This consensus has developed a diagnosis and management flow chart based on current domestic and foreign guidelines, as well as relevant research evidence in China. The aim is to improve the standard diagnosis and treatment of PFAS and provide guidance to allergists, healthcare professionals, and general practitioners for accurate understanding, diagnosis, and standardized management of PFAS.

[Component-resolved diagnosis of tree pollen allergen: identify key allergens to develop treatment plans].

With the increasing global prevalence of tree pollen allergies, there has been a significant impact on the quality of life for populations. In North and Central China, birch pollen, cypress pollen, and plane tree pollen are the most common allergens for springtime pollen allergy sufferers. The distribution of plants and patterns of pollen transmission in different geographical areas result in varying pollen exposure outcomes, further complicating the challenges in diagnosis and individualized treatment. This article delves into the research progress and clinical application of tree pollen allergies based on the "Molecular Allergology User's Guide 2.0 (MAUG 2.0) " published by the European Academy of Allergy and Clinical Immunology (EAACI). It discusses major allergen families and component proteins of tree pollen such as PR-10 proteins, profilins, polcalcins, as well as cross-reactive components that may cause pollen-food allergy syndrome. Allergen component diagnostics can distinguish true allergy sufferers from those with multiple allergen reactions, enabling more targeted selection of allergens for specific immunotherapy, thus enhancing treatment effectiveness. Bet v 1 and Cup a 1, for instance, are specific indicators for immunotherapy in birch and cypress allergy patients. Overall, this article provides cutting-edge information for professionals in the field of tree pollen allergies, offering in-depth exploration of tree pollen allergen component proteins, clinical manifestations, and treatment-related research, aiding in better understanding and addressing the challenges of tree pollen allergies.

Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial.

INTRODUCTION: There is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. METHODS: Thirty-seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test >3 mm and/or IgE to birch and timothy >0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5-grass pollen allergen extracts on aluminium hydroxide (10,000 SQ-U/ml; ALK-Abelló) or placebo using ultrasound-guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen-induced cytokine and chemokine production were analysed using flow cytometry and ELISA. RESULTS: There were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass-induced IFN-γ levels increased only in the actively treated group. CONCLUSION: In this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment.

RNA sequencing of single allergen-specific memory B cells after grass pollen immunotherapy: Two unique cell fates and CD29 as a biomarker for treatment effect.

BACKGROUND: Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen-specific IgG4 . IgG4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B-cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen-specific Bmem subsets induced by SLIT for grass pollen allergy. METHODS: Blood samples were collected twice outside the pollen season from twenty-seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne) and seasonal rhinoconjunctivitis. Thirteen received 4-month pre-seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single-cell RNA sequencing was performed on FACS-purified Lol p 1-specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort. RESULTS: Four months of SLIT increased RGP-specific IgE and IgG4 in serum and induced two Lol p 1-specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG4 ), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1+ Bmem expressing surface IgG4 , CD23, and CD29 after SLIT. CONCLUSIONS: A clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface-expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.

Impact of antiallergy agents on CPAP therapy and sleep quality with spring pollinosis in Japanese.

PURPOSE: Allergic rhinitis (AR) is associated with obstructive sleep apnea (OSA) and nasal obstruction causes decreased adherence to continuous positive airway pressure (CPAP). The purpose is to evaluate the effects of antiallergic agents on CPAP adherence and sleep quality. METHODS: A longitudinal study was made of patients who use CPAP for OSA and treated with antiallergy agents for spring pollinosis. We compared the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), nasal symptoms scores (NSS), and data from CPAP before and after treatment. Then, we classified the subjects into two groups based on the baseline PSQI score: one group without a decreased sleep quality (PSQI < 6) and the other group with decreased sleep quality (PSQI ≥ 6). RESULTS: Of 28 subjects enrolled, 13 had good sleep quality and 15 had poor sleep quality. PSQI showed significant improvements after medication (p = 0.046). ESS showed no significant differences after AR medication (p = 0.565). Significant improvement was observed after the prescription of antiallergy agents in all items of NSS (sneezing, p < 0.05; rhinorrhea, p < 0.01; nasal obstruction, p < 0.01; QOL, p < 0.01). The percentage of days with CPAP use more than 4 h increased significantly after the administration of rhinitis medication (p = 0.022). In the intragroup comparisons of PSQI ≥ 6 group, PSQI decreased significantly (p < 0.05). For the NSS in intragroup comparisons of PSQI ≥ 6 group, all parameters showed significant improvement (sneezing, p = 0.016; rhinorrhea, p = 0.005; nasal obstruction, p < 0.005; QOL, p < 0.005). CONCLUSION: The use of antiallergy agents can improve CPAP adherence and sleep quality in patients with OSA on CPAP.