House Dust Mite-induced Allergic Rhinitis Research Articles

Sanfeng Tongqiao Dripping Pills alleviate House Dust Mite-induced allergic rhinitis in mice by inhibiting Th2 differentiation and repairing the nasal epithelial barrier

BackgroundSanfeng Tongqiao Dripping Pills (SFTQ) has clinically demonstrated a promising therapeutic effect on allergic rhinitis (AR). However, the active ingredients and underlying mechanisms of SFTQ remain unclear. PurposeExploring the effects, mechanisms, and active ingredients of SFTQ in the treatment of AR is valuable. Study designThe mechanisms of SFTQ and its active ingredients in treating AR were investigated through in vivo and in vitro studies. MethodsA HDM-induced AR model was established in BALB/c mice. The effects of SFTQ in treating AR were evaluated by AR-like symptoms, EOS count, and pathological changes in the nasal tissue in vivo. The effects of SFTQ active components on epithelial cells (ECs) were evaluated in Poly(I:C) and TNF-α co-stimulated human nasal ECs (RPMI-2650). Additionally, the effects of SFTQ active components on splenocytes proliferation and Th cell differentiation were assessed. A co-culture system of ECs and T lymphocytes was established to investigate the impact of Th2 cells on the structure and function of ECs. The effects of SFTQ ingredients on ECs, T lymphocytes, and the HDM-induced AR model were further confirmed through in vivo and in vivo studies, respectively. ResultsSFTQ significantly alleviated AR-like symptoms and pathological changes in the nasal tissue of AR mice. The treatment elevated the expression of Occludin and E-cadherin in the nasal epithelium and reduced the percentage of Th2 cells in cervical lymph nodes (CLN). Among the active compounds of SFTQ, L-Menthone and Pulegone notably downregulated IL-33 levels in activated ECs, while Hesperetin significantly decreased TSLP and IL-33 levels. In the co-culture system of ECs and Th2 cells, exposure to Baicalin, Wogonin, and Pulegone increased the TEER value of ECs, while notably inhibiting the production of TSLP and IL-33. Furthermore, in HDM-induced AR mice, treatments with Baicalin, Luteolin, and Hesperetin effectively inhibited AR-like symptoms. Additionally, Luteolin and Hesperetin significantly reduced the inflammatory cells infiltration and the population of Th2 cells in AR mice. ConclusionSFTQ and its active ingredients effectively alleviated HDM-induced AR in mice by inhibiting Th2 cell differentiation and repairing the nasal epithelial barrier. Our study can provide a scientific basis for SFTQ to be used in clinical treatment of AR.

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

PurposeThis 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 methodsAR/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. ResultsAt 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. ConclusionThe 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.

Comparison of subcutaneous and sublingual immunotherapy in house dust mite-induced allergic rhinitis

Comparison of subcutaneous and sublingual immunotherapy in house dust mite-induced allergic rhinitis

Short-term and long-term efficacy of sublingual immunotherapy in different courses for house dust mite-induced allergic rhinitis

PurposeSublingual immunotherapy (SLIT) has been proven to be an effective and safe treatment for patients with house dust mite (HDM)-induced allergic rhinitis (AR) to achieve short-term and long-term efficacy. This study aimed to investigate the relationship between SLIT duration and long-term efficacy. Materials and methodsThis study involved 134 patients who underwent SLIT between 2019 and 2021 (in the 2-year group), between 2018 and 2021(in the 3-year group), or between 2017 and 2021 (in the 4-year group). The total nasal symptoms score (TNSS), total medication score (TMS), visual analogue scale (VAS), the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) and adverse events (AEs) were assessed at baseline, after treatment (2021) and one year after the treatment completion (2022). The correlation between MiniRQLQ and other indicators was also analyzed. ResultsAfter SLIT, patients in all three groups showed significant improvements in TNSS, TMS, VAS and MiniRQLQ scores (all p < 0.001). These improvements were sustained even one year after SLIT. Patients who received 3–4 years of SLIT showed significant improvement compared with those who received 2 years of SLIT in all clinical outcomes (all p < 0.01). The analysis showed positive correlations between the MiniRQLQ and TNSS, TMS, and VAS (all p < 0.001). No significant difference was observed in the AE rate in all three groups (p > 0.05). ConclusionDifferent duration of HDM SLIT could generate various short-term and long-term clinical efficacy. The MiniRQLQ could be applied to evaluate SLIT efficacy in clinical practice.

Evaluation of genetic variants in ferroptosis-related genes and house dust mite-induced allergic rhinitis risk.

Ferroptosis-related genes disrupt iron homeostasis and enhance lipid peroxidation to initiate respiratory system diseases. However, the association between genetic variants in the ferroptosis-related genes with house dust mite (HDM)-induced allergic rhinitis (AR) susceptibility remains unclear. A case-control study, involving 222 cases and 237 healthy controls from a Chinese population, was conducted to evaluate the relationship between single nucleotide polymorphisms (SNPs) in ferroptosis-related genes and HDM-induced AR risk. A gene-based analysis was performed by multi-marker analysis of genomic annotation (MAGMA) to identify candidate associated ferroptosis-related genes. A logistic regression model and joint analysis were used to assess the effect of SNPs on HDM-induced AR susceptibility. Two independent SNPs (rs2305128 in ENPP2 and rs1868088 in EPAS1) were significantly associated with HDM-induced AR risk (OR=1.82, 95% CI=1.19-2.79, P=5.98×10-3, PFDR=4.88×10-2; OR=2.14, 95% CI=1.23-3.72, P=6.95×10-3, PFDR=4.87×10-2, respectively). Moreover, combined analysis of these two SNPs revealed that an increased risk of HDM-induced AR was positively associated with an increasing number of risk genotypes (Ptrend= 8.48×10-5). The stratification analysis showed that the cumulative effect of two SNPs on HDM-induced AR risk was more pronounced among patients presenting more serious symptoms and harboring one or two risk genotypes. These findings suggest that the genetic variants in ferroptosis-related genes ENPP2 and EPAS1 may increase HDM-induced AR risk and serve as potential predictors of HDM-induced AR susceptibility.

Immunotherapy in reducing clinical symptoms of children with house dust mite-induced allergic rhinitis

Allergic rhinitis in children is mostly caused by house dust mites (HDM). It requires long-term therapy and decreases the quality of life of patients and their caregivers. Immunotherapy provides long-term improvement of clinical symptoms in children with allergic rhinitis. However, there are not many studies on the benefit of immunotherapy in children with allergic rhinitis in Indonesia. This study aimed to analyze the benefits of immunotherapy in reducing clinical symptoms in children with HDM-induced allergic rhinitis. A secondary data-based retrospective cohort study was conducted on HDM-induced allergic rhinitis children between 2015-2019 in Surabaya. The diagnosis of HDM-induced allergic rhinitis was established from typical allergic symptoms and a positive skin prick test result for HDM allergens. The improvement of clinical symptoms was assessed based on total symptom score (TSS), total medication score (TMS), and combination of symptom and medication score (CSMS) of the EAACI/WAO scoring. Observation on each score was carried out at the time of initial diagnosis and after 18 months of therapy. Mann-Whitney comparative analysis statistical test was for comparing immunotherapy group and non-immunotherapy group. TSS, TMS, and CSMS of the immunotherapy group were significantly lower (p&lt;0.05) than in the non-immunotherapy group.

Identification of Robust Biomarkers for Early Predicting Efficacy of Subcutaneous Immunotherapy in Children With House Dust Mite-Induced Allergic Rhinitis by Multiple Cytokine Profiling.

BackgroundSubcutaneous immunotherapy (SCIT) is an effective treatment for children with allergic rhinitis (AR), but its efficacy fluctuates among patients. There are no reliable candidate biomarkers for monitoring and predicting the response to SCIT. The present study aims to identify novel biomarkers for early predicting the efficacy of SCIT in pediatric AR patients based on multiple cytokine profiling.MethodsWe prospectively recruited 72 children with house dust mite (HDM)-induced AR who were assigned to receive SCIT. The serum samples were collected and multiple cytokine profiling was conducted by Luminex assay at baseline. All patients were followed-up for 1 year and then categorized into effective and ineffective group based on their efficacy, and levels of 48 selected cytokines were tested and compared between the two groups. The potential cytokines were further validated by enzyme-linked immunosorbent assay (ELISA) in a cohort with 54 responders and 26 non-responders.ResultsSixty-nine of 72 children completed one-year follow-up schedule with 46 included in effective group and 23 in ineffective group. The results of multiple cytokine profiling showed that 15 cytokines (eotaxin, G-CSF, GM-CSF, IFN-γ, IL-12(p40), IL-13, IL-15, IL-16, IL-4, MIF, MIP-1α, RANTES, SCF, SDF-1α and VEGF) were dysregulated between effective and ineffective group (all P < 0.05). Unadjusted and adjusted multivariate analysis models highlighted that serum eotaxin, IFN-γ, IL-4 and MIF levels closely associated with the efficacy of SCIT in pediatric HDM-induced AR patients. In addition, receiver operating characteristic (ROC) curves revealed potential values of these four biomarkers in predicting the response to SCIT. Further ELISA validation results in the cohort of 80 pediatric patients demonstrated that serum eotaxin and IL-4 levels were elevated in responders while IFN-γ levels decreased in responders (all P < 0.05). ROC curves demonstrated that serum IL-4 exhibited more reliable accuracy in predicting SCIT efficacy than eotaxin and IFN-γ.ConclusionOur discover–validation study suggested that cytokines including IL-4, eotaxin and IFN- γ may serve as robust biomarkers for early predicting response of SCIT in children with HDM-induced AR. These results strengthen the evidence that cytokines were associated with the response of SCIT and contributed to understand its underlying therapeutic mechanisms.

Serum Soluble ST2 Correlated with Symptom Severity and Clinical Response of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis Patients.

Background Suppressor of tumorigenicity 2 (ST2) is a key biomarker in inflammation and cardiovascular diseases, but limited data is available on its role in allergic rhinitis (AR). Objective The aim of this study is to explore the role of serum soluble ST2 (sST2) in evaluating disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in house dust mite- (HDM-) induced AR patients. Methods Eighty healthy controls (HC group) and 160 HDM-induced AR patients, including 40 mild patients (MAR group) and 120 moderate-severe patients (MSAR group), were recruited in this study. Serum was collected from all participants and levels of sST2 were determined by ELISA and the relationship between sST2 levels and disease severity was assessed. In the MSAR group, 109 patients received 3 years of SLIT, and the relationship between serum levels of sST2 and efficacy of SLIT was exampled. Results Serum sST2 levels were increased in HDM-induced AR patients compared to the HC group (P < 0.001), and the concentrations were higher in the MSAR group than in the MAR group and HC group (all P < 0.05). Moreover, sST2 levels positively correlated with the total nasal symptom score (TNSS), visual analogue scale (VAS), and specific IgE levels (P < 0.05). Seventy-eight MSAR patients accomplished SLIT, and they were divided into an effective group (n = 40) and an ineffective group (n = 38). The serum sST2 levels in the effective group were lower than those in the ineffective group (P < 0.001). In addition, patients in the effective group levels exhibited significantly lower sST2 levels post-SLIT than pre-SLIT (P < 0.001), but no statistic difference was observed in the ineffective group (P > 0.05). Receiver operating characteristic (ROC) curve showed promising accuracy for predicting clinical efficacy of SLIT in AR patients (area under the curve = 0.839, P < 0.001). Conclusion Serum sST2 is a potential biomarker for assessing disease severity and may serve as a sensitive biomarker for predicting the therapeutic response of SLIT in HDM-induced AR patients.

Effect of fexofenadine/pseudoephedrine combination tablet on nasal obstruction in patients with allergic rhinitis using rhinomanometry: A randomized controlled trial.

A fexofenadine/pseudoephedrine combination tablet (F/P) is an optimal product for nasal obstruction. It contains fexofenadine hydrochloride, a histamine H1-receptor antagonist for sneezing and rhinorrhea and pseudoephedrine hydrochloride, an α-adrenergic agonist. The effect of an antihistamine-decongestant on nasal obstruction has been demonstrated in previous studies, but onset of action and efficacy data on nasal obstruction are limited. We estimated the efficacy of F/P on nasal obstruction in patients with house dust mite-induced allergic rhinitis (AR) versus fexofenadine (F) using objective methods. In this single-center, single-dose, prospective, randomized, parallel-group study, 24 adult patients with a history of at least 2 years of AR and nasal obstruction were randomized to receive F/P or F. The effect on nasal obstruction was evaluated using nasal airflow and visual analog scale (VAS) score measured at 30-minute intervals before and for 8 hours after dosing. The primary end point was onset of action, based on a comparison of absolute change from baseline in nasal airflow between F/P and F. The protocol was registered in a clinical trial registry as UMIN 000041845. The onset of action for F/P was 30 minutes based on nasal airflow and 60 minutes based on VAS. F/P maintained a significant beneficial effect after onset of effect, while F showed no significant change during the test period. We found F/P had a clear effect on nasal obstruction associated with perennial AR when compared with F. There was a time lag in nasal airflow improvement and nasal obstruction relief.

Sensitization to Furry Animals and Clinical Relevance of House Dust Mite-Induced Allergic Rhinitis in Guangzhou, China

Introduction: The impact of furry animal allergens on house dust mite (HDM)-induced allergic rhinitis (AR) is unclear. Objective: We aimed to investigate the co-sensitization and cross-sensitization of furry animal allergens and assess their clinical relevance with HDM-induced AR. Methods: We enrolled 268 patients with HDM-induced AR who were diagnosed with skin prick tests positive for dogs and/or cats. Specific immunoglobulin E (sIgE) for dogs (e1) and cats (e2), their components (Can f 1–5 and Fel d 1–2), and other uncommon furry animal extracts were measured. Symptoms and quality of life were assessed with a visual analog scale (VAS). Results: The VAS scores for the AR and asthma (AS; n = 166), moderate-to-severe persistent-AR (n = 132), and e1P (positive)-e2P (n = 89) groups were higher than those for single AR (n = 102), other AR classifications, and other AR sensitization profiles, respectively. The IgE positivity rates for components such as Can f 1–3 and Fel d 2 and those for rats, sheep, mice, cows, and horses were highest in e1P-e2P patients. Can f 1–4, Fel d 1, Fel d 2, or the combined allergens were positively correlated with VAS scores. AR combined with AS and sensitization to Can f 4, Fel d 1, or mice were risk factors for HDM-induced AR with VAS scores ≥5. Conclusions: Extensive cross-sensitization or co-sensitization was found between Can f 1–3, Fel d 2, or rat, sheep, mouse, cow, and horse extracts. Higher sIgE levels for Can f 1–4 and Fel d 1–2 or a higher number of furry animal allergens lead to more severe symptoms and a reduced quality of life. Combined with AS, sensitization to Can f 4, Fel d 1, or mice were risk factors for moderate-to-severe HDM-induced AR.

Efficacy and adherence of sublingual immunotherapy in patients aged 60 to 75years old with house dust mite-induced allergic rhinitis.

This study aimed to evaluate the efficacy and adherence of sublingual immunotherapy (SLIT) for house dust mite (HDM)-induced allergic rhinitis (AR) patients over 60years old. Eighty-six AR patients aged 60-75years old were randomly divided in the control and treatment group as 1:1 ratio. The control group was treated with standard pharmacotherapy while the treatment group was treated with SLIT plus pharmacotherapy on demand. Patients adherence, combined symptom and medication score (CSMS), visual analog scale (VAS), and presence of adverse events were evaluated in the baseline and after 6-months, 12-months and 24-months treatment. Twenty-five (58.1%) subjects in the treatment group and 20 (46.5%) subjects in the control group completed the study (P>0.05). The major reasons for premature cessation were out of touch and relieved symptoms. At the same time, CSMS and VAS of the patients over 60years old in both groups significantly decreased from baseline to any post-baseline time point (all P<0.05). The comparison of CSMS and VAS between the two groups revealed statistically significant differences in favor of the SLIT group at month 24 (P<0.05), whereas no differences at month 6 and month 12 (all P>0.05). 41.9% of the patients dropped out within 2years of SLIT treatment and the major reasons for premature cessation were out of touch and relieved symptoms. This study suggested that SLIT plus pharmacotherapy provided a greater clinical benefit than pharmacotherapy alone at two years.

Enhanced Efficacy of Dust Mite Sublingual Immunotherapy in Low-Response Allergic Rhinitis Patients after Dose Increment at 6 Months: A Prospective Study

Background: Several studies have suggested that sublingual immunotherapy (SLIT) involves a dose-response relationship and inadequate dosage might not achieve a favorable clinical effect. Objective: The aim of this prospective study was to investigate the efficacy and safety of increasing SLIT dosage at 6 months in patients with house dust mite-induced allergic rhinitis (AR) who had low response to treatment. Methods: A total of 157 AR participants aged 4–60 years were enrolled and received SLIT with Dermatophagoides farinae drops. After 6 months of SLIT, patients were interviewed and then classified into a high-response (HR) group and a low-response (LR) group based on the combined symptom and medication score (CSMS) reduction rate. Patients with a CSMS reduction rate over 50% were defined as HR and continued the original dose, while patients with a CSMS reduction rate ranging from 20 to 50% were defined as LR and received an increased dose (percentage of dosage increment, 33.33% for patients aged <14 years and 50% for patients aged ≥14 years). Patients with a CSMS reduction rate below 20% were considered nonresponse (NR) and recommended to withdraw from SLIT. CSMS, visual analog scale (VAS), and adverse events were assessed at 0.5, 1, 2, and 3 years during the 3-year treatment. Results: A total of 54 and 56 patients completed the treatment in the HR and LR groups, respectively. The CSMS and VAS of both groups decreased significantly at 6 months (p < 0.05). Significant differences between the two groups were found in CSMS and VAS at 6 months and 1 year (p < 0.05), but not in later follow-ups (p > 0.05). The improvement of adults in the LR group was significantly lower than that of children at 6 months (p < 0.05), but there was no difference in later follow-ups (p > 0.05). There was no difference in CSMS or VAS in patients with monosensitization and polysensitization in the same treatment group at 1 year and in subsequent visits (p> 0.05). Overall, 47 patients withdrew from this study due to NR (n = 22) and other reasons (n = 25). Conclusions: Six months might be a critical time point for efficacy assessment and dosage adjustment for AR patients after SLIT. In patients with low response, dosage enhancement within a certain range may enhance the effectiveness of SLIT.

GWAS-identified variants to allergic disease and early environmental exposure in Chinese schoolchildren with allergic rhinitis induced by house dust mite.

There is growing evidence that environmental exposure in early life is associated with the development of childhood allergic rhinitis. To investigate whether polymorphisms in previously published genome wide association studies (GWAS) allergic disease loci are associated with childhood house dust mite-induced allergic rhinitis (HDM-AR) and interaction effects of genetic and environmental factors on it. 156 cases diagnosed by HDM-AR and 173 controls were enrolled. Potential confounders were analyzed by using Logistic regression. Twenty-one single nucleotide polymorphisms (SNPs) of GWAS-related allergic diseases including EMSY-LRRC32, IL18R1, IL18RAP, IL13, IL4, HLA region, KIF3A were genopyped and analyzed using the improved multiplex ligation detection reaction (imLDR) technique in all the subjects. Only IL18R1_rs2287037 was associated with HDM-AR in children. After adjusting for several likely confounders, the protective TT genotype of IL18R1_rs2287037 was found in the population analyzed with the fittest recessive model. (adjusted odds ratio [aOR]: 0.44; 95% confidence interval [CI]: 0.21-0.95). The rs2287037_ TT might interact with early-life exclusive breastfeeding in the first 4 months (aOR: 0.33; 95%CI: 014-0.97) or full-term birth (aOR: 0.45; 95%CI: 0.19-0.95) exposure to decrease the risk of HDM-AR. These data suggest that IL18R1 polymorphism may play a role in controlling risk to HDM-AR and underline the importance of early environmental exposure into studies of genetic risk factors.

SQ house dust mite sublingual immunotherapy for the treatment of adults with house dust mite-induced allergic rhinitis

ABSTRACTIntroduction: Allergic rhinitis (AR) is one of the most common chronic conditions affecting both children and adults. The house dust mites (HDM) account for a substantial part of the overall sources of allergens. In patients where allergen avoidance and symptom-relieving pharmacotherapy do not provide adequate disease control, specific allergen immunotherapy (AIT) is indicated. While subcutaneous injection (SCIT) is considered as a time-consuming and invasive treatment regimen, sublingual allergy immunotherapy (SLIT) appears as more convenient treatment strategy.Areas covered: This Drug Profile reviews the clinical data behind the development of the SQ HDM SLIT-tablet, including both the early studies and the pivotal studies, which formed the basis for regulatory approval in Europe, Japan, and the U.S.Expert opinion: The clinical trials behind the development of the SQ HDM-SLIT have demonstrated that the tablet provides a safe, well-tolerated and robust efficacy in the treatment of HDM-induced allergic rhinoconjunctivitis. Further, studies show that the SQ HDM SLIT-tablet is a cost-effective treatment option compared with SCIT.

House Dust Mite-Induced Allergic Rhinitis: Is Prevention an Option?

The aim of this paper is to review and summarise the current knowledge of prevention of house dust mite (HDM)-induced allergic rhinitis (AR). AR can be either classified as seasonal/intermittent (for example hay fever occurring summer and autumn) or perennial/persistent (occurring throughout the year). The commonest trigger for seasonal AR is pollen whereas HDMs are the key allergic trigger for perennial AR. HDMs are a recognised indoor allergen that is crucial in the development of AR, asthma, and atopic dermatitis. Preventive strategies have gained acceptance for the management scheme in the treatment of patients with AR. Specifically, preventive measures include allergen avoidance, environmental control, and immunotherapy. The primary goal of medical treatment is to reduce the burden of disease, improve quality of life and to prevent the development of the sequelae of AR such as bronchial asthma. Prevention is a viable option and key component in HDM-AR management. As urbanisation and lifestyle changes lead to the increase of HDM-AR, there should be a more concerted effort towards prevention.

The analysis of Th2 cell subsets in house dust mite allergic rhinitis patients after sublingual immunotherapy

Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR). Meanwhile, the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, the phenotype of the pathogenic Th2 cells (Tpath2) cells in house dust mite-induced AR (HDM-AR) and the relation between Tpath2 and SLIT efficacy have not been clarified. Therefore we analyzed the cytokine production and frequency of HDM-reactive T-cell subsets in peripheral blood mononuclear cells (PBMCs) using flow cytometry in 89 HDM-AR patients (placebo; n = 43 and HDM 300 IR; n = 46) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. HDM-reactive IL-5+IL-13+CD27-CD161+CD4+ cells and ST2+CD45RO+CD4+ cells were observed in the PBMCs from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2+CD45RO+CD4+ cells were significantly lower in active-responders. In conclusion, HDM-reactive ST2+CD45RO+CD4+ cells or those combined with IL-5+IL-13+CD27-CD161+CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of HDM-AR as Tpath2.

The analysis of Th2 cell subsets in house dust mite allergic rhinitis patients after sublingual immunotherapy

Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR). Meanwhile, the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, the phenotype of the pathogenic Th2 cells (Tpath2) cells in house dust mite-induced AR (HDM-AR) and the relation between Tpath2 and SLIT efficacy have not been clarified. Therefore we analyzed the cytokine production and frequency of HDM-reactive T-cell subsets in peripheral blood mononuclear cells (PBMCs) using flow cytometry in 89 HDM-AR patients (placebo; n = 43 and HDM 300 IR; n = 46) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. HDM-reactive IL-5+IL-13+CD27-CD161+CD4+ cells and ST2+CD45RO+CD4+ cells were observed in the PBMCs from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2+CD45RO+CD4+ cells were significantly lower in active-responders. In conclusion, HDM-reactive ST2+CD45RO+CD4+ cells or those combined with IL-5+IL-13+CD27-CD161+CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of HDM-AR as Tpath2.

Sublingual Immunotherapy Tablets Relieve Symptoms in Adults with Allergic Rhinitis: A Meta-analysis of Randomized Clinical Trials.

Background:Sublingual immunotherapy (SLIT) has been proven to be effective against house dust mite-induced allergic rhinitis. However, the efficacy in adults with allergic rhinitis has never been reported on SLIT tablets. The current meta-analysis aimed to illustrate the differentiated efficacy of SLIT tablets on allergic rhinitis.Methods:Our systematic review and meta-analysis were performed on allergic rhinitis patients and aimed to summarize those randomized controlled studies (RCTs). PubMed, EMBASE, Cochrane library, and MEDLINE were screened for associated articles. We included RCTs on allergic rhinitis patients undergoing SLIT therapy and reporting outcomes on symptom relief and serum-specific IgE levels. The effect of SLIT tablets on the Rhinitis Quality Life Questionnaire Score (RQLQ), Rhinitis Total Symptom Score (RTSS), and serum-specific IgE levels was evaluated using RevMan 5.3.Results:Seven studies were included, with 2723 patients identified. All of the studies were RCT. The included seven studies were all conducted on adults. Among the included seven articles, five researches administered patients with SLIT tablets and were eligible for meta-analysis of RTSS, consisting of 1490 patients. Overall, RTSS was significantly reduced in the SLIT tablet group compared with that in the placebo group (standard mean difference = −0.33, 95% confidence interval [−0.54, −0.13], P < 0.01). There was no significant difference in specific IgE levels between SLIT and placebo patients.Conclusions:SLIT tablets effectively relieve rhinitis symptoms in adults with allergic rhinitis. Nevertheless, the current evidence may be limited due to sample size and the heterogeneity between studies. Large sample size and multiple center RCTs on the efficacy of different formulations of SLIT drugs are still needed to provide further evidence and a more precise recommendation.

Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy.

Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite-induced AR (HDM-AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified. The cytokine production and frequency of HDM-reactive T-cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM-AR patients (placebo [n=43] and HDM 300 IR [n=46]) who participated in a placebo-controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52-week study. The PBMCs were stained with CellTrace™ Violet (CTV) before culture with HDM extract, and HDM-reactive T cells were detected as the proliferated cells with diminished CTV. HDM-reactive IL-5+ IL-13+ CD27- CD161+ CD4+ cells and ST2+ CD45RO+ CD4+ cells were observed in the peripheral blood from each patient with HDM-AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM-reactive ST2+ CD45RO+ CD4+ cells were significantly lower in active-responders. Allergen-reactive ST2+ CD45RO+ CD4+ cells or those combined with IL-5+ IL-13+ CD27- CD161+ CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.

Long-term safety of subcutaneous immunotherapy with TO-204 in Japanese patients with house dust mite-induced allergic rhinitis and allergic bronchial asthma: Multicenter, open label clinical trial

BackgroundTo evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial. MethodsJapanese patients aged 5–65 years were eligible for the study, if they had HDM-induced allergic rhinitis (AR), allergic bronchial asthma (BA), or both. TO-204 was administered in a dose titration scheme, and the maintenance dose was determined according to the predefined criteria. The treatment period was 52 weeks, and patients who were willing to continue the treatment received TO-204 beyond 52 weeks. This clinical trial is registered at the Japan Pharmaceutical Information Center (Japic CTI-121900). ResultsBetween July 2012 and May 2015, 44 patients (28 with AR and 16 with allergic BA) were enrolled into the study. All patients were included in the analysis. The duration of treatment ranged from 23 to 142 weeks and the median maintenance dose was 200 Japanese allergy units (JAU). Adverse events occurred in 22 patients (50%). The most common adverse event was local reactions related to the injection sites. Four patients experienced anaphylactic reactions when they were treated with the dose of 500 JAU. Two patients experienced anaphylactic shock with the doses of 1000 JAU at onset. These 6 patients could continue the study with dose reduction. ConclusionsSafety profile of TO-204 was acceptable in Japanese patients with HDM-induced AR or allergic BA. Higher doses should be administered carefully, because the risk of anaphylaxis increased at doses of 500 or 1000 JAU.