Manifestation and associated factors of systemic and local allergy among patients with allergic fungal rhinosinusitis: An observational study.

Allergic fungal rhinosinusitis (AFRS) is a subtype of chronic rhinosinusitis, characterized by excessive immune responses to environmental molds or fungi. The diagnosis and classification of AFRS into systemic and local types remain clinically challenging due to overlapping characteristics. This study investigated the prevalence of AFRS, its manifestation and associated factors in systemic and local AFRS. A total of 200 patients diagnosed with fungal rhinosinusitis underwent both skin provocation tests (SPT) and nasal provocation tests (NPT) to confirm AFRS and classify systemic and local types. Patients were considered to have AFRS if either the SPT or NPT was positive. Among these, patients with systemic AFRS were those who had a SPT positive. Local AFRS was when patients had a negative SPT and a positive NPT. Medical history, serum total IgE level, nasal endoscopy examinations, and CT scans were also recorded. Most patients were female (65.8%), with a mean age of 55.6 years (SD = 14.4). Based on the SPT and NPT results, 31% of patients (n = 62) were diagnosed with AFRS. Among these, 54.8% (n = 34) had systemic AFRS, while 45.2% (n = 28) had local AFRS. Patients with AFRS exhibited significantly higher levels of total IgE, eosinophils, and more pronounced signs and symptoms compared to those without AFRS. However, no statistically significant differences were observed between patients with systemic AFRS and those with local AFRS. AFRS was prevalent in our study. Among patients with AFRS, both systemic AFRS and local AFRS were also prevalent. While allergic indicators and clinical presentations can aid in AFRS diagnosis, minimal distinctions were observed between systemic and local AFRS. A comprehensive assessment incorporating both local and systemic allergic responses through provocation tests, such as a combination of skin and nasal tests, is imperative for optimizing AFRS diagnosis and management.

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.

Cyp2e1 protects against OVA-induced allergic rhinitis through the inhibition of Th2 cell activation and differentiation: Mediated by MAFB.

Allergic rhinitis (AR) is a common allergic disease. Cytochrome P450, family 2, subfamily e, polypeptide 1 (Cyp2e1) is a member of the cytochrome P450 family of enzymes, while its role in AR is still unveiled. In AR mice, T cell-specific overexpression of Cyp2e1 relieved the AR symptoms. Overexpressed-Cyp2e1 restrained the infiltration of eosinophils and mast cells in the nasal mucosa of mice, and the inflammatory cells in nasal lavage fluid (NALF). Cyp2e1 overexpressed mice exhibited decreased goblet cell hyperplasia and mucus secretion as well as decreased MUC5AC expression in nasal mucosa. The epithelial permeability and integrity of nasal mucosa were improved upon Cyp2e1 overexpression in AR mice, as evidenced by decreased fluorescein isothiocyanate-dextran 4 content in serum, increased expression of IL-25, IL-33, and TSLP in NALF, and increased expression of ZO-1 and occluding in nasal mucosa. Cyp2e1 inhibited Th2 immune response by decreasing the expression and secretion of IL-4, IL-5, and IL-13 as well as the expression of GATA-3 in NALF or nasal mucosa. We proved that Cyp2e1 inhibited the differentiation of naïve CD4+ T cells toward the Th2 subtype, which was regulated by MAFB by binding to Cyp2e1 promoter to activate its transcription. Overall, these results show the potential role of Cyp2e1 in alleviating AR symptoms by restraining CD4+ T cells to Th2 cell differentiation. Our findings provide further insight into the AR mechanism.

Allergic Rhinitis: A Review.

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.

Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

BACKGROUND: The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. OBJECTIVE: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. METHODS: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. RESULTS: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. CONCLUSION AND CLINICAL RELEVANCE: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.

Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.

Accurate determination of house dust mite sensitization in asthma and allergic rhinitis through cytometric detection of Der p 1 and Der p 2 binding on basophils (CytoBas).

BACKGROUND: House dust mite (HDM) is the most common allergen trigger globally for allergic rhinitis and atopic asthma. OBJECTIVES: To expedite accurate confirmation of allergen sensitization, we designed fluorescent allergen tetramers to directly stain specific IgE on basophils to detect specific allergen sensitization using the flow cytometric CytoBas assay. METHODS: Recombinant proteins of major HDM allergens (component), Der f 1, Der p 1, and Der p 2 were biotinylated and conjugated with fluorochrome streptavidins as tetramers. Blood samples from 64 patients who are HDM-allergic and 26 controls that are non-HDM-sensitized were incubated with allergen tetramers for evaluation of basophil binding (CytoBas) and activation (BAT) with flow cytometry. RESULTS: The tetramers effectively bound and activated basophils from patients who are allergic but not from controls who are nonsensitized. CytoBas with Der p 1 as a single allergen had comparable sensitivity and specificity (92% and 100%) to BAT (91% and 100%) in detecting allergen sensitization, as did CytoBas with Der p 2 (95% and 96%) to BAT (95% and 87%). A positive staining for Der p 1 and/or Der p 2 in CytoBas was 100% sensitive and 96% specific for HDM allergy. CONCLUSIONS: CytoBas has diagnostic accuracy for group 1 and group 2 HDM allergens that is comparable to BAT, but with additional advantages of multiple allergen components in a single tube and no requirement for in vitro basophil activation. These findings endorse a single, multiplex CytoBas assay for accurate and component-resolved diagnosis of aeroallergen sensitization in patients with allergic asthma and/or rhinitis.

Clinical Relevance of Lepidoglyphus destructor Sensitisation in Allergic Rhinitis: Nasal Provocation Test as in vivo Assessment.

BACKGROUND: Dust mites are the leading cause of respiratory allergic diseases worldwide. Allergy to storage mites (SMs) has mostly been related to occupational exposures. However, recent studies have shown that sensitisation to SM, such as Lepidoglyphus destructor (Lep d), is of considerable importance also in urban populations, with high prevalence in dust samples of domestic environments. Co-sensitisation between house dust mites (HDMs) and SM is now regarded as very frequent in some regions, and cross-reactivity between them seems to be narrow. Therefore, SM allergenic capacity is increasingly a subject of study. The nasal provocation test (NPT), as an in vivo technique, could be considered the gold standard for the clinical relevance assessment of an allergen, in polysensitised rhinitis patients. OBJECTIVE: The objective of this study was to analyse the clinical relevance of the SM Lep d, by assessing the relationship between in vivo sensitisation and expression of allergic respiratory disease in an urban setting. PATIENTS AND METHODS: In our study, we enrolled a total of 32 allergic patients with rhinitis (with or without asthma) with proven sensitisation by skin prick test (SPT) and specific IgE (sIgE) to HDMs and/or SM. Patients underwent NPT with Lep d using subjective (Lebel Symptom Score Scale) and objective measurements (peak nasal inspiratory flow [PNIF]) for assessment of nasal response. RESULTS: Most of the patients with positive SPT and sIgE to Lep d had a positive NPT (24/27; 89%). True Lep d allergy, assessed by a positive NPT, could be predicted by a SPT wheal size >9.7 mm and a sIgE >0.42 kUA/L, with 100%/95.7% sensitivity and 75.0%/83.3% specificity, respectively. Co-sensitisation between Lep d and Der p was high, 75.0%. Asthma was more frequent in the positive Lep d NPT group (54 vs. 12%, p < 0.05). Significantly more patients from this group reported physical exercise, nonspecific irritants, and respiratory infections as relevant triggers of respiratory symptoms (p < 0.01-p < 0.05). CONCLUSIONS: To our knowledge, this is the first study to show that sensitisation to Lep d may have clinical relevance in a non-occupational setting. In this group, there seems to be a relationship between allergy to Lep d and severity of respiratory disease, with more bronchial inflammation, when comparing with mite-allergic patients sensitised only to HDM. Therefore, the authors consider that sensitisation to Lep d should be considered when assessing and treating allergic respiratory disease in urban environments.

Allergic rhinitis phenotypes with distinct transcriptome profiles in children: A birth cohort.

BACKGROUND: Allergic rhinitis (AR) phenotypes in childhood are unclear. OBJECTIVES: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics. METHODS: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype. RESULTS: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response. CONCLUSIONS: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.

Glucocorticoid-Induced Transcript 1(GLCCI1) SNP rs37937 Is Associated With the Risk of Developing Allergic Rhinitis and the Response to Intranasal Corticosteroids in a Chinese Han Population.

BACKGROUND: Evidence has shown that glucocorticoid-induced transcript 1 (GLCCI1) single nucleotide polymorphism (SNP) rs37937 is associated with asthma. OBJECTIVES: The objective of this study was to investigate whether the GLCCI1 SNP rs37937 is a risk factor for allergic rhinitis (AR) in a Chinese Han population. METHODS: A total of 220 individuals including 109 AR patients and 111 healthy subjects were included. The genotyping of GLCCI1 rs37973 was performed by the SNaPshot method. The correlations of rs37973 polymorphism, AR risk, and clinical characteristics were further analyzed, as well as the treatment response to intranasal corticosteroids (INCS) in AR patients of different genotypes. RESULTS: Three GLCCI1 rs37973 SNP genotypes were identified in both AR patients and healthy subjects. Significant association between rs37973 polymorphism and AR under allele model, dominant model, heterozygote model, and homozygote model were shown. The A allele frequency of SNP rs37973 in AR was significantly higher than that in controls. The serum total immunoglobulin E (IgE) in AR patients of AA genotype was significantly higher than in patients of GA and GG genotype, and the serum total IgE in GA genotype was significantly higher than in GG genotype. Interestingly, after 4 weeks of INCS treatment for AR patients, the improvement of the nasal itching score, sneezing score, runny nose score, total nasal symptom score, and visual analog scale score of the GG genotype were worse than the AA or GA genotype. CONCLUSION: The GLCCI1 rs37937 polymorphism is associated with the risk of developing AR and the response to INCS treatment in the Chinese Han population.

Gene Signatures and Associated Transcription Factors of Allergic Rhinitis: KLF4 Expression Is Associated with Immune Response.

This study is aimed at investigating the potential molecular features of allergic rhinitis (AR) and identifying gene signatures and related transcription factors using transcriptome analysis and in silico datasets. Transcriptome profiles were obtained using three independent cohorts (GSE101720, GSE19190, and GSE46171) comprising healthy controls (HC) and patients with AR. The pooled dataset (n = 82) was used to identify the critical signatures of AR compared with HC. Subsequently, key transcription factors were identified by a combined analysis using transcriptome and in silico datasets. Gene ontology: bioprocess (GO: BP) analysis using differentially expressed genes (DEGs) revealed that immune response-related genes were significantly enriched in AR compared with HC. Among them, IL1RL1, CD274, and CD44 were significantly higher in AR patients. We also identified key transcription factors between HC and AR using the in silico dataset and found that AR samples frequently express KLF transcription factor 4 (KLF4), which regulates immune response-related genes including IL1RL1, CD274, and CD44 in human nasal epithelial cells. Our integrative analysis of transcriptomic regulation provides new insights into AR, which may help in developing precision management for patients with AR.

Peripheral Multiple Cytokine Profiles Identified CD39 as a Novel Biomarker for Diagnosis and Reflecting Disease Severity in Allergic Rhinitis Patients.

Background: Allergic rhinitis (AR) is a common clinical problem, and immune cells and cytokines were proven to be pivotal in its pathogenesis. Our aim is to measure the peripheral concentrations of multiple cytokines in AR patients and identify novel biomarkers for diagnosis and disease severity. Methods: Peripheral blood samples were collected from 50 AR patients, including 25 mild AR (MAR) patients and 25 moderate-severe AR patients (MSAR), and 22 healthy controls (HCs), and multiple cytokine profiling was outlined by Luminex assay. Cytokine levels were compared among the three groups, and their correlations with disease severity were evaluated. The candidate cytokines were further verified by enzyme-linked immunosorbent assay (ELISA) in a validation cohort. Results: Multiple cytokine profiling revealed that CD39 and interferon (IFN)-γ levels were reduced, and interleukin (IL)-13, IL-5, IL-33, and thymic stromal lymphopoietin (TSLP) levels were elevated in the AR group than the HC group (P < 0.05). Receiver operating characteristic (ROC) curves presented that serum CD39 and IL-33 exhibited strong diagnostic abilities, and serum CD39 and IL-10 presented capacities in distinguishing disease severity (AUC > 0.8, P < 0.05). Moreover, CD39 concentrations were decreased, and IL-10, IL-5, and TSLP concentrations were enhanced in the MSAR group more than in the MAR group. Correlation analysis results showed that serum CD39, IL-5, and TSLP levels were associated with total nasal symptom score (TNSS) and visual analogue score (VAS) (P < 0.05). Further data in the validation cohort suggested that serum CD39 levels were reduced, and IL-5 and TSLP levels were increased in AR patients, especially in MSAR patients (P < 0.05). ROC results revealed potential values of serum CD39 in diagnosis and disease severity evaluation in AR patients (P < 0.05). Conclusion: This study highlighted that peripheral multiple cytokine profiles were significantly varied in AR patients and associated with disease severity. The results in discover-validation cohorts implied that serum CD39 might serve as a novel biomarker for diagnosing AR and reflecting its disease severity.

Aeroallergen sensitization in school-age children with allergic rhinitis: What has changed during the COVID-19 pandemic?

Background: Pandemic period may affect aeroallergen sensitization. Objective: The study aimed to investigate changes in allergen sensitivities of skin prick test (SPT) in patients with allergic rhinitis (AR) during pandemic and to evaluate relationship with disease severity. Methods: In all, 164 AR patients with or without asthma, aged 6–17 years, who have undergone SPTs prior to the pandemic and after October 1, 2021 (18th month of the pandemic), were evaluated retrospectively. The wheal size of allergens in performed SPTs during and prior to the pandemic were compared. Detected changes in allergen sensitivities via SPT results were compared with changes in the disease severity parameters (AR severity, asthma severity, and the number of asthma exacerbations per year), frequency of upper respiratory tract infections and antibiotic use, laboratory parameters, demographic characteristics, and visual analogue scores (VAS). Results: House dust mites (HDMs), cat, pollen, Artemisia, and Cupressus sensitization increased in AR patients during the Coronavirus disease 2019 (COVID-19) pandemic. HDM, mold, and pollen wheal diameters increased in SPTs. Proportion of polysensitization increased during the pandemic, compared to pre-pandemic period (9.1% vs 3%; P < 0.001), and number of non-sensitized patients decreased during the pandemic period compared to the pre-pandemic period (7.9% vs 22.6%; P < 0.001). An increase in HDM sensitivity in SPTs was correlated with VAS for nasal blockage, and an increase in cat sensitivity was correlated with VAS for all nasal symptoms. Conclusion: We believe that inhalant allergen sensitization might have been affected by the lifestyle changes of patients during the pandemic. Hence, it is important to evaluate patients for allergen sensitization, especially patients with moderate/severe AR, to revise disease control measurements (AU)

LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response to therapy in allergic rhinitis patients

Objective: Long intergenic noncoding RNA 00632 (LINC00632) regulates nasal inflammation and CD4+ T cell differentiation into T helper (Th) 2 cells in allergic rhinitis (AR). This study aimed to explore the relationship between LINC00632 and Th1/Th2 balance, and the clinical value of LINC00632 in AR patients. Methods: In total, 120 AR patients, 20 non-atopic obstructive snoring patients as disease controls (DCs), and 20 healthy controls (HCs) were recruited. Their LINC00632 expressions in peripheral blood mononuclear cells were detected by RT-qPCR. Results: LINC00632 expression was declined in AR patients compared with DCs and HCs (both P ˂ 0.001). Moreover, LINC00632 could distinguish AR patients from DCs with an area under curve (AUC) of 0.795 (95% confidence interval [CI]: 0.701–0.889), and from HCs with an AUC of 0.895 (95%CI: 0.831–0.960). LINC00632 was positively related to Th1 cells (P = 0.037) and Th1/Th2 axis (P ˂ 0.001) in AR patients. In addition, LINC00632 was inversely associated with Th2 cells (P ˂ 0.001) and interleukin (IL)-4 (P = 0.010) in AR patients. Besides, LINC00632 was negatively related to rhinorrhea score (P = 0.019), itching score (P = 0.008), sneezing score (P = 0.004), and total nasal symptom score (TNSS) (P ˂ 0.001), but no correlation between LINC00632 and congestion score was observed (P = 0.093). During treatment, LINC00632 was elevated, while TNSS score was reduced (both P ˂ 0.001). Furthermore, LINC00632 increment was associated with the reduction of TNSS score during the therapy (P = 0.005). Conclusion: LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response during 4-week therapy in AR patients (AU)

Correlation between B-cell lymphoma 6 with the balance of T helper-1/2 and severity of allergic rhinitis

Objective: Allergic rhinitis (AR) is a prevailing immune disorder affecting the nasal mucosa. B-cell lymphoma 6 (BCL6) imposes essential roles in immunity. This study probed into the serum expression of BCL6 and its effect on AR diagnosis and patients’ quality of life (QOL). Methods: A total of 113 patients with AR including 38 cases with mild AR (MAR) and 75 cases with moderate-severe AR (MSAR) were enrolled, with 101 healthy people enrolled as control. Serum expression of BCL6 was detected by RT-qPCR and the diagnostic efficacy of BCL6 for AR was analyzed using the receiver operating characteristic curve. The proportion of T helper-1/2 (Th1/Th2) cells in CD4+ T cells in peripheral blood mononuclear cells was detected using flow cytometry. The correlation between BCL6 and Th1/Th2 cells and the effects of BCL6 expression on patients’ QOL were assessed by Pearson analysis and Mini-RQLQ questionnaire. Results: BCL6 was downregulated in patients with AR, serum BCL6 level < 0.8450 had certain auxiliary diagnostic values for AR, and serum BCL6 level < 0.5400 could assist the diagnosis of AR severity. Th1 cell proportion in CD4+ T cells was decreased, whereas Th2 cell proportion was increased with AR severity. BCL6 was positively-linked with Th1 cells but inversely-correlated with Th2 cells in patients with AR. Patients with AR with low BCL6 expression had a poorer QOL compared with high BCL6 expression. The domains most affected by BCL6 expression were practical problems, nasal symptoms, and lacrimation. Conclusion: Serum BCL6 is downregulated and low BCL6 expression greatly deteriorates QOL in patients with AR (AU)

Roles of regulatory B cells in the pathogenesis of allergic rhinitis

Allergic rhinitis (AR) is a common otolaryngologic disease with frequent episodes of sneezing, clear nasal discharge flow and nasal congestion. The mechanisms of AR are complex and considered generally caused by the immune tolerance deficiency. Regulatory B cells (Bregs) are immunosuppressive cells that can modulate immune responses by the secretion of IL-10, IL-35, and tumor growth factor-β (TGF-β) and via the interaction of membrane surface molecules. However, Bregs are numerically deficient and/or dysfunctional in airway allergic diseases such as AR and allergic asthma, and the related mechanisms remain unclear. In this review, we summarize the role of Bregs in AR pathogenesis and highlight the importance of Bregs in maintaining immune tolerance. It is believed that further research on Bregs will contribute to developing new treatments and finding specific biomarkers that could help to predict disease progression (AU)

Conditioned medium from the bone marrow mesenchymal stem cells modulates immune response via signal transduction and activator of transcription 6 signaling pathway in an allergic rhinitis mouse model

Background: Allergic rhinitis (AR) is a common immune disease of the nasal mucosa character-ized with immunoglobulin E (IgE)-mediated allergic inflammation after exposure to allergens in susceptible population. Previous reports have demonstrated that the bone marrow mesenchy-mal stem cells (BMSCs) could reduce allergic inflammation. However, there is little knowledge about whether the culture supernatant of BMSCs (conditioned medium, CM) has similar anti-inflammatory potential in treating AR. Objective: The study aimed to evaluate the immunoregulatory effects of conditioned medium derived from BMSCs (BMSC-CM) on allergic inflammation in an AR mouse model.Material and Methods: The AR murine model was induced by repeated sensitization and chal-lenges with ovalbumin (OVA). Subsequently the allergic symptoms of AR mice, cytokine levels, the histopathological features of the nasal mucosa and T helper 1 (Th1) : T helper 2 (Th2) cells ratio were evaluated.Results: Treatment with BMSC-CM was found as effective as BMSCs in reducing allergic symp-toms and inhibiting eosinophilic infiltration in the nasal mucosa. After BMSC-CM or BMSCs administration, the OVA-specific IgE and interleukin 4 levels in serum decreased and interferon gamma level increased compared with AR mice treated with uncultured fresh medium. Flow cytometry analysis revealed a decrease in Th1:Th2 cells ratio after OVA-sensitization and the ratio was reversed by BMSC-CM and BMSCs treatments. Furthermore, the data revealed that BMSC-CM suppressed the production of signal transduction and activator of transcription 6 (STAT6) at messenger RNA and protein levels in the nasal mucosa (AU)

lncRNA FR215775 Regulates Th2 Differentiation in Murine Allergic Rhinitis.

To identify the effect of long noncoding RNA (lncRNA) FR215775 in regulating CD4+ T cells on murine models of allergic rhinitis (AR), the expression of lncRNA FR215775 in primary Th2 cells was detected through qRT-PCR. After knocking down the expression of lncRNA FR215775 via Sh-FR215775-Ads, Cell Counting Kit-8, cytometric bead array, and fluorescence-activated cell sorting were performed to determine its functions in vitro. Moreover, lncRNA FR215775-silencing or nonsilencing cells were injected intravenously into AR mice. Then, hematoxylin and eosin, Alcian blue-periodic acid Schiff, and toluidine blue staining were performed, and the levels of IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, IFN-γ, and TNF in the AR mice were also determined. We found that the expression of lncRNA FR215775 was specifically higher in the murine primary Th2 cells. After the knockdown of lncRNA FR215775, the proliferation of CD4+ T cells was inhibited, and the expressions of IL-4 and IL-5 in the cell culture supernatant were significantly decreased (P < 0.001), along with the percentage of Th2 cells (P < 0.05). The lncRNA FR215775-silencing AR group showed less serious allergic symptoms and a low level of ovalbumin-specific immunoglobulin E (P < 0.01). Meanwhile, the eosinophilia inflammation, goblet cell hyperplasia, and mast cell inflammation in the nasal mucosa all decreased, which indicated attenuated allergic inflammation in the lncRNA FR215775-silencing AR group. In addition, the Th2-related cytokines IL-4 and IL-5 were downregulated in the serum and nasal lavage fluid of this group (P < 0.01). In conclusion, lncRNA FR215775 may play a vital role in the function and differentiation of Th2 cells, which may encourage allergic inflammation. These results may provide significant insights into AR pathogenesis and offer new treatment targets for alleviating AR.

Successful Elosulfase Alfa Desensitization Protocol in a Patient With Morquio A Syndrome.

Patients with lysosomal storage diseases may require modifications to standard drug desensitization protocols; personalized medicine as well as development of new treatment options are needed.