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.

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.

Acupuncture at "Die E acupoint" alleviates inflammatory reaction via inhibiting TLR4/MyD88/NF-κB signaling in rats with allergic rhinitis. / 基于Tollæ ·å—ä½“4/é«“æ ·åˆ†åŒ–å› å­88/æ ¸è½¬å½•å› å­κB信号通路探讨针刺"è¶è ­ç©´"æ”¹å–„å˜åº”æ€§é¼»ç‚Žå¤§é¼ å ç–«ç‚Žæ€§ååº”çš„æœºåˆ¶.

OBJECTIVES: To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. METHODS: Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. RESULTS: After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. CONCLUSIONS: Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

Allergen skin test responses in broad U.S. asthma population in those with and without rhinitis.

Background: Asthma and allergic rhinitis are pathologically interlinked conditions. Despite skin testing (ST) being pivotal for evaluating allergic sensitization, U.S. data that date back to 1960s on ST reactivity patterns in subjects with asthma remain sparse. Objective: The purpose of this study was to elucidate seasonal, perennial ST responses, and their relationship with asthma severity, early versus late onset disease, and immunoglobulin E (IgE) levels. Methods: Five hundred patients with asthma were randomly selected from the National Jewish Health electronic medical record over a 3-year span. Demographic, clinical, and allergen ST reactivity data for a battery of seasonal and perennial allergens were procured, including total IgE levels, asthma onset, and severity, by using t-tests, χ² tests, and Analysis of Variance (ANOVA), patterns of reactivity were assessed for overall, seasonal, and perennial allergens in relation to IgE levels, asthma onset, and severity. Results: Of the 500 patients, 398 were analyzed. 63.3% were women, 50.1% had adult-onset asthma, and 86.1% had rhinitis; 75.3% tested positive to one or more allergens, with men demonstrating higher overall (p = 0.039) and perennial (p = 0.035) sensitization. ST reactivity varied based on the presence of rhinitis for seasonal (p = 0.028) but not perennial (p = 0.733) allergens. Asthma severity was not significantly associated with ST reactivity (p > 0.10). ST positivity for perennial (p < 0.001) but not seasonal (p = 0.128) allergens was higher in childhood-onset asthma versus adult-onset asthma despite both groups having a large percentage of reactors. Elevated IgE levels correlated with ST reactivity (p < 0.01). Conclusion: Our study represents a unique comprehensive evaluation of ST reactivity in a U.S. asthma population, which is lacking in the literature, when factoring in asthma onset, severity, and IgE levels. Our findings underscore the importance of allergen sensitization in asthma, regardless of severity, concurrent rhinitis symptoms, or asthma onset, which challenge some of the prevailing assumptions about the relationship between allergen sensitization and asthma onset.

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.

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.

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.

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.

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.

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.

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.

MiR-150-5p regulates the functions of type 2 innate lymphoid cells via the ICAM-1/p38 MAPK axis in allergic rhinitis.

Type 2 innate lymphoid cells (ILC2s) exert an increasingly important influence on the pathological process of allergic rhinitis (AR), which is affected by microRNAs-mediated post-transcriptional regulation. This study aims to investigate the function of miR-150-5p in AR patients and the mouse model of AR. The mouse model of AR was established using the OVA challenge. The expressions of miR-150-5p, ICAM-1, p-p38 and p-GATA-3 were evaluated via RT-qPCR and western blot analysis. The level of ILC2s was examined with flow cytometry. Concentrations of OVA-specific IgE, IL-13 and IL-5 in serum were evaluated using ELISA. Histopathological examination was conducted through H&E staining. The interplay between ICAM-1 and miR-150-5p was determined through the DLR assay. The decreased miR-150-5p expression and increased ICAM-1, p-p38 and p-GATA-3 expressions and ILC2s levels were detected in AR patients and AR mice compared with controls. Treatment with miR-150-5p lentivirus alleviated AR symptoms (sneezing, rubbing, mucosa inflammation, serum type 2 cytokines and OVA-specific IgE) and lowered the ILC2s level in AR mice. MiR-150-5p was found to directly bind to 3'-UTR of ICAM-1 and downregulate ICAM-1 expression, thereby descending the level of p-p38, p-GATA-3 and suppressing ILC2s function to alleviate AR symptoms. Treatment with Lenti-ICAM-1 counteracted these protective effects of miR-150-5p. Upregulation of miR-150-5p repressed the ICAM-1/p38 axis which was vital to ILC2s development and function, thereby alleviating allergic symptoms of AR.

Differential Correlations among Allergy Tests According to Indoor Allergens in Allergic Rhinitis.

OBJECTIVES: Several allergy tests are used for the diagnosis of allergic rhinitis; however, few studies have reported a direct comparison of the skin prick test (SPT), multiple allergen simultaneous test (MAST), and ImmunoCAP according to specific allergens. This study aimed to evaluate the correlations between each test and allergic rhinitis symptoms and to evaluate the correlations of the MAST and ImmunoCAP with the SPT for representative indoor allergens in Korea. METHODS: Electronic medical charts were retrospectively reviewed, and 698 patients with allergic rhinitis who had performed SPT, MAST, and ImmunoCAP were enrolled. Correlations between each allergy test for 4 representative indoor allergens and the symptoms of allergic rhinitis were analyzed. Agreements of the MAST and ImmunoCAP with the SPT were compared according to each allergen. RESULTS: The SPT showed higher correlations with allergic rhinitis symptoms for 4 indoor allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, and dog allergens) than the MAST or ImmunoCAP. In comparison between the MAST and SPT, the least correlation was observed for the dog allergen, whereas between the ImmunoCAP and SPT, the least correlation was observed for the cat allergen. The correlation between the ImmunoCAP and SPT was higher than that between the MAST and SPT for the dog allergen, whereas no significant differences were noted for other allergens. CONCLUSIONS: Overall, the SPT showed a higher correlation with allergic rhinitis symptoms than the MAST or ImmunoCAP for 4 indoor allergens. ImmunoCAP showed similar reactivity to MAST; however, it showed better positivity with dog allergen in patients who were reactive to the allergen in the SPT. Care should be taken while evaluating dog allergen sensitization using the MAST.