Allergic Rhinitis and House Dust Mite Sensitization Determine Persistence of Asthma in Children

Objective To specify clinical and immunological parameters of the mechanisms, which may lead to development of persistent asthma, or regression of the disease symptoms. Methods Eighty children with childhood asthma, diagnosed in the past by using the modifed Asthma Predicted Index (mAPI), were divided into two groups: remission group and persistent group. There were 3 study visits (baseline, at 6 mo, and at 12 mo). Clinical remission of asthma was defned as the absence of asthma symptoms for at least 12 mo without treatment. The patients could switch from one group to another during the 12 mo of follow-up. Clinical, infammatory, and immunoregulatory predictors of asthma remission/persistence were analyzed. Results The presence of mAPI criteria as well as house dust mite (HDM) allergy and allergic rhinitis at 7–10 y, were associated with a reduced prevalence of asthma remission. The increased eosinophil blood count in mAPI criteria was associated with a lower expression of CD25 positive cells. HDM allergy was associated with a higher fractional exhaled nitric oxide (FeNO) level (p=0.0061) and higher expression of CD25CD71 (p=0.0232). Allergic rhinitis was associated with a higher expression of PPAR (p=0.0493) and CD25CD71 (p=0.0198), and lower expression of glycoprotein A repetitions predominant (GARP). Conclusions Persistence of childhood asthma was largely determined by the presence of allergic rhinitis and sensitization to HDM. Additionally, API criteria but not immunoregulation processes, were related to asthma persistence.

Experimental study of irisin alleviates house dust mite-induced airway epithelial cells inflammation and apoptosis via the NF-κB and JNK signaling pathways / 中国临床药理学与治疗学

AlM: To explore the effects of irisin on house dust mite (HDM)-induced inflammation and apoptosis in human airway epithelial cells. METHODS: The human bronchial epithelial cell (16HBE) were cultured with in RPMI1640 culture medium with 10% of fetal bovine serum. After cells reached 85% confluence, the medium was replaced with serum-free culture medium for 12 h. Then the 16HBE cells were treated with various concentrations of HDM (0, 400, 800, 12 00 U/mL) for 24 h. Reactive oxygen species assay kit was used to detected the intracellular ROS generation. And qPCR was used to measure the interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α) mRNA expression of the HDM-induced 16HBE cell. The cells were pre-treated with or without irisin for 2 h before exposure to various concentration of HDM for 24 h. Then reactive oxygen species assay kit was used to detected the intracellular ROS generation. The IL-6, TNF-α mRNA expression of 16HBE cell were measured by qPCR. Meanwhile, the phosphorylated and total P65 NF-κB and JNK proteins were detected by western blot. The pro-apoptosis protein cleaved-caspase3BAX and the anti-apoptosis protein were also detected by western blot. RESULTS: The quantitative assay showed that intracellular ROS in different concentrations of HDM stimulus group were obviously higher than NC group (P < 0.05). And RT-PCR analysis showed a higher expression level of pro-inflammatory cytokine TNF-α and IL-6 mRNA in different concentrations of HDM than in NC group (P < 0.05). Compared with the HDM group, Irisin significantly decreased the level of intracellular ROS of the 16HBE cells (P < 0.05). The released of the pro-inflammatory cytokine TNF-α and IL-6 mRNA was also decreased in irisin treated 16HBE cells (P < 0.05). And compared with control group, BCL-XL anti-apoptosis protein level was decreased and BAX and c-caspase3 pro-apoptosis protein levels were increased in HDM group (P < 0.05), irisin intervention significantly increased the level of BCL-XL and decreased the levels of BAX and cleaved-caspase 3 (P < 0.05). Compared the control group, phosphorylated P65 NF-κB and JNK protein levels were significantly increased after HDM stimulated (P < 0.05), and irisin intervention decreased the protein levels of phosphorylated P65 NF-κB and JNK (P < 0.05). CONCLUSlON: Irisin can effectively improve the inflammation and apoptosis of HDM-induced 16HBE cells, and this protective effect may be related to its inhibition of NF-κB and JNK MAPK signaling pathways. Irisin may be a potential drug for treating lung inflammation.

HSP90α exacerbates house dust mite-induced asthmatic airway inflammation by upregulating endoplasmic reticulum stress in bronchial epithelial cells / 南方医科大学学报

OBJECTIVE@#To explore the role of heat shock protein 90α (HSP90α) and endoplasmic reticulum (ER) stress pathway in allergic airway inflammation induced by house dust mite (HDM) in bronchial epithelial cells.@*METHODS@#A HDM- induced asthmatic cell model was established in human bronchial epithelial (HBE) cells by exposure to a concentration gradient (200, 400 and 800 U/mL) of HDM for 24 h. To test the effect of siHSP90α and HSP90 inhibitor 17-AAG on HDM-induced asthmatic inflammation, HBE cells were transfected with siHSP90α (50 nmol, 12 h) or pretreated with 17-AAG (900 nmol, 6 h) prior to HDM exposure (800 U/mL) for 24 h, and the changes in the expression of HSP90α and ER stress markers were assessed. We also tested the effect of nasal drip of 17-AAG, HDM, or their combination on airway inflammation and ER stress in C57BL/6 mice.@*RESULTS@#In HBE cells, HDM exposure significantly up-regulated the expression of HSP90α protein (P=0.011) and ER stress markers XBP-1 (P=0.044), ATF-6α (P=0.030) and GRP-78 (P=0.027). Knocking down HSP90α and treatment with 17-AAG both significantly inhibited HDM-induced upregulation of XBP-1 (P=0.008). In C57BL/6 mice, treatment with 17-AAG obviously improved HDM-induced airway inflammation and significantly reduced the number of inflammatory cells in the airway (P=0.014) and lowered the levels of IL-4 (P=0.030) and IL-5 (P=0.035) in alveolar lavage fluid. Immunohistochemical staining showed that the expressions of XBP-1 and GRP-78 in airway epithelial cells decreased significantly after the treatment of 17-AAG.@*CONCLUSIONS@#HSP90α promotes HDM-induced airway allergic inflammation possibly by upregulating ER stress pathway in bronchial epithelial cells.

Comparative study on establishing an immune tolerance model for allergic conjunctivitis in mice with different methods / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To establish an immune tolerance model for allergic conjunctivitis in newborn mice with different methods and observe the impact of environmental factors on allergic conjunctivitis in early life.METHOD: A total of 50 Balb/c newborn mice were randomly divided into blank control group, ovalbumin(OVA)+subcutaneous injection group, OVA+nebulized inhalation group, OVA+gastric group, ragweed pollen(RW)+subcutaneous injection group, RW+nebulized inhalation group, RW+gastric group, house dust mite(HDM)+subcutaneous injection group, HDM+nebulized inhalation group, HDM+intragastric group(n=5 animals/group). Except for the blank control group, mice in each group were individually exposed to the corresponding antigens to induce immune tolerance early in life and stimulated with the corresponding antigens in adulthood. The ocular surface was visualized by anterior segment photography. The relative expression level of conjunctival RANTES and IL-17 mRNA was measured by RT-qPCR and serum IL-17 concentration was measured by ELISA.RESULTS: Compared with the blank control group, the relative expression level of conjunctiva IL-17 mRNA in RW+gastric group was the highest, and it was the lowest in RW+subcutaneous group(all P&#x003C;0.05). The relative expression level of conjunctiva RANTES mRNA was the highest in RW+gastric group(P&#x003C;0.001). Compared with the blank control group, the serum concentration of IL-17 was increased in all treatment groups except OVA+nebulizer group and RW+subcutaneous group(P&#x003C;0.05).CONCLUSION: The immune tolerance of allergic conjunctivitis induced by subcutaneous injection of antigen was the most suitable method in the early life of mice.

Epithelial PI3K-δ Promotes House Dust Mite-Induced Allergic Asthma in NLRP3 Inflammasome-Dependent and -Independent Manners

PURPOSE: Phosphoinositide 3-kinase (PI3K)-δ-dependent Akt activation is known to play critical roles in various immune responses of white blood cells in which PI3K-δ isoform is mostly expressed in contrast to the classes IA PI3Ks p110α and p110β. However, the immunological role of PI3K-δ isoform is still controversial in airway epithelium under house dust mite (HDM)-induced allergic response. This study aimed to evaluate the role of PI3K-δ isoform in HDM-induced allergic responses, focusing on NLRP3 inflammasome activation in airway epithelium.METHODS: We used wild-type mice and PI3K-δ knock-out (KO) mice for HDM-induced asthma animal model and also performed in vitro experiments using primary cultured murine tracheal epithelial cells and human airway epithelial cells.RESULTS: PI3K-δ activated HDM-induced NLRP3 inflammasome and epithelial cell-derived cytokines in the lung including airway epithelial cells. PI3K-δ KO mice or knock-down of PI3K-δ using siRNA exhibited the significant reduction in allergic asthmatic features and the suppression of NLRP3 inflammasome assembly as well as epithelial cell-derived cytokines. Interestingly, significantly increased expression of PI3K-δ isoform was observed in stimulated airway epithelial cells and the increases in epithelial cell-derived cytokines were markedly suppressed by blocking PI3K-δ, while these cytokine levels were independent of NLRP3 inflammasome activation.CONCLUSIONS: The results of this study suggest that PI3K-δ-isoform can promote HDM-induced allergic airway inflammation via NLRP3 inflammasome-dependent response as well as via NLRP3 inflammasome-independent epithelial cell activation.

Dynamic changes in peripheral type Ⅱ innate lymphoid cell (ILC2) subpopulation and its clinical significance in children with hay fever during the pollen season / 中华微生物学和免疫学杂志

Objective@#To analyze the dynamic changes in the expression and function of peripheral type Ⅱ innate lymphoid cell (ILC2) subpopulation and the activity of signal transducers and activators of transcription (STAT6) in children with hay fever during pollen season.@*Methods@#A total of 10 patients with hay fever, 10 patients with house dust mite (HDM)-sensitized asthma and 12 healthy controls (HC) were enrolled in this study. Changes in peripheral ILC2 and the intracellular expression of Th2-related cytokines were detected by flow cytometry during and outside the pollen season. Peripheral Lin- cell population was isolated from each group and cultured with the presence of IL-25 or IL-33 for 7 d. The concentrations of IL-5 and IL-13 in culture supernatants were measured by ELISA. Expression of phospho-STAT6 at protein level was quantified by Western blot.@*Results@#Within the pollen season, the percentage of peripheral ILC2 cells was significantly higher in children with hay fever [(23.09±7.86)%] than in children with HDM-sensitized asthma [(6.84±3.85)%, P<0.05] and healthy children[(1.69±0.87)%, P<0.05]. In the non-pollen season, the peripheral ILC2 cells in children with hay fever presented a decreasing trend [(11.30±2.45)%], but was still higher than that in HDM-sensitized asthmatics [(3.76±1.96)%, P<0.05] and HC [(1.32±0.91)%, P<0.05] at the same time point. Moreover, peripheral IL-13+ ILC2 cells in children with hay fever [(6.94±3.16)% vs(4.17±1.98)%, P<0.05] and in HDM-sensitized asthmatics [(1.89±0.70)% vs(1.44±0.55)%, P<0.05] during the pollen season were significantly higher than those in the non-pollen season. After the in vitro stimulation with IL25 or IL-33, the levels of IL-5 and IL-13 in culture supernatants were both increased in children with hay fever and HDM-sensitized asthmatics, and a synergistic action was observed when IL25 and IL-33 were used in combination. Meanwhile, the protein level of phospho-STAT4 in Lin- cells was significantly up-regulated in the hay fever group after stimulation with IL25 and IL-33.@*Conclusions@#During the pollen season, the abnormal number and function of ILC2 subpopulation in children with hay fever might be another cause of the occurrence of clinical symptoms in a short period of time or acute exacerbation.

Dynamic changes in peripheral type Ⅱ innate lymphoid cell ( ILC2 ) subpopulation and its clinical significance in children with hay fever during the pollen season / 中华微生物学和免疫学杂志

Objective To analyze the dynamic changes in the expression and function of peripher-al typeⅡinnate lymphoid cell (ILC2) subpopulation and the activity of signal transducers and activators of transcription (STAT6) in children with hay fever during pollen season. Methods A total of 10 patients with hay fever, 10 patients with house dust mite ( HDM)-sensitized asthma and 12 healthy controls ( HC) were enrolled in this study. Changes in peripheral ILC2 and the intracellular expression of Th2-related cyto-kines were detected by flow cytometry during and outside the pollen season. Peripheral Lin- cell population was isolated from each group and cultured with the presence of IL-25 or IL-33 for 7 d. The concentrations of IL-5 and IL-13 in culture supernatants were measured by ELISA. Expression of phospho-STAT6 at protein level was quantified by Western blot. Results Within the pollen season, the percentage of peripheral ILC2 cells was significantly higher in children with hay fever [(23. 09±7. 86)％] than in children with HDM-sen-sitized asthma [(6. 84±3. 85)％, P<0. 05] and healthy children[(1. 69±0. 87)％, P<0. 05]. In the non-pollen season, the peripheral ILC2 cells in children with hay fever presented a decreasing trend [(11. 30±2. 45)％], but was still higher than that in HDM-sensitized asthmatics [(3. 76±1. 96)％, P<0. 05] and HC [(1. 32±0. 91)％, P<0. 05] at the same time point. Moreover, peripheral IL-13+ILC2 cells in children with hay fever [(6. 94±3. 16)％ vs(4. 17±1. 98)％, P<0. 05] and in HDM-sensitized asthmatics [(1. 89 ±0. 70)％ vs(1. 44±0. 55)％, P<0. 05] during the pollen season were significantly higher than those in the non-pollen season. After the in vitro stimulation with IL25 or IL-33, the levels of IL-5 and IL-13 in culture supernatants were both increased in children with hay fever and HDM-sensitized asthmatics, and a synergis-tic action was observed when IL25 and IL-33 were used in combination. Meanwhile, the protein level of phospho-STAT4 in Lin-cells was significantly up-regulated in the hay fever group after stimulation with IL25 and IL-33. Conclusions During the pollen season, the abnormal number and function of ILC2 subpopula-tion in children with hay fever might be another cause of the occurrence of clinical symptoms in a short period of time or acute exacerbation.

Oral exposure to lead for Japanese children and pregnant women, estimated using duplicate food portions and house dust analyses

BACKGROUND@#Lead is a toxic metal abundant in the environment. Consumption of food contaminated at low levels of lead, especially by small children and pregnant women, raises a health concern.@*METHODS@#Duplicated food portions and drinking water were collected over 3 days from 88 children and 87 pregnant women in Shimotsuke, Tochigi, Japan. Participants were recruited in this study between January 2014 and October 2015. Dust was also collected from their homes. Lead concentrations were measured and consequent oral lead exposure levels were estimated for this population at high risk to environmental toxicants. Lead concentrations of peripheral and cord blood, taken from children and pregnant women, and were also analyzed.@*RESULTS@#Lead concentrations in food, drinking water, and house dust were low in general. Oral lead exposure to lead was higher for children (Mean ± SEM; 5.21 ± 0.30 μg/kg BW/week) than in pregnant women (1.47 ± 0.13 μg/kg BW/week). Food and house dust were main sources of lead contamination, but the contribution of house dust widely varied. Means ± SEM of peripheral and cord blood lead concentrations were 0.69 ± 0.04 μg/dL and 0.54 ± 0.05 μg/dL, respectively for pregnant women and 1.30 ± 0.07 μg/dL (peripheral only) in children. We detect no correlation between smoking situations and blood lead concentration in pregnant women.@*CONCLUSION@#We conclude that oral lead exposure levels for Japanese children and pregnant women were generally low, with higher concentrations and exposure for children than for pregnant women. More efforts are necessary to clarify the sources of lead contamination and reduce lead exposure of the population at high risk even in Japan.

Effects of Vacuuming Mattresses on Allergic Rhinitis Symptoms in Children

PURPOSE: To evaluate the effects of daily vacuuming of mattresses on the concentration of house dust mite (HDM) allergens and on allergic rhinitis (AR) symptoms in children sensitized to HDM. METHODS: Forty children between the ages of 6 and 12 years with mild persistent AR and sensitized only to HDM were enrolled and randomly allocated to 2 groups. Caregivers of children in the experimental group cleaned the children's rooms and vacuumed their mattresses daily for 2 weeks. Caregivers of children in the control group cleaned the children's rooms without vacuuming mattresses. Symptoms of AR were checked weekly and dust samples were collected from the mattresses before and after the study. RESULTS: Demographics at the beginning of the study were not significantly different between the 2 groups. In the experimental group, symptoms of AR and dust weight were significantly decreased after 2 weeks (total symptoms of AR, P <0.001; sneezing, P < 0.001; rhinorrhea, P <0.001; nasal obstruction, P < 0.001; itching, P <0.001; and dust weight, P = 0.006). The concentrations of HDM allergens were not changed significantly (Der p1, P = 0.333; Der f1, P = 0.841). In the control group, there were no significant changes in symptoms of AR, dust weight, or the concentration of HDM allergens. CONCLUSIONS: Our findings showed that daily vacuuming of mattresses reduced dust weight and symptoms of AR. However, the concentration of HDM allergens did not significantly decrease.

House Dust Mite Allergy Under Changing Environments

Environmental variations induced by industrialization and climate change partially explain the increase in prevalence and severity of allergic disease. One possible mechanism is the increase in allergen production leading to more exposure and sensitization in susceptible individuals. House dust mites (HDMs) are important sources of allergens inducing asthma and rhinitis, and experimentally they have been demonstrated to be very sensitive to microenvironment modifications; therefore, global or regional changes in temperature, humidity, air pollution or other environmental conditions could modify natural HDM growth, survival and allergen production. There is evidence that sensitization to HDMs has increased in some regions of the world, especially in the subtropical and tropical areas; however, the relationship of this increase with environmental changes is not so clear as has reported for pollen allergens. In this review, we address this point and explore the effects of current and predicted environmental changes on HDM growth, survival and allergen production, which could lead to immunoglobulin E (IgE) sensitization and allergic disease prevalence. We also assess the role of adjuvants of IgE responses, such as air pollution and helminth infections, and discuss the genetic and epigenetic aspects that could influence the adaptive process of humans to drastic and relatively recent environmental changes we are experiencing.

Comparison of Long-term Efficacy of Subcutaneous Immunotherapy in Pediatric and Adult Patients With Allergic Rhinitis

PURPOSE: Data comparing the long-term efficacy and safety of subcutaneous immunotherapy (SCIT) using house dust mite (HDM) in children and adults with allergic rhinitis (AR) are limited. This study aimed to compare the long-term effects of HDM-SCIT in a cohort of Chinese pediatric and adult patients with AR. METHODS: A total of 124 pediatric and adult AR patients received HDM-SCIT for 3 years, with 118 patients being followed-up for 2 years. Prior to treatment (baseline), at the end of the 3-year treatment periods (third year) and 2 years after the discontinuation of treatment (fifth year), all patients were evaluated for total nasal symptom scores (TNSS), daily medication score (DMS), total combined score (TCS; symptoms [nasal + ocular] + DMS) and quality of life (QoL). Safety was assessed according to adverse events reported. RESULTS: After 3-year treatment, HDM-SCIT significantly improved symptoms and QoL scores at the end of the third and fifth years in both groups. Better improvements were observed in the third and fifth years based on baseline, in children compared to adults (TNSSΔ3: 6.66 vs. 5.41, P = 0.011; TCSΔ3: 4.30 vs. 3.83, P = 0.027 and TNSSΔ5: 6.16 vs. 4.86, P = 0.037; TCSΔ5: 4.11 vs. 3.62, P = 0.044).Shorter duration of AR history before SCIT (<10 vs. ≥10 years) resulted in better improvements at the end of the third and fifth years (TCSΔ3: 4.12 vs. 3.13, P = 0.036; TCSΔ5: 3.90 vs. 3.09, P = 0.033). HDM-SCIT was safe and comparable in both children and adults with AR. CONCLUSIONS: Children with AR may achieve better long-term efficacy of HDM-SCIT than adults with AR.

Effect of Lyn on expression of MUC5AC in human bronchial epithelial cells induced by house dust mite and its mechanism / 吉林大学学报(医学版)

Objective: To investigate the effect of Lyn on the expression of MUC5AC in human bronchial epithelial cells induced by house dust mite (HDM), and to explore its possible mechanism. Methods: The human bronchial epithelial cells 16HBE) were divided into PBS group and HDM group 1 μg · L-1 HDM). The cells were transfected by liposome. The luciferase report gene of MUC5AC promoter was constructed. The relative luciferase unit (RLU) was detected by double luciferase report gene assay. The expression of MUC5AC in the cells was detected by immunofluorescence technique and observed by confocal microscope. The expression level of STAT6 in the 16HBE cells was detected by Western blotting method. Results: The results of double luciferase report gene assay showed that the RLU in HDM group was higher than that in PBS group (P<0.05). The RLU of cells in HDM group treated with LynsiRNA intervention was higher than that of the cells without LynsiRNA intervention (P<0.05). The immunofluorescence results demonstrated that the expression level of MUC5AC in HDM group was higher than that in PBS group (P<0.05), and the expression level of MUC5AC in HDM group was increased after LynsiRNA intervention (P<0.05). The Western blotting results indicated that the expression level of STAT6 was up-regulated in HDM group when the cells were intervened with LynsiRNA (P<0.05). Conclusion: Deficiency of Lyn can increase the expression of MUC5AC in the human bronchial epithelial cells, and its mechanism may be related to regulating the STAT6 signal pathway by Lyn.

Housedustmite Allergy as the Cause of Eosinophilic Collitis: A Case Report

@#There are only few cases of Eosinophilic Collitis(EC) have been reported worldwide. The mechanism and aetiology of EC are still unclear. We describe a 35 years old man presented with chief complaints of gastrointestinal symptoms. In blood examination, his total IgE and specific IgE to house dust mites were very high. Colonoscopy was done and histological examination from biopsy specimens reported infiltration of lymphoplasmacytic cells and eosinophils, compatible with Eosinophilic colitis. The patient was treated with antihistamine and short course of antibiotics. He was been advised to avoid house dust mites. He was then remained asymptomatic. Our report suggests house dust mites allergy as the causes of EC. Combination of antihistamine, antibiotics and avoidance of house dust mites are helpful in treating EC in this particular case.

Changes in basophil activation during immunotherapy with house dust mite and mugwort in patients with allergic rhinitis

BACKGROUND: The basophil activation test (BAT) is a promising tool for monitoring allergen-specific immunotherapy responses. OBJECTIVE: We aimed to investigate the changes in basophil activation in response to the inhalant allergens of house dust mite (HDM) and mugwort pollen during immunotherapy in patients with allergic rhinitis. METHODS: We enrolled patients with allergic rhinitis who were to receive subcutaneous immunotherapy for the inhalant allergens HDM or mugwort. A BAT was performed to assess CD63 upregulation in response to allergen stimulation using peripheral blood collected from the patients prior to immunotherapy and at 3, 6, 12, and 24 months after beginning immunotherapy. Rhinitis symptoms were evaluated using the rhinitis quality of life questionnaire (RQLQ) at 1-year intervals. RESULTS: Seventeen patients (10 with HDM sensitivity, 3 with mugwort sensitivity, and 4 with sensitivity to both HDM and mugwort) were enrolled in the study. Basophil reactivity to HDM did not change significantly during 24 months of immunotherapy. However, a significant reduction in basophil reactivity to mugwort was observed at 24-month follow-up. There was no significant association between the change in clinical symptoms by RQLQ and the change in basophil reactivity to either allergen. The change in allergen-specific basophil reactivity to HDM was well correlated with the change in nonspecific basophil activation induced by anti-FcεRI antibody, although basophil reactivity to anti-FcεRI antibody was not significantly reduced during immunotherapy. CONCLUSION: Suppression of CD63 upregulation in the BAT was only observed with mugwort at 2-year follow-up. However, the basophil response did not reflect the clinical response to immunotherapy.

Effect of Lyn on expression of MUC5AC in human bronchial epithelial cells induced by house dust mite and its mechanism / 吉林大学学报(医学版)

Objective:To investigate the effect of Lyn on the expression of MUC5AC in human bronchial epithelial cells induced by house dust mite(HDM),and to explore its possible mechanism.Methods:The human bronchial epithelial cells(16 HBE)were divided into PBS group and HDM group(1 μg·L-1HDM).The cells were transfected by liposome.The luciferase report gene of MUC5AC promoter was constructed.The relative luciferase unit(RLU)was detected by double luciferase report gene assay.The expression of MUC5AC in the cells was detected by immunofluorescence technique and observed by confocal microscope.The expression level of STAT6 in the 16HBE cells was detected by Western blotting method.Results:The results of double luciferase report gene assay showed that the RLU in HDM group was higher than that in PBS group(P<0.05).The RLU of cells in HDM group treated with LynsiRNA intervention was higher than that of the cells without LynsiRNA intervention(P<0.05).The immunofluorescence results demonstrated that the expression level of MUC5AC in HDM group was higher than that in PBS group(P<0.05),and the expression level of MUC5AC in HDM group was increased after LynsiRNA intervention(P<0.05).The Western blotting results indicated that the expression level of STAT6 was up-regulated in HDM group when the cells were intervened with LynsiRNA(P<0.05). Conclusion:Deficiencyof Lyn can increase the expression of MUC5AC in the human bronchial epithelial cells,and its mechanism may be related to regulating the STAT6 signal pathway by Lyn.

Decreased CRTH2 Expression and Response to Allergen Re-stimulation on Innate Lymphoid Cells in Patients With Allergen-Specific Immunotherapy

PURPOSE: Group 2 innate lymphoid cells (ILC2s) have been implicated in the pathogenesis of allergic disease. However, the effect of allergen-specific immunotherapy (AIT) on ILCs remains to be clarified. The aim of this study was to evaluate the levels of ILC subsets in allergic rhinitis (AR) patients in response to house dust mite (HDM)-specific immunotherapy. METHODS: We enrolled 37 AR patients undergoing AIT (16 responders and 11 non-responders) for 2 years, 35 HDM AR patients and 28 healthy subjects. Peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry to identify ILC subsets. Stimulation of ILC2s with recombinant allergen-specific protein was used to determine ILC2's activation (CD69 expression). RESULTS: Responder AIT patients and healthy subjects had a decreased frequency of circulating ILC2s compared to non-responder AIT and AR patients. Conversely, ILC1s from responder AIT patients and healthy subjects showed increased frequency compared to non-responder AIT and AR patients. The frequency of ILC3s natural cytotoxicity receptor (NCR)+ and NCR− in responder AIT patients was significantly lower compared to AR patients and healthy subjects. The ILC1: ILC2 proportion in responder AIT patients was similar to that of healthy subjects. PBMCs from patients who were responders to AIT had a significantly lower expression of the activation marker CD69 on ILC2s in response to allergen re-stimulation compared to AR patients, but no difference compared to non-responder AIT patients and healthy subjects. CONCLUSIONS: We propose that AIT might affect ILC responses. The activation of ILC2s was reduced in AR patients treated with AIT. Our results indicate that a relative ILC1/ILC2 skewed response is a possible key to successful AIT.

Efficacy and Safety of Sublingual Immunotherapy in Elderly Rhinitis Patients Sensitized to House Dust Mites

PURPOSE: This study aims to determine the efficacy and safety of house dust mite (HDM)-sublingual immunotherapy (SLIT) in elderly patients with AR. METHODS: A total of 45 patients aged ≥ 60 years with HDM-induced AR who had ≥ 3 A/H ratio on skin prick test and/or ≥ 0.35 IU/L to both Dermatophagoides farinae and Dermatophagoides pteronyssinus by ImmunoCAP were enrolled in 4 university hospitals. To evaluate additional effects of HDM-SLIT, they were randomized to the SLIT-treated group (n = 30) or control group (n = 15). Rhinoconjunctivitis total symptom score (RTSS), rhinoscopy score, Korean rhinoconjunctivitis quality of life questionnaire, rhinitis control assessment test, asthma control test scores, and adverse reactions, were assessed at the first visit (V1) and after 1 year of treatment (V5); for immunological evaluation, serum levels of HDM-specific immunoglobulin A/IgE/IgG1/IgG4 antibodies and basophil response to HDMs were compared between V1 and V5 in both groups. RESULTS: There were no significant differences in demographics, RTSS, skin reactivity to HDMs, or serum total/specific IgE levels to HDMs (P < 0.05, respectively) between the 2 groups. Nasal symptom score and RTSS decreased significantly at year 1 in the 2 groups (P < 0.05). There were no significant differences in percent decrease in nasal symptom score and RTSS at year 1 between the 2 groups (P < 0.05); however, rhinoscopic nasal symptom score decreased significantly in the SLIT-treated group (P < 0.05). Immunological studies showed that serum specific IgA levels (not specific IgE/IgG) and CD203c expression on basophils decreased significantly at V5 in the SLIT-treated group (P = 0.011 and P = 0.001, respectively), not in the control group. The control group required more medications compared to the treatment group, but there were no differences in adverse reactions. CONCLUSIONS: It is suggested that HDM-SLIT for 1 year could induce symptom improvement and may induce immunomodulation in elderly rhinitis patients.

Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation

PURPOSE: The use of tolerogenic dendritic cells (TolDCs) to control exacerbated immune responses may be a prophylactic and therapeutic option for application in autoimmune and allergic conditions. The objective of this work was to evaluate the effects of TolDC administration in a mouse model of allergic airway inflammation caused by mite extract. METHODS: Mouse bone marrow-derived TolDCs were induced by incubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and dexamethasone, and then characterized by flow cytometry and cytokine production by enzyme-linked immunosorbent assay (ELISA). For the in vivo model of Blomia tropicalis-induced allergy, mice transplanted with antigen-pulsed TolDCs were sensitized intraperitoneally with B. tropicalis mite extract (BtE) adsorbed to aluminium hydroxide. After challenge by nasal administration of BtE, bronchoalveolar lavage fluid (BALF), lungs, spleen and serum were collected for analysis. RESULTS: Induction of TolDCs was efficiently achieved as shown by low expression of major histocompatibility complex (MHC) II, programmed death-ligand (PD-L) 2 and pro-inflammatory cytokine production, and up-regulation of interleukin (IL)-10, upon LPS stimulation in vitro. Transplantation of 1 or 2 doses of BtE-pulsed TolDCs reduced the number of inflammatory cells in BALF and lungs as well as mucus deposition. Moreover, compared to saline-injected controls, TolDC-treated mice showed lower serum levels of anti-BtE immunoglobulin E (IgE) antibodies as well as reduced Gata3 and IL-4 gene expression in the lungs and decreased IFN-γ levels in the supernatant of splenocyte cultures Transplantation of TolDCs increased the percentage of the regulatory T cells in the spleen and the lungs. CONCLUSIONS: Preventive treatment with TolDCs protects against dust mite-induced allergy in a mouse model, reinforcing the use of tolerogenic dendritic cells for the management of allergic conditions.

A Retrospective Study of Clinical Response Predictors in Subcutaneous Allergen Immunotherapy With House Dust Mites for Allergic Rhinitis

PURPOSE: House dust mites (HDM) are major allergens that cause allergic rhinitis (AR). Allergen-specific subcutaneous immunotherapy (SCIT) has been shown to be clinically beneficial in many clinical trials. Such trials, however, are not reflective of all patient populations. The aim of this study was to describe the efficacy and safety of SCIT in routine clinical practice in Korean adults with AR sensitized to HDM. METHODS: We reviewed medical records of 304 patients with AR treated at an allergy clinic of a tertiary hospital using SCIT with aluminum hydroxide-adsorbed allergen extract targeting HDM alone or with pollens for at least 1 year from 2000 to 2012. Patients with asthma were excluded. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Specific immunoglobulin E (IgE) levels to HDM were categorized into 6 classes. RESULTS: The mean time until achieving remission was 4.9±0.1 years, and the cumulative incidence of remission from AR was 76.6%. Severe AR (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.23-0.69; P=0.001), specific IgE levels to HDM ≥17.5 kU/L (OR, 1.85; 95% CI, 1.01-3.37; P=0.045), and duration of immunotherapy ≥3 years (OR, 7.37; 95% CI, 3.50-15.51; P<0.001) were identified as significant predictors of clinical remission during SCIT for patients with AR sensitized to HDM. Overall, 73 patients (24.0%) experienced adverse reactions to SCIT, and only 1 case of anaphylaxis (0.3%) developed. CONCLUSIONS: SCIT with HDM was found to be effective and safe for patients with AR. Specific IgE levels to HDM and a duration of SCIT ≥3 years may be predictors of clinical responses to SCIT in AR patients.

Comparison of Multiple Allergen Simultaneous Test and ImmunoCAP for the Diagnosis of Allergic Rhinitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Specific IgE assays are important in the diagnosis and treatment of allergic rhinitis (AR). Among the diagnostic tests of AR, multiple allergen simultaneous test (MAST) and ImmunoCAP have been frequently used as simple, safe, and economical methods. In this study, we compared the diagnostic outcomes of MAST and ImmunoCAP in patients with AR. SUBJECTS AND METHOD: Seventy-eight patients (52 men, 26 women, mean age 34.5 years: range 6–80 years), who have nasal symptoms of allergy and no clinical factors to influence the test results, underwent routine skin prick test (SPT) and MAST, and ImmunoCAP for eight major allergens. The diagnosis of AR was based on the criteria of SPT. The class 1 responses or more were regarded as positive for both MAST and ImmunoCAP. The agreements, sensitivities, and specificities of MAST and ImmunoCAP were evaluated along with the correlation between the two tests. RESULTS: Total agreement rates of MAST and ImmunoCAP amounted to 91.5 and 92.1%, respectively. The overall sensitivity and specificity of MAST were 73.4 and 95.3%, respectively, and those of ImmunoCAP were 81.4 and 94.5%, respectively. The correlations between MAST and ImmunoCAP showed statistical significance for Dermatophagoides pteronyssinus/Dermatophagoides farinae. CONCLUSION: Our study demonstrated the diagnostic usefulness of both MAST and ImmunoCAP in AR, especially for the most prevalent allergens of house dust mites. Moreover, ImmunoCAP, which showed higher sensitivity than MAST, can be effectively used in rhinology clinics.