Characteristics of allergen component in dust mite-induced allergic rhinitis patients / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the characteristics of allergen component in dust mite（DM） -induced allergic rhinitis（AR） patients, and provide reference for the diagnosis and treatment of AR. Methods:DM-induced AR patients with or without allergic asthma（AA） who visited the Allergy Department of Tongji Hospital, Huazhong University of Science and Technology between 2021 and 2022 were enrolled. Patients'age, gender, and visual analog scale（VAS） for symptoms were recorded. sIgE and sIgG4 levels of allergen components such as Der f1, Der f2, Der p1, Der p2, Der p7, Der p10, Der p21, and Der p23 were detected using a protein chip method. The sensitization characteristics of the allergen components in the patients were observed, and the correlation between sIgE, sIgG of each component and VAS as well as the component differences between AR and AR with AA（AR&AA） were evaluated. Results:A total of 87 DM-induced AR patients were enrolled, with 42.5% of them were AR&AA, their VAS scores were significantly higher than those of AR patients（6.38±1.95 vs 5.25±1.85, P=0.009 8）. The order of sensitization rates for DM components was as follows: Der p2（82.8%）, Der f2（81.6%）, Der p1（74.7%）, Der f1（70.1%）, and Der p23（35.6%）. The order of positive rates for sIgG4 was: Der p2（21.8%）, Der f2（13.8%）, Der p21（8.0%）, and Der p7（6.9%）. There were no correlation between the sIgE, sIgG4 levels or positive numbers of components and VAS scores, but there were positive correlations between sIgE, sIgG4 concentrations of components. Compared with AR patients, AR&AA patients had higher levels of sIgE for Der p（60.5[7.2-91.1]vs 14.0[4.8-45.1], P=0.02）, Der f（49.8[15.7-81.6]vs 21.3[7.0-50.2], P=0.04）, Der p1（27.2[0.7-51.5]vs 2.6[0.2-24.9], P=0.02）, Der p2（20.0[1.4-60.6]vs 5.5[0.6-19.1], P=0.004）, and Der f2（58.9[16.0-89.2]vs 23.4[0.9-56.8], P=0.009）, and a higher proportion of AR with AA patients had sIgE levels of Der p1（70.3% vs 48.0%, P=0.038） and Der p23（27.0% vs 14.0%, P=0.039） that were ≥3 grades. Conclusion:Der p1/f1, Der p2/f3, and Der p23 are the major components of DM sensitized AR patients. Multiple component sensitization and sIgE, sIgG4 levels of each component are not correlated with the severity of AR. The sIgE levels of the Der p1/f1, Der p2/f3, and Der p23 components in AR&AA patients are higher than AR.

Value of allergen nasal provocation test in assessment of the efficacy of house dust mites specific immunotherapy / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the value of nasal provocation test（NPT） in evaluating the efficacy of allergen immunotherapy（AIT） in patients with dust mite induced allergic rhinitis（AR）. Methods:A total of 83 patients with dust mite induced AR with/without asthma were included. Symptom score（SS）, daily medication score（DMS）, combined symptom and medication score（CSMS）, rhinoconjunctivitis quality of life questionnaire（RQLQ）, NPT and skin prick test（SPT） were assessed before and after 1 year AIT. Results:There were statistical differences in SS（P<0.000 1）, DMS（P<0.000 1）, CSMS（P<0.000 1）, and RQLQ（P<0.000 1） after 1 year of AIT compared with pre-treatment. The effective rate of CSMS was 73.49%, and the effective rate of NPT was 42.17%. CSMS was consistent with NPT in efficacy assessment（Kappa=0.437, P<0.001）; while in 54 patients with pre-treatment NPT concentrations other than the original concentration, CMSM and NPT showed better consistence（Kappa=0.895, P<0.001）. Among the 48 patients with ineffective NPT assessment in the first year, 25 patients completed the second-year follow-up, and 12 patients（48.00%） showed effective in NPT. However, 10 out of 12 patients（83.33%） with NPT concentration other than original solution pre-treatment showed effective NPT at the second year. Conclusion:NPT can be used as one of the indicators for efficacy evaluation for dust mite induced AR patients, especially for patients with positive NPT induced at lower concentrations before treatment.

Inmunogenicidad y capacidad protectora de variantes de la nueva vacuna antialérgica PROLINEM DS / mmunogeni city and protective efficacy of variants of a novel PROLINEM DS anti - allergic vaccine

Introducción: La vacuna antialérgica de segunda generación PROLINEM-DS está compuesta por alérgenos del ácaro Dermatophagoides siboney y la combinación de adyuvantes: proteoliposoma de N. meningitidis B y gel de hidróxido de aluminio. La adsorción del alérgeno es relevante para la seguridad y eficacia clínica de las vacunas adsorbidas en gel de hidróxido de aluminio en estudios previos se demostró la influencia negativa de los iones fosfato en la adsorción del alérgeno. Objetivo: Evaluar la inmunogenicidad y capacidad protectora de cuatro variantes de formulación obtenidas dentro del espacio de diseño de la vacuna PROLINEM DS. Métodos: Se emplearon 4 variantes de formulación con diferentes contenidos de tampón fosfato salino y gel de hidróxido de aluminio. Se administraron a ratones BALB/c 3 dosis subcutáneas una por semana. Luego, los ratones fueron sometidos a reto alergénico por aerosol. Resultados: Todas las variantes indujeron anticuerpos IgG1 e IgG2a alérgeno específico. Este efecto se correlacionó con el balance de citoquinas proinflamatorias Th1/Th2 en los pulmones y en los ganglios. La variante con reducción de tampón fosfato salino y gel de hidróxido de aluminio fue la de mayor índice IgG/IgE después de la vacunación. Esta relación muestra, en una variable, el equilibrio entre los componentes potencialmente bloqueadores y efectores. La tolerancia local en el lugar de la inyección mostró una reducción de los granulomas en los ratones vacunados con menos gel de hidróxido de aluminio. Conclusiones: La reducción del contenido de gel de hidróxido de aluminio y fosfatos se consideran mejoras farmacéuticas sin inconvenientes en cuanto a la inmunogenicidad de esta vacuna con un perfil de seguridad satisfactorio para futuros ensayos clínicos en humanos.

Introduction: The second generation anti allergic vaccine named PROLINEM DS is based on allergens from D. siboney house dust mite and a combination adjuvant containing PL and Alum. Allergen adsorption is relevant both safety and clinical efficacy in alum-adsorbed vaccines. Negative influence of phosphate ions on allergen adsorption was demonstrated in previous researches. Objective: To evaluate immunogenicity and protective efficacy of four variants obtained within design space of PROLINEM DS vaccine. Methods: Four variants were differentiated from each other by both phosphate and alum contents. Balb/c mice were administered with 3 doses by subcutaneous route. Further, mice were subjected to allergen aerosol challenge. Results: Specific IgG1 and IgG2a antibodies were induced by four vaccine variants. It was correlated with pro inflammatory cytokines balance Th1/Th2 both in lungs and lymphatic nodes. Formulation with lower PBS and Alum levels showed the highest IgG/IgE ratio at the end of vaccination schedule. This ratio shows in one variable the balance between potentially blocking and effector components. Mice injected with lower level of Alum showed a reduction of granuloma size in the site of vaccine administration. Conclusion: Decrease both alum and phosphate contents were a pharmaceutical improvement for antiallergic vaccines formulation. Safety and efficacy in this vaccine are crucial for future human clinical trials.

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.

Changes and significance of T follicular regulatory cells/T follicular helper cells and related cytokines in peripheral blood of children with dust mite allergic asthma / 中华实用儿科临床杂志

Objective:To explore the changes of T follicular regulatory (T FR) cells/T follicular helper (T FH) cells and their related cytokines in peripheral blood of children with dust mite allergic asthma, and their clinical significance. Methods:A total of 25 children with acute dust mite allergic asthma (the asthma group) in Affiliated Hospital of Jiangnan University from January to December 2021 and 16 age- and sex-matched healthy volunteers (the healthy control group) at the same time were enrolled in the retrospective study.The percentages of peripheral T FR cells and T FH cells of the 2 groups were measured by flow cytometry.The plasma levels of cytokines[interleukin (IL)-10, IL-21] of the 2 groups were assessed by the flow cytometric microsphere-based array technology.The specific IgE (sIgE) levels of dust mites in 2 groups were detected by fluorescence enzyme immunoassay.The percentage of eosinophils in peripheral blood detected by blood cell analyzer.Data between groups were compared by t-test, and the correlation among indicators was analyzed by Spearman rank correlation analysis. Results:The asthma group had evident T FR cells/T FH cells immune imbalance.Compared with the healthy control group, the asthma group had a significantly lower T FR cells level[(0.11±0.03)% vs.(0.13±0.03)%], a significantly higher T FH cells level[(5.07±1.75)% vs.(3.80 ± 1.60)%], and a significantly lower ratio of T FR cells /T FH cells(0.02±0.01 vs.0.05±0.03) ( t=2.29, 2.30, 3.71; all P<0.05). Compared with the healthy control group, the asthma group had a significantly higher IL-21 level[(547.85±195.13) ng/L vs.(404.94±110.41) ng/L], and a significantly lower IL-10 level[(10.18±3.49) ng/L vs.(14.79±5.65) ng/L] ( t=2.60, 3.15; all P<0.05). The ratio of T FR cells/T FH cells in asthma group was negatively correlated with sIgE ( r=-0.444 2, P=0.026 1), but not related to the eosinophil percentage ( r=-0.135 2, P=0.519 3). Conclusions:Children with dust mite allergic asthma suffer from T FR cells/T FH cells subset imbalance.The imbalanced T FR cells, T FH cells and their related cytokines IL-10 and IL-21 may play a role in regulating the production of asthma sIgE.

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.

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.

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.

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.

Progress in sensitized protein components and subcutaneous specific immunotherapy for dust mites / 国际儿科学杂志

Dust mites are one of the most common inhalant allergens in the world.The prevalence of dust mite allergy is on the rise in the worldwide,it is a chronic worldwide health problem that seriously affects the work,study and daily life of patients.This review demonstrates the allergic diseases caused by dust mite,the sensitized protein components of the dust mite and the research progress of allergen-specific immunotherapy,and the application of anti-IgE monoclonal antibodies to IgE-mediated allergic reactions is also briefly described.

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.

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.

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.

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.

Effects of dust mite immunotherapy on hormonal dosage, specific immunoglobulins G4 level and pulmonary function in children with asthma / 中国医师进修杂志

Objective To study the effects of dust mite immunotherapy on the hormonal dosage, specific immunoglobulins G4(sIgG4)level and pulmonary function in asthmatic children.Methods One hundred and twenty-four cases of asthmatic children were randomly divided into specific immunotherapy treatment(SIT) group (62 cases, treated with the dust mite immunotherapy) and inhaled corticosteroids (ICS) group (62 cases, treated with ICS). The changes of clinical symptoms, serum sIgG4 level, pulmonary function and ICS dosage before and after treatment were compared between two groups. Results After treatment for 12,18,and 24 months, the scores of childhood asthma control test(C-ACT) in SIT group were significantly higher than those in ICS group:(23.84 ± 1.15)scores vs.(22.75 ± 1.08) scores, (24.29 ± 1.27)scores vs.(23.17 ± 1.22)scores, (24.83 ± 1.40)scores vs.(23.88 ± 1.34)scores, there were significant differences (P<0.05). After treatment for 12, 24 months, the level of serum sIgG4 in SIT group were significantly higher than those in ICS group:(308.75 ± 102.96) μg/L vs. (239.64 ± 79.35) μg/L, (542.28 ± 113.37) μg/L vs. (243.65 ± 80.21) μg/L, there were significant differences (P<0.05). After treatment for 12, 24 months, the levels of percentage of forced expiratory volume in 1 second (FEV1%), percentage of maximal expiratory flow rate (PEF%) in SIT group were significantly higher than those in ICS group: FEV1%:(95.82 ± 7.64)% vs. (92.79 ± 8.52)%, (99.52 ± 8.17)% vs.(95.89 ± 7.53)%;PEF%:(95.78 ± 5.85)% vs.(93.54 ± 6.18)%,(99.77 ± 5.69)% vs. (97.61 ± 5.56)%, there were significant differences (P<0.05). After treatment for 12, 24 months, the scores of daytime asthma symptoms scale (DAS) and nocturnal asthma symptoms scale (NAS) in SIT group were significantly lower than those in ICS group:DAS:(1.75 ± 0.54)scores vs.(1.96 ± 0.60)scores, (0.84 ± 0.27) scores vs. (1.19 ± 0.38) scores;NAS: (0.75 ± 0.27) scores vs.(0.92 ± 0.30) scores, (0.55 ± 0.18)scores vs.(0.81 ± 0.24)scores, there were significant differences(P<0.05).After treatment for 12, 24 months, the dosage in SIT group was significantly lower than those in ICS group:(172.08±16.73)μg/d vs.(194.63 ± 14.17)μg/d,(138.09 ± 16.23)μg/d vs.(163.15 ± 15.38)μg/d, there were significant differences(P<0.05).Conclusions Dust mite immunotherapy can effectively improve the clinical symptoms and pulmonary function in children with dust mite allergy asthma and reduce the ICS dosage, it may be related to the increase of protective antibody sIgG4 in children.

Dust mite sublingual immunotherapy in asthmatic children / 国际儿科学杂志

Bronchial asthma is one of the most common chronic inflammatory disorders in children.Pharmacotherapy can effectively control the chronic airway inflammation,improve the lung function,but it is difficult to improve the underlying immune response and natural progression of allergic diseases.Allergen specific immunotherapy can modify the course of allergic disease,reducing the risk of new allergic sensitizations,deterring the development of clinical asthma in children treated for allergic rhinitis and induce specific immune tolerance.The principal types of AIT are subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT).Dust mite is a common type of allergen.Dust mite SLIT has been widely used in clinic due to its effectiveness and safety.

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.