Treatment with inhaled formulation of angiotensin-(1-7) reverses inflammation and pulmonary remodeling in a model of chronic asthma

Asthma is characterized by inflammation, pulmonary remodeling and bronchial hyperresponsiveness. We have previously shown that treatment with angiotensin-(1-7) [Ang-(1-7)] promotes resolution of eosinophilic inflammation and prevents chronic allergic lung inflammation. Here, we evaluated the effect of treatment with the inclusion compound of Ang-(1-7) in hydroxypropyl β-cyclodextrin (HPβCD) given by inhalation on pulmonary remodeling in an ovalbumin (OVA)-induced chronic allergic lung inflammation. Mice were sensitized to ovalbumin (OVA; 4 injections over 42 days, 14 days apart) and were challenged 3 times per week, for 4 weeks (days 21–46). After the 2nd week of challenge, mice were treated with Ang-(1-7) by inhalation (4.5 μg of Ang-(1-7) included in 6.9 μg of HPβCD for 14 days, i.e. days 35–48). Mice were killed 72 h after the last challenge and blood, bronchoalveolar lavage fluid (BALF) and lungs were collected. Histology and morphometric analysis were performed in the lung. Metalloproteinase (MMP)-9 and MMP-12 expression and activity, IL-5, CCL11 in the lung and plasma IgE were measured. After 2 weeks of OVA challenge there was an increase in plasma IgE and in inflammatory cells infiltration in the lung of asthmatic mice. Treatment with inhaled administration of Ang-(1-7)/HPβCD for 14 days reduced eosinophils, IL5, CCL11 in the lung and plasma IgE. Treatment of asthmatic mice with Ang-(1-7)/HPβCD by inhalation reversed pulmonary remodeling by reducing collagen deposition and MMP-9 and MMP-12 expression and activity. These results show for the first time that treatment by inhalation with Ang-(1-7) can reverse an installed asthma, inhibiting pulmonary inflammation and remodeling.     

南京地区过敏性紫癜患儿血清过敏原特异性IgE结果分析

目的 回顾性分析南京医科大学附属儿童医院过敏性紫癜(Henoch-Schonlein purpura,HSP)患儿的过敏原检测情况,为临床诊治提供参考。方法 采用德国MEDIWISS过敏原体外检测系统,检测本院最近四年内接诊的1026例HSP患儿的血清过敏原特异性免疫球蛋白E(specific immunoglobulin E,sIgE)的含量。结果 432例HSP患儿血清sIgE检出为阳性,阳性率为42.11%(432/1026),该432例HSP患儿血清过敏原sIgE分布以1~2级为主,学龄组患儿血清过敏原sIgE阳性率占总人数的65.74%(284/432),远高于婴幼儿组(27例)和学龄前组(121例)(F值分别为7.71和4.05,P值均<0.05)。结论 患儿体内sIgE水平不同程度的增高对HSP的诊治具有一定意义。控制患儿与过敏原接触是防治HSP的关键。     

Association between sensitized to food allergens and childhood allergic respiratory diseases in Taiwan

BackgroundSensitization to allergen has long been known to be relate to childhood allergic diseases. Polysensitised children have more severe atopic diseases, whereas allergic rhinitis or asthma children with cosensitized to food and inhalant allergens were under-researched.ObjectiveTo realize the association between sensitization to food allergens and pediatric allergic rhinitis and asthma in Taiwan.MethodsWe included 138 participants with sensitized to allergen as assessed by serum-specific IgE. 87 of 138 participants had allergic rhinitis and 51 participants had asthma. All participants underwent a physical examination and measurement of serum total and specific IgE values. Besides, nasal peak expiratory flow rate (nPEFR) that was performed by the participants with allergic rhinitis and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ). Lung function test and asthma control test (ACT)/child asthma control test (C-ACT) were performed by the participants with asthma.Results39 of 87 allergic rhinitis participants with sensitized to food and inhalant allergens (AR food group), 48 of 87 allergic rhinitis participants with sensitized to inhalant allergen alone (AR inhalant group). The AR food group had significantly lower nPEFR values and higher total IgE values (p < 0.05) compared with the AR inhalant group. The AR food group had higher PRQLQ scores than the AR inhalant group. 24 of 51 asthma participants with sensitized to food and inhalant allergens (Asthma food group), 27 of 51 asthma participants with sensitized to inhalant allergen alone (Asthma inhalant group). The Asthma food group had significantly higher total IgE values (p < 0.05) compared with the Asthma inhalant group. The Asthma food group had lower lung function test values and asthma control test (ACT) scores than the other group.ConclusionsChildren with cosensitized to food and inhalant allergens have more severe clinical symptoms and abnormal laboratory findings. Sensitization to food allergen was more related to pediatric allergic rhinitis than asthma. We may need larger, longer and extended studies to confirm these findings.     

Suppression of immunoglobulin production in human peripheral blood mononuclear cells by monocytes via secretion of heavy-chain ferritin

In vitro antigen stimulation of peripheral blood mononuclear cells (PBMCs) does not induce immunoglobulin (Ig) production. However, pretreatment of PBMCs with l-leucyl-l-leucine methyl ester (LLME) prior to in vitro stimulation removes the suppression of Ig production. In the present study, we attempted to identify the target cells of LLME and determine the mechanisms by which Ig production in PBMCs is suppressed. We found that CD14⁺ monocytes are involved in the suppression of Ig production in PBMCs. Furthermore, we confirmed that heavy-chain ferritin derived from CD14⁺ monocytes suppresses Ig production in PBMCs, possibly through iron sequestration.     

Total IgE plasma levels vary according to gender and age in Brazilian patients with allergic rhinitis

OBJECTIVE:

Allergic rhinitis is a disease that affects the upper airways and causes inflammation of the nasal mucosa and it is mediated by IgE antibodies produced after sensitization to environmental allergens. Previous reports have indicated that this disease affects males more often than females. The objective of this study was to verify whether total IgE plasma levels vary between genders in patients suffering from allergic rhinitis.

METHODS:

A total of 171 adult patients suffering from allergic rhinitis (55 males and 116 females) were enrolled. Total IgE plasma levels were determined using commercial kits, with 140 IU/mL considered as a reference value. The mean total IgE plasma levels were compared according to gender and age.

RESULTS:

The mean age of the overall patient group with allergic rhinitis was 38.4±19.0 years and a significant difference in age was observed between genders (males: 32.2±17.8 years; females: 41.4±18.9 years; p = 0.0027). Additionally, the mean total IgE plasma levels were higher in males (413.0±143.0 IU/mL) than in females (147.9±98.0 IU/mL) (p<0.0001). These differences persisted even when males and females were stratified by age (up to or older than 20 years of age).

CONCLUSIONS:

In conclusion, total IgE plasma levels are higher in young adult males than in females suffering from allergic rhinitis. Evaluating total IgE plasma levels can be useful to identify patients at risk of allergic rhinitis in areas with low industrial pollution.     

特异性异尖线幼虫感染IgE抗体阳性与高危妊娠的相关性分析

【目的】探讨异尖线幼虫感染IgE抗体阳性与高危妊娠的相关性。【方法】选择2017年1月至2019年12月在本院诊治的高危妊娠孕妇738例(观察组),另外选择同期在本院产检健康孕妇500例作为对照组。采集所有孕妇的静脉血,检测其血清特异性异尖线幼虫IgE抗体,并分析孕妇血清IgE抗体阳性的影响因素及与高危妊娘的相关性。【结果】观察组IgE抗体阳性率为24.8%(183/738),显著高于对照组的20.0%(100/500),其差异有统计学意义(P<0.05);IgE阳性组孕妇的平均年龄显著大于IgE阴性组,顺产比例、初产比例显著低于IgE阴性组,产后住院时间显著长于IgE阴性组,妊娠期间检查次数显著少于IgE阴性组。孕妇分娩的新生儿中,IgE阳性组孕妇所产的新生儿体质量、胎龄均显著小于IgE阴性组,新生儿监护病房(NICU)患儿比例显著高于IgE阴性组。高危妊娠是孕妇异尖线幼虫感染IgE抗体阳性的独立危险因素。【结论】高危妊娠是孕妇异尖线幼虫感染IgE抗体阳性的独立危险因素,影响妊娘结局。     

Increased frequency of the immunoglobulin enhancer HS1,2 allele 2 in coeliac disease

Background: Coeliac disease (CD) is characterized by increased immunological responsiveness to ingested gliadin in genetically predisposed individuals. This genetic predisposition is not completely defined. A dysregulation of immunoglobulins (Ig) is present in CD: since antiendomysium antibodies (anti-EMA) are of the IgA class. One polymorphic enhancer within the locus control region (LCR) of the immunoglobulin heavy chain cluster at the 3′ of the C alpha-1 gene was investigated. The correlation of the penetrance of the four different alleles of the HS1,2-A enhancer of the LCR-1 3′ to C alpha-1 in CD patients compared to a control population was analysed. Methods: A total of 115 consecutive CD outpatients, on a gluten-free diet, and 248 healthy donors, age- and sex-matched, from the same geographical area were enrolled in the study. HS1,2-A allele frequencies were investigated by nested polymerase chain reaction (PCR). Results: The frequency of allele 2 of the enhancer HS1,2-A gene was increased by 30.8% as compared to the control frequency. The frequency of homozygosity for allele 2 was significantly increased in CD patients. Crude odds ratio (OR) showed that those with 2/2 and 2/4 (OR 2.63, P?&;lt;?0.001 and OR 2.01, P?=?0.03) have a significantly higher risk of developing the disease. In contrast, allele 1/2 may represent a protective genetic factor against CD (OR 0.52, P?=?0.01). Conclusions: These data provide further evidence of a genetic predisposition in CD. Because of the Ig dysregulation in CD, the enhancer HS1,2-A may be involved in the pathogenesis.     

过敏性紫癜患者中性粒细胞及其IgA Fc受体对血管内皮细胞凋亡的影响及机制

目的 研究中性粒细胞及其IgA Fc受体(CD89)在过敏性紫癜(HSP)发病中的作用和对血管内皮细胞的损伤效应及调控机制.方法 入组30例急性期HSP患儿及9例健康对照儿童,分离外周血中性粒细胞;Jacalin亲和层析分离HSP患者血清IgA后,采用聚丙烯葡聚糖凝胶纯化IgA.实时定量PCR(qPCR)、Western印迹分别检测中性粒细胞CD89 mRNA和蛋白表达,流式细胞仪分析中性粒细胞活化标志分子CD11b的表达.分别将HSP患儿中性粒细胞、健康对照中性粒细胞与血管内皮细胞HUVEC共培养,以HSP患儿血清分离的IgA (HSP IgA)、单体IgA(mIgA)、磷酸盐缓冲液(空白对照组)分别处理,流式细胞仪检测HUVEC细胞凋亡,ELISA检测上清液中白细胞介素8(IL-8)、肿瘤坏死因子α(TNF-α)水平.结果 HSP患儿组中性粒细胞CD89 mRNA表达与健康对照组差异无统计学意义(P=0.98),但蛋白表达(0.60±0.16)低于健康对照组(0.83±0.24,P=0.03).HSP患者中性粒细胞CD11b表达(1 880.25±388.29)显著高于健康对照组(1 109.25±364.25,P＜0.01).与HSP患者中性粒细胞共培养组HUVEC凋亡率(37.44％±5.49％)高于与健康对照中性粒细胞共培养组(17.14％±4.45％,P＜ 0.01).HSP IgA处理组HUVEC凋亡率明显高于mIgA处理组(均P＜0.01)和空白对照组(P＜0.01),且上清液中IL-8、TNF-α浓度明显高于mIgA处理组(均P＜0.01)和空白对照组(P值分别为0.01、0.02).结论 HSP患者外周血中性粒细胞活化,并可诱导血管内皮细胞凋亡.而且HSP IgA能促进中性粒细胞介导的血管内皮细胞凋亡和炎症因子IL-8、TNF-α分泌,而mIgA则可能具有一定抑制效应.