C. Gonczi, Fadi Touma, T. Daigneault, Chelsea Pozzebon, Kelly Burchell-Reyes, P. Darlington
Background
Upon activation, helper T (Th) cells produce cytokines such as IL-17A and IFNγ, which may exacerbate inflammatory disease and disorders. Adrenergic drugs are emerging as immunomodulatory agents to treat pro-inflammatory diseases, but their function is not completely understood. Th Cells express the β2-adrenergic receptor (β2AR) that is encoded by ADRB2. Agonists of the β2AR decrease IFNγ but can increase IL-17A from Th cells. We compared a β2AR agonist to an inverse-agonist, and assessed the influence of ADRB2 polymorphisms on IL-17A and IFNγ responses.
Methods
Peripheral blood mononuclear cells (PBMCs) from venous blood of healthy human participants were cultured with T cell activators anti-CD3 and anti-CD28 antibodies. Terbutaline, a β2AR agonist or nebivolol, a β1AR antagonist and β2AR inverse-agonist, were added in vitro. Cytokines IL-17A and IFNγ were measured using enzyme-linked immunosorbent assay. Genomic ADRB2 and its immediate upstream region were sequenced using Sanger's method. Cytokine response to drug was analyzed based on ADRB2 polymorphisms.
Results
Terbutaline consistently inhibited IFNγ from activated PBMC samples. In contrast, it increased IL-17A in PBMC homozygous for Gly16 codon of ADRB2. Nebivolol inhibited IL-17A and IFNγ from activated Th cells. When applied to activated-PBMCs, nebivolol inhibited IL-17A but did not significantly inhibit IFNγ although a trend was observed. The ability of nebivolol to inhibit IL-17A was attenuated by a β2AR-specific antagonist. Cellular proliferation and viability was not significantly changed by nebivolol. Nebivolol suppressed IL-17A in all of the samples regardless of ADRB2 polymorphisms.
Conclusions
This data demonstrates that terbutaline inhibited IFNγ, however, it increased IL-17A in samples with the common Gly16 polymorphism of ADRB2. Nebivolol inhibited IL-17A regardless of ADRB2 polymorphisms. Thus, nebivolol is a strong candidate for treating inflammatory diseases or disorders where IL-17A exacerbates symptoms.
{"title":"Modulation of IL-17A and IFNγ by β2-adrenergic agonist terbutaline and inverse-agonist nebivolol, influence of ADRB2 polymorphisms","authors":"C. Gonczi, Fadi Touma, T. Daigneault, Chelsea Pozzebon, Kelly Burchell-Reyes, P. Darlington","doi":"10.3934/allergy.2021017","DOIUrl":"https://doi.org/10.3934/allergy.2021017","url":null,"abstract":"<abstract><sec> <title>Background</title> <p>Upon activation, helper T (Th) cells produce cytokines such as IL-17A and IFNγ, which may exacerbate inflammatory disease and disorders. Adrenergic drugs are emerging as immunomodulatory agents to treat pro-inflammatory diseases, but their function is not completely understood. Th Cells express the β2-adrenergic receptor (β2AR) that is encoded by <italic>ADRB2</italic>. Agonists of the β2AR decrease IFNγ but can increase IL-17A from Th cells. We compared a β2AR agonist to an inverse-agonist, and assessed the influence of <italic>ADRB2</italic> polymorphisms on IL-17A and IFNγ responses.</p> </sec><sec> <title>Methods</title> <p>Peripheral blood mononuclear cells (PBMCs) from venous blood of healthy human participants were cultured with T cell activators anti-CD3 and anti-CD28 antibodies. Terbutaline, a β2AR agonist or nebivolol, a β1AR antagonist and β2AR inverse-agonist, were added <italic>in vitro</italic>. Cytokines IL-17A and IFNγ were measured using enzyme-linked immunosorbent assay. Genomic <italic>ADRB2</italic> and its immediate upstream region were sequenced using Sanger's method. Cytokine response to drug was analyzed based on <italic>ADRB2</italic> polymorphisms.</p> </sec><sec> <title>Results</title> <p>Terbutaline consistently inhibited IFNγ from activated PBMC samples. In contrast, it increased IL-17A in PBMC homozygous for Gly16 codon of <italic>ADRB2</italic>. Nebivolol inhibited IL-17A and IFNγ from activated Th cells. When applied to activated-PBMCs, nebivolol inhibited IL-17A but did not significantly inhibit IFNγ although a trend was observed. The ability of nebivolol to inhibit IL-17A was attenuated by a β2AR-specific antagonist. Cellular proliferation and viability was not significantly changed by nebivolol. Nebivolol suppressed IL-17A in all of the samples regardless of <italic>ADRB2</italic> polymorphisms.</p> </sec><sec> <title>Conclusions</title> <p>This data demonstrates that terbutaline inhibited IFNγ, however, it increased IL-17A in samples with the common Gly16 polymorphism of <italic>ADRB2</italic>. Nebivolol inhibited IL-17A regardless of <italic>ADRB2</italic> polymorphisms. Thus, nebivolol is a strong candidate for treating inflammatory diseases or disorders where IL-17A exacerbates symptoms.</p> </sec></abstract>","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70184217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autoimmune blistering skin disorders are rare. According to direct immunofluorescence studies, three categories are described: pemphigus group, pemphigoid group and dermatitis herpetiformis. Among these diseases, bullous pemphigoid is the most common. Patients with typical bullous pemphigoid disease are usually elderly and have many comorbidities. Considering that topical and systemic corticosteroids are the first choice therapy, these patients also have increased morbidity and risk of death. The main characteristic of bullous pemphigoid as an acquired autoimmune blistering disease is the formation of autoantibodies against hemidesmosomal antigens BP180 and BP230. Although IgG autoantibodies predominate within the plasma and skin of BP patients, some features of the disease cannot be explained solely by IgG-mediated mechanisms. Epitope spreading phenomena, immunoglobulin class switch and the relevance of IgM and IgE autoantibodies are discussed in this article.
{"title":"Bullous pemphigoid autoantibodies","authors":"F. Delli, E. Sotiriou, E. Vakirlis, D. Ioannides","doi":"10.3934/allergy.2021019","DOIUrl":"https://doi.org/10.3934/allergy.2021019","url":null,"abstract":"Autoimmune blistering skin disorders are rare. According to direct immunofluorescence studies, three categories are described: pemphigus group, pemphigoid group and dermatitis herpetiformis. Among these diseases, bullous pemphigoid is the most common. Patients with typical bullous pemphigoid disease are usually elderly and have many comorbidities. Considering that topical and systemic corticosteroids are the first choice therapy, these patients also have increased morbidity and risk of death. The main characteristic of bullous pemphigoid as an acquired autoimmune blistering disease is the formation of autoantibodies against hemidesmosomal antigens BP180 and BP230. Although IgG autoantibodies predominate within the plasma and skin of BP patients, some features of the disease cannot be explained solely by IgG-mediated mechanisms. Epitope spreading phenomena, immunoglobulin class switch and the relevance of IgM and IgE autoantibodies are discussed in this article.","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70184279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viral infection can lead to dangerous and severe manifestations associated with immunosuppression and a cytokine storm. The last is typical for influenza A virus infection of H1N1 subtype, when the level of cytokines in the peripheral blood is significantly elevated, leading to severe inflammatory damage and pathogenesis. In the present study, we performed a comparative computer analysis of amino acid fragments of host immune system proteins homologous to amino acids fragments of viral proteins of influenza A viruses of H1N1 subtype and avian influenza viruses of H5N1 and H7N9 subtypes. Homologous amino acid sequences of cellular protein integrin-α L and NALP1 were found in PB2 proteins of all studied viruses, as well TNF-α—in NP proteins. In addition, amino acid sequences homologous in IL-36 to NA proteins and C9 in M1 in H1N1 and H5N1 subtypes were found. At the same time, avian influenza viruses significantly differ from human influenza viruses in the composition of mimicking cellular proteins. In particular, avian influenza viruses have fragments homologous to different proteins of the NALP family (3, 13), TLR, IL-13, CD22, CD55, that are absent in human influenza A (H1N1)pdm09 viruses. Bioinformatic analysis data on the detection of fragments in the structure of influenza virus proteins that mimic the proteins of the innate and adaptive human immune system will serve as the basis for experimental studies to identify the role of homologous fragments in the regulation of the host immune system.
病毒感染可导致与免疫抑制和细胞因子风暴相关的危险和严重的表现。最后一种是典型的甲型流感病毒感染H1N1亚型时，外周血细胞因子水平显著升高，导致严重的炎症损伤和发病机制。在本研究中，我们对H1N1亚型甲型流感病毒和H5N1、H7N9亚型禽流感病毒的宿主免疫系统蛋白氨基酸片段与病毒蛋白氨基酸片段同源进行了计算机比较分析。在所研究的所有病毒的PB2蛋白和TNF-α - in NP蛋白中均发现了同源的细胞蛋白整合素-α L和NALP1氨基酸序列。此外，在H1N1和H5N1亚型的M1中发现IL-36与NA蛋白和C9同源的氨基酸序列。同时，禽流感病毒在模拟细胞蛋白的组成上与人流感病毒有很大的不同。特别是禽流感病毒具有与NALP家族(3,13)、TLR、IL-13、CD22、CD55等不同蛋白同源的片段，而这些在人甲型H1N1流感pdm09病毒中是不存在的。流感病毒蛋白结构中模拟人类先天免疫系统和适应性免疫系统蛋白的片段检测的生物信息学分析数据将作为实验研究的基础，以确定同源片段在宿主免疫系统调节中的作用。
{"title":"Mimicry between proteins of human and avian influenza viruses and host immune system proteins","authors":"I. Zhilinskaya, V. Marchenko, E. P. Kharchenko","doi":"10.3934/ALLERGY.2021006","DOIUrl":"https://doi.org/10.3934/ALLERGY.2021006","url":null,"abstract":"Viral infection can lead to dangerous and severe manifestations associated with immunosuppression and a cytokine storm. The last is typical for influenza A virus infection of H1N1 subtype, when the level of cytokines in the peripheral blood is significantly elevated, leading to severe inflammatory damage and pathogenesis. In the present study, we performed a comparative computer analysis of amino acid fragments of host immune system proteins homologous to amino acids fragments of viral proteins of influenza A viruses of H1N1 subtype and avian influenza viruses of H5N1 and H7N9 subtypes. Homologous amino acid sequences of cellular protein integrin-α L and NALP1 were found in PB2 proteins of all studied viruses, as well TNF-α—in NP proteins. In addition, amino acid sequences homologous in IL-36 to NA proteins and C9 in M1 in H1N1 and H5N1 subtypes were found. At the same time, avian influenza viruses significantly differ from human influenza viruses in the composition of mimicking cellular proteins. In particular, avian influenza viruses have fragments homologous to different proteins of the NALP family (3, 13), TLR, IL-13, CD22, CD55, that are absent in human influenza A (H1N1)pdm09 viruses. Bioinformatic analysis data on the detection of fragments in the structure of influenza virus proteins that mimic the proteins of the innate and adaptive human immune system will serve as the basis for experimental studies to identify the role of homologous fragments in the regulation of the host immune system.","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.7,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70183964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shkar Rzgar K. Rostam, K. Shekhany, Harem O. Smail
Background: Nowadays food allergy is the public health problem worldwide and prevalence of food allergy was increased that causes morbidity, there is no prevalence study to determine and reported most of the food allergen in Erbil City. Aims: To determine the prevalence of most common food allergy in Erbil City, and determination of intensity of allergic response among allergic patients against 36 identified food allergens items. Methods: A total number of 170 patients with suspected of food allergy were checked in the present study. The study was carried out for patients who visited the private clinical sectors in between (2018–2020), in Erbil Province, Kurdistan Region of Iraq. Determination of specific IgE (s‐IgE) antibody was examined for suspected patients using “Food Iraq1” kit (Catalog no: DP 3436‐1601‐1 E, IVD‐approved, and CE‐certified EUROLINE immunoblot), contains strip for 36 different allergens. Results: The present study illustrated that the food allergy prevalence (measured by specific IgE concentration). The rate of occurrence of food allergy is 10% among males and 12.35% among females. Furthermore, data also revealed that allergy prevalence was 12.35% among individuals aged 13–30 and 10% among those 31–52 years. Seafood mix (13.15%), grain mix (9.21%) and soybean (6.57%) in both male and female patients are the highest allergic response to food allergens often reported among these products respectively with different percentages. The most susceptible food allergens are the combination of fish (12.76%), chicken (7.44%), garlic and sesame (5.31%). Seafood mix, chicken and grain mix showed the highest incidence of food allergies respectively, with regard to aged groups.Conclusions: Based on the results in present study, we conclude that, the prevalence of food allergy was differing in between males and females in different age groups. Our study reached to that, there are no association between food allergens in males and age group of 13–30 years, but in other hand the association between food allergens in females and age group 31–52 years observed.
背景:食物过敏是当今世界范围内普遍存在的公共卫生问题，食物过敏的发病率呈上升趋势，但埃尔比勒市大部分食物过敏原尚无流行病学研究确定和报道。目的:确定埃尔比勒市最常见的食物过敏的患病率，并确定过敏患者对36种确定的食物过敏原的过敏反应强度。方法:对170例疑似食物过敏患者进行检查。该研究是在伊拉克库尔德斯坦地区埃尔比勒省(2018-2020年)期间访问私营临床部门的患者中进行的。使用“Food iraqi”试剂盒(目录号:DP 3436‐1601‐1 E, IVD批准和CE认证的EUROLINE免疫印迹)检测疑似患者的特异性IgE (s‐IgE)抗体，包含36种不同过敏原的条带。结果:本研究表明，食物过敏的患病率(以特定的IgE浓度衡量)。男性食物过敏发生率为10%，女性为12.35%。此外，数据还显示13-30岁人群的过敏患病率为12.35%，31-52岁人群的过敏患病率为10%。在这些产品中，男性和女性患者对食物过敏原的过敏反应最高的分别是海鲜混合物(13.15%)、谷物混合物(9.21%)和大豆混合物(6.57%)，所占比例不同。最易受影响的食物过敏原为鱼(12.76%)、鸡肉(7.44%)、大蒜和芝麻(5.31%)。在年龄组中，海鲜混合、鸡肉和谷物混合的食物过敏发生率分别最高。结论:根据本研究结果，我们得出结论，在不同年龄组，男性和女性的食物过敏患病率存在差异。我们的研究得出，男性食物过敏原与13-30岁年龄组之间没有相关性，而女性食物过敏原与31-52岁年龄组之间存在相关性。
{"title":"Prevalence of common food allergies in Erbil Province, Kurdistan Region of Iraq","authors":"Shkar Rzgar K. Rostam, K. Shekhany, Harem O. Smail","doi":"10.3934/allergy.2020010","DOIUrl":"https://doi.org/10.3934/allergy.2020010","url":null,"abstract":"Background: Nowadays food allergy is the public health problem worldwide and prevalence of food allergy was increased that causes morbidity, there is no prevalence study to determine and reported most of the food allergen in Erbil City. Aims: To determine the prevalence of most common food allergy in Erbil City, and determination of intensity of allergic response among allergic patients against 36 identified food allergens items. Methods: A total number of 170 patients with suspected of food allergy were checked in the present study. The study was carried out for patients who visited the private clinical sectors in between (2018–2020), in Erbil Province, Kurdistan Region of Iraq. Determination of specific IgE (s‐IgE) antibody was examined for suspected patients using “Food Iraq1” kit (Catalog no: DP 3436‐1601‐1 E, IVD‐approved, and CE‐certified EUROLINE immunoblot), contains strip for 36 different allergens. Results: The present study illustrated that the food allergy prevalence (measured by specific IgE concentration). The rate of occurrence of food allergy is 10% among males and 12.35% among females. Furthermore, data also revealed that allergy prevalence was 12.35% among individuals aged 13–30 and 10% among those 31–52 years. Seafood mix (13.15%), grain mix (9.21%) and soybean (6.57%) in both male and female patients are the highest allergic response to food allergens often reported among these products respectively with different percentages. The most susceptible food allergens are the combination of fish (12.76%), chicken (7.44%), garlic and sesame (5.31%). Seafood mix, chicken and grain mix showed the highest incidence of food allergies respectively, with regard to aged groups.Conclusions: Based on the results in present study, we conclude that, the prevalence of food allergy was differing in between males and females in different age groups. Our study reached to that, there are no association between food allergens in males and age group of 13–30 years, but in other hand the association between food allergens in females and age group 31–52 years observed.","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":" ","pages":""},"PeriodicalIF":0.7,"publicationDate":"2020-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43264287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: fungi are a common trigger of allergic diseases. Inspite of that fungal clinical allergies are underdiagnosed. In Saudi, fungi are a common indoor triggers. Objective: to determine allergic diseases associated with mold sensitization (MS) in Jeddah-Saudi. Methods: a retrospective study between period of (March 2016 to March 2017). Sample size is 51 patients with positive MS. Data was extracted by medical students from Laluna private clinic in Jeddah, Saudi. Test panel used was 30 RAST sIgE in vitro inhalant allergens (MEDIWISS Analytic GmbH company). This panel contain the most common inhalant allergens in Saudi. Each allergen is separate with severity scores from zero to 6. Allergic diseases diagnosis (and any other clinical diagnosis) was extracted from the same files. Results were collected in excel sheet in several columns: demographic data, allergic diseases, common molds in Saudi and other positive inhalants sensitization. Results: sample is 51 patients with MS. Gender distribution: females 28 (55%), males 23 (45%). Most common MSs are: aspergillus fumigatus 35 (69%), alternaria 32 (63%), 29 (57%), candida 13 (25%) and penicillium 9 (18%). Allergic diseases associated with MS are: allergic rhinitis and allergic fungal sinusitis 23 (45%), asthma 14 (27%), urticaria and angioedema 11 (22%) and atopic dermatitis (AD) 10 (20%). Other disease associated with MS are: hypothyroidism, obesity and facial pigmentations. Conclusion: Unfortunately, mold allergic diseases are underdiagnosed inspite of its high prevalence. In Jeddah, Saudi, the commonest MSs are: aspergillus fumigatus, alternaria followed by cladosporium, candida. Most common diseases associated with MSs are: respiratory allergic diseases (allergic rhinitis, allergic fungal sinusitis, asthma) followed by skin allergic diseases (urticaria, angioedema and AD). MSs are of mild class severity, however clinical allergic diseases due to mold are sever. This mean that sensitization class level don’t reflect the clinical severity.
{"title":"The relationship between mold sensitization and allergic diseases: a retrospective study (Jeddah, Saudi)","authors":"M. M. S. Tayeb","doi":"10.3934/allergy.2020002","DOIUrl":"https://doi.org/10.3934/allergy.2020002","url":null,"abstract":"Background: fungi are a common trigger of allergic diseases. Inspite of that fungal clinical allergies are underdiagnosed. In Saudi, fungi are a common indoor triggers. Objective: to determine allergic diseases associated with mold sensitization (MS) in Jeddah-Saudi. Methods: a retrospective study between period of (March 2016 to March 2017). Sample size is 51 patients with positive MS. Data was extracted by medical students from Laluna private clinic in Jeddah, Saudi. Test panel used was 30 RAST sIgE in vitro inhalant allergens (MEDIWISS Analytic GmbH company). This panel contain the most common inhalant allergens in Saudi. Each allergen is separate with severity scores from zero to 6. Allergic diseases diagnosis (and any other clinical diagnosis) was extracted from the same files. Results were collected in excel sheet in several columns: demographic data, allergic diseases, common molds in Saudi and other positive inhalants sensitization. Results: sample is 51 patients with MS. Gender distribution: females 28 (55%), males 23 (45%). Most common MSs are: aspergillus fumigatus 35 (69%), alternaria 32 (63%), 29 (57%), candida 13 (25%) and penicillium 9 (18%). Allergic diseases associated with MS are: allergic rhinitis and allergic fungal sinusitis 23 (45%), asthma 14 (27%), urticaria and angioedema 11 (22%) and atopic dermatitis (AD) 10 (20%). Other disease associated with MS are: hypothyroidism, obesity and facial pigmentations. Conclusion: Unfortunately, mold allergic diseases are underdiagnosed inspite of its high prevalence. In Jeddah, Saudi, the commonest MSs are: aspergillus fumigatus, alternaria followed by cladosporium, candida. Most common diseases associated with MSs are: respiratory allergic diseases (allergic rhinitis, allergic fungal sinusitis, asthma) followed by skin allergic diseases (urticaria, angioedema and AD). MSs are of mild class severity, however clinical allergic diseases due to mold are sever. This mean that sensitization class level don’t reflect the clinical severity.","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":" ","pages":""},"PeriodicalIF":0.7,"publicationDate":"2020-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45752499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The numbers of deaths due to asthma have decreased because of the development of inhaled corticosteroid (ICS) treatment. However, about 5% of patients with asthma are still difficult to control with ICS treatment. In severe uncontrolled asthma, the balance between type 2 inflammation and non-type 2 inflammation is assumed to be different. Asthma can be said to be a heterogeneous disease; however, several biologics have recently been developed for use in severe uncontrolled asthma. Omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab, targeting type 2 inflammation, have been approved for use worldwide. Severe uncontrolled asthma is heterogeneous, and it is becoming necessary to classify phenotype and endotype for individual patients to determine treatment options. This review will explain treatment options for severe uncontrolled asthma, with a focus on biologics.
{"title":"The treatment of severe uncontrolled asthma using biologics","authors":"N. Kodaka, C. Nakano, T. Oshio, H. Matsuse","doi":"10.3934/allergy.2020001","DOIUrl":"https://doi.org/10.3934/allergy.2020001","url":null,"abstract":"The numbers of deaths due to asthma have decreased because of the development of inhaled corticosteroid (ICS) treatment. However, about 5% of patients with asthma are still difficult to control with ICS treatment. In severe uncontrolled asthma, the balance between type 2 inflammation and non-type 2 inflammation is assumed to be different. Asthma can be said to be a heterogeneous disease; however, several biologics have recently been developed for use in severe uncontrolled asthma. Omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab, targeting type 2 inflammation, have been approved for use worldwide. Severe uncontrolled asthma is heterogeneous, and it is becoming necessary to classify phenotype and endotype for individual patients to determine treatment options. This review will explain treatment options for severe uncontrolled asthma, with a focus on biologics.","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":" ","pages":""},"PeriodicalIF":0.7,"publicationDate":"2020-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47792032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-28DOI: 10.3934/Allergy.2019.1.13
D. McKernan
The intestinal epithelium consists of a barrier one cell thick found along the length of the gastrointestinal tract composed of many cell subtypes such as absorptive enterocytes and secretory Paneth cells, Goblet cells and enteroendocrine cells. Primarily known as a cell layer used to absorb nutrients from the products of digestion and as a protective barrier from infection, this has changed in recent years with numerous discoveries indicating its importance in priming and tolerising immune cells. Toll-like receptors are a family of pathogen recognition receptors that are widely expressed in human cells including the intestinal epithelium and are known primarily as initiators of inflammatory responses. However, recent evidence suggest that they may have a variety of roles and are involved in cross-talk with a variety of cell types. This review discusses TLR signalling pathways in the context of the intestinal epithelial microenvironment, namely innate and adaptive immune cells as well as microorganisms that resident in the lumen of the gut. TLR signalling is not only involved in defence against such microorganisms but also in communicating with the underlying immune cells. This review describes the many mechanisms by which such communication is executed. It also highlights potential sources of variation in such signalling in the general population in particular the effects of genetic variation, diversity of the microbiota, concomitant disease, diet and age.
{"title":"Toll-like receptors and immune cell crosstalk in the intestinal epithelium","authors":"D. McKernan","doi":"10.3934/Allergy.2019.1.13","DOIUrl":"https://doi.org/10.3934/Allergy.2019.1.13","url":null,"abstract":"The intestinal epithelium consists of a barrier one cell thick found along the length of the gastrointestinal tract composed of many cell subtypes such as absorptive enterocytes and secretory Paneth cells, Goblet cells and enteroendocrine cells. Primarily known as a cell layer used to absorb nutrients from the products of digestion and as a protective barrier from infection, this has changed in recent years with numerous discoveries indicating its importance in priming and tolerising immune cells. Toll-like receptors are a family of pathogen recognition receptors that are widely expressed in human cells including the intestinal epithelium and are known primarily as initiators of inflammatory responses. However, recent evidence suggest that they may have a variety of roles and are involved in cross-talk with a variety of cell types. This review discusses TLR signalling pathways in the context of the intestinal epithelial microenvironment, namely innate and adaptive immune cells as well as microorganisms that resident in the lumen of the gut. TLR signalling is not only involved in defence against such microorganisms but also in communicating with the underlying immune cells. This review describes the many mechanisms by which such communication is executed. It also highlights potential sources of variation in such signalling in the general population in particular the effects of genetic variation, diversity of the microbiota, concomitant disease, diet and age.","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":" ","pages":""},"PeriodicalIF":0.7,"publicationDate":"2019-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48876696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-23DOI: 10.3934/ALLERGY.2019.1.1
Kremena Naydenova, T. Velikova, V. Dimitrov
Allergic rhinitis (AR) and bronchial asthma (BA) could be described as different aspects of one systemic disorder, where a mutual relationship is suggested founded on the well-known link between distinct mucosal sites in the organism. Moreover, several studies discuss the intimate association between AR and BA, including the observation that AR occurs usually as the first manifestation of the allergic respiratory (atopic) march. This review focuses on the various aspects of nose and lungs interaction during the course of the allergic disease. The dysfunction of the upper and lower airways is observed often simultaneously. It is thought that AR and BA share common pathogenic features and embryological, histological, anatomical and physiological characteristics. Furthermore, the data on the common nasal-bronchial reflex, inflammatory mechanisms, similar triggers, and genetic factors, clinical and epidemiological observations, the effect from the administered therapy, all confirm the suggested relation between AR and BA. The nasal-bronchial cross-talk rely on three different pathways: the immunological in the respiratory mucosa, the neural, and the circulatory pathway. In conclusion, AR and BA often occur simultaneously and share similar pathophysiological mechanisms. Nevertheless, the observation that the similar treatment is effective in both patients, gives hope for the management and prognosis of these patients.
{"title":"Interactions of allergic rhinitis and bronchial asthma at mucosal immunology level","authors":"Kremena Naydenova, T. Velikova, V. Dimitrov","doi":"10.3934/ALLERGY.2019.1.1","DOIUrl":"https://doi.org/10.3934/ALLERGY.2019.1.1","url":null,"abstract":"Allergic rhinitis (AR) and bronchial asthma (BA) could be described as different aspects of one systemic disorder, where a mutual relationship is suggested founded on the well-known link between distinct mucosal sites in the organism. Moreover, several studies discuss the intimate association between AR and BA, including the observation that AR occurs usually as the first manifestation of the allergic respiratory (atopic) march. This review focuses on the various aspects of nose and lungs interaction during the course of the allergic disease. The dysfunction of the upper and lower airways is observed often simultaneously. It is thought that AR and BA share common pathogenic features and embryological, histological, anatomical and physiological characteristics. Furthermore, the data on the common nasal-bronchial reflex, inflammatory mechanisms, similar triggers, and genetic factors, clinical and epidemiological observations, the effect from the administered therapy, all confirm the suggested relation between AR and BA. The nasal-bronchial cross-talk rely on three different pathways: the immunological in the respiratory mucosa, the neural, and the circulatory pathway. In conclusion, AR and BA often occur simultaneously and share similar pathophysiological mechanisms. Nevertheless, the observation that the similar treatment is effective in both patients, gives hope for the management and prognosis of these patients.","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":"1 1","pages":""},"PeriodicalIF":0.7,"publicationDate":"2019-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43083313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-01-01Epub Date: 2018-03-21DOI: 10.3934/allergy.2018.1.24
Michael D Caponegro, Jeremy Tetsuo Miyauchi, Stella E Tsirka
Immunotherapies are becoming a promising strategy for malignant disease. Selectively directing host immune responses to target cancerous tissue is a milestone of human health care. The roles of the innate and adaptive immune systems in both cancer progression and elimination are now being realized. Defining the immune cell environment and identifying the contributions of each sub-population of these cells has lead to an understanding of the immunotherapeutic processes, and demonstrated the potential of the immune system to drive cancer shrinkage and sustained immunity against disease. Poorly treated diseases, such as high-grade glioma, suffer from lack of therapeutic efficacy and rapid progression. Immunotherapeutic success in other solid malignancies, such as melanoma, now provides the principals for which this treatment paradigm can be adapted for primary brain cancers. The central nervous system is complex, and relative contributions of immune sub-populations to high grade glioma progression are not fully characterized. Here, we summarize recent research in both animal and humans which add to the knowledge base of how innate and adaptive immune cells contribute to glioma progression, and outline work which has demonstrated their potential to elicit anti-tumorigenic responses. Additionally, we highlight Neuropilin 1, a cell surface receptor protein, describe its signaling functions in the context of immunity, and point to its potential to slow glioma progression.
{"title":"Contributions of immune cell populations in the maintenance, progression, and therapeutic modalities of glioma.","authors":"Michael D Caponegro, Jeremy Tetsuo Miyauchi, Stella E Tsirka","doi":"10.3934/allergy.2018.1.24","DOIUrl":"10.3934/allergy.2018.1.24","url":null,"abstract":"<p><p>Immunotherapies are becoming a promising strategy for malignant disease. Selectively directing host immune responses to target cancerous tissue is a milestone of human health care. The roles of the innate and adaptive immune systems in both cancer progression and elimination are now being realized. Defining the immune cell environment and identifying the contributions of each sub-population of these cells has lead to an understanding of the immunotherapeutic processes, and demonstrated the potential of the immune system to drive cancer shrinkage and sustained immunity against disease. Poorly treated diseases, such as high-grade glioma, suffer from lack of therapeutic efficacy and rapid progression. Immunotherapeutic success in other solid malignancies, such as melanoma, now provides the principals for which this treatment paradigm can be adapted for primary brain cancers. The central nervous system is complex, and relative contributions of immune sub-populations to high grade glioma progression are not fully characterized. Here, we summarize recent research in both animal and humans which add to the knowledge base of how innate and adaptive immune cells contribute to glioma progression, and outline work which has demonstrated their potential to elicit anti-tumorigenic responses. Additionally, we highlight Neuropilin 1, a cell surface receptor protein, describe its signaling functions in the context of immunity, and point to its potential to slow glioma progression.</p>","PeriodicalId":40916,"journal":{"name":"AIMS Allergy and Immunology","volume":"2 1","pages":"24-44"},"PeriodicalIF":0.7,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38368709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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