Lindsey B. Cundra, Manasa Vallabhaneni, Kevin V. Houston, Michael Saadeh, Alejandra Vargas, Steve M. D’Souza, David A. Johnson
The intestinal mucosal barrier plays a critical role in maintaining the integrity of the gastrointestinal (GI) tract and protecting the body from harmful toxins and pathogens. Nutrition additionally serves as a vital component in maintaining bodily homeostasis. Macronutrients, micronutrients, and specific dietary habits exert profound effects on the immune system. The complex interactions of the immune system reflect a multifaceted, integrated epithelial and immune cell-mediated regulatory system. While several factors can influence the intestinal mucosal barrier and its pro- and anti-inflammatory processes, such as myeloid cell, regulatory T cell (Treg), or intraepithelial lymphocyte populations, there is growing evidence that macronutrients play an essential role in regulating its function. Herein this is a review of the peer-reviewed literature pertaining to dietary effects on mucosal integrity, including intraepithelial lymphocyte populations and immune function. This review is intended to explore the underlying mechanisms by which macronutrients impact and modulate the mucosal immune system.
肠粘膜屏障在维持胃肠道（GI）的完整性以及保护人体免受有害毒素和病原体侵害方面发挥着至关重要的作用。此外，营养也是维持身体平衡的重要组成部分。宏量营养素、微量营养素和特定的饮食习惯对免疫系统有着深远的影响。免疫系统复杂的相互作用反映了一个多层面、综合的上皮细胞和免疫细胞介导的调节系统。虽然有多种因素可影响肠粘膜屏障及其促炎和抗炎过程，如髓细胞、调节性 T 细胞（Treg）或上皮内淋巴细胞群，但越来越多的证据表明，宏量营养素在调节肠粘膜屏障功能方面发挥着至关重要的作用。本文综述了有关饮食对粘膜完整性（包括上皮内淋巴细胞群和免疫功能）影响的同行评审文献。本综述旨在探讨宏量营养素影响和调节粘膜免疫系统的内在机制。
{"title":"Nutritional effects on mucosal integrity and immune function","authors":"Lindsey B. Cundra, Manasa Vallabhaneni, Kevin V. Houston, Michael Saadeh, Alejandra Vargas, Steve M. D’Souza, David A. Johnson","doi":"10.37349/ei.2024.00130","DOIUrl":"https://doi.org/10.37349/ei.2024.00130","url":null,"abstract":"The intestinal mucosal barrier plays a critical role in maintaining the integrity of the gastrointestinal (GI) tract and protecting the body from harmful toxins and pathogens. Nutrition additionally serves as a vital component in maintaining bodily homeostasis. Macronutrients, micronutrients, and specific dietary habits exert profound effects on the immune system. The complex interactions of the immune system reflect a multifaceted, integrated epithelial and immune cell-mediated regulatory system. While several factors can influence the intestinal mucosal barrier and its pro- and anti-inflammatory processes, such as myeloid cell, regulatory T cell (Treg), or intraepithelial lymphocyte populations, there is growing evidence that macronutrients play an essential role in regulating its function. Herein this is a review of the peer-reviewed literature pertaining to dietary effects on mucosal integrity, including intraepithelial lymphocyte populations and immune function. This review is intended to explore the underlying mechanisms by which macronutrients impact and modulate the mucosal immune system.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"259 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140420798","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 : 2024-02-22DOI: 10.37349/10.37349/ei.2024.00129
Michael Athanasopoulos, Pinelopi Samara, Ioannis Athanasopoulos
Autoimmune and autoinflammatory diseases affecting the inner ear can cause symptoms such as hearing loss, imbalance, vertigo, and tinnitus, presenting demanding and often underdiagnosed conditions. Diagnostic challenges arise due to their diverse manifestations, potential long-term consequences, and the absence of specific serological markers, necessitating a multidisciplinary approach combining clinical evaluation, audiological assessments, and imaging techniques. Various autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome, have been implicated in immune-mediated damage to auditory structures, resulting in inner ear dysfunction. Inflammatory processes in autoinflammatory diseases like Cogan’s syndrome and relapsing polychondritis can also affect the inner ear. While the exact mechanisms of inner ear involvement in these conditions are still being studied, immune-mediated inflammation, damage to auditory structures, and vascular involvement play significant roles in auditory impairments. Treatment strategies primarily focus on immunomodulation and inflammation control using corticosteroids, immunosuppressants, and targeted biologic agents to ameliorate symptoms and preserve hearing function. Hearing aids and cochlear implants may be also considered for severe hearing loss. Individualized approaches are necessary due to patient response heterogeneity. This review provides a concise overview of key autoimmune and autoinflammatory diseases impacting the inner ear, highlighting clinical manifestations, diagnostics, pathophysiology, and treatment options. Early recognition and appropriate management are crucial for optimizing patient outcomes. Further research is needed to understand underlying mechanisms and identify novel therapeutic targets. Collaboration between otolaryngologists, rheumatologists, and immunologists is crucial for improving the quality of life in these complex conditions.
{"title":"Decoding the impact of autoinflammatory/autoimmune diseases on inner ear harmony and hearing loss","authors":"Michael Athanasopoulos, Pinelopi Samara, Ioannis Athanasopoulos","doi":"10.37349/10.37349/ei.2024.00129","DOIUrl":"https://doi.org/10.37349/10.37349/ei.2024.00129","url":null,"abstract":"Autoimmune and autoinflammatory diseases affecting the inner ear can cause symptoms such as hearing loss, imbalance, vertigo, and tinnitus, presenting demanding and often underdiagnosed conditions. Diagnostic challenges arise due to their diverse manifestations, potential long-term consequences, and the absence of specific serological markers, necessitating a multidisciplinary approach combining clinical evaluation, audiological assessments, and imaging techniques. Various autoimmune disorders, including systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome, have been implicated in immune-mediated damage to auditory structures, resulting in inner ear dysfunction. Inflammatory processes in autoinflammatory diseases like Cogan’s syndrome and relapsing polychondritis can also affect the inner ear. While the exact mechanisms of inner ear involvement in these conditions are still being studied, immune-mediated inflammation, damage to auditory structures, and vascular involvement play significant roles in auditory impairments. Treatment strategies primarily focus on immunomodulation and inflammation control using corticosteroids, immunosuppressants, and targeted biologic agents to ameliorate symptoms and preserve hearing function. Hearing aids and cochlear implants may be also considered for severe hearing loss. Individualized approaches are necessary due to patient response heterogeneity. This review provides a concise overview of key autoimmune and autoinflammatory diseases impacting the inner ear, highlighting clinical manifestations, diagnostics, pathophysiology, and treatment options. Early recognition and appropriate management are crucial for optimizing patient outcomes. Further research is needed to understand underlying mechanisms and identify novel therapeutic targets. Collaboration between otolaryngologists, rheumatologists, and immunologists is crucial for improving the quality of life in these complex conditions.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140441945","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}
Mammals depend on the secretion of milk to rear their offspring, which exposes the organ in charge of the function, the mammary gland (MG), to bacterial threat. The essential driving force that conditions the interactions of bacteria with the MG is the abundant secretion of milk, a nutritious fluid which endows the common mastitis-causing pathogens with a doubling time of less than 30 min. From this angle, mammals rely on a potential bacterial bioreactor for the survival of their offspring. The MG is lined with a two-layered epithelium devoid of protective mucus. This means that the mammary epithelium is exposed directly to bacteria once they have passed through the opening lactiferous canal. To cope with the threat, the MG resorts to neutrophilic inflammation to check bacterial proliferation in its lumen and at its epithelial lining. Promptness of neutrophil recruitment is a necessity, which requires a low threshold of activation on the part of the mammary epithelium. Constrained by natural selection, the MG has evolved an innate and adaptive immunity intolerant to bacteria regardless of their level of virulence. The evolutionary issue has been to find a compromise between the deleterious tissue-damaging side effects of inflammation and the maintenance of the secretory function indispensable for the offspring’s survival. It appears that the MG relies mainly on neutrophilic inflammation for its protection and is regulated by type 3 immunity. Advances in knowledge of type 3 immunity in the MG will be necessary to induce immune protection adapted to the physiology of this peculiar organ.
{"title":"The mammary gland is intolerant to bacterial intrusion","authors":"Pascal Rainard","doi":"10.37349/ei.2024.00128","DOIUrl":"https://doi.org/10.37349/ei.2024.00128","url":null,"abstract":"Mammals depend on the secretion of milk to rear their offspring, which exposes the organ in charge of the function, the mammary gland (MG), to bacterial threat. The essential driving force that conditions the interactions of bacteria with the MG is the abundant secretion of milk, a nutritious fluid which endows the common mastitis-causing pathogens with a doubling time of less than 30 min. From this angle, mammals rely on a potential bacterial bioreactor for the survival of their offspring. The MG is lined with a two-layered epithelium devoid of protective mucus. This means that the mammary epithelium is exposed directly to bacteria once they have passed through the opening lactiferous canal. To cope with the threat, the MG resorts to neutrophilic inflammation to check bacterial proliferation in its lumen and at its epithelial lining. Promptness of neutrophil recruitment is a necessity, which requires a low threshold of activation on the part of the mammary epithelium. Constrained by natural selection, the MG has evolved an innate and adaptive immunity intolerant to bacteria regardless of their level of virulence. The evolutionary issue has been to find a compromise between the deleterious tissue-damaging side effects of inflammation and the maintenance of the secretory function indispensable for the offspring’s survival. It appears that the MG relies mainly on neutrophilic inflammation for its protection and is regulated by type 3 immunity. Advances in knowledge of type 3 immunity in the MG will be necessary to induce immune protection adapted to the physiology of this peculiar organ.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"151 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139859480","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}
Mammals depend on the secretion of milk to rear their offspring, which exposes the organ in charge of the function, the mammary gland (MG), to bacterial threat. The essential driving force that conditions the interactions of bacteria with the MG is the abundant secretion of milk, a nutritious fluid which endows the common mastitis-causing pathogens with a doubling time of less than 30 min. From this angle, mammals rely on a potential bacterial bioreactor for the survival of their offspring. The MG is lined with a two-layered epithelium devoid of protective mucus. This means that the mammary epithelium is exposed directly to bacteria once they have passed through the opening lactiferous canal. To cope with the threat, the MG resorts to neutrophilic inflammation to check bacterial proliferation in its lumen and at its epithelial lining. Promptness of neutrophil recruitment is a necessity, which requires a low threshold of activation on the part of the mammary epithelium. Constrained by natural selection, the MG has evolved an innate and adaptive immunity intolerant to bacteria regardless of their level of virulence. The evolutionary issue has been to find a compromise between the deleterious tissue-damaging side effects of inflammation and the maintenance of the secretory function indispensable for the offspring’s survival. It appears that the MG relies mainly on neutrophilic inflammation for its protection and is regulated by type 3 immunity. Advances in knowledge of type 3 immunity in the MG will be necessary to induce immune protection adapted to the physiology of this peculiar organ.
{"title":"The mammary gland is intolerant to bacterial intrusion","authors":"Pascal Rainard","doi":"10.37349/ei.2024.00128","DOIUrl":"https://doi.org/10.37349/ei.2024.00128","url":null,"abstract":"Mammals depend on the secretion of milk to rear their offspring, which exposes the organ in charge of the function, the mammary gland (MG), to bacterial threat. The essential driving force that conditions the interactions of bacteria with the MG is the abundant secretion of milk, a nutritious fluid which endows the common mastitis-causing pathogens with a doubling time of less than 30 min. From this angle, mammals rely on a potential bacterial bioreactor for the survival of their offspring. The MG is lined with a two-layered epithelium devoid of protective mucus. This means that the mammary epithelium is exposed directly to bacteria once they have passed through the opening lactiferous canal. To cope with the threat, the MG resorts to neutrophilic inflammation to check bacterial proliferation in its lumen and at its epithelial lining. Promptness of neutrophil recruitment is a necessity, which requires a low threshold of activation on the part of the mammary epithelium. Constrained by natural selection, the MG has evolved an innate and adaptive immunity intolerant to bacteria regardless of their level of virulence. The evolutionary issue has been to find a compromise between the deleterious tissue-damaging side effects of inflammation and the maintenance of the secretory function indispensable for the offspring’s survival. It appears that the MG relies mainly on neutrophilic inflammation for its protection and is regulated by type 3 immunity. Advances in knowledge of type 3 immunity in the MG will be necessary to induce immune protection adapted to the physiology of this peculiar organ.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"226 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139799600","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}
Many acquired bleeding and thrombotic complications are provoked by autoantibodies to blood coagulation factors, or to hemostasis inhibitors and regulatory proteins. If occurrence of those antibodies remains rare or ultra-rare, affected patients are not always well-identified and associated pathologies are not always understood. Today, autoantigens tend to be better characterized. New available methods allow investigating structural changes of body components, responsible for auto-immunization. This renders it possible to develop laboratory assays for detecting autoantibodies and estimating their blood concentration. This review analyzes the major autoantibodies reported to be associated with hemorrhagic or thrombotic pathologies and their possible inducing causes when known. Pathogenicity is strongly patient- and context-dependent and is related to autoantibodies’ concentration, avidity, and capacity to bind to autoantigen structures in-vivo, misdirecting the immune system to the own body’s cells or organs. Identification of autoantigens allows for developing laboratory methods for testing autoantibodies and following their evolution kinetics. In-vitro investigations concern functional assays, to evaluate autoantibody’s capacity to inhibit physiological activities, or autoantigen-capture-based assays to detect autoantibodies, like with enzyme-linked immuno-sorbent assay (ELISA) methods. Exploring patients with autoimmune complications remains difficult as few specific assays are available. They mainly concern diseases with the highest incidence, like anti-phospholipid antibodies, lupus anticoagulants, or heparin-dependent antibodies. The present understanding suggests that antibodies to ubiquitous components, like phospholipids or polysaccharides, are actually targeted to proteins with a strong affinity binding to those components: Autoantibodies are not directed to phospholipids, but to phospholipid-binding proteins, and heparin-dependent antibodies are not directed to anticoagulant polysaccharides, but to platelet factor 4. Most pathogenic autoantibodies are of immunoglobulin G (IgG) isotype, but in some cases, IgM or IgA isotypes can be involved. Identification and characterization of autoantibodies associated to hemorrhagic or thrombotic pathologies remains complex at the laboratory level, although they are of high relevance for the right management of concerned patients.
许多后天性出血和血栓并发症都是由凝血因子或止血抑制剂和调节蛋白自身抗体引起的。如果这些抗体的出现仍然罕见或超乎寻常，受影响的患者就不一定能被很好地识别，相关的病理变化也不一定能被理解。如今，自身抗原的特征越来越清晰。现有的新方法可以研究导致自身免疫的身体成分的结构变化。这使得开发实验室检测自身抗体和估计其血液浓度成为可能。本综述分析了据报道与出血性或血栓性病症有关的主要自身抗体，以及已知的可能诱因。致病性与患者和环境密切相关，并与自身抗体的浓度、亲和力以及在体内与自身抗原结构结合的能力有关，从而将免疫系统误导至自身的细胞或器官。确定自身抗原后，就可以开发实验室方法来检测自身抗体并跟踪其演变动力学。体外研究涉及功能检测，以评估自身抗体抑制生理活动的能力，或基于自身抗原捕获的检测自身抗体的方法，如酶联免疫吸附试验（ELISA）方法。由于可用的特异性检测方法很少，因此对患有自身免疫并发症的患者进行检测仍然很困难。它们主要涉及发病率最高的疾病，如抗磷脂抗体、狼疮抗凝物或肝素依赖性抗体。目前的认识表明，针对无处不在的成分（如磷脂或多糖）的抗体实际上是针对与这些成分有很强亲和力的蛋白质：自身抗体不是针对磷脂，而是针对磷脂结合蛋白；肝素依赖性抗体不是针对抗凝多糖，而是针对血小板因子 4。大多数致病性自身抗体为免疫球蛋白 G（IgG）同型，但在某些病例中也可能涉及 IgM 或 IgA 同型。与出血性或血栓性病症相关的自身抗体的鉴定和特征描述在实验室层面上仍然很复杂，尽管它们与相关患者的正确治疗密切相关。
{"title":"Generation and pathogenicity of autoantibodies associated to thrombosis and hemostasis","authors":"Jean Amiral","doi":"10.37349/ei.2024.00127","DOIUrl":"https://doi.org/10.37349/ei.2024.00127","url":null,"abstract":"Many acquired bleeding and thrombotic complications are provoked by autoantibodies to blood coagulation factors, or to hemostasis inhibitors and regulatory proteins. If occurrence of those antibodies remains rare or ultra-rare, affected patients are not always well-identified and associated pathologies are not always understood. Today, autoantigens tend to be better characterized. New available methods allow investigating structural changes of body components, responsible for auto-immunization. This renders it possible to develop laboratory assays for detecting autoantibodies and estimating their blood concentration. This review analyzes the major autoantibodies reported to be associated with hemorrhagic or thrombotic pathologies and their possible inducing causes when known. Pathogenicity is strongly patient- and context-dependent and is related to autoantibodies’ concentration, avidity, and capacity to bind to autoantigen structures in-vivo, misdirecting the immune system to the own body’s cells or organs. Identification of autoantigens allows for developing laboratory methods for testing autoantibodies and following their evolution kinetics. In-vitro investigations concern functional assays, to evaluate autoantibody’s capacity to inhibit physiological activities, or autoantigen-capture-based assays to detect autoantibodies, like with enzyme-linked immuno-sorbent assay (ELISA) methods. Exploring patients with autoimmune complications remains difficult as few specific assays are available. They mainly concern diseases with the highest incidence, like anti-phospholipid antibodies, lupus anticoagulants, or heparin-dependent antibodies. The present understanding suggests that antibodies to ubiquitous components, like phospholipids or polysaccharides, are actually targeted to proteins with a strong affinity binding to those components: Autoantibodies are not directed to phospholipids, but to phospholipid-binding proteins, and heparin-dependent antibodies are not directed to anticoagulant polysaccharides, but to platelet factor 4. Most pathogenic autoantibodies are of immunoglobulin G (IgG) isotype, but in some cases, IgM or IgA isotypes can be involved. Identification and characterization of autoantibodies associated to hemorrhagic or thrombotic pathologies remains complex at the laboratory level, although they are of high relevance for the right management of concerned patients.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"10 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139803890","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}
Many acquired bleeding and thrombotic complications are provoked by autoantibodies to blood coagulation factors, or to hemostasis inhibitors and regulatory proteins. If occurrence of those antibodies remains rare or ultra-rare, affected patients are not always well-identified and associated pathologies are not always understood. Today, autoantigens tend to be better characterized. New available methods allow investigating structural changes of body components, responsible for auto-immunization. This renders it possible to develop laboratory assays for detecting autoantibodies and estimating their blood concentration. This review analyzes the major autoantibodies reported to be associated with hemorrhagic or thrombotic pathologies and their possible inducing causes when known. Pathogenicity is strongly patient- and context-dependent and is related to autoantibodies’ concentration, avidity, and capacity to bind to autoantigen structures in-vivo, misdirecting the immune system to the own body’s cells or organs. Identification of autoantigens allows for developing laboratory methods for testing autoantibodies and following their evolution kinetics. In-vitro investigations concern functional assays, to evaluate autoantibody’s capacity to inhibit physiological activities, or autoantigen-capture-based assays to detect autoantibodies, like with enzyme-linked immuno-sorbent assay (ELISA) methods. Exploring patients with autoimmune complications remains difficult as few specific assays are available. They mainly concern diseases with the highest incidence, like anti-phospholipid antibodies, lupus anticoagulants, or heparin-dependent antibodies. The present understanding suggests that antibodies to ubiquitous components, like phospholipids or polysaccharides, are actually targeted to proteins with a strong affinity binding to those components: Autoantibodies are not directed to phospholipids, but to phospholipid-binding proteins, and heparin-dependent antibodies are not directed to anticoagulant polysaccharides, but to platelet factor 4. Most pathogenic autoantibodies are of immunoglobulin G (IgG) isotype, but in some cases, IgM or IgA isotypes can be involved. Identification and characterization of autoantibodies associated to hemorrhagic or thrombotic pathologies remains complex at the laboratory level, although they are of high relevance for the right management of concerned patients.
许多后天性出血和血栓并发症都是由凝血因子或止血抑制剂和调节蛋白的自身抗体引起的。如果这些抗体的出现仍然罕见或超乎寻常，受影响的患者就不一定能被很好地识别，相关的病理变化也不一定能被理解。如今，自身抗原的特征越来越清晰。现有的新方法可以研究导致自身免疫的身体成分的结构变化。这使得开发实验室检测自身抗体和估计其血液浓度成为可能。本综述分析了据报道与出血性或血栓性病症有关的主要自身抗体，以及已知的可能诱因。致病性与患者和环境密切相关，并与自身抗体的浓度、亲和力以及在体内与自身抗原结构结合的能力有关，从而将免疫系统误导至自身的细胞或器官。确定自身抗原后，就可以开发实验室方法来检测自身抗体并跟踪其演变动力学。体外研究涉及功能检测，以评估自身抗体抑制生理活动的能力，或基于自身抗原捕获的检测自身抗体的方法，如酶联免疫吸附试验（ELISA）方法。由于可用的特异性检测方法很少，因此对患有自身免疫并发症的患者进行检测仍然很困难。它们主要涉及发病率最高的疾病，如抗磷脂抗体、狼疮抗凝物或肝素依赖性抗体。目前的认识表明，针对无处不在的成分（如磷脂或多糖）的抗体实际上是针对与这些成分有很强亲和力的蛋白质：自身抗体并非针对磷脂，而是针对磷脂结合蛋白；肝素依赖性抗体并非针对抗凝多糖，而是针对血小板因子 4。大多数致病性自身抗体为免疫球蛋白 G（IgG）同型，但在某些病例中也可能涉及 IgM 或 IgA 同型。与出血性或血栓性病症相关的自身抗体的鉴定和特征描述在实验室层面上仍然很复杂，尽管它们与相关患者的正确治疗密切相关。
{"title":"Generation and pathogenicity of autoantibodies associated to thrombosis and hemostasis","authors":"Jean Amiral","doi":"10.37349/ei.2024.00127","DOIUrl":"https://doi.org/10.37349/ei.2024.00127","url":null,"abstract":"Many acquired bleeding and thrombotic complications are provoked by autoantibodies to blood coagulation factors, or to hemostasis inhibitors and regulatory proteins. If occurrence of those antibodies remains rare or ultra-rare, affected patients are not always well-identified and associated pathologies are not always understood. Today, autoantigens tend to be better characterized. New available methods allow investigating structural changes of body components, responsible for auto-immunization. This renders it possible to develop laboratory assays for detecting autoantibodies and estimating their blood concentration. This review analyzes the major autoantibodies reported to be associated with hemorrhagic or thrombotic pathologies and their possible inducing causes when known. Pathogenicity is strongly patient- and context-dependent and is related to autoantibodies’ concentration, avidity, and capacity to bind to autoantigen structures in-vivo, misdirecting the immune system to the own body’s cells or organs. Identification of autoantigens allows for developing laboratory methods for testing autoantibodies and following their evolution kinetics. In-vitro investigations concern functional assays, to evaluate autoantibody’s capacity to inhibit physiological activities, or autoantigen-capture-based assays to detect autoantibodies, like with enzyme-linked immuno-sorbent assay (ELISA) methods. Exploring patients with autoimmune complications remains difficult as few specific assays are available. They mainly concern diseases with the highest incidence, like anti-phospholipid antibodies, lupus anticoagulants, or heparin-dependent antibodies. The present understanding suggests that antibodies to ubiquitous components, like phospholipids or polysaccharides, are actually targeted to proteins with a strong affinity binding to those components: Autoantibodies are not directed to phospholipids, but to phospholipid-binding proteins, and heparin-dependent antibodies are not directed to anticoagulant polysaccharides, but to platelet factor 4. Most pathogenic autoantibodies are of immunoglobulin G (IgG) isotype, but in some cases, IgM or IgA isotypes can be involved. Identification and characterization of autoantibodies associated to hemorrhagic or thrombotic pathologies remains complex at the laboratory level, although they are of high relevance for the right management of concerned patients.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"64 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139863454","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}
O. S. Sahoo, Karthikeyan Pethusamy, A. Nayek, Rashmi Minocha, Ruby Dhar, S. Karmakar
The coronavirus disease 2019 (COVID-19) pandemic cost 7–8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in acute respiratory distress syndrome (ARDS) and lung injury. Anti-inflammatory intervention with anti-interleukin-6 (anti-IL-6) receptor monoclonal antibodies (mAbs; e.g., sarilumab and tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and/or steroid-based approach leads to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this review, the authors have summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus-host immune cross talks and presenting the possibilities of therapeutic intervention.
{"title":"Paradigm of immune dysregulation in coronavirus disease-2019 infection","authors":"O. S. Sahoo, Karthikeyan Pethusamy, A. Nayek, Rashmi Minocha, Ruby Dhar, S. Karmakar","doi":"10.37349/ei.2024.00126","DOIUrl":"https://doi.org/10.37349/ei.2024.00126","url":null,"abstract":"The coronavirus disease 2019 (COVID-19) pandemic cost 7–8 million deaths worldwide, creating an unprecedented health and economic crisis. Affecting 700 million people globally, the magnitude of this pandemic is far from anything that humanity has encountered in recent times. A detailed investigation revealed that more than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the hyperactive immune system mediated injury as the real cause of mortality. Cytokine storm following viral infection leads to the surge of proinflammatory cytokines resulting in acute respiratory distress syndrome (ARDS) and lung injury. Anti-inflammatory intervention with anti-interleukin-6 (anti-IL-6) receptor monoclonal antibodies (mAbs; e.g., sarilumab and tocilizumab) and anti-IL-6 mAbs (i.e., siltuximab) and/or steroid-based approach leads to substantial protection and prevent death thereby implying the role of inflammation in COVID-19. In this review, the authors have summarized the dysregulated immune system in COVID-19 infection, investigating in detail the virus-host immune cross talks and presenting the possibilities of therapeutic intervention.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"321 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140474274","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}
Yuto Sasaki, Shoya Kawahara, Y. Sekine, J. Kashiwakura, K. Oritani, T. Matsuda
Adaptor proteins are involved in various immune responses via the modulation of many signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that contains typical domains such as the pleckstrin homology (PH) domain, Src homology domain, and a proline-rich region from the N-terminal region. In T cells, STAP-2 positively regulates T cell receptor (TCR)-mediated signaling by associating with CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (LCK). Therefore, a peptide that inhibits the interaction between STAP-2 and CD3ζ ITAMs is likely to suppress TCR-mediated T cell activation, as well as T cell-mediated diseases. As expected, the peptide successfully inhibited the STAP-2/CD3ζ ITAM interaction and suppressed TCR-mediated signaling, cell proliferation, and interleukin (IL)-2 production in human/murine T cells. Furthermore, this inhibitor suppressed the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which is widely recognized as a mouse model of multiple sclerosis, via the downregulation of T cell activation and infiltration of T helper (Th) 1/Th17 cells. These results suggest a new strategy for the treatment of multiple sclerosis and other immune diseases.
适配蛋白通过调节多种信号通路参与各种免疫反应。信号转导适配蛋白-2（STAP-2）是一种适配蛋白，含有典型的结构域，如pleckstrin homology（PH）结构域、Src同源结构域和N端富含脯氨酸的区域。在 T 细胞中，STAP-2 通过与 CD3ζ 免疫受体酪氨酸基激活基序（ITAMs）和淋巴细胞特异性蛋白酪氨酸激酶（LCK）结合，积极调节 T 细胞受体（TCR）介导的信号转导。因此，抑制 STAP-2 与 CD3ζ ITAMs 之间相互作用的多肽可能会抑制 TCR 介导的 T 细胞活化以及 T 细胞介导的疾病。不出所料，该多肽成功抑制了 STAP-2/CD3ζ ITAM 的相互作用，并抑制了人/鼠 T 细胞中 TCR 介导的信号传导、细胞增殖和白细胞介素（IL）-2 的产生。此外，这种抑制剂还通过下调 T 细胞活化和 T 辅助细胞（Th）1/Th17 的浸润，抑制了实验性自身免疫性脑脊髓炎（EAE）的发病机制，EAE 是公认的多发性硬化症小鼠模型。这些结果为治疗多发性硬化症和其他免疫性疾病提供了一种新策略。
{"title":"Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases","authors":"Yuto Sasaki, Shoya Kawahara, Y. Sekine, J. Kashiwakura, K. Oritani, T. Matsuda","doi":"10.37349/ei.2023.00125","DOIUrl":"https://doi.org/10.37349/ei.2023.00125","url":null,"abstract":"Adaptor proteins are involved in various immune responses via the modulation of many signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that contains typical domains such as the pleckstrin homology (PH) domain, Src homology domain, and a proline-rich region from the N-terminal region. In T cells, STAP-2 positively regulates T cell receptor (TCR)-mediated signaling by associating with CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (LCK). Therefore, a peptide that inhibits the interaction between STAP-2 and CD3ζ ITAMs is likely to suppress TCR-mediated T cell activation, as well as T cell-mediated diseases. As expected, the peptide successfully inhibited the STAP-2/CD3ζ ITAM interaction and suppressed TCR-mediated signaling, cell proliferation, and interleukin (IL)-2 production in human/murine T cells. Furthermore, this inhibitor suppressed the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which is widely recognized as a mouse model of multiple sclerosis, via the downregulation of T cell activation and infiltration of T helper (Th) 1/Th17 cells. These results suggest a new strategy for the treatment of multiple sclerosis and other immune diseases.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"54 s51","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139150310","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}
G. Blanck, Taha I. Huda, Konrad J. Cios, George Angelakakis, Joanna J Song
Exome and RNAseq files prepared from blood samples can be mined for adaptive immune receptor recombinations and thus for the complementarity determining region-3 (CDR3) amino acid (AA) sequences, important for antigen binding. In this report, the T-cell receptor gamma (TRG) recombinations were mined from amyotrophic lateral sclerosis (ALS) blood sample exome and RNAseq files, mainly inspired by: (i) a high level of gamma-delta T-cells in Parkinson’s disease and (ii) TRG CDR3 AA features associated with a higher Braak stage in Alzheimer’s disease. Results indicated a high percentage of V9-JP recombinations from ALS blood sample genomics files, in comparison to TRG recombinations obtained from a large number of blood and other tissue samples not representing ALS. This result is discussed in the context of potential phospholipid sponging by adaptive immune receptors and potential impacts on membrane rigidity and amyloid development.
从血液样本中制备的外显子组和 RNAseq 文件可以挖掘适应性免疫受体重组，从而挖掘对抗原结合非常重要的互补决定区-3（CDR3）氨基酸（AA）序列。本报告从肌萎缩性脊髓侧索硬化症（ALS）血液样本外显子组和 RNAseq 文件中挖掘出了 T 细胞受体 gamma（TRG）重组，主要受到以下启发：(i) 帕金森病中γ-δ T 细胞水平较高，(ii) TRG CDR3 AA 特征与阿尔茨海默病中较高的 Braak 分期相关。结果表明，与从大量血液和其他非 ALS 组织样本中获得的 TRG 重组相比，ALS 血液样本基因组学文件中的 V9-JP 重组比例较高。这一结果将在适应性免疫受体的潜在磷脂海绵化以及对膜刚性和淀粉样蛋白发展的潜在影响的背景下进行讨论。
{"title":"High percentage of blood-based T-cell receptor gamma V9-JP recombinations associated with amyotrophic lateral sclerosis: extensive retention of the JP KKIK amino acid motif","authors":"G. Blanck, Taha I. Huda, Konrad J. Cios, George Angelakakis, Joanna J Song","doi":"10.37349/ei.2023.00124","DOIUrl":"https://doi.org/10.37349/ei.2023.00124","url":null,"abstract":"Exome and RNAseq files prepared from blood samples can be mined for adaptive immune receptor recombinations and thus for the complementarity determining region-3 (CDR3) amino acid (AA) sequences, important for antigen binding. In this report, the T-cell receptor gamma (TRG) recombinations were mined from amyotrophic lateral sclerosis (ALS) blood sample exome and RNAseq files, mainly inspired by: (i) a high level of gamma-delta T-cells in Parkinson’s disease and (ii) TRG CDR3 AA features associated with a higher Braak stage in Alzheimer’s disease. Results indicated a high percentage of V9-JP recombinations from ALS blood sample genomics files, in comparison to TRG recombinations obtained from a large number of blood and other tissue samples not representing ALS. This result is discussed in the context of potential phospholipid sponging by adaptive immune receptors and potential impacts on membrane rigidity and amyloid development.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"22 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138947119","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}
Aim: To observe the effects of Ningmitai capsule on semen parameters of infertile patients with chronic prostatitis (CP) and explore the mechanisms. Methods: A total of 43 patients diagnosed with CP were included in the study and administered Ningmitai capsules (4 capsules per dose) for a duration of 6 weeks. Subsequently, assessments were conducted on parameters including sperm concentration, forward progressive motility, total motility, oxidative and anti-oxidative indicators, as well as the concentration of interleukin-8 (IL-8) in seminal plasma before and after the treatment period. Results: Compared to pre-treatment, forward progressive motility and total motility of the semen increased significantly (37.15% ± 18.77% vs. 45.44% ± 19.08%, P < 0.05 and 42.56% ± 21.22% vs. 51.64% ± 19.48%, P < 0.05). And the expression of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) increased significantly after treatment as well (11.36 μmol/L ± 3.28 μmol/L vs. 12.79 μmol/L ± 2.87 μmol/L, P < 0.05 and 9.34 U/mL ± 3.22 U/mL vs. 11.21 U/mL ± 4.87 U/mL, P < 0.05). In addition, the expression of malondialdehyde (MDA) and IL-8 decreased significantly after treatment (41.06 μmol/L ± 24.39 μmol/L vs. 32.17 μmol/L ± 15.04 μmol/L, P < 0.05 and 79.69 ng/L ± 26.24 ng/L vs. 61.35 ng/L ± 23.41 ng/L, P < 0.05). No significant difference in sperm concentration and sperm DNA fragmentation index was observed after the treatment (P > 0.05). Conclusions: Ningmitai capsule can enhance the antioxidant capacity and down-regulate the expression of cytokines in the semen, thereby improving the semen parameters of infertile patients with CP.
目的：观察宁泌泰胶囊对慢性前列腺炎（CP）不育患者精液参数的影响，并探讨其机制：方法：研究共纳入43名确诊为慢性前列腺炎的患者，他们服用宁泌泰胶囊（每次4粒），疗程为6周。随后，对治疗前后精浆中的精子浓度、前向运动能力、总运动能力、氧化和抗氧化指标以及白细胞介素-8（IL-8）浓度等参数进行评估：与治疗前相比，精液的前向运动能力和总运动能力显著增加（37.15% ± 18.77% vs. 45.44% ± 19.08%，P < 0.05；42.56% ± 21.22% vs. 51.64% ± 19.48%，P < 0.05）。超氧化物歧化酶（SOD）和总抗氧化能力（T-AOC）的表达在治疗后也显著增加（11.36 μmol/L ± 3.28 μmol/L vs. 12.79 μmol/L ± 2.87 μmol/L，P < 0.05；9.34 U U/mL ± 3.22 U/mL vs. 11.21 U U/mL ± 4.87 U/mL，P < 0.05）。此外，治疗后丙二醛（MDA）和IL-8的表达也显著下降（41.06 μmol/L ± 24.39 μmol/L vs. 32.17 μmol/L ± 15.04 μmol/L，P < 0.05；79.69 ng/L ± 26.24 ng/L vs. 61.35 ng/L ± 23.41 ng/L，P < 0.05）。治疗后精子浓度和精子DNA碎片指数无明显差异（P > 0.05）：结论：宁神胶囊能增强精液的抗氧化能力，下调精液中细胞因子的表达，从而改善CP不育患者的精液指标。
{"title":"Ningmitai capsule improves the semen quality of male infertile with chronic prostatitis by antioxidant and anti-inflammatory","authors":"Xiaoyu Wu, Zhen Ye, Li-hua Li, Huiping Zhang, Xunbing Huang, Jingsong Chai, Xinzong Zhang","doi":"10.37349/ei.2023.00123","DOIUrl":"https://doi.org/10.37349/ei.2023.00123","url":null,"abstract":"Aim: To observe the effects of Ningmitai capsule on semen parameters of infertile patients with chronic prostatitis (CP) and explore the mechanisms.\u0000Methods: A total of 43 patients diagnosed with CP were included in the study and administered Ningmitai capsules (4 capsules per dose) for a duration of 6 weeks. Subsequently, assessments were conducted on parameters including sperm concentration, forward progressive motility, total motility, oxidative and anti-oxidative indicators, as well as the concentration of interleukin-8 (IL-8) in seminal plasma before and after the treatment period.\u0000Results: Compared to pre-treatment, forward progressive motility and total motility of the semen increased significantly (37.15% ± 18.77% vs. 45.44% ± 19.08%, P < 0.05 and 42.56% ± 21.22% vs. 51.64% ± 19.48%, P < 0.05). And the expression of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) increased significantly after treatment as well (11.36 μmol/L ± 3.28 μmol/L vs. 12.79 μmol/L ± 2.87 μmol/L, P < 0.05 and 9.34 U/mL ± 3.22 U/mL vs. 11.21 U/mL ± 4.87 U/mL, P < 0.05). In addition, the expression of malondialdehyde (MDA) and IL-8 decreased significantly after treatment (41.06 μmol/L ± 24.39 μmol/L vs. 32.17 μmol/L ± 15.04 μmol/L, P < 0.05 and 79.69 ng/L ± 26.24 ng/L vs. 61.35 ng/L ± 23.41 ng/L, P < 0.05). No significant difference in sperm concentration and sperm DNA fragmentation index was observed after the treatment (P > 0.05).\u0000Conclusions: Ningmitai capsule can enhance the antioxidant capacity and down-regulate the expression of cytokines in the semen, thereby improving the semen parameters of infertile patients with CP.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":"19 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138971588","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}
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