Pub Date : 2023-02-01DOI: 10.1007/s12016-022-08925-1
Maria Elena Laino, Angela Ammirabile, Francesca Motta, Maria De Santis, Victor Savevski, Marco Francone, Arturo Chiti, Lorenzo Mannelli, Carlo Selmi, Lorenzo Monti
The cardiovascular system is frequently affected by coronavirus disease-19 (COVID-19), particularly in hospitalized cases, and these manifestations are associated with a worse prognosis. Most commonly, heart involvement is represented by myocarditis, myocardial infarction, and pulmonary embolism, while arrhythmias, heart valve damage, and pericarditis are less frequent. While the clinical suspicion is necessary for a prompt disease recognition, imaging allows the early detection of cardiovascular complications in patients with COVID-19. The combination of cardiothoracic approaches has been proposed for advanced imaging techniques, i.e., CT scan and MRI, for a simultaneous evaluation of cardiovascular structures, pulmonary arteries, and lung parenchyma. Several mechanisms have been proposed to explain the cardiovascular injury, and among these, it is established that the host immune system is responsible for the aberrant response characterizing severe COVID-19 and inducing organ-specific injury. We illustrate novel evidence to support the hypothesis that molecular mimicry may be the immunological mechanism for myocarditis in COVID-19. The present article provides a comprehensive review of the available evidence of the immune mechanisms of the COVID-19 cardiovascular injury and the imaging tools to be used in the diagnostic workup. As some of these techniques cannot be implemented for general screening of all cases, we critically discuss the need to maximize the sustainability and the specificity of the proposed tests while illustrating the findings of some paradigmatic cases.
{"title":"Advanced Imaging Supports the Mechanistic Role of Autoimmunity and Plaque Rupture in COVID-19 Heart Involvement.","authors":"Maria Elena Laino, Angela Ammirabile, Francesca Motta, Maria De Santis, Victor Savevski, Marco Francone, Arturo Chiti, Lorenzo Mannelli, Carlo Selmi, Lorenzo Monti","doi":"10.1007/s12016-022-08925-1","DOIUrl":"https://doi.org/10.1007/s12016-022-08925-1","url":null,"abstract":"<p><p>The cardiovascular system is frequently affected by coronavirus disease-19 (COVID-19), particularly in hospitalized cases, and these manifestations are associated with a worse prognosis. Most commonly, heart involvement is represented by myocarditis, myocardial infarction, and pulmonary embolism, while arrhythmias, heart valve damage, and pericarditis are less frequent. While the clinical suspicion is necessary for a prompt disease recognition, imaging allows the early detection of cardiovascular complications in patients with COVID-19. The combination of cardiothoracic approaches has been proposed for advanced imaging techniques, i.e., CT scan and MRI, for a simultaneous evaluation of cardiovascular structures, pulmonary arteries, and lung parenchyma. Several mechanisms have been proposed to explain the cardiovascular injury, and among these, it is established that the host immune system is responsible for the aberrant response characterizing severe COVID-19 and inducing organ-specific injury. We illustrate novel evidence to support the hypothesis that molecular mimicry may be the immunological mechanism for myocarditis in COVID-19. The present article provides a comprehensive review of the available evidence of the immune mechanisms of the COVID-19 cardiovascular injury and the imaging tools to be used in the diagnostic workup. As some of these techniques cannot be implemented for general screening of all cases, we critically discuss the need to maximize the sustainability and the specificity of the proposed tests while illustrating the findings of some paradigmatic cases.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The current COVID-19 global pandemic poses immense challenges to global health, largely due to the difficulty to detect infection in the early stages of the disease, as well as the current lack of effective antiviral therapy. Research and understanding of the human immune system can provide important theoretical and technical support for the clinical diagnosis and treatment of COVID-19, the clinical implementations of which include immunoassays and immunotherapy, which play a crucial role in the fight against the pandemic. This review consolidates the current scientific evidence for immunoassay, which includes multiple methods of detecting antigen and antibody against SARS-CoV-2. We compared the characteristics, advantages and disadvantages, and clinical applications of these three detection techniques. In addition to detecting viral infections, knowledge on the body's immunity against the virus is desirable; thus, the immunotherapy-based neutralizing antibody (nAb) detection methods were discussed. We also gave a brief introduction to the new immunoassay technology such as biosensing. This was followed by an in-depth and extensive review on a variety of immunotherapy methods. It includes convalescent plasma therapy, neutralizing antibody-based treatments targeting different regions of SARS-CoV-2, immunotherapy targeted on the host cell including inhibiting the host cell receptor and cytokine storm, as well as cocktail antibodies, cross-neutralizing antibodies, and immunotherapy based on cross-reactivity between viral epitopes and autoepitopes and autoantibody. Despite the development of various immunological testing methods and antibody therapies, the current global situation of COVID-19 is still tense. We need more efficient detection methods and more reliable antibody therapies. The up-to-date knowledge on therapeutic strategies will likely help clinicians worldwide to protect patients from life-threatening viral infections.
{"title":"Clinical Application of Antibody Immunity Against SARS-CoV-2: Comprehensive Review on Immunoassay and Immunotherapy.","authors":"Zhangkai J Cheng, Bizhou Li, Zhiqing Zhan, Zifan Zhao, Mingshan Xue, Peiyan Zheng, Jiali Lyu, Chundi Hu, Jianxing He, Ruchong Chen, Baoqing Sun","doi":"10.1007/s12016-021-08912-y","DOIUrl":"https://doi.org/10.1007/s12016-021-08912-y","url":null,"abstract":"<p><p>The current COVID-19 global pandemic poses immense challenges to global health, largely due to the difficulty to detect infection in the early stages of the disease, as well as the current lack of effective antiviral therapy. Research and understanding of the human immune system can provide important theoretical and technical support for the clinical diagnosis and treatment of COVID-19, the clinical implementations of which include immunoassays and immunotherapy, which play a crucial role in the fight against the pandemic. This review consolidates the current scientific evidence for immunoassay, which includes multiple methods of detecting antigen and antibody against SARS-CoV-2. We compared the characteristics, advantages and disadvantages, and clinical applications of these three detection techniques. In addition to detecting viral infections, knowledge on the body's immunity against the virus is desirable; thus, the immunotherapy-based neutralizing antibody (nAb) detection methods were discussed. We also gave a brief introduction to the new immunoassay technology such as biosensing. This was followed by an in-depth and extensive review on a variety of immunotherapy methods. It includes convalescent plasma therapy, neutralizing antibody-based treatments targeting different regions of SARS-CoV-2, immunotherapy targeted on the host cell including inhibiting the host cell receptor and cytokine storm, as well as cocktail antibodies, cross-neutralizing antibodies, and immunotherapy based on cross-reactivity between viral epitopes and autoepitopes and autoantibody. Despite the development of various immunological testing methods and antibody therapies, the current global situation of COVID-19 is still tense. We need more efficient detection methods and more reliable antibody therapies. The up-to-date knowledge on therapeutic strategies will likely help clinicians worldwide to protect patients from life-threatening viral infections.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8760112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10607712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1007/s12016-021-08848-3
Bryan Oronsky, Christopher Larson, Terese C Hammond, Arnold Oronsky, Santosh Kesari, Michelle Lybeck, Tony R Reid
Persistent post-COVID syndrome, also referred to as long COVID, is a pathologic entity, which involves persistent physical, medical, and cognitive sequelae following COVID-19, including persistent immunosuppression as well as pulmonary, cardiac, and vascular fibrosis. Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life. Inhibiting transforming growth factor beta (TGF-β), an immuno- and a fibrosis modulator, may attenuate these post-COVID sequelae. Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID-19 and its presymptomatic and prodromal periods; by comparison, the postdrome, which occurs in the aftermath of COVID-19, which we refer to as persistent post-COVID-syndrome, has received little attention. Potential long-term effects from post-COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital, placing a burden on healthcare systems, patients' families, and society in general to care for these medically devastated COVID-19 survivors. This review explores underlying mechanisms and possible manifestations of persistent post-COVID syndrome, and presents a framework of strategies for the diagnosis and management of patients with suspected or confirmed persistent post-COVID syndrome.
{"title":"A Review of Persistent Post-COVID Syndrome (PPCS).","authors":"Bryan Oronsky, Christopher Larson, Terese C Hammond, Arnold Oronsky, Santosh Kesari, Michelle Lybeck, Tony R Reid","doi":"10.1007/s12016-021-08848-3","DOIUrl":"https://doi.org/10.1007/s12016-021-08848-3","url":null,"abstract":"<p><p>Persistent post-COVID syndrome, also referred to as long COVID, is a pathologic entity, which involves persistent physical, medical, and cognitive sequelae following COVID-19, including persistent immunosuppression as well as pulmonary, cardiac, and vascular fibrosis. Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life. Inhibiting transforming growth factor beta (TGF-β), an immuno- and a fibrosis modulator, may attenuate these post-COVID sequelae. Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID-19 and its presymptomatic and prodromal periods; by comparison, the postdrome, which occurs in the aftermath of COVID-19, which we refer to as persistent post-COVID-syndrome, has received little attention. Potential long-term effects from post-COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital, placing a burden on healthcare systems, patients' families, and society in general to care for these medically devastated COVID-19 survivors. This review explores underlying mechanisms and possible manifestations of persistent post-COVID syndrome, and presents a framework of strategies for the diagnosis and management of patients with suspected or confirmed persistent post-COVID syndrome.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/s12016-021-08848-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10679076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1007/s12016-021-08908-8
Rundong Qin, Li He, Zhaowei Yang, Nan Jia, Ruchong Chen, Jiaxing Xie, Wanyi Fu, Hao Chen, Xinliu Lin, Renbin Huang, Tian Luo, Yukai Liu, Siyang Yao, Mei Jiang, Jing Li
Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4+ T/CD8+ T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3+ T,CD4+T and CD8+T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4+ and CD8+ T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.
一些观察性研究报道了与COVID-19患者疾病严重程度和死亡率相关的异常免疫指标。然而,在这些研究中,患者特征和研究方法存在明显的异质性。我们的目的是提供免疫相关指标与COVID-19预后之间关联的最新综合。我们对PubMed、Scopus、Ovid、Willey、Web of Science、Cochrane library和CNKI进行了电子检索,以获取报告在不同严重程度和结局的COVID-19住院患者中检测的免疫学和/或免疫相关参数(包括血液学、炎症、凝血和生化变量)的研究。目前的荟萃分析共纳入145项研究,包括26项免疫学、11项血液学、5项炎症、4项凝血和10项生化变量。其中,危重患者或非幸存者IL-1β、IL-1Ra、IL-2R、IL-4、IL-6、IL-8、IL-10、IL-18、TNF-α、IFN-γ、IgA、IgG、CD4+ T/CD8+ T细胞比值、WBC、中性粒细胞、血小板、ESR、CRP、铁蛋白、SAA、d -二聚体、FIB、LDH等细胞因子水平均显著升高。此外,非重症患者或幸存者的淋巴细胞、单核细胞、淋巴细胞/单核细胞比率、嗜酸性粒细胞、CD3+ T、CD4+T和CD8+T细胞、B细胞和NK细胞的计数均显著较高。当前更新的荟萃分析主要确定了与COVID-19严重程度和死亡率相关的高细胞素血症谱,其中含有IL-1β、IL-1Ra、IL-2R、IL-4、IL-6、IL-8、IL-10、IL-18、TNF-α和IFN-γ。先天免疫和适应性免疫反应受损是预后不良患者的显著特征,表现为嗜酸性粒细胞、淋巴细胞、单核细胞、B细胞、NK细胞、T细胞及其亚型CD4+和CD8+ T细胞减少,炎症增强、凝血功能障碍和非肺器官损伤。因此,免疫反应功能障碍参数结合炎症、凝血或非肺器官损伤指标可能对预测重症患者和非幸存者更为敏感。
{"title":"Identification of Parameters Representative of Immune Dysfunction in Patients with Severe and Fatal COVID-19 Infection: a Systematic Review and Meta-analysis.","authors":"Rundong Qin, Li He, Zhaowei Yang, Nan Jia, Ruchong Chen, Jiaxing Xie, Wanyi Fu, Hao Chen, Xinliu Lin, Renbin Huang, Tian Luo, Yukai Liu, Siyang Yao, Mei Jiang, Jing Li","doi":"10.1007/s12016-021-08908-8","DOIUrl":"https://doi.org/10.1007/s12016-021-08908-8","url":null,"abstract":"<p><p>Abnormal immunological indicators associated with disease severity and mortality in patients with COVID-19 have been reported in several observational studies. However, there are marked heterogeneities in patient characteristics and research methodologies in these studies. We aimed to provide an updated synthesis of the association between immune-related indicators and COVID-19 prognosis. We conducted an electronic search of PubMed, Scopus, Ovid, Willey, Web of Science, Cochrane library, and CNKI for studies reporting immunological and/or immune-related parameters, including hematological, inflammatory, coagulation, and biochemical variables, tested on hospital admission of COVID-19 patients with different severities and outcomes. A total of 145 studies were included in the current meta-analysis, with 26 immunological, 11 hematological, 5 inflammatory, 4 coagulation, and 10 biochemical variables reported. Of them, levels of cytokines, including IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, IFN-γ, IgA, IgG, and CD4<sup>+</sup> T/CD8<sup>+</sup> T cell ratio, WBC, neutrophil, platelet, ESR, CRP, ferritin, SAA, D-dimer, FIB, and LDH were significantly increased in severely ill patients or non-survivors. Moreover, non-severely ill patients or survivors presented significantly higher counts of lymphocytes, monocytes, lymphocyte/monocyte ratio, eosinophils, CD3<sup>+</sup> T,CD4<sup>+</sup>T and CD8<sup>+</sup>T cells, B cells, and NK cells. The currently updated meta-analysis primarily identified a hypercytokinemia profile with the severity and mortality of COVID-19 containing IL-1β, IL-1Ra, IL-2R, IL-4, IL-6, IL-8, IL-10, IL-18, TNF-α, and IFN-γ. Impaired innate and adaptive immune responses, reflected by decreased eosinophils, lymphocytes, monocytes, B cells, NK cells, T cells, and their subtype CD4<sup>+</sup> and CD8<sup>+</sup> T cells, and augmented inflammation, coagulation dysfunction, and nonpulmonary organ injury, were marked features of patients with poor prognosis. Therefore, parameters of immune response dysfunction combined with inflammatory, coagulated, or nonpulmonary organ injury indicators may be more sensitive to predict severe patients and those non-survivors.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10608207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The outbreak of the coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an evolving global health crisis. Currently, a number of risk factors have been identified to have a potential impact on increasing the morbidity of COVID-19 in adults, including old age, male sex, pre-existing comorbidities, and racial/ethnic disparities. In addition to these factors, changes in laboratory indices and pro-inflammatory cytokines, as well as possible complications, could indicate the progression of COVID-19 into a severe and critical stage. Children predominantly suffer from mild illnesses due to COVID-19. Similar to adults, the main risk factors in pediatric patients include age and pre-existing comorbidities. In contrast, supplementation with a healthy diet and sufficient nutrition, COVID-19 vaccination, and atopic conditions may act as protective factors against the infection of SARS-CoV-2. COVID-19 vaccination not only protects vulnerable individuals from SARS-CoV-2 infection, more importantly, it may also reduce the development of severe disease and death due to COVID-19. Currently used therapies for COVID-19 are off-label and empiric, and their impacts on the severity and mortality of COVID-19 are still unclear. The interaction between asthma and COVID-19 may be bidirectional and needs to be clarified in more studies. In this review, we highlight the clinical evidence supporting the rationale for the risk and protective factors for the morbidity, severity, and mortality of COVID-19.
{"title":"Risk and Protective Factors for COVID-19 Morbidity, Severity, and Mortality.","authors":"Jin-Jin Zhang, Xiang Dong, Guang-Hui Liu, Ya-Dong Gao","doi":"10.1007/s12016-022-08921-5","DOIUrl":"https://doi.org/10.1007/s12016-022-08921-5","url":null,"abstract":"<p><p>The outbreak of the coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an evolving global health crisis. Currently, a number of risk factors have been identified to have a potential impact on increasing the morbidity of COVID-19 in adults, including old age, male sex, pre-existing comorbidities, and racial/ethnic disparities. In addition to these factors, changes in laboratory indices and pro-inflammatory cytokines, as well as possible complications, could indicate the progression of COVID-19 into a severe and critical stage. Children predominantly suffer from mild illnesses due to COVID-19. Similar to adults, the main risk factors in pediatric patients include age and pre-existing comorbidities. In contrast, supplementation with a healthy diet and sufficient nutrition, COVID-19 vaccination, and atopic conditions may act as protective factors against the infection of SARS-CoV-2. COVID-19 vaccination not only protects vulnerable individuals from SARS-CoV-2 infection, more importantly, it may also reduce the development of severe disease and death due to COVID-19. Currently used therapies for COVID-19 are off-label and empiric, and their impacts on the severity and mortality of COVID-19 are still unclear. The interaction between asthma and COVID-19 may be bidirectional and needs to be clarified in more studies. In this review, we highlight the clinical evidence supporting the rationale for the risk and protective factors for the morbidity, severity, and mortality of COVID-19.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8767775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10608212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01Epub Date: 2021-12-15DOI: 10.1007/s12016-021-08905-x
Ozlem Bulut, Gizem Kilic, Jorge Domínguez-Andrés
Non-specific innate and antigen-specific adaptive immunological memories are vital evolutionary adaptations that confer long-lasting protection against a wide range of pathogens. Adaptive memory is established by memory T and B lymphocytes following the recognition of an antigen. On the other hand, innate immune memory, also called trained immunity, is imprinted in innate cells such as macrophages and natural killer cells through epigenetic and metabolic reprogramming. However, these mechanisms of memory generation and maintenance are compromised as organisms age. Almost all immune cell types, both mature cells and their progenitors, go through age-related changes concerning numbers and functions. The aging immune system renders the elderly highly susceptible to infections and incapable of mounting a proper immune response upon vaccinations. Besides the increased infectious burden, older individuals also have heightened risks of metabolic and neurodegenerative diseases, which have an immunological component. This review discusses how immune function, particularly the establishment and maintenance of innate and adaptive immunological memory, regulates and is regulated by epigenetics, metabolic processes, gut microbiota, and the central nervous system throughout life, with a focus on old age. We explain in-depth how epigenetics and cellular metabolism impact immune cell function and contribute or resist the aging process. Microbiota is intimately linked with the immune system of the human host, and therefore, plays an important role in immunological memory during both homeostasis and aging. The brain, which is not an immune-isolated organ despite former opinion, interacts with the peripheral immune cells, and the aging of both systems influences the health of each other. With all these in mind, we aimed to present a comprehensive view of the aging immune system and its consequences, especially in terms of immunological memory. The review also details the mechanisms of promising anti-aging interventions and highlights a few, namely, caloric restriction, physical exercise, metformin, and resveratrol, that impact multiple facets of the aging process, including the regulation of innate and adaptive immune memory. We propose that understanding aging as a complex phenomenon, with the immune system at the center role interacting with all the other tissues and systems, would allow for more effective anti-aging strategies.
{"title":"Immune Memory in Aging: a Wide Perspective Covering Microbiota, Brain, Metabolism, and Epigenetics.","authors":"Ozlem Bulut, Gizem Kilic, Jorge Domínguez-Andrés","doi":"10.1007/s12016-021-08905-x","DOIUrl":"https://doi.org/10.1007/s12016-021-08905-x","url":null,"abstract":"<p><p>Non-specific innate and antigen-specific adaptive immunological memories are vital evolutionary adaptations that confer long-lasting protection against a wide range of pathogens. Adaptive memory is established by memory T and B lymphocytes following the recognition of an antigen. On the other hand, innate immune memory, also called trained immunity, is imprinted in innate cells such as macrophages and natural killer cells through epigenetic and metabolic reprogramming. However, these mechanisms of memory generation and maintenance are compromised as organisms age. Almost all immune cell types, both mature cells and their progenitors, go through age-related changes concerning numbers and functions. The aging immune system renders the elderly highly susceptible to infections and incapable of mounting a proper immune response upon vaccinations. Besides the increased infectious burden, older individuals also have heightened risks of metabolic and neurodegenerative diseases, which have an immunological component. This review discusses how immune function, particularly the establishment and maintenance of innate and adaptive immunological memory, regulates and is regulated by epigenetics, metabolic processes, gut microbiota, and the central nervous system throughout life, with a focus on old age. We explain in-depth how epigenetics and cellular metabolism impact immune cell function and contribute or resist the aging process. Microbiota is intimately linked with the immune system of the human host, and therefore, plays an important role in immunological memory during both homeostasis and aging. The brain, which is not an immune-isolated organ despite former opinion, interacts with the peripheral immune cells, and the aging of both systems influences the health of each other. With all these in mind, we aimed to present a comprehensive view of the aging immune system and its consequences, especially in terms of immunological memory. The review also details the mechanisms of promising anti-aging interventions and highlights a few, namely, caloric restriction, physical exercise, metformin, and resveratrol, that impact multiple facets of the aging process, including the regulation of innate and adaptive immune memory. We propose that understanding aging as a complex phenomenon, with the immune system at the center role interacting with all the other tissues and systems, would allow for more effective anti-aging strategies.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8671603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39604458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01Epub Date: 2022-09-01DOI: 10.1007/s12016-022-08952-y
Benjamin Greiner, Savannah Nicks, Michael Adame, Jennifer McCracken
Chronic spontaneous urticaria (CSU) is characterized by recurring wheals that last 6 weeks or longer without an identifiable cause. The estimated point prevalence of CSU worldwide is 1%. Furthermore, it has a significant impact on quality of life in both adults and pediatric patients and their families. Although it is most often a self-limited disease, some patients have urticaria refractory to first-line treatment: second-generation H1 antihistamines. In these patients, the use of targeted monoclonal antibodies is necessary. While omalizumab is the only Food and Drug Administration-approved monoclonal antibody for CSU, others, including ligelizumab, dupilumab, benralizumab, and several orally administered Bruton's tyrosine kinase inhibitors, are also promising therapeutics for reducing the morbidity of CSU. Novel therapies, among others discussed here, are rapidly being developed with new trials and therapeutics being released nearly monthly. Thus, we performed a scoping literature review of randomized controlled trials studying targeted therapies for CSU. We also discuss the pathophysiology, diagnosis, prognosis, and future research directions in CSU.
{"title":"Pathophysiology, Diagnosis, and Management of Chronic Spontaneous Urticaria: A Literature Review.","authors":"Benjamin Greiner, Savannah Nicks, Michael Adame, Jennifer McCracken","doi":"10.1007/s12016-022-08952-y","DOIUrl":"https://doi.org/10.1007/s12016-022-08952-y","url":null,"abstract":"<p><p>Chronic spontaneous urticaria (CSU) is characterized by recurring wheals that last 6 weeks or longer without an identifiable cause. The estimated point prevalence of CSU worldwide is 1%. Furthermore, it has a significant impact on quality of life in both adults and pediatric patients and their families. Although it is most often a self-limited disease, some patients have urticaria refractory to first-line treatment: second-generation H1 antihistamines. In these patients, the use of targeted monoclonal antibodies is necessary. While omalizumab is the only Food and Drug Administration-approved monoclonal antibody for CSU, others, including ligelizumab, dupilumab, benralizumab, and several orally administered Bruton's tyrosine kinase inhibitors, are also promising therapeutics for reducing the morbidity of CSU. Novel therapies, among others discussed here, are rapidly being developed with new trials and therapeutics being released nearly monthly. Thus, we performed a scoping literature review of randomized controlled trials studying targeted therapies for CSU. We also discuss the pathophysiology, diagnosis, prognosis, and future research directions in CSU.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40337416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01Epub Date: 2022-09-19DOI: 10.1007/s12016-022-08930-4
Gemma Lepri, Martina Catalano, Silvia Bellando-Randone, Serena Pillozzi, Elisa Giommoni, Roberta Giorgione, Cristina Botteri, Marco Matucci-Cerinic, Lorenzo Antonuzzo, Serena Guiducci
The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lung fibrosis and a long standing SSc pulmonary involvement have been largely proposed as lung cancer risk factors, and the exposure to cyclophosphamide and an upper gastrointestinal involvement have been traditionally linked to bladder and oesophagus cancers, respectively. Furthermore, immune checkpoint inhibitors used for cancer therapy can induce immune-related adverse events, which are more frequent and severe in patients with pre-existing autoimmune diseases such as SSc. The strong association between SSc and cancer occurrence steers clinicians to carefully survey SSc patients performing periodical malignancy screening. In the present review, the most relevant bilateral relationships between SSc and cancer will be addressed.
{"title":"Systemic Sclerosis Association with Malignancy.","authors":"Gemma Lepri, Martina Catalano, Silvia Bellando-Randone, Serena Pillozzi, Elisa Giommoni, Roberta Giorgione, Cristina Botteri, Marco Matucci-Cerinic, Lorenzo Antonuzzo, Serena Guiducci","doi":"10.1007/s12016-022-08930-4","DOIUrl":"https://doi.org/10.1007/s12016-022-08930-4","url":null,"abstract":"<p><p>The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lung fibrosis and a long standing SSc pulmonary involvement have been largely proposed as lung cancer risk factors, and the exposure to cyclophosphamide and an upper gastrointestinal involvement have been traditionally linked to bladder and oesophagus cancers, respectively. Furthermore, immune checkpoint inhibitors used for cancer therapy can induce immune-related adverse events, which are more frequent and severe in patients with pre-existing autoimmune diseases such as SSc. The strong association between SSc and cancer occurrence steers clinicians to carefully survey SSc patients performing periodical malignancy screening. In the present review, the most relevant bilateral relationships between SSc and cancer will be addressed.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9674744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40369493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01Epub Date: 2022-09-19DOI: 10.1007/s12016-022-08954-w
Bo Xie, Jiayi Sun, Xiuzu Song
Alopecia areata (AA) is characterized by common non-scarring alopecia due to autoimmune disorders. To date, the specific pathogenesis underlying AA remains unknown. Thus, AA treatment in the dermatological clinic is still a challenge. Numerous clinical observations and experimental studies have established that melanocytes may be the trigger point that causes hair follicles to be attacked by the immune system. A possible mechanism is that the impaired melanocytes, under oxidative stress, cannot be repaired in time and causes apoptosis. Melanocyte-associated autoantigens are released and presented, inducing CD8+ T cell attacks. Thereafter, amplification of the immune responses further spreads to the entire hair follicle (HF). The immune privilege of HF subsequently collapses, leading to AA. Herein, we present a narrative review on the roles of melanocytes in AA pathogenesis, aiming to provide a better understanding of this disease from the melanocyte's perspective.
{"title":"Hair Follicle Melanocytes Initiate Autoimmunity in Alopecia Areata: a Trigger Point.","authors":"Bo Xie, Jiayi Sun, Xiuzu Song","doi":"10.1007/s12016-022-08954-w","DOIUrl":"https://doi.org/10.1007/s12016-022-08954-w","url":null,"abstract":"<p><p>Alopecia areata (AA) is characterized by common non-scarring alopecia due to autoimmune disorders. To date, the specific pathogenesis underlying AA remains unknown. Thus, AA treatment in the dermatological clinic is still a challenge. Numerous clinical observations and experimental studies have established that melanocytes may be the trigger point that causes hair follicles to be attacked by the immune system. A possible mechanism is that the impaired melanocytes, under oxidative stress, cannot be repaired in time and causes apoptosis. Melanocyte-associated autoantigens are released and presented, inducing CD8<sup>+</sup> T cell attacks. Thereafter, amplification of the immune responses further spreads to the entire hair follicle (HF). The immune privilege of HF subsequently collapses, leading to AA. Herein, we present a narrative review on the roles of melanocytes in AA pathogenesis, aiming to provide a better understanding of this disease from the melanocyte's perspective.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40369494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01Epub Date: 2022-09-17DOI: 10.1007/s12016-022-08953-x
Elisabeth Hodara, Peck Y Ong
Eczema herpeticum (EH) is a viral skin infection caused by herpes simplex virus (HSV) superimposed on eczematous skin lesions in atopic dermatitis (AD). Though the pathogenesis of EH has yet to be fully elucidated, the fact that EH is relatively rare despite a majority of adults showing serologic evidence of HSV exposure points to a genetic component predisposing to the disease. A number of genetic variants have been isolated in EH which may help distinguish a subgroup of patients susceptible to developing the condition. These unique genetic characteristics include deficiencies in skin barrier function and hydration, as well as at the level of the immune system. In this review, we summarize the genetic findings associated with EH identified to date. Isolating genetic markers in EH will be instrumental in stratifying patients at risk for EH and will have significant implications in the development and tailoring of targeted therapies.
{"title":"The Genetics of Eczema Herpeticum.","authors":"Elisabeth Hodara, Peck Y Ong","doi":"10.1007/s12016-022-08953-x","DOIUrl":"https://doi.org/10.1007/s12016-022-08953-x","url":null,"abstract":"<p><p>Eczema herpeticum (EH) is a viral skin infection caused by herpes simplex virus (HSV) superimposed on eczematous skin lesions in atopic dermatitis (AD). Though the pathogenesis of EH has yet to be fully elucidated, the fact that EH is relatively rare despite a majority of adults showing serologic evidence of HSV exposure points to a genetic component predisposing to the disease. A number of genetic variants have been isolated in EH which may help distinguish a subgroup of patients susceptible to developing the condition. These unique genetic characteristics include deficiencies in skin barrier function and hydration, as well as at the level of the immune system. In this review, we summarize the genetic findings associated with EH identified to date. Isolating genetic markers in EH will be instrumental in stratifying patients at risk for EH and will have significant implications in the development and tailoring of targeted therapies.</p>","PeriodicalId":10423,"journal":{"name":"Clinical Reviews in Allergy & Immunology","volume":null,"pages":null},"PeriodicalIF":9.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40364577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}