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Altered pre-existing SARS-CoV-2-specific T cell responses in elderly individuals 老年人先前存在的sars - cov -2特异性T细胞反应的改变
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2021.12.001
Naoyuki Taira , Sakura Toguchi , Mio Miyagi , Tomoari Mori , Hiroaki Tomori , Koichi Oshiro , Osamu Tamai , Mitsuo Kina , Masatake Miyagi , Kentaro Tamaki , Mary K Collins , Hiroki Ishikawa

Pre-existing SARS-CoV-2-specific T cells, but not antibodies, have been detected in some unexposed individuals. This may account for some of the diversity in clinical outcomes ranging from asymptomatic infection to severe COVID-19. Although age is a risk factor for COVID-19, how age affects SARS-CoV-2-specific T cell responses remains unknown. We found that pre-existing T cell responses to specific SARS-CoV-2 proteins, Spike (S) and Nucleoprotein (N), were significantly lower in elderly donors (>70 years old) than in young donors. However, substantial pre-existing T cell responses to the viral membrane (M) protein were detected in both young and elderly donors. In contrast, young and elderly donors exhibited comparable T cell responses to S, N, and M proteins after infection with SARS-CoV-2. These data suggest that although SARS-CoV-2 infection can induce T cell responses specific to various viral antigens regardless of age, diversity of target antigen repertoire for long-lived memory T cells specific for SARS-CoV-2 may decline with age; however, memory T cell responses can be maintained by T cells reactive to specific viral proteins such as M. A better understanding of the role of pre-existing SARS-CoV-2-specific T cells that are less susceptible to age-related loss may contribute to development of more effective vaccines for elderly people.

在一些未暴露的个体中检测到预先存在的sars - cov -2特异性T细胞,但没有抗体。这可能解释了从无症状感染到严重COVID-19的临床结果的一些差异。虽然年龄是COVID-19的一个危险因素,但年龄如何影响sars - cov -2特异性T细胞反应仍不清楚。我们发现,老年供者(70岁)对特异性SARS-CoV-2蛋白Spike (S)和核蛋白(N)的预先存在的T细胞反应明显低于年轻供者。然而,在年轻和老年供者中都检测到大量预先存在的T细胞对病毒膜(M)蛋白的反应。相比之下,年轻和老年供者在感染SARS-CoV-2后对S、N和M蛋白表现出相似的T细胞反应。这些数据表明,尽管SARS-CoV-2感染可以诱导对各种病毒抗原特异性的T细胞反应,而与年龄无关,但SARS-CoV-2特异性的长寿命记忆T细胞的靶抗原库的多样性可能随着年龄的增长而下降;然而,记忆T细胞反应可以通过T细胞对特定病毒蛋白(如M.)的反应来维持。更好地了解预先存在的sars - cov -2特异性T细胞的作用,这些细胞不太容易受到年龄相关损失的影响,可能有助于开发更有效的老年人疫苗。
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引用次数: 2
Hepatitis E virus sero-prevalence among pregnant women in Khyber Pakhtunkhwa Pakistan 戊型肝炎病毒在巴基斯坦开伯尔-普赫图赫瓦省孕妇的血清患病率
Pub Date : 2022-12-01 DOI: 10.1016/j.clicom.2022.04.001
Shahzad Ahmad Khan , Zafran Khan , Zahoor Alam , Haris Sana , Muhammad Ali , Nasib Zaman , Daniya Ualiveya , Muhammad Rizwan , Muhammad Suleman

In Pakistan, the Hepatitis E virus (HEV) is prevalent. HEV exposure is deadly during pregnancy, with high infection rates in both the mother and the baby, even in asymptomatic situations. The researcher examined HEV-negative pregnant women with acute hepatitis or increased renal characteristic assessments at 12 medical sites in Khyber Pakhtunkhwa, Pakistan, to identify maternal and fetal disease risks from August to December 2018. Except for one during the entire pregnancy, twenty-five of the 135 females were HEV-free and in the perinatal period. HEV infection was found in 0.19% of newly pregnant women. Also, 11 cases of forcible induction of labor, 7 cases of normal labor, 5 cases of normal labor (full-term), 2 cases of death, and 1 case of intrauterine death were reported before going to the doctor a girl had an abortion. There were eight postpartum deaths: five from infections, four from miscarriages, and two from miscarriages. While 18 mothers who survived voluntarily or intentionally induced abortions and three women who continued to get pregnant but did not deliver died as a result of abortion. The current study found that HEV infection during pregnancy raised the death rate by 14.2%.

在巴基斯坦,戊型肝炎病毒(HEV)很流行。妊娠期间接触戊型肝炎病毒是致命的,即使在无症状的情况下,母亲和婴儿的感染率都很高。2018年8月至12月,研究人员在巴基斯坦开伯尔-普赫图赫瓦省的12个医疗站点检查了患有急性肝炎或肾脏特征评估增加的hev阴性孕妇,以确定母体和胎儿疾病的风险。135名女性中,除1名在整个怀孕期间外,其余25名女性在围产期没有感染hiv病毒。新孕妇感染HEV的比例为0.19%。此外,在去看医生之前报告了11例强行引产、7例正常分娩、5例正常分娩(足月)、2例死亡和1例宫内死亡。有8人死于产后:5人死于感染,4人死于流产,2人死于流产。而18名自愿或故意堕胎幸存的母亲和3名继续怀孕但没有分娩的妇女因堕胎而死亡。目前的研究发现,妊娠期感染HEV可使死亡率提高14.2%。
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引用次数: 2
Efficacy and safety of current treatments for paroxysmal nocturnal hemoglobinuria: A systematic review 目前治疗阵发性夜间血红蛋白尿的有效性和安全性:一项系统综述
Pub Date : 2022-11-23 DOI: 10.1016/j.clicom.2022.11.002
Yara Maria da Silva Pires , Aline de Fátima Bonetti , Jessica Telma Ciecilinsky , Astrid Wiens Souza

Paroxysmal nocturnal hemoglobinuria (PNH) is a non-malignant clonal disorder of the pluripotent hematopoietic stem cell. Currently, Eculizumab, Ravulizumab, and Pegcetacoplan are the approved drugs to treat PNH. In order to assess the efficacy and safety of different medications available for PNH, we performed a systematic search. The primary efficacy endpoint was the percentage change in lactate dehydrogenase, transfusion avoidance, and stabilized hemoglobin. Key secondary endpoints included the proportion of patients with breakthrough hemolysis, anemia, adverse events, number of deaths, and discontinuation of treatment. From 2526 articles retrieved from electronic databases and manual searches, a total of five studies were included in this review: 1 observational study and 4 randomized clinical trials. For all efficacy and safety endpoints, Ravulizumab and Pegcetacoplan achieved noninferiority compared with the first standardized treatment Eculizumab. The use of complement inhibition therapy can further improve hematological outcomes in PNH patients.

阵发性夜间血红蛋白尿症(PNH)是一种多能干细胞的非恶性克隆性疾病。目前,Eculizumab、Ravulizumab和Pegcetacoplan是已批准的治疗PNH的药物。为了评估可用于PNH的不同药物的疗效和安全性,我们进行了系统搜索。主要疗效终点是乳酸脱氢酶、避免输血和稳定血红蛋白的百分比变化。关键的次要终点包括突破性溶血、贫血、不良事件、死亡人数和停止治疗的患者比例。从电子数据库和手动搜索中检索到的2526篇文章中,共有5项研究被纳入本综述:1项观察性研究和4项随机临床试验。对于所有疗效和安全性终点,与第一种标准化治疗Eculizumab相比,Ravulizumab和Pegcetacoplan实现了非劣效性。补体抑制疗法的使用可以进一步改善PNH患者的血液学结果。
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引用次数: 0
Pfizer-biontech COVID-19 RNA vaccination induces phosphatidylserine autoantibodies, cryoglobulinemia, and digital necrosis in a patient with pre-existing autoimmunity. 辉瑞-生物技术公司的 COVID-19 RNA 疫苗接种会诱发一名已存在自身免疫的患者出现磷脂酰丝氨酸自身抗体、低温球蛋白血症和数字坏死。
Pub Date : 2021-12-01 Epub Date: 2021-09-27 DOI: 10.1016/j.clicom.2021.08.001
Sandy Nasr, Sara Khalil, Bernard J Poiesz, Katalin Banki, Andras Perl

We describe a 64-year-old Caucasian female with a history of Raynaud's disease, hand arthritis, photosensitivity, Sjogren's syndrome and leukocytoclastic vasculitis who presented with progressively worsening fingertip necrosis that began three days after receiving a first dose of Pfizer-BioNTech COVID-19 RNA vaccine. Our workup revealed cryoglobulinemia, hypocomplementemia, elevated antinuclear antibodies (ANA) and IgM antiphospholipid autoantibodies (aPL) directed against phosphatidylserine (aPL-PS), suggesting a diagnosis of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). The patient failed to develop anti-spike IgG antibodies up to two months following vaccination. Disease progression was halted by plasmapheresis, anticoagulation, and immune suppression. We conclude that the vaccine RNA moiety may induce SLE manifesting in APS, cryoglobulinemia, hypocomplementemia, and digital necrosis.

我们描述了一名 64 岁的白种女性,她有雷诺氏病、手关节炎、光敏感性、Sjogren 综合征和白细胞凝集性血管炎病史,在接种第一剂辉瑞-生物技术公司 COVID-19 RNA 疫苗三天后开始出现逐渐加重的指尖坏死。我们的检查发现了低温球蛋白血症、低补体血症、抗核抗体(ANA)升高和针对磷脂酰丝氨酸的 IgM 抗磷脂自身抗体(aPL)(aPL-PS),提示诊断为系统性红斑狼疮(SLE)和抗磷脂综合征(APS)。患者在接种疫苗后两个月内未能产生抗尖峰蛋白 IgG 抗体。通过血浆置换、抗凝和免疫抑制阻止了疾病进展。我们的结论是,疫苗的 RNA 分子可能会诱发系统性红斑狼疮,表现为 APS、低温球蛋白血症、低补体血症和数字坏死。
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引用次数: 0
The “original antigenic sin” and its relevance for SARS-CoV-2 (COVID-19) vaccination “原始抗原原罪”及其与COVID-19疫苗接种的相关性
Pub Date : 2021-12-01 DOI: 10.1016/j.clicom.2021.10.001
Ger T. Rijkers , Frans J. van Overveld

Imprinting of the specific molecular image of a given protein antigen into immunological memory is one of the hallmarks of immunity. A later contact with a related, but different antigen should not trigger the memory response (because the produced antibodies would not be effective). The preferential expansion of cross-reactive antibodies, or T-lymphocytes for that matter, by a related antigen has been termed the original antigenic sin and was first described by Thomas Francis Jr. in 1960. The phenomenon was initially described for influenza virus, but also has been found for dengue and rotavirus. The antibody dependent enhancement observed in feline coronavirus vaccination also may be related to the original antigenic sin. For a full interpretation of the effectivity of the immune response against SARS-CoV-2, as well as for the success of vaccination, the role of existing immunological memory against circulating corona viruses is reviewed and analyzed.

将特定蛋白抗原的分子图像印入免疫记忆是免疫的标志之一。后来与相关的,但不同的抗原接触不应该触发记忆反应(因为产生的抗体不会有效)。交叉反应抗体或t淋巴细胞在相关抗原作用下的优先扩张被称为原始抗原原罪,并由小托马斯·弗朗西斯(Thomas Francis Jr.)于1960年首次描述。这种现象最初被描述为流感病毒,但也发现了登革热和轮状病毒。在猫冠状病毒疫苗接种中观察到的抗体依赖性增强也可能与原始抗原有关。为了全面解释针对SARS-CoV-2的免疫反应的有效性,以及疫苗接种的成功,本文回顾和分析了针对循环冠状病毒的现有免疫记忆的作用。
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引用次数: 15
Prevalence of asymptomatic SARS-CoV-2 infection in an Austrian cohort. 奥地利队列中无症状 SARS-CoV-2 感染的流行率。
Pub Date : 2021-12-01 Epub Date: 2021-10-07 DOI: 10.1016/j.clicom.2021.08.002
Elisabeth Mara, Verena Breitsching, Tanja Schuster, Thomas Pekar

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged at the end of 2019, causing the coronavirus disease (COVID-19). The main sources of infections are infected and asymptomatic persons. One major problem of the pandemic are the diverse symptoms and the varying manifestations of the illness. In this study, the IgG level recognizing the RBD of SARS-CoV-2 was determined within 336 volunteers from the environment of the University of Applied Sciences Wiener Neustadt. The aims of this study were to identify the estimated number of undiscovered COVID-19 infections and the corresponding antibody levels. In total, 11.3% of the nonvaccinated probands had a positive IgG antibody titer against SARS-CoV-2, whereas 4.0% did not test positive for SARS-CoV-2 or had never been tested at the time of sampling. Probands in this study reported tiredness (57,5%), ageusia/anosmia (55%) and headache (47,5%) as most frequent symptoms.

严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)于 2019 年底首次出现,引起冠状病毒病(COVID-19)。主要传染源是感染者和无症状者。该流行病的一个主要问题是症状多样,表现各异。本研究测定了维也纳诺伊施塔特应用科学大学 336 名志愿者体内识别 SARS-CoV-2 RBD 的 IgG 水平。这项研究的目的是确定未被发现的 COVID-19 感染者的估计人数以及相应的抗体水平。在未接种疫苗的受试者中,共有 11.3% 的人对 SARS-CoV-2 IgG 抗体滴度呈阳性,而 4.0% 的人在采样时未对 SARS-CoV-2 检测呈阳性或从未接受过检测。在这项研究中,最常见的症状是疲倦(57.5%)、苍老/乏力(55%)和头痛(47.5%)。
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引用次数: 0
Anti-telomerase immune response predicts disease progression in chronic lymphocytic leukemia 抗端粒酶免疫反应预测慢性淋巴细胞白血病的疾病进展
Pub Date : 2021-12-01 DOI: 10.1016/j.clicom.2021.11.002
Claire Germain , Julie Garibal , Valérie Doppler , Fanny Baran-Marszak , Florence Cymbalista , Julien Caumartin , Pierre Langlade-Demoyen , Maria Wehbe , Thierry Huet

Human telomerase reverse transcriptase (hTERT) is broadly expressed in many cancers. High hTERT expression have been described in chronic lymphocytic leukemia (CLL). Here we investigated the relationship between anti-hTERT immunity and disease progression in 49 CLL patients. Anti-hTERT T cell responses were evaluated by IFNγ-ELISpot. Complementary flow cytometry analyses were performed, and data were analyzed in regards of the treatment received by CLL patients afterward and disease progression. Anti-hTERT responses were more frequently observed in non-progressive watch and wait patients, and in progressive patients scheduled to receive ibrutinib, as compared to patients scheduled to receive other types of treatment. In vitro, addition of the anti-PD-1 antibody nivolumab increased anti-hTERT responses. Importantly, Kaplan Meier analyses showed significantly longer progression-free survival in patients with anti-hTERT immune responses at diagnosis as compared to non-responder patients. Our results show that anti-hTERT T cell responses represent a new potential biomarker predictive of CLL clinical outcome.

人类端粒酶逆转录酶(hTERT)在许多癌症中广泛表达。hTERT在慢性淋巴细胞白血病(CLL)中有高表达。在这里,我们研究了49例CLL患者的抗htert免疫与疾病进展的关系。采用ifn - γ- elispot检测抗htert T细胞反应。进行补充流式细胞术分析,并分析CLL患者随后接受的治疗和疾病进展的数据。与计划接受其他类型治疗的患者相比,非进展性观察和等待患者以及计划接受伊鲁替尼的进展性患者更常观察到抗htert反应。在体外,添加抗pd -1抗体nivolumab可增加抗htert反应。重要的是,Kaplan Meier分析显示,诊断时具有抗htert免疫应答的患者的无进展生存期明显长于无应答患者。我们的研究结果表明,抗htert T细胞反应是预测CLL临床结果的一种新的潜在生物标志物。
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引用次数: 0
Beneficial immune-regulatory effects of novel strains of Aureobasidium pullulans AFO-202 and N-163 produced beta glucans in Sprague Dawley rats 新型普鲁兰小孢子菌AFO-202和N-163在Sprague Dawley大鼠体内产生β葡聚糖的有益免疫调节作用
Pub Date : 2021-12-01 DOI: 10.1016/j.clicom.2021.11.001
Nobunao Ikewaki , Kadalraja Raghavan , Vidyasagar Devaprasad Dedeepiya , Suryaprakash Vaddi , Masaru Iwasaki , Rajappa Senthilkumar , Senthilkumar Preethy , Samuel JK Abraham

The beneficial immunomodulation effects of a biological response modifier glucan (BRMG) produced by two strains of Aureobasidium pullulans, AFO-202 and N-163, have already been reported. Herein, we compared their efficacy on immune-inflammatory parameters in Sprague Dawley (SD) rats. This study was performed on four groups of healthy SD rats, n=6 in each group: Group 1, euthanised on Day 0 for baseline values; Group 2, control (drinking water); Group 3, AFO-202 beta glucan, 200 mg/kg/day; and Group 4, N-163 beta glucan, 300 mg/kg/day. The neutrophil to lymphocyte ratio (NLR) decreased and leukocyte-to C-reactive protein ratio (LeCR) increased in Group 3 (AFO-202) at 15 and 29 days whereas the lymphocyte to C-reactive protein ratio (LCR) increased in group 4 (N-163), within the normal physiological range. These promising results warrant further investigations in larger numbers of healthy and diseased models to develop appropriate strategies for balancing immune system dysregulation.

两株普鲁兰金黄色小孢子菌AFO-202和N-163产生的生物反应调节剂葡聚糖(BRMG)具有有益的免疫调节作用。在此,我们比较了它们对SD大鼠免疫炎症参数的影响。本研究采用四组健康SD大鼠,每组n=6只:第一组,基线值为第0天安乐死;第二组,对照组(饮用水);第3组,AFO-202 β葡聚糖,200 mg/kg/天;第4组,N-163 β葡聚糖,300 mg/kg/天。第3组(AFO-202)在15和29 d中性粒细胞/淋巴细胞比率(NLR)降低,白细胞/ c反应蛋白比率(LeCR)升高,而第4组(N-163)淋巴细胞/ c反应蛋白比率(LCR)升高,均在正常生理范围内。这些有希望的结果值得在更多的健康和患病模型中进一步研究,以制定平衡免疫系统失调的适当策略。
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引用次数: 0
COVID-19 in a patient with Good's syndrome and in 13 patients with common variable immunodeficiency 1例古德氏综合征患者和13例常见可变免疫缺陷患者的COVID-19
Pub Date : 2021-12-01 DOI: 10.1016/j.clicom.2021.08.003
Hannes Lindahl , C I Edvard Smith , Peter Bergman

Antibody deficiencies constitute the majority of primary immunodeficiencies in adults. These patients have a well-established increased risk of bacterial infections but there is a lack of knowledge regarding the relative risks upon contracting COVID-19. In this monocentric study the disease course of COVID-19 in 1 patient with Good's syndrome and in 13 patients with common variable immunodeficiency (CVID) is described. The severity of disease ranged from very mild to severe. Several patients required hospitalization and immunomodulatory treatment but all survived. Although viral infections are not a typical feature of humoral immunodeficiencies we recommend that vigilance is increased in the management of patients with Good's syndrome and CVID during the COVID-19 pandemic.

抗体缺陷是成人原发性免疫缺陷的主要原因。这些患者已经确定细菌感染的风险增加,但对感染COVID-19后的相对风险缺乏了解。在这项单中心研究中,描述了1例Good's综合征患者和13例常见可变免疫缺陷(CVID)患者的COVID-19病程。疾病的严重程度从非常轻微到严重不等。几名患者需要住院治疗和免疫调节治疗,但全部存活。尽管病毒感染不是体液性免疫缺陷的典型特征,但我们建议在COVID-19大流行期间,在古德氏综合征和CVID患者的管理中提高警惕。
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引用次数: 2
Antibodies to cytomegalovirus are elevated in myasthenia gravis 重症肌无力患者巨细胞病毒抗体升高
Pub Date : 2021-12-01 DOI: 10.1016/j.clicom.2021.09.001
Victoria Probst , Nicole H Trier , Gunnar Houen

Myasthenia gravis (MG) is an autoimmune disease characterised by muscular degeneration and autoantibodies to components of the neuromuscular junction. Development of MG is thought to occur from a combination of genetic and environmental factors, and viral infections have been suggested to be involved in the onset of MG through molecular mimicry and/or chronic inflammation. In this work, we analysed sera from MG patients for antibodies to members of the human herpes virus family and other selected pathogens to determine the virus antibody status in the sera of these patients. Enzyme-linked immunosorbent assay, western blotting and line blotting analyses using MG serum pools showed an association between elevated IgG antibody titers to cytomegalovirus (CMV) and MG. These results were replicated using individual serum samples, and showed significant differences in CMV antibody titer between MG patients and healthy controls. Other viruses did not show the same tendency.

重症肌无力(MG)是一种自身免疫性疾病,其特征是肌肉变性和对神经肌肉连接处成分的自身抗体。MG的发生被认为是遗传和环境因素共同作用的结果,病毒感染被认为通过分子模仿和/或慢性炎症参与MG的发病。在这项工作中,我们分析了MG患者血清中对人类疱疹病毒家族成员和其他选定病原体的抗体,以确定这些患者血清中的病毒抗体状态。酶联免疫吸附试验、western blotting和line blotting分析显示,巨细胞病毒(CMV) IgG抗体滴度升高与MG存在关联。使用个体血清样本重复这些结果,并显示MG患者和健康对照组之间巨细胞病毒抗体滴度存在显著差异。其他病毒没有表现出同样的趋势。
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引用次数: 0
期刊
Clinical Immunology Communications
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