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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
Prevalence of asymptomatic SARS-CoV-2 infection in an Austrian cohort 奥地利人群中无症状SARS-CoV-2感染的流行情况
Pub Date : 2021-12-01 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.

严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)于2019年底首次出现,引起冠状病毒病(COVID-19)。感染的主要来源是感染者和无症状者。该流行病的一个主要问题是该疾病的各种症状和各种表现。在本研究中,我们检测了来自维也纳新城应用科学大学的336名志愿者中识别SARS-CoV-2 RBD的IgG水平。本研究的目的是确定未发现的COVID-19感染的估计数量和相应的抗体水平。总体而言,11.3%未接种疫苗的先证者具有针对SARS-CoV-2的IgG抗体滴度阳性,而4.0%未检测出SARS-CoV-2阳性或在采样时从未检测过。在这项研究中,先证者报告疲倦(57.5%)、老年/嗅觉丧失(55%)和头痛(47.5%)是最常见的症状。
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引用次数: 2
Challenges and insights raised by comorbidity with FMF and selective IgA deficiency FMF和选择性IgA缺乏症的合并症带来的挑战和见解
Pub Date : 2021-12-01 DOI: 10.1016/j.clicom.2021.10.002
Leonardo Oliveira Mendonça , Tania Sih , Morton Scheinberg , Daniel Alvarenga , Alex Isidoro Ferreira Prado , Jorge Kalil , Luiz Augusto Marcondes Fonseca , Fabio Fernandes Morato Castro , Myrthes Anna Maragna Toledo Barros , Avi Livneh

Background

: Familial Mediterranean Fever (FMF) is the most common form of genetic autoinflammatory disease worldwide. In turn, selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency, yet most patients remain asymptomatic. Case Presentation: A Jewish Brazilian female came to our attention due to recurrent inflammatory febrile episodes since very early in life, initially attributed to unexplained infections linked to SIgAD. At the age of 15 years, disabling buttock pain prompted a sacroiliac MRI, which demonstrated sacroiliitis. Direct genetic sequencing of the MEFV gene confirmed the diagnosis of FMF. After severe gastrointestinal intolerance to colchicine was observed, canakinumab achieved clinical and radiological control, enabling the reinstatement of colchicine. Conclusion: Here we report the first case of concomitant FMF and SIgAD in a Brazilian patient, highlighting the relevance of these comorbidities in the patient's diagnosis and follow-up. This coincidental association also provides insight into interactions between serum and mucosal IgA and the pyrin inflammasome in the control of inflammation and gut dysbiosis.

背景:家族性地中海热(FMF)是世界上最常见的遗传性自身炎症疾病。反过来,选择性IgA缺乏症(SIgAD)是最常见的体液性原发性免疫缺陷,但大多数患者仍无症状。病例介绍:一名犹太裔巴西女性由于在生命早期就反复出现炎症性发热发作而引起我们的注意,最初归因于与SIgAD相关的不明原因感染。在15岁的时候,臀部疼痛导致了骶髂核磁共振检查,结果显示为骶髂炎。MEFV基因的直接基因测序证实了FMF的诊断。在观察到严重的胃肠对秋水仙碱不耐受后,canakinumab获得了临床和放射学控制,使秋水仙碱得以恢复。结论:在这里,我们报告了巴西患者的第一例伴发FMF和SIgAD,强调了这些合并症在患者诊断和随访中的相关性。这种巧合的关联也为血清和粘膜IgA与pyrin炎性体在炎症和肠道生态失调控制中的相互作用提供了见解。
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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 在已有自身免疫的患者中,辉瑞生物技术公司的COVID-19 RNA疫苗可诱导磷脂酰丝氨酸自身抗体、冷球蛋白血症和数字坏死
Pub Date : 2021-12-01 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岁的白人女性,她有雷诺病、手部关节炎、光敏性、干燥综合征和白细胞分裂性血管炎的病史,在接受第一剂辉瑞- biontech COVID-19 RNA疫苗后三天开始出现逐渐恶化的指尖坏死。我们的检查结果显示冷球蛋白血症、低补体血症、抗核抗体(ANA)和针对磷脂酰丝氨酸(aPL- ps)的IgM抗磷脂自身抗体(aPL)升高,提示诊断为系统性红斑狼疮(SLE)和抗磷脂综合征(APS)。该患者在接种疫苗两个月后仍未产生抗刺突IgG抗体。通过血浆置换、抗凝和免疫抑制,疾病进展得以停止。我们得出结论,疫苗RNA片段可能诱发SLE,表现为APS、冷球蛋白血症、低补体血症和指状坏死。
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引用次数: 6
Clinical Immunology Communications: Inaugural Edition 临床免疫学通讯:创刊号
Pub Date : 2021-12-01 DOI: 10.1016/j.clicom.2021.06.001
Antonio La Cava (Editor-in-Chief)
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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 : 2021-11-01 DOI: 10.1016/j.clicom.2021.11.002
C. Germain, J. Garibal, V. Doppler, F. Baran-Marszak, F. Cymbalista, J. Caumartin, P. Langlade‐Demoyen, Maria Wehbe, T. Huet
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引用次数: 0
Challenges and insights raised by comorbidity with FMF and Selective IgA Deficiency FMF和选择性IgA缺乏症的合并症带来的挑战和见解
Pub Date : 2021-10-01 DOI: 10.1016/j.clicom.2021.10.002
L. Mendonça, T. Sih, M. Scheinberg, D. Alvarenga, A. Prado, J. Kalil, L. A. Fonseca, F. Castro, M. Toledo-Barros, A. Livneh
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引用次数: 0
期刊
Clinical Immunology Communications
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