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Journal of Translational Autoimmunity最新文献

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IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/b978-0-12-822564-6.09992-4
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引用次数: 0
Regulation of immunological tolerance and human autoimmunity by NF-κB NF-κB对人体免疫耐受和自身免疫的调节作用
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/b978-0-12-822564-6.00019-7
M. Cook
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引用次数: 0
Index 指数
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/b978-0-12-824390-9.09993-x
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引用次数: 0
Autoantibodies in Sjögren's syndrome and its classification criteria Sjögren综合征的自身抗体及其分类标准
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/j.jtauto.2021.100138
Sharon Veenbergen , Ana Kozmar , Paul L.A. van Daele , Marco W.J. Schreurs

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by immune-mediated injury of exocrine glands. Extensive lymphocytic infiltrates may contribute to the destruction and loss of secretory function of glands. B-cell hyperactivity is a key feature of the disease resulting in the production of a diverse array of autoantibodies in these patients. Although not specific for SS, anti-Ro/SSA and anti-La/SSB antibodies have been useful biomarkers for disease classification and diagnosis. During recent years, novel autoantibodies have been discovered in SS. In this review, we summarize the historical role and clinical relevance that autoantibodies have played in the classification criteria of Sjögren's syndrome, discuss laboratory aspects in antibody detection and review the role of novel autoantibodies in predicting particular stages of the disease, clinical phenotypes and long-term complications.

Sjögren综合征(SS)是一种以免疫介导的外分泌腺损伤为特征的系统性自身免疫性疾病。广泛的淋巴细胞浸润可导致腺体分泌功能的破坏和丧失。b细胞过度活跃是该疾病的一个关键特征,导致这些患者产生多种自身抗体。虽然抗ro /SSA和抗la /SSB抗体不是SS特异性的,但它们已成为疾病分类和诊断的有用生物标志物。近年来,在SS中发现了新的自身抗体。在这篇综述中,我们总结了自身抗体在Sjögren综合征分类标准中的历史作用和临床相关性,讨论了抗体检测的实验室方面,并回顾了新型自身抗体在预测疾病特定阶段、临床表型和长期并发症中的作用。
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引用次数: 10
Impact of autoimmune serology test results on RA classification and diagnosis 自身免疫血清学检测结果对类风湿关节炎分类和诊断的影响
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/j.jtauto.2022.100142
Lieve Van Hoovels , Paul Studenic , Daniela Sieghart , Günter Steiner , Xavier Bossuyt , Johan Rönnelid

Rheumatoid arthritis (RA) is the most common systemic autoimmune disease and also the most severe arthritic disorder. The measurement of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) in serum supports the diagnosis of RA, which gained increasing significance over the last 65 years. However, a high variability between RF and ACPA methods has been described, impacting the diagnostic performance of the current ACR/EULAR RA classification criteria.

The great number of commercially available assays, often lacking traceability to an international standard, is a major factor attributing to this in-between assay variability. The adoption of an international standard for ACPA, as is since long available for rheumatoid factor, is therefore highly desirable.

Further harmonization in clinical interpretation of RF/ACPA assays could be obtained by harmonization of the cut-offs, for both the low and high antibody levels, based on predefined specificity in disease controls. Reporting test result specific likelihood ratios (LR) adds value in the interpretation of autoantibody tests. However, a good understanding of the control population used to define antibody test result interval-associated LRs is crucial in defining the diagnostic performance characteristics of antibody serology.

Finally, specificity in RA classification can be improved by refining serological weight scoring taking into account the nature of the antibody, the antibody level and double RF + ACPA positivity.

类风湿性关节炎(RA)是最常见的系统性自身免疫性疾病,也是最严重的关节炎疾病。血清中类风湿因子(RF)和抗瓜氨酸化蛋白抗体(ACPA)的测定支持RA的诊断,这在过去65年中越来越重要。然而,RF和ACPA方法之间的高度可变性已经被描述,影响了当前ACR/EULAR RA分类标准的诊断性能。大量的市售检测,往往缺乏对国际标准的可追溯性,是导致这种中间检测可变性的主要因素。因此,采用ACPA的国际标准是非常可取的,因为长期以来可用于类风湿因子。基于疾病控制中预定义的特异性,通过协调低抗体水平和高抗体水平的截止值,可以进一步协调RF/ACPA检测的临床解释。报告测试结果特异性似然比(LR)增加了自身抗体测试解释的价值。然而,很好地了解用于定义抗体检测结果间隔相关LRs的对照人群对于定义抗体血清学的诊断性能特征至关重要。最后,考虑到抗体的性质、抗体水平和RF + ACPA双阳性,可以通过改进血清学权重评分来提高RA分类的特异性。
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引用次数: 13
Rational development and application of biomarkers in the field of autoimmunity: A conceptual framework guiding clinicians and researchers 生物标志物在自身免疫领域的合理开发和应用:指导临床医生和研究人员的概念框架
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/j.jtauto.2022.100151
Mirjam Kolev , Michael P. Horn , Nasser Semmo , Michael Nagler

Clear guidance is needed in the development and implementation of laboratory biomarkers in medicine. So far, no standardized phased approach is established that would pilot researchers and clinicians in this process. This leads to often incompletely validated biomarkers, which can bear the consequence of wrong applications, misinterpretation and inadequate management in the clinical context.

In this conceptual article, we describe a stepwise approach to develop and comprehensively validate laboratory biomarkers. We will delineate basic steps including technical performance, pre-analytical issues, and biological variation, as well as advanced aspects of biomarker utility comprising interpretability, diagnostic and prognostic accuracy, and health-care outcomes. These aspects will be illustrated by using well-known examples from the field of immunology.

The application of this conceptual framework will guide researchers in conducting meaningful projects to develop and evaluate biomarkers for the use in clinical practice. Furthermore, clinicians will be able to adequately interpret pre-clinical and clinical diagnostic literature and rationally apply biomarkers in clinical practice. Improvement in the implementation and application of biomarkers might relevantly change the management and outcomes of our patients for the better.

在医学实验室生物标志物的开发和实施中需要明确的指导。到目前为止,还没有建立标准化的分阶段方法来指导研究人员和临床医生在这一过程中进行试验。这导致生物标记物经常不完全验证,这可能承担错误应用的后果,在临床环境中误解和管理不足。在这篇概念性文章中,我们描述了一种逐步开发和全面验证实验室生物标志物的方法。我们将描述基本步骤,包括技术性能、分析前问题和生物变异,以及生物标志物实用的高级方面,包括可解释性、诊断和预后准确性以及医疗保健结果。这些方面将通过使用免疫学领域的著名例子来说明。这一概念框架的应用将指导研究人员开展有意义的项目,以开发和评估用于临床实践的生物标志物。此外,临床医生将能够充分解释临床前和临床诊断文献,并在临床实践中合理应用生物标志物。生物标志物的实施和应用的改进可能会改变我们患者的管理和预后。
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引用次数: 0
Mycophenolate mofetil as second line treatment in autoimmune hepatitis – A retrospective single center analysis 霉酚酸酯作为自身免疫性肝炎的二线治疗——一项回顾性单中心分析
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/j.jtauto.2022.100172
Mirjam Kolev , Stefan Diem , Lara Diem , Susana G. Rodrigues , Annalisa Berzigotti , Guido Stirnimann , Nasser Semmo

Background

Most patients with autoimmune hepatitis respond to standard treatment with steroids and azathioprine. While the disease is usually fatal if untreated, patients who respond well to therapy have an excellent prognosis. Nevertheless, second-line treatment is necessary in approximately 20% of patients, due to either intolerance or insufficient response to first line treatment.

While data for mycophenolate mofetil (MMF) in patients intolerant to azathioprine is encouraging, MMF seems of less benefit in patients with insufficient response to first line treatment, but analyzed data on this issue is limited.

Aim

To evaluate the efficacy and safety of MMF as a second-line therapy in patients with AIH.

Methods

Retrospective analysis of a monocentric database of AIH patients who received medical care from 2000 to 2022. Clinical, immunological and biochemical parameters were assessed at different time points including last follow-up.

Results

Overall, 144 patients with AIH were identified. Fifty out of 144 (35%) AIH patients received MMF. Forty (80%) received MMF due to first line treatment intolerance, while ten (20%) due to insufficient response to first line treatment.

Remission with MMF monotherapy was 81.5% in the intolerance group versus 30% in the insufficient response group. Patients switched to MMF because of an insufficient response, more often needed additional prednisolone doses higher than 5 mg/day, a switch to third-line treatment or combination regiments, to achieve disease control.

Conclusions

Patients treated with MMF because of intolerance to first line treatment show a good disease control under MMF in the majority of cases. Efficacy is considerably lower in the patients switched to MMF because of an insufficient response to first line treatment.

大多数自身免疫性肝炎患者对类固醇和硫唑嘌呤的标准治疗有反应。虽然这种疾病如果不治疗通常是致命的,但对治疗反应良好的患者预后良好。然而,由于不耐受或对一线治疗反应不足,大约20%的患者需要二线治疗。虽然霉酚酸酯(MMF)用于硫唑嘌呤不耐受患者的数据令人鼓舞,但对于对一线治疗反应不足的患者,MMF的益处似乎较小,但有关这一问题的分析数据有限。目的评价MMF作为AIH患者二线治疗的疗效和安全性。方法回顾性分析2000年至2022年接受治疗的AIH患者的单中心数据库。在包括最后一次随访在内的不同时间点评估临床、免疫学和生化指标。结果共发现144例AIH患者。144例AIH患者中有50例(35%)接受了MMF治疗。40例(80%)患者因一线治疗不耐受而接受MMF治疗,10例(20%)患者因一线治疗反应不足而接受MMF治疗。MMF单药治疗的缓解率在不耐受组为81.5%,而在反应不足组为30%。由于反应不足,患者转而使用MMF,更经常需要额外的强的松龙剂量高于5mg /天,转而使用三线治疗或联合治疗,以实现疾病控制。结论对一线治疗不耐受的患者,绝大多数在MMF治疗下病情控制良好。由于对一线治疗反应不足,转而使用MMF的患者的疗效明显较低。
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引用次数: 1
Systemic immune response to vimentin and granuloma formation in a model of pulmonary sarcoidosis 肺结节病模型中对弧菌蛋白和肉芽肿形成的全身免疫反应
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/j.jtauto.2022.100153
Harini Bagavant , Katarzyna Cizio , Antonina M. Araszkiewicz , Joanna A. Papinska , Lori Garman , Chuang Li , Nathan Pezant , Wonder P. Drake , Courtney G. Montgomery , Umesh S. Deshmukh

A characteristic feature of sarcoidosis is a dysregulated immune response to persistent stimuli, often leading to the formation of non-necrotizing granulomas in various organs. Although genetic susceptibility is an essential factor in disease development, the etiology of sarcoidosis is not fully understood. Specifically, whether autoimmunity contributes to the initiation or progression of the disease is uncertain. In this study, we investigated systemic autoimmunity to vimentin in sarcoidosis. IgG antibodies to human vimentin were measured in sera from sarcoidosis patients and healthy controls. Mice immunized with recombinant murine vimentin were challenged intravenously with vimentin-coated beads to mimic pulmonary sarcoidosis. Lungs from treated mice were studied for cellular infiltration, granuloma formation, and gene expression. Immune cells in the bronchoalveolar lavage fluid were evaluated by flow cytometry. Compared to healthy controls, sarcoidosis patients had a higher frequency and levels of circulating anti-vimentin IgG. Vimentin-immunized mice developed lung granulomas following intravenous challenge with vimentin-coated beads. These sarcoidosis-like granulomas showed the presence of Langhans and foreign body multinucleated giant cells, CD4 T cells, and a heterogeneous collection of MHC II positive and arginase 1-expressing macrophages. The lungs showed upregulated pro-inflammatory gene expression, including Ifng, Il17, and Tnfa, reflecting TH1/TH17 responses typical of sarcoidosis. In addition, genes in the TH2 canonical pathway were also upregulated, congruent with increased numbers of ILC2 in the bronchoalveolar lavage. Overall, these results further validate vimentin as an autoantigen in sarcoidosis and provide evidence for an anti-vimentin immune response in disease pathogenesis. Our study also highlights the possible role of ILC2-driven TH2-like responses in the formation of lung granulomas in sarcoidosis.

结节病的一个特征是对持续刺激的免疫反应失调,通常导致各器官形成非坏死性肉芽肿。虽然遗传易感性是疾病发展的重要因素,但结节病的病因尚不完全清楚。具体而言,自身免疫是否有助于疾病的发生或进展尚不确定。在这项研究中,我们研究了结节病患者对弧菌蛋白的全身自身免疫。检测了结节病患者和健康对照血清中人源蛋白IgG抗体。用重组小鼠弧菌蛋白免疫小鼠,静脉注射弧菌蛋白包被微球模拟肺结节病。研究了处理后小鼠肺的细胞浸润、肉芽肿形成和基因表达。用流式细胞术检测支气管肺泡灌洗液中的免疫细胞。与健康对照相比,结节病患者有更高的频率和循环抗vimentin IgG水平。静脉注射涂有弧菌素的微球后,免疫弧菌素的小鼠出现肺肉芽肿。这些结节样肉芽肿表现为朗汉斯和异物多核巨细胞、CD4 T细胞以及MHC II阳性和表达精氨酸酶1的巨噬细胞的异质集合。肺显示促炎基因表达上调,包括Ifng、Il17和Tnfa,反映结节病典型的TH1/TH17反应。此外,TH2典型通路的基因也上调,与支气管肺泡灌洗液中ILC2数量增加一致。总之,这些结果进一步证实了vimentin在结节病中的自身抗原作用,并为疾病发病机制中的抗vimentin免疫反应提供了证据。我们的研究还强调了ilc2驱动的th2样反应在结节病肺肉芽肿形成中的可能作用。
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引用次数: 8
Acknowledgment 鸣谢
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/b978-0-12-822564-6.09998-5
N. Rezaei
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引用次数: 0
Plasmocyte depletion in autoimmune diseases 自身免疫性疾病中的浆细胞耗竭
IF 3.9 Q2 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1016/b978-0-12-824390-9.00018-9
N. Sturm, B. Huard
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引用次数: 0
期刊
Journal of Translational Autoimmunity
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