类风湿关节炎的自身抗体:历史背景和新发现。

IF 8.4 2区 医学 Q1 ALLERGY Clinical Reviews in Allergy & Immunology Pub Date : 2022-10-01 DOI:10.1007/s12016-021-08890-1
Maria V Sokolova, Georg Schett, Ulrike Steffen
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引用次数: 25

摘要

自身抗体是类风湿关节炎(RA)的标志,其中类风湿因子(RF)和抗瓜氨酸化蛋白(ACPA)的抗体是最公认的。与所谓的“血清阴性”患者相比,RF和/或ACPA阳性(“血清阳性”)的RA患者通常表现出不同的病因和病程。尽管如此,血清阴性患者群体是非常异质性的,并没有很好地表征。由于近年来新的自身抗体的发现和风湿病诊断的进步,血清阴性患者的群体在不断缩小。除了针对各种翻译后修饰的抗体外,最近的研究还描述了针对某些天然蛋白的自身抗体,进一步拓宽了识别抗原的范围。除了检测新的自身抗体组外,许多研究已经完成,以回答自身抗体是否以及如何促进RA发病的问题。由于自身抗体可以在RA发病前数年检测到,因此它们的存在是否足以引发该疾病是一个争论的问题。然而,越来越多的证据表明,自身抗体的直接效应作用,如在体外实验中刺激破骨细胞的发生和滑膜成纤维细胞的迁移。此外,自身抗体阳性患者表现出较差的临床病程和较强的影像学进展。在这篇综述中,我们讨论了不同自身抗体类型的最新发现,潜在的疾病驱动机制,Fab和Fc糖基化的作用和临床意义。
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Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings.

Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA ("seropositive") in general display a different etiology and disease course compared to so-called "seronegative" patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new autoantibodies and advancements in the diagnosis of rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from antibodies towards various post-translational modifications, recent studies describe autoantibodies targeting some native proteins, further broadening the spectrum of recognized antigens. Next to the detection of new autoantibody groups, much research has been done to answer the question if and how autoantibodies contribute to the pathogenesis of RA. Since autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition, autoantibody positive patients display a worse clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.

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来源期刊
CiteScore
22.30
自引率
1.10%
发文量
58
审稿时长
6-12 weeks
期刊介绍: Clinical Reviews in Allergy & Immunology is a scholarly journal that focuses on the advancement of clinical management in allergic and immunologic diseases. The journal publishes both scholarly reviews and experimental papers that address the current state of managing these diseases, placing new data into perspective. Each issue of the journal is dedicated to a specific theme of critical importance to allergists and immunologists, aiming to provide a comprehensive understanding of the subject matter for a wide readership. The journal is particularly helpful in explaining how novel data impacts clinical management, along with advancements such as standardized protocols for allergy skin testing and challenge procedures, as well as improved understanding of cell biology. Ultimately, the journal aims to contribute to the improvement of care and management for patients with immune-mediated diseases.
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