Mewar D, Wilson A G
School of Medicine and Biomedical Sciences, Beech Hill Rd, Sheffield S10 2RX, UK.
Biomed Pharmacother. 2006 Dec;60(10):648-55. doi: 10.1016/j.biopha.2006.09.002. Epub 2006 Oct 10.
Emerging insights into the importance of B cells in the pathogenesis of rheumatoid arthritis (RA) as highlighted by the efficacy of B cell depletion is one factor that has contributed to the upsurge of interest in the potential role of autoantibodies both as disease markers and with respect to a pathogenic role. Since the initial description of rheumatoid factor (RF), a large number of both disease-specific and non-specific autoantibodies have been described in patients with RA including antibodies to type II collagen (CII), immunoglobulin binding protein (BiP) and antibodies directed at citrullinated peptides (anti-CCP) and other citrullinated proteins such as vimentin (anti-Sa) . Despite some overlap the serological profile of RA does appear to be distinct from other diseases such as SLE . Although the precise mechanisms responsible for the formation of these antibodies have not been well defined their presence must reflect the interaction between T and B cells believed to be relevant to the pathogenesis of RA. The specificity of the association of such factors as anti-CCP and anti-BiP with RA may reflect unique pathogenic events leading to the processing and presentation of the "cryptic self" . Ease of measurement and stability make autoantibodies attractive diagnostic and prognostic markers particularly in early disease when it may be difficult to distinguish self-limiting synovitis from persistent disease . The purpose of this article is to provide an overview of the current state of knowledge of the spectrum of autoantibodies thus far characterised in individuals with rheumatoid arthritis, and discuss their diagnostic, prognostic and pathogenetic relevance.
B细胞耗竭疗法的疗效凸显了B细胞在类风湿关节炎(RA)发病机制中的重要性,这一最新认识是人们对自身抗体作为疾病标志物及其致病作用的潜在作用兴趣激增的一个因素。自从类风湿因子(RF)首次被描述以来,RA患者中已发现大量疾病特异性和非特异性自身抗体,包括抗II型胶原(CII)抗体、免疫球蛋白结合蛋白(BiP)抗体以及针对瓜氨酸化肽的抗体(抗CCP)和其他瓜氨酸化蛋白(如波形蛋白,抗Sa)。尽管存在一些重叠,但RA的血清学特征似乎确实与系统性红斑狼疮(SLE)等其他疾病不同。虽然这些抗体形成的确切机制尚未明确,但它们的存在必定反映了T细胞和B细胞之间的相互作用,而这被认为与RA的发病机制相关。抗CCP和抗BiP等因素与RA关联的特异性可能反映了导致“隐蔽自身”加工和呈递的独特致病事件。自身抗体易于检测且稳定性好,使其成为有吸引力的诊断和预后标志物,尤其是在早期疾病中,此时可能难以区分自限性滑膜炎和持续性疾病。本文旨在概述目前对类风湿关节炎患者中已鉴定的自身抗体谱的认识状况,并讨论它们在诊断、预后和发病机制方面的相关性。