Klareskog Lars, Widhe Mona, Hermansson Monika, Rönnelid Johan
Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
Curr Opin Rheumatol. 2008 May;20(3):300-5. doi: 10.1097/BOR.0b013e3282fbd22a.
The purpose of this review is to describe how the current knowledge of antibodies to citrullinated protein antigens in rheumatoid arthritis and related conditions emerged; to discuss the diagnostic and prognostic value associated with antibodies to citrullinated protein antigens as a biomarker; and most importantly for this review, to discuss the potential pathogenetic significance of these antibodies.
Antibodies to citrullinated protein antigens have evolved from being mainly a diagnostic marker, to being recognized as something that can help us understand fundamental etiologic and pathogenetic features of rheumatoid arthritis. Fundamental in this context is the finding that rheumatoid arthritis can be divided into two distinct subsets by means of presence or absence of antibodies to citrullinated protein antigens. Thus, several genetic as well as environmental risk factors differ between these two variants of rheumatoid arthritis. From analysis of these genetic and environmental risk factors, new testable hypotheses have been produced concerning triggering of antibodies to citrullinated protein antigens, and potential pathogenicity of antibodies to citrullinated protein antigens and accompanying immune reactions.
The implications of the findings are that antibodies to citrullinated protein antigens can be used for early and precise diagnosis of a subset of rheumatoid arthritis with worse prognosis than other polyarthritides, and that a new basis is formed for etiologic and pathogenetic studies of antibodies to citrullinated protein antigens-positive rheumatoid arthritis.
本综述旨在描述类风湿关节炎及相关病症中瓜氨酸化蛋白抗原抗体的现有知识是如何形成的;讨论瓜氨酸化蛋白抗原抗体作为生物标志物的诊断和预后价值;而对于本综述而言最重要的是,讨论这些抗体潜在的致病意义。
瓜氨酸化蛋白抗原抗体已从主要作为一种诊断标志物,演变为被认为有助于我们理解类风湿关节炎基本病因和发病机制特征的物质。在此背景下,一个重要发现是类风湿关节炎可根据是否存在瓜氨酸化蛋白抗原抗体分为两个不同的亚组。因此,这两种类风湿关节炎变体在一些遗传和环境风险因素方面存在差异。通过对这些遗传和环境风险因素的分析,已经产生了关于瓜氨酸化蛋白抗原抗体触发机制、瓜氨酸化蛋白抗原抗体潜在致病性及伴随免疫反应的新的可验证假设。
这些发现的意义在于,瓜氨酸化蛋白抗原抗体可用于早期精确诊断类风湿关节炎的一个亚组,该亚组的预后比其他多关节炎更差,并且为瓜氨酸化蛋白抗原抗体阳性类风湿关节炎的病因和发病机制研究奠定了新基础。