Department of Biomedical Chemistry, IQAC-CSIC, Jordi Girona 18-26, Barcelona, Spain.
J Med Chem. 2011 Nov 10;54(21):7486-92. doi: 10.1021/jm200563u. Epub 2011 Oct 7.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients.
类风湿关节炎(RA)是一种慢性自身免疫性疾病,可导致炎症,并且在许多情况下,导致关节破坏。为了防止进行性和不可逆转的结构损伤,早期诊断 RA 至关重要。本研究旨在寻找新的 RA 瓜氨酸化抗原,以补充或补充现有的诊断/预后检测。为此,使用合成肽来绘制抗瓜氨酸化波形蛋白抗体的表位。为了提高敏感性/特异性的平衡,选择了一个波形蛋白肽,并对其环状类似物进行了与纤维蛋白和角蛋白相关肽的组合,以生成嵌合肽。我们的研究结果强调了这些嵌合肽在 RA 诊断系统设计中的潜在应用,并暗示需要进行不止一项血清学检测,才能根据 ACPA 的存在与否对 RA 患者进行分类。这里报告的每个靶分子(纤维蛋白、波形蛋白、角蛋白)在识别特定亚组的 RA 患者方面都有特定的用途。