Papini Anna Maria
Laboratory of Peptide & Protein Chemistry & Biology, Department of Chemistry, University of Florence, Polo Scientifico e Tecnologico, Via della Lastruccia 13, I-50019 Sesto Fiorentino, Italy.
J Pept Sci. 2009 Oct;15(10):621-8. doi: 10.1002/psc.1166.
Biomarkers are decision-making tools at the basis of clinical diagnostics and essential for guiding therapeutic treatments. In this context, autoimmune diseases represent a class of disorders that need early diagnosis and steady monitoring. These diseases are usually associated with humoral or cell-mediated immune reactions against one or more of the body's own constituents. Autoantibodies fluctuating in biological fluids can be used as disease biomarkers and they can be, thus, detected by diagnostic immunoassays using native autoantigens. However, it is now accepted that post-translational modifications may affect the immunogenicity of self-protein antigens, triggering an autoimmune response and creating neo-antigens. In this case, post-translationally modified peptides represent a more valuable tool with respect to isolated or recombinant proteins. In fact, synthetic peptides can be specifically modified to mimic neo-antigens and to selectively detect autoantibodies as disease biomarkers. A 'chemical reverse approach' to select synthetic peptides, bearing specific post-translational modifications, able to fishing out autoantibodies from patients' biological fluids, can be successfully applied for the development of specific in vitro diagnostic/prognostic assays of autoimmune diseases. Herein, we report the successful application of this approach to the identification of biomarkers in different autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.
生物标志物是临床诊断的决策工具，也是指导治疗的关键。在此背景下，自身免疫性疾病是一类需要早期诊断和持续监测的病症。这些疾病通常与针对人体自身一种或多种成分的体液或细胞介导免疫反应相关。生物体液中波动的自身抗体可作为疾病生物标志物，因此可以通过使用天然自身抗原的诊断免疫测定法进行检测。然而，现在人们已经认识到，翻译后修饰可能会影响自身蛋白抗原的免疫原性，引发自身免疫反应并产生新抗原。在这种情况下，翻译后修饰的肽相对于分离的或重组的蛋白是一种更有价值的工具。事实上，合成肽可以进行特异性修饰，以模拟新抗原并选择性地检测作为疾病生物标志物的自身抗体。一种“化学反向方法”，用于选择带有特定翻译后修饰的合成肽，能够从患者生物体液中筛选出自身抗体，可成功应用于自身免疫性疾病特异性体外诊断/预后测定的开发。在此，我们报告了该方法在系统性红斑狼疮、类风湿性关节炎和多发性硬化症等不同自身免疫性疾病生物标志物鉴定中的成功应用。
