Department of Chemistry, Technical University of Denmark, Kongens Lyngby, Region Hovedstaden, Denmark.
Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Region Syddanmark, Denmark.
PLoS One. 2018 Apr 11;13(4):e0195381. doi: 10.1371/journal.pone.0195381. eCollection 2018.
In this study, we developed a series of synthetic oligonucleotides that allowed us to investigate the details on the antigen recognition by autoimmune antibodies in localized scleroderma subjects. Besides dramatically improved analytical specificity of the assay, our data suggests a potential linking for antibodies to DNA to the biological status of disease state in localized scleroderma. Moreover, introducing chemical modifications into short synthetic deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) molecules completely changed the binding titers of corresponding antibodies and their clinical relevance. The strongest observed effect was registered for the localized scleroderma skin damage index (LoSDI) on the IgG antibodies to TC dinucleotide-rich double-stranded antigen (p < 0.001). In addition to providing valuable tools for diagnosis of clinically relevant biomarkers, we believe that this work opens up new opportunities for research on antibodies to nucleic acids in localized scleroderma and other autoimmune diseases.
在这项研究中,我们开发了一系列合成寡核苷酸,使我们能够研究自身免疫抗体在局限性硬皮病患者中对抗原识别的细节。除了大大提高了检测方法的分析特异性外,我们的数据还表明,抗体与 DNA 的结合可能与局限性硬皮病的疾病状态的生物学状态有关。此外,在短的合成脱氧核糖核酸 (DNA) 和核糖核酸 (RNA) 分子中引入化学修饰完全改变了相应抗体的结合效价及其临床相关性。在局限性硬皮病皮肤损伤指数 (LoSDI) 上观察到的最强效应是针对富含 TC 二核苷酸的双链抗原的 IgG 抗体 (p < 0.001)。除了为临床相关生物标志物的诊断提供有价值的工具外,我们相信这项工作为研究局限性硬皮病和其他自身免疫性疾病中的核酸抗体开辟了新的机会。