Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification
Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification
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DOI：
10.1136/annrheumdis-2018-214950
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发表时间：
2019-07-01
影响因子：
27.4
通讯作者：
Toes, Rene E. M.
中科院分区：
文献类型：
--
作者：
Kampstra, Arieke Suzanna Berendina;Dekkers, Jacqueline Stephanie;Toes, Rene E. M.
目的类风湿性关节炎（RA）的一个重要标志是抗关节炎后修饰蛋白的自身抗体（抗修饰蛋白抗体或AMPA）。目前已在RA中描述了针对蛋白质上的不同修饰（如瓜氨酸、氨甲酰化和乙酰化）的多种AMPA。目前，还没有一个概念性的框架来解释RA中不同AMPA反应的同时存在或相互关系。在这里，我们的目的是获得理解的共同发生的AMPA的假设，AMPA响应共享一个共同的“背景”，可以演变成不同类别的AMPAs.Methods小鼠免疫与修改的抗原和分析AMPA的反应。此外，AMPA纯化RA患者对不同的修饰antigens的反应determined.Results免疫与氨甲酰化蛋白诱导AMPA识别氨甲酰化蛋白，也乙酰化蛋白。类似地，乙酰化蛋白质也产生（自身反应性）AMPA来对抗其他修饰。对RA患者的抗瓜氨酸化蛋白抗体的分析显示，这些抗体也显示出对乙酰化和氨甲酰化抗原的反应性。同样，抗氨甲酰化蛋白抗体对所有三个翻译后modification.Conclusions交叉反应，可以出现不同的AMPA反应暴露于只有一种类型的修饰蛋白。这些研究结果表明，不同的AMPA反应可以起源于一个共同的B细胞反应，该反应多样化为多种不同的AMPA反应，并解释了RA中多种AMPA的存在，这是该疾病的标志之一。
Objectives Autoantibodies against post-translationally modified proteins (anti-modified protein antibodies or AMPAs) are a hallmark of rheumatoid arthritis (RA). A variety of classes of AMPAs against different modifications on proteins, such as citrullination, carbamylation and acetylation, have now been described in RA. At present, there is no conceptual framework explaining the concurrent presence or mutual relationship of different AMPA responses in RA. Here, we aimed to gain understanding of the co-occurrence of AMPA by postulating that the AMPA response shares a common 'background' that can evolve into different classes of AMPAs.Methods Mice were immunised with modified antigens and analysed for AMPA responses. In addition, reactivity of AMPA purified from patients with RA towards differently modified antigens was determined.Results Immunisation with carbamylated proteins induced AMPAs recognising carbamylated proteins and also acetylated proteins. Similarly, acetylated proteins generated (autoreactive) AMPAs against other modifications as well. Analysis of anti-citrullinated protein antibodies from patients with RA revealed that these also display reactivity to acetylated and carbamylated antigens. Similarly, anti-carbamylated protein antibodies showed cross-reactivity against all three post-translational modifications.Conclusions Different AMPA responses can emerge from exposure to only a single type of modified protein. These findings indicate that different AMPA responses can originate from a common B-cell response that diversifies into multiple distinct AMPA responses and explain the presence of multiple AMPAs in RA, one of the hallmarks of the disease.