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首页> 外文期刊>Scandinavian journal of clinical and laboratory investigation. >The dependency on neighboring amino acids for reactivity of anti-citrullinated protein antibodies to citrullinated proteins
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The dependency on neighboring amino acids for reactivity of anti-citrullinated protein antibodies to citrullinated proteins

机译：抗瓜氨酸化蛋白抗体与瓜氨酸化蛋白的反应性对相邻氨基酸的依赖性

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摘要

Rheumatoid arthritis (RA) is an autoimmune connective tissue disease, associated with the presence of anti-citrullinated protein antibodies (ACPA). These antibodies have been found in approximately 70% of patients suffering from RA and they are currently used for diagnosis of RA. Although they exhibit an absolute need for citrulline for antibody reactivity, no precise cognate antigen for these antibodies has been determined. In this study, we analyzed the reactivity of ACPA to various citrullinated peptides by modified enzyme-linked immunosorbent assays, in order to determine the dependency of specific amino acids for antibody reactivity. A non-human protein (ovalbumin) and antigens directly related to RA were used as templates for synthesis of non-modified and citrullinated peptides, becoming potential target epitopes. Mainly peptides containing a Cit-Gly motif were recognized by ACPAs, while no particular amino acids N-terminal of citrulline were found to be essential for antibody reactivity. Moreover, ACPA reactivity was not restricted to antigens known to be associated with ACPA-positive RA alone, but also to proteins without relation to RA, primarily illustrating that any protein in theory can be turned into an RA autoantigen, by introducing Cit-Gly motifs. Knowledge about the interaction between ACPAs and their citrullinated targets is important for understanding autoimmune ACPA responses in RA, which are known to contribute to the pathophysiology.
机译：类风湿关节炎（RA）是一种自身免疫性结缔组织疾病，与抗瓜氨酸化蛋白抗体（ACPA）的存在有关。在大约70％患有RA的患者中发现了这些抗体，目前将其用于RA的诊断。尽管它们显示出瓜氨酸对抗体反应性的绝对需要，但尚未确定这些抗体的精确同源抗原。在这项研究中，我们通过修饰的酶联免疫吸附分析法分析了ACPA对各种瓜氨酸化肽的反应性，以确定抗体对反应性氨基酸的依赖性。非人类蛋白（卵清蛋白）和与RA直接相关的抗原被用作合成未修饰和瓜氨酸化肽的模板，成为潜在的目标表位。 ACPA识别主要包含Cit-Gly基序的肽，而未发现瓜氨酸N端的特定氨基酸对于抗体反应性必不可少。此外，ACPA反应性不仅限于已知与ACPA阳性RA单独相关的抗原，还限于与RA不相关的蛋白质，主要说明通过引入Cit-Gly基序，理论上任何蛋白质都可以转化为RA自身抗原。 。关于ACPA及其瓜氨酸化靶标之间相互作用的知识对于理解RA中的自身免疫ACPA反应非常重要，已知RA可导致病理生理。

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