Research Institute in Biomedical Sciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, Mexico.
Research Institute in Biomedical Sciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, Mexico.
Autoimmun Rev. 2018 Feb;17(2):94-102. doi: 10.1016/j.autrev.2017.11.023. Epub 2017 Dec 2.
Rheumatoid arthritis (RA) is the most common rheumatic autoimmune disease worldwide, which causes progressive joint damage and can lead to functional disability. Despite prominent advances in RA diagnosis and treatment during the last 20years, there is still a need for novel biomarkers that aid in diagnosis and prognosis of this heterogeneous disease. Citrullination is a key post-translational modification implicated on anti-citrullinated protein/peptide antibodies (ACPA) production in RA, catalyzed by human peptidylarginine deiminases (PADs). Among these enzymes, PAD4 has been recognized as an important player in RA pathogenesis and the enzyme itself is a target of autoantibodies (anti-PAD4) in a subgroup of RA patients. Accumulating evidence suggests that anti-PAD4 autoantibodies may be useful as a severity biomarker in RA and recent studies have also shed light on the functional significance of these autoantibodies. This review summarizes the evidence on anti-PAD4 autoantibodies in RA, and addresses its usefulness for disease diagnosis and prognosis. Novel immunological aspects of anti-PAD4 antibodies and their relevance to RA pathogenesis are also discussed.
类风湿关节炎（RA）是全球最常见的风湿性自身免疫性疾病，可导致进行性关节损伤，并可导致功能障碍。尽管在过去 20 年中，RA 的诊断和治疗取得了显著进展，但仍需要新的生物标志物来辅助这种异质性疾病的诊断和预后。瓜氨酸化是一种关键的翻译后修饰，参与抗瓜氨酸化蛋白/肽抗体（ACPA）在 RA 中的产生，由人类肽基精氨酸脱亚氨酶（PADs）催化。在这些酶中，PAD4 已被认为是 RA 发病机制中的重要参与者，而该酶本身是 RA 患者亚组中自身抗体（抗-PAD4）的靶标。越来越多的证据表明，抗-PAD4 自身抗体可能作为 RA 的严重程度生物标志物有用，最近的研究也揭示了这些自身抗体的功能意义。本文综述了 RA 中抗-PAD4 自身抗体的证据，并讨论了其在疾病诊断和预后中的用途。还讨论了抗-PAD4 抗体的新免疫方面及其与 RA 发病机制的相关性。
