The presence of autoantibodies and autoreactive T cells to citrullinated proteins and citrullinating enzymes in patients with rheumatoid arthritis (RA), together with the accumulation of citrullinated proteins in rheumatoid joints, provides substantial evidence that dysregulated citrullination is a hallmark feature of RA. However, understanding mechanisms that dysregulate citrullination in RA has important challenges. Citrullination is a normal process in immune and non-immune cells, which is likely activated by different conditions (eg, inflammation) with no pathogenic consequences. In a complex inflammatory environment such as the RA joint, unique strategies are therefore required to dissect specific mechanisms involved in the abnormal production of citrullinated proteins. Here, we will review current models of citrullination in RA and discuss critical components that, in our view, are relevant to understanding the accumulation of citrullinated proteins in the RA joint, collectively referred to as the RA citrullinome. In particular, we will focus on potential caveats in the study of citrullination in RA and will highlight methods to precisely detect citrullinated proteins in complex biological samples, which is a confirmatory approach to mechanistically link the RA citrullinome with unique pathogenic pathways in RA.

中文翻译：

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深入了解类风湿性关节炎中瓜氨酸组的研究和起源。

类风湿性关节炎 (RA) 患者中存在针对瓜氨酸化蛋白和瓜氨酸化酶的自身抗体和自身反应性 T 细胞，以及瓜氨酸化蛋白在类风湿性关节中的积累，提供了大量证据，表明瓜氨酸化失调是 RA 的标志性特征。然而，了解 RA 中瓜氨酸化失调的机制具有重要的挑战。瓜氨酸化是免疫细胞和非免疫细胞的正常过程，它很可能被不同条件（例如炎症）激活而没有致病性后果。在复杂的炎症环境中，例如 RA 关节，因此需要独特的策略来剖析参与瓜氨酸蛋白异常产生的特定机制。这里，我们将回顾 RA 中瓜氨酸化的当前模型，并讨论在我们看来与理解 RA 关节中瓜氨酸化蛋白质（统称为 RA 瓜氨酸组）积累相关的关键组成部分。特别是，我们将重点关注 RA 瓜氨酸化研究中的潜在注意事项，并将重点介绍在复杂生物样品中精确检测瓜氨酸化蛋白的方法，这是将 RA 瓜氨酸组与 RA 中独特的致病途径机械联系起来的一种验证方法。