Dipartimento di Medicina Interna e Specialità Mediche, Reumatologia - Sapienza Università di Roma, Rome, Italy.
Dipartimento di Medicina Interna e Specialità Mediche, Reumatologia - Sapienza Università di Roma, Rome, Italy.
Autoimmun Rev. 2015 Jun;14(6):490-7. doi: 10.1016/j.autrev.2015.01.013. Epub 2015 Jan 28.
Autoimmune diseases are characterized by the body's own immune system attack to the self-tissues, a condition enabled, in predisposed subjects, by the reduction of self-tolerance. A central role has been recently recognized to post-translational modifications, since they can promote generation of neo-(auto)antigens and in turn an autoimmune response. During the last years great attention has been paid to citrullination, because of its role in inducing anti-citrullinated proteins/peptide antibodies (ACPA), a class of autoantibodies with diagnostic, predictive and prognostic value for Rheumatoid Arthritis (RA). Nonetheless, citrullination has been reported to be a process present in a wide range of inflammatory tissues. Indeed, citrullinated proteins have been detected also in other inflammatory arthritides and in inflammatory conditions other than arthritides (polymyositis, inflammatory bowel disease and chronic tonsillitis). Moreover, environmental exposure to cigarette smoke and nanomaterials of air pollution may be able to induce citrullination in lung cells prior to any detectable onset of inflammatory responses, suggesting that protein citrullination could be considered as a sign of early cellular damage. Accordingly, citrullination seems to be implicated in all those para-physiological processes, such as cells death pathways, in which intracellular calcium concentration raises to higher levels than in physiologic conditions: hence, peptidylarginine deiminases enzymes are activated during apoptosis, autophagy and NETosis, processes which are well-known to be implicated in autoimmunity. Taken together, these data support the hypothesis that rather than being a disease-dependent process, citrullination is an inflammatory-dependent condition that plays a central role in autoimmune diseases.
自身免疫性疾病的特征是人体自身免疫系统攻击自身组织，这种情况在易感性个体中是由于自身耐受性的降低而发生的。最近，人们认识到翻译后修饰在其中起着核心作用，因为它们可以促进新的（自身）抗原的产生，并进而引发自身免疫反应。在过去的几年中，人们对瓜氨酸化给予了极大的关注，因为它在诱导抗瓜氨酸化蛋白/肽抗体（ACPA）中的作用，ACPA 是一类对类风湿关节炎（RA）具有诊断、预测和预后价值的自身抗体。尽管如此，瓜氨酸化已被报道是一种存在于广泛的炎症组织中的过程。事实上，在其他炎症性关节炎和炎症性疾病（多发性肌炎、炎症性肠病和慢性扁桃体炎）中也检测到了瓜氨酸化蛋白。此外，环境暴露于香烟烟雾和空气污染纳米材料可能能够在任何可检测到的炎症反应发生之前诱导肺细胞中的瓜氨酸化，这表明蛋白质瓜氨酸化可以被认为是早期细胞损伤的标志。因此，瓜氨酸化似乎与所有那些异常生理过程有关，如细胞死亡途径，其中细胞内钙离子浓度升高到高于生理条件的水平：因此，肽基精氨酸脱亚氨酶酶在细胞凋亡、自噬和 NETosis 期间被激活，这些过程已知与自身免疫有关。综上所述，这些数据支持了这样一种假设，即瓜氨酸化不是一种依赖于疾病的过程，而是一种依赖于炎症的条件，它在自身免疫性疾病中起着核心作用。
