Ryan Brent J, Nissim Ahuva, Winyard Paul G
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Centre for Biochemical Pharmacology, William Harvey Research Institute, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK.
Redox Biol. 2014 May 28;2:715-24. doi: 10.1016/j.redox.2014.05.004. eCollection 2014.
Tissue inflammation results in the production of numerous reactive oxygen, nitrogen and chlorine species, in addition to the products of lipid and sugar oxidation. Some of these products are capable of chemically modifying amino acids. This in turn results in changes to the structure and function of proteins. Increasing evidence demonstrates that such oxidative post-translational modifications result in the generation of neo-epitopes capable of eliciting both innate and adaptive immune responses. In this paper, we focus on how free radicals and related chemical species generated in inflammatory environments modulate the antigenicity of self-proteins, resulting in immune responses which involve the generation of autoantibodies against key autoantigens in autoimmune diseases. As examples, we will focus on Ro-60 and C1q in systemic lupus erythematosus, along with type-II collagen in rheumatoid arthritis. This review also covers some of the emerging literature which demonstrates that neo-epitopes generated by oxidation are conserved, as exemplified by the evolutionarily conserved pathogen-associated molecular patterns (PAMPs). We discuss how these observations relate to the pathogenesis of both human autoimmune diseases and inflammatory disease, such as atherosclerosis. The potential for these neo-epitopes and the immune responses against them to act as biomarkers or therapeutic targets is also discussed.
组织炎症除了会产生脂质和糖氧化产物外，还会导致大量活性氧、氮和氯物种的产生。这些产物中的一些能够对氨基酸进行化学修饰。这进而导致蛋白质的结构和功能发生变化。越来越多的证据表明，这种氧化后翻译修饰会导致新表位的产生，从而引发先天性和适应性免疫反应。在本文中，我们关注炎症环境中产生的自由基和相关化学物质如何调节自身蛋白质的抗原性，从而导致免疫反应，这种免疫反应涉及在自身免疫性疾病中产生针对关键自身抗原的自身抗体。例如，我们将重点关注系统性红斑狼疮中的Ro-60和C1q，以及类风湿性关节炎中的II型胶原蛋白。本综述还涵盖了一些新出现的文献，这些文献表明氧化产生的新表位是保守的，进化上保守的病原体相关分子模式（PAMP）就是例证。我们讨论了这些观察结果与人类自身免疫性疾病和炎症性疾病（如动脉粥样硬化）发病机制的关系。还讨论了这些新表位及其免疫反应作为生物标志物或治疗靶点的潜力。
