Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases.
Oxidative post-translational modifications and their involvement in the pathogenesis of autoimmune diseases.
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DOI：
10.1016/j.redox.2014.05.004
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发表时间：
2014
期刊：
影响因子：
11.4
通讯作者：
Winyard PG
中科院分区：
文献类型：
--
作者：
Ryan BJ;Nissim A;Winyard PG
除了脂质和糖氧化的产物外，组织炎症还导致大量活性氧、氮和氯的产生。其中一些产品能够对氨基酸进行化学修饰。这反过来又导致了蛋白质结构和功能的变化。越来越多的证据表明，这种氧化翻译后修饰导致能够引发先天和适应性免疫反应的新表位的产生。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的抗原性，从而导致自身免疫性疾病中针对关键自身抗原产生自身抗体的免疫反应。作为例子，我们将关注Ro-60和C1q在系统性红斑狼疮中的作用，以及ii型胶原在类风湿关节炎中的作用。这篇综述还涵盖了一些新兴的文献，这些文献表明氧化产生的新表位是保守的，例如进化保守的病原体相关分子模式（PAMPs）。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）的发病机制之间的关系。这些新表位和针对它们的免疫反应作为生物标志物或治疗靶点的潜力也进行了讨论。氧化剂可以在蛋白质上产生稳定的翻译后修饰（PTMs）。氧化PTMs在进化保守的先天免疫反应中被识别。这些ptm可以代表自身免疫性疾病中破坏耐受性的新表位。在类风湿性关节炎和系统性红斑狼疮等疾病中，针对这些PTMs的抗体可以作为生物标志物。
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. Oxidants can generate stable post-translational modifications (PTMs) on proteins. Oxidative PTMs are recognised in evolutionarily-conserved innate immune responses. These PTMs can represent neo-epitopes that break tolerance in autoimmune disease. Antibodies targeting these PTMs in diseases e.g. RA and SLE, can be biomarkers.
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影响因子：
7.3
作者：
De Sanctis F;Sandri S;Ferrarini G;Pagliarello I;Sartoris S;Ugel S;Marigo I;Molon B;Bronte V
通讯作者：
Bronte V
影响因子：
4.6
作者：
Burska AN;Hunt L;Boissinot M;Strollo R;Ryan BJ;Vital E;Nissim A;Winyard PG;Emery P;Ponchel F
通讯作者：
Ponchel F
影响因子：
7.7
作者：
DORMAN, JS;LAPORTE, RE;DRASH, AL
通讯作者：
DRASH, AL
影响因子：
5.5
作者：
de Leeuw, K.;Graaff, R.;Bijl, M.
通讯作者：
Bijl, M.
影响因子：
4.1
作者：
BRUENNER, BA;JONES, AD;GERMAN, JB
通讯作者：
GERMAN, JB