Eggleton P, Haigh R, Winyard P G
Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, Devon EX1 2LU, UK.
Rheumatology (Oxford). 2008 May;47(5):567-71. doi: 10.1093/rheumatology/ken014. Epub 2008 Mar 3.
Post-translational modifications play a central role in determining the function of proteins. Such protein modifications come in a great variety of guises, and include phosphorylation, proteolysis, glycosylation, citrullination and oxidative modifications. In relation to inflammatory autoimmune diseases, some post-translational modifications appear to result in the generation of new antigens, and hence autoantibodies. Examples include: the induction of peptide immunogenicity by the spontaneous conversion of aspartic acid residues to isoaspartic acid; granzyme B-mediated cleavage of SLE autoantigens; the oxidative modification--on the surface of apoptotic cells--of lipids and proteins, rendering them immunogenic; and the presence of antibodies to oxidatively modified type II collagen and C1q in RA and SLE patients, respectively. The measurement of autoantibodies to citrullinated proteins has been verified as a very useful diagnostic tool in RA. Proteomics techniques, in principle, allow the detection of all types of in vivo protein modifications, and the increasing application of such technologies to the study of rheumatological diseases will further our understanding of autoantigenicity.
翻译后修饰在决定蛋白质功能方面起着核心作用。此类蛋白质修饰形式多样，包括磷酸化、蛋白水解、糖基化、瓜氨酸化和氧化修饰。就炎性自身免疫性疾病而言，一些翻译后修饰似乎会导致新抗原的产生，进而产生自身抗体。例如：天冬氨酸残基自发转化为异天冬氨酸会诱导肽的免疫原性；颗粒酶B介导的系统性红斑狼疮自身抗原的裂解；凋亡细胞表面脂质和蛋白质的氧化修饰，使其具有免疫原性；类风湿关节炎和系统性红斑狼疮患者分别存在针对氧化修饰的II型胶原和C1q的抗体。检测抗瓜氨酸化蛋白的自身抗体已被证实是类风湿关节炎中一种非常有用的诊断工具。蛋白质组学技术原则上能够检测所有类型的体内蛋白质修饰，此类技术在风湿病研究中的应用不断增加，将加深我们对自身抗原性的理解。
