Elkon K B
Hospital for Special Surgery-Cornell University Medical College, New York, NY 10021.
Mol Biol Rep. 1992 Jun;16(3):207-12. doi: 10.1007/BF00464709.
The rapid progress made over the last 10 years in the identification of individual autoantigens and in the localization of the epitopes involved, has resulted in a parallel reduction in the complexity of the antigen required for the detection of autoantibodies. The ability to use synthetic peptides as antigens is a remarkable culmination of this process considering that many antigenic particles contain multiple proteins (eg. Sm consist of 8 or more individual proteins). Despite the fact that patients with SLE have a polyclonal hypergammaglobulinemia, excellent correlations between ELISAs utilizing the P2 or SmB/B' synthetic peptides, ELISAs utilizing r proteins and immunoblotting were obtained [28, 38, 50]. However, false positive/non-specific binding to a P2-BSA-glutaraldehyde conjugate has been observed with serum from old MRL/lpr mice (unpublished observations). In addition, some of the results obtained in human autoimmune diseases suggest that non-specific binding may be problematic in some instances. It is difficult, at present, to know whether the higher frequencies of detection of autoantibodies to certain synthetic peptide antigens reflect increased sensitivity or decreased specificity. Synthetic peptide antigens have been used to detect autoantibodies in both organ specific and multisystem autoimmune diseases. In only a small number of cases have these reagents been rigorously tested for sensitivity and specificity. Despite this, synthetic peptides have been shown to be valuable for detection and quantification of autoantibodies in certain clinical situations. Undoubtedly, further progress in epitope mapping of autoantigens coupled with technological advances in protein synthesis and improved prediction of protein structure will lead to a large number of synthetic peptide antigens for research and clinical applications.(ABSTRACT TRUNCATED AT 250 WORDS)
在过去10年中,在鉴定单个自身抗原以及确定相关表位的定位方面取得了快速进展,这使得检测自身抗体所需抗原的复杂性相应降低。考虑到许多抗原颗粒包含多种蛋白质(例如,Sm由8种或更多种单个蛋白质组成),使用合成肽作为抗原的能力是这一过程的显著成果。尽管系统性红斑狼疮(SLE)患者存在多克隆高丙种球蛋白血症,但利用P2或SmB/B'合成肽的酶联免疫吸附测定(ELISA)、利用重组蛋白的ELISA与免疫印迹之间仍获得了良好的相关性[28, 38, 50]。然而,已观察到来自老年MRL/lpr小鼠的血清与P2 - 牛血清白蛋白 - 戊二醛偶联物存在假阳性/非特异性结合(未发表的观察结果)。此外,在人类自身免疫性疾病中获得的一些结果表明,在某些情况下非特异性结合可能存在问题。目前很难知道针对某些合成肽抗原检测自身抗体的较高频率是反映了敏感性增加还是特异性降低。合成肽抗原已被用于检测器官特异性和多系统自身免疫性疾病中的自身抗体。在仅少数情况下,这些试剂经过了敏感性和特异性的严格测试。尽管如此,合成肽已被证明在某些临床情况下对于检测和定量自身抗体具有价值。毫无疑问,自身抗原表位作图的进一步进展,再加上蛋白质合成技术的进步以及蛋白质结构预测的改进,将产生大量用于研究和临床应用的合成肽抗原。(摘要截取自250字)