Davies J M, Mackay I R, Rowley M J
Department of Biochemistry and Molecular Biology, Monash University, Clayton Vic, Australia.
Autoimmunity. 1999;30(1):53-9. doi: 10.3109/08916939908994760.
Antibodies to type II collagen, and to Epstein Barr virus nuclear antigen-1 (EBNA-1) have been associated with rheumatoid arthritis (RA). In studies involving probing of phage-displayed random peptide libraries with an antibody to type II collagen, CII-C1, we observed that among 17 phagotopes selected 5 expressed peptides with homology with the sequence of EBNA-1. The residues in common were RLPFG. Hence we tested sera from 50 patients with RA, of whom 26 had antibodies to native type II collagen, and 43 healthy controls, for reactivity by ELISA with a phagotope selected 4 times, which expressed the peptide RRLPFGSQM. Eight RA sera (16%) but no normal sera reacted with the phagotope (p = 0.025). This reactivity could not be correlated with reactivity of RA sera with EBNA-1 by semi-quantitative western blot, with which reactivity occurred in 78% of RA patients and 81% of controls. Evidence for molecular mimicry was not found insofar as the phagotope did not inhibit reactivity of RA sera with EBNA-1 and CII-C1 was not reactive with EBNA-1. We conclude that the reactivity of the RA sera with the phagotope is most likely due to the phagotope being a mimic of an epitope of type II collagen for a proportion of RA sera.
抗II型胶原蛋白抗体以及抗Epstein Barr病毒核抗原-1（EBNA-1）抗体已与类风湿性关节炎（RA）相关联。在一项研究中，我们用抗II型胶原蛋白抗体CII-C1对噬菌体展示随机肽库进行筛选，结果发现在挑选出的17个噬菌体表位中，有5个表达的肽与EBNA-1的序列具有同源性。共同的残基为RLPFG。因此，我们用一种被挑选了4次的噬菌体表位（该表位表达肽RRLPFGSQM）通过酶联免疫吸附测定法（ELISA）检测了50例RA患者（其中26例有抗天然II型胶原蛋白抗体）的血清以及43例健康对照的血清的反应性。8例RA患者的血清（16%）与该噬菌体表位发生反应，而正常血清均未出现反应（p = 0.025）。通过半定量蛋白质印迹法，这种反应性与RA患者血清和EBNA-1的反应性并无关联，在蛋白质印迹法中，78%的RA患者和81%的对照出现了反应性。由于该噬菌体表位并未抑制RA患者血清与EBNA-1的反应性，且CII-C1与EBNA-1无反应性，因此未发现分子模拟的证据。我们得出结论，RA患者血清与该噬菌体表位的反应性很可能是因为对于一部分RA患者血清而言，该噬菌体表位是II型胶原蛋白一个表位的模拟物。
