Embers Monica E, Jacobs Mary B, Johnson Barbara J B, Philipp Mario T
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University Health Sciences Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
Clin Vaccine Immunol. 2007 Aug;14(8):931-6. doi: 10.1128/CVI.00075-07. Epub 2007 Jun 13.
Lyme borreliosis (LB) is a disease for which antibody-based detection assays are often required for diagnosis. The variable surface molecule VlsE and IR6, one of its invariable regions, are commonly targeted by the antibody response in infected individuals. A series of enzyme-linked immunosorbent assays was performed to comparatively examine the antibody responses of North American LB patients (n = 37) to VlsE and invariable segments of this molecule. Both immunoglobulin M (IgM) and IgG responses to full-length VlsE and to peptides reproducing invariable regions 2, 4, and 6, as well as the invariable domains at the amino and carboxyl termini of VlsE, were assessed. The proportions and specificities of reactivity to the invariable segments were tested by using cognate peptides as competitors for VlsE binding by patient serum antibodies. IR6 epitopes (by the C6 peptide) were found to dominate the response to invariable segments. IR6 (C6)-specific antibodies were detected in 78% of the serum specimens, whereas <40% of patients generated antibodies that bound the N- or C-terminal domain and <12% of patients responded to either IR2 or IR4. Interestingly, 15 of 37 patients generated IgG antibodies that reacted with C6 but not with VlsE. Conversely, IgM responses were frequent for VlsE but not for invariable segments. A representative number of the serum specimens (n = 8) that contained IgG antibodies reacting with both C6 and VlsE was assessed in competition experiments, using C6 as a competitor. Only half of these specimens contained IgG antibodies whose binding to VlsE could be inhibited >50% by competition with the added C6 peptide. The median percent inhibition was 45.5%. These findings indicate that IR6 epitopes are largely concealed from the VlsE molecular surface and that full-length VlsE-based diagnosis likely detects antibodies to conformational and/or variable region epitopes.
莱姆病（LB）是一种通常需要基于抗体的检测方法进行诊断的疾病。可变表面分子VlsE及其恒定区之一IR6是感染个体抗体反应的常见靶点。进行了一系列酶联免疫吸附试验，以比较北美莱姆病患者（n = 37）对VlsE及其该分子恒定片段的抗体反应。评估了免疫球蛋白M（IgM）和IgG对全长VlsE、对复制恒定区2、4和6的肽以及VlsE氨基和羧基末端恒定结构域的反应。通过使用同源肽作为患者血清抗体与VlsE结合的竞争剂，测试了对恒定片段反应的比例和特异性。发现IR6表位（通过C6肽）在对恒定片段的反应中占主导地位。在78%的血清标本中检测到IR6（C6）特异性抗体，而<40%的患者产生了与N端或C端结构域结合的抗体，<12%的患者对IR2或IR4有反应。有趣的是，37名患者中有15名产生了与C6反应但不与VlsE反应的IgG抗体。相反，VlsE的IgM反应频繁，而恒定片段的IgM反应不频繁。在竞争实验中，使用C6作为竞争剂，评估了一定数量代表性的（n = 8）含有与C6和VlsE都反应的IgG抗体的血清标本。这些标本中只有一半含有IgG抗体，其与VlsE的结合可被添加的C6肽竞争抑制>50%。抑制百分比的中位数为45.5%。这些发现表明，IR6表位在很大程度上隐藏于VlsE分子表面，基于全长VlsE的诊断可能检测到针对构象和/或可变区表位的抗体。
