Weber Laura K, Isse Awale, Rentschler Simone, Kneusel Richard E, Palermo Andrea, Hubbuch Jürgen, Nesterov-Mueller Alexander, Breitling Frank, Loeffler Felix F
Institute of Microstructure Technology Karlsruhe Institute of Technology Karlsruhe Germany.
DIARECT AG Freiburg Germany.
Eng Life Sci. 2017 Jul 20;17(10):1078-1087. doi: 10.1002/elsc.201700062. eCollection 2017 Oct.
Lyme disease is the most common tick-borne infectious disease in Europe and North America. Previous studies discovered the immunogenic role of a surface-exposed lipoprotein (VlsE) of . We employed high density peptide arrays to investigate the antibody response to the VlsE protein in VlsE-positive patients by mapping the protein as overlapping peptides and subsequent in-depth epitope substitution analyses. These investigations led to the identification of antibody fingerprints represented by a number of key residues that are indispensable for the binding of the respective antibody. This approach allows us to compare the antibody specificities of different patients to the resolution of single amino acids. Our study revealed that the sera of VlsE-positive patients recognize different epitopes on the protein. Remarkably, in those cases where the same epitope is targeted, the antibody fingerprint is almost identical. Furthermore, we could correlate two fingerprints with human autoantigens and an Epstein-Barr virus epitope; yet, the link to autoimmune disorders seems unlikely and must be investigated in further studies. The other three fingerprints are much more specific for . Since antibody fingerprints of longer sequences have proven to be highly disease specific, our findings suggest that the fingerprints could function as diagnostic markers that can reduce false positive test results.
莱姆病是欧洲和北美最常见的蜱传传染病。先前的研究发现了一种表面暴露脂蛋白(VlsE)的免疫原性作用。我们采用高密度肽阵列,通过将VlsE蛋白映射为重叠肽并随后进行深入的表位替换分析,来研究VlsE阳性患者对VlsE蛋白的抗体反应。这些研究导致鉴定出由许多关键残基代表的抗体指纹,这些残基对于相应抗体的结合是必不可少的。这种方法使我们能够将不同患者的抗体特异性比较到单个氨基酸的分辨率。我们的研究表明,VlsE阳性患者的血清识别该蛋白上的不同表位。值得注意的是,在那些靶向相同表位的情况下,抗体指纹几乎相同。此外,我们可以将两个指纹与人类自身抗原和一个爱泼斯坦 - 巴尔病毒表位相关联;然而,与自身免疫性疾病的联系似乎不太可能,必须在进一步的研究中进行调查。另外三个指纹对……更具特异性。由于较长序列的抗体指纹已被证明具有高度的疾病特异性,我们的研究结果表明这些指纹可以作为诊断标志物,减少假阳性检测结果。