Serum Epitope Repertoire Analysis Enables Early Detection of Lyme Disease with Improved Sensitivity in an Expandable Multiplex Format.
Serum Epitope Repertoire Analysis Enables Early Detection of Lyme Disease with Improved Sensitivity in an Expandable Multiplex Format.
复制标题
血清表位曲目分析可早期检测莱姆病，并以可扩展的多重形式提高灵敏度。
DOI：
10.1128/jcm.01836-20
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发表时间：
2021-01-21
影响因子：
9.4
通讯作者：
Daugherty PS
中科院分区：
文献类型：
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作者：
Reifert J;Kamath K;Bozekowski J;Lis E;Horn EJ;Granger D;Theel ES;Shon J;Sawyer JR;Daugherty PS
广泛使用的莱姆病诊断抗体血清学，被称为标准两层测试（STTT），在早期莱姆病中表现出不够的灵敏度，每年产生数千个假阴性测试结果。鉴于这个问题，我们应用血清抗体库分析（SERA），或下一代测序（NGS）为基础的血清学，发现IgG和IgM抗体表位基序能够检测莱姆病特异性抗体具有高灵敏度和特异性。来自莱姆病受试者（n = 264）和对照受试者（n = 391）的表位库的迭代基序发现和生物信息学分析产生了代表20个不同IgG抗体表位的一组28个表位基序和代表21个不同IgM表位的一组38个表位基序，其在STTT阳性样品的大验证队列中表现等同。广泛使用的莱姆病诊断抗体血清学，被称为标准两层测试（STTT），在早期莱姆病中表现出不够的灵敏度，每年产生数千个假阴性测试结果。鉴于这个问题，我们应用血清抗体库分析（SERA），或下一代测序（NGS）为基础的血清学，发现IgG和IgM抗体表位基序能够检测莱姆病特异性抗体具有高灵敏度和特异性。来自莱姆病受试者（n = 264）和对照受试者（n = 391）的表位库的迭代基序发现和生物信息学分析产生了代表20个不同IgG抗体表位的一组28个表位基序和代表21个不同IgM表位的一组38个表位基序，其在STTT阳性样品的大验证队列中表现等同。在来自患有临床定义的早期莱姆病（n = 119）和对照（n = 257）的受试者的第二验证集中，相对于STTT，SERA莱姆病IgG和IgM测定显示出显著改善的灵敏度（77%对62%; Z检验; P = 0.013）和改善的特异性（99%对97%）。相对于患有莱姆病关节炎的受试者，早期莱姆病受试者表现出显着较少的反应性表位（Mann-Whitney U检验; P < 0.0001）。因此，SERA莱姆病IgG和M面板在早期莱姆病中以易于扩展的多重测定形式提供了更高的准确性。
Widely employed diagnostic antibody serology for Lyme disease, known as standard two-tier testing (STTT), exhibits insufficient sensitivity in early Lyme disease, yielding many thousands of false-negative test results each year. Given this problem, we applied serum antibody repertoire analysis (SERA), or next-generation sequencing (NGS)-based serology, to discover IgG and IgM antibody epitope motifs capable of detecting Lyme disease-specific antibodies with high sensitivity and specificity. Iterative motif discovery and bioinformatic analysis of epitope repertoires from subjects with Lyme disease (n = 264) and controls (n = 391) yielded a set of 28 epitope motifs representing 20 distinct IgG antibody epitopes and a set of 38 epitope motifs representing 21 distinct IgM epitopes, which performed equivalently in a large validation cohort of STTT-positive samples. Widely employed diagnostic antibody serology for Lyme disease, known as standard two-tier testing (STTT), exhibits insufficient sensitivity in early Lyme disease, yielding many thousands of false-negative test results each year. Given this problem, we applied serum antibody repertoire analysis (SERA), or next-generation sequencing (NGS)-based serology, to discover IgG and IgM antibody epitope motifs capable of detecting Lyme disease-specific antibodies with high sensitivity and specificity. Iterative motif discovery and bioinformatic analysis of epitope repertoires from subjects with Lyme disease (n = 264) and controls (n = 391) yielded a set of 28 epitope motifs representing 20 distinct IgG antibody epitopes and a set of 38 epitope motifs representing 21 distinct IgM epitopes, which performed equivalently in a large validation cohort of STTT-positive samples. In a second validation set from subjects with clinically defined early Lyme disease (n = 119) and controls (n = 257), the SERA Lyme IgG and IgM assay exhibited significantly improved sensitivity relative to STTT (77% versus 62%; Z-test; P = 0.013) and improved specificity (99% versus 97%). Early Lyme disease subjects exhibited significantly fewer reactive epitopes (Mann-Whitney U test; P < 0.0001) relative to subjects with Lyme arthritis. Thus, SERA Lyme IgG and M panels provided increased accuracy in early Lyme disease in a readily expandable multiplex assay format.