Wang Tiehui, Wang Alex, Zindrili Rodanthi, Melis Elena, Guntupalli Swapna, Brittain-Long Robin, Delibegovic Mirela, Secombes Christopher J, Mody Nimesh, Mavin Sally, Buks Ralfs
EpitogenX Ltd, Foresterhill Health Campus, Aberdeen, United Kingdom.
University of Aberdeen, Aberdeen, United Kingdom.
Microbiol Spectr. 2024 Oct 22;12(12):e0167524. doi: 10.1128/spectrum.01675-24.
Lyme Borreliosis (LB), or Lyme disease, is a growing health concern caused by (Bbsl) bacteria transmitted through tick bites, and untreated cases can lead to severe health complications. Existing serology tests, while valuable, have low sensitivity in early infection stages where diagnosis is vital, interpretation variability, and false positives from cross-reactivity, while direct detection methods also suffer from low sensitivity, due to the inconsistent presence of Bbsl components in clinical samples. This study validated the diagnostic performance of the novel Epitogen Lyme Detect IgG enzyme-linked immunosorbent assay (ELISA) based on scaffold-displayed peptide antigens, using 120 specific immunodominant epitopes selected from 37 antigenic bacterial proteins corresponding to the main pathogenic Bbsl genospecies. Using 220 serum samples from Scottish patients with early, late, and disseminated LB, the assay's sensitivity was compared with that of the LIAISON Borrelia IgG CLIA, while specificity was assessed with 198 control samples, including healthy individuals and patients with diseases that are humorally similar. The Epitogen Lyme Detect IgG assay demonstrated comparable performance to the LIAISON Borrelia IgG in disseminated and late LB (Lyme neuroborreliosis, acrodermatitis chronica atrophicans, and Lyme arthritis). Notably, the Epitogen Lyme Detect IgG showed significantly higher sensitivity in patients with suspected erythema migrans, while maintaining high specificity. The Epitogen Lyme Detect IgG ELISA offers a promising advancement in LB diagnostics, demonstrating its potential for more accurate and timely diagnosis, particularly in the early stages of LB infection.IMPORTANCELyme Borreliosis (LB), caused by bacteria, poses significant health risks if undiagnosed or diagnosed late. Current diagnostic tests have limitations, especially in early-stage detection. This study validates the Epitogen Lyme Detect IgG enzyme-linked immunosorbent assay, demonstrating superior sensitivity in early LB detection while maintaining high specificity. The Epitogen Lyme Detect IgG comprises a suite of 120 immunodominant IgG epitopes/peptides from 37 bacterial antigens, covering the main LB-causing species: , , , and . The novel design of multiplexing peptide antigens onto a scaffold to facilitate expression, correct folding, and orientation of the relevant peptides offers a promising advancement, potentially leading to more accurate and timely LB diagnoses and improving patient outcomes.
莱姆病（LB），即莱姆疏螺旋体病，是一种日益受到关注的健康问题，由通过蜱虫叮咬传播的伯氏疏螺旋体（Bbsl）细菌引起，未经治疗的病例可能导致严重的健康并发症。现有的血清学检测虽然有价值，但在早期感染阶段（此时诊断至关重要）灵敏度较低，存在解读变异性以及交叉反应导致的假阳性，而直接检测方法也因临床样本中Bbsl成分存在不一致而灵敏度较低。本研究基于支架展示肽抗原，验证了新型Epitogen莱姆检测IgG酶联免疫吸附测定（ELISA）的诊断性能，该测定使用了从与主要致病性Bbsl基因种相对应的37种抗原性细菌蛋白中选出的120个特异性免疫显性表位。使用来自苏格兰早期、晚期和播散性莱姆病患者的220份血清样本，将该测定的灵敏度与LIAISON伯氏疏螺旋体IgG化学发光免疫分析（CLIA）的灵敏度进行比较，同时用198份对照样本（包括健康个体和体液免疫相似疾病患者）评估其特异性。Epitogen莱姆检测IgG测定在播散性和晚期莱姆病（莱姆神经疏螺旋体病、慢性萎缩性肢端皮炎和莱姆关节炎）中表现出与LIAISON伯氏疏螺旋体IgG相当的性能。值得注意的是，Epitogen莱姆检测IgG在疑似游走性红斑患者中显示出显著更高的灵敏度，同时保持高特异性。Epitogen莱姆检测IgG ELISA在莱姆病诊断方面有前景，证明其在更准确和及时诊断方面的潜力，特别是在莱姆病感染的早期阶段。
重要性
由细菌引起的莱姆病（LB），如果未被诊断或诊断较晚，会带来重大健康风险。当前的诊断测试存在局限性，尤其是在早期检测方面。本研究验证了Epitogen莱姆检测IgG酶联免疫吸附测定，在早期莱姆病检测中显示出卓越的灵敏度，同时保持高特异性。Epitogen莱姆检测IgG包含来自37种细菌抗原的一组120个免疫显性IgG表位/肽，涵盖主要的致莱姆病物种： 、 、 和 。将肽抗原多路复用至支架上以促进相关肽的表达、正确折叠和定向的新颖设计有前景，可能导致更准确和及时的莱姆病诊断并改善患者预后。
