Abstract：
Lyme borreliosis, caused by Borrelia burgdorferi sensu lato, is the most common tickborne disease. Its neuronal form, neuroborreliosis, comprises 3 to 38% of borreliosis cases in Europe. Borrelia outer surface proteins and virulence factors, OspE and BBK32, have been previously reported to help cause infection by promoting attachment to human host epithelial cells and evading complement attack. We assessed the serological responses to BBK32 and OspE in 19 individuals diagnosed with neuroborreliosis to see whether antibodies that could both target the bacteria and neutralize the virulence mechanisms on the microbial surface emerge. Results evaluate levels of total protein, IgG and the chemokine CXCL13, a determinant for B-cell recruitment during neuroinflammation, in patients\' cerebrospinal fluid samples. Antibody levels against BBK32 and OspE correlated with those against VlsE, a well-characterized diagnostic serological marker of the disease. A dual serological profile of the patients was observed. K-means clustering split the cohort into two discrete groups presenting distinct serological and CNS responses. One group contained young patients with low levels of anti-BBK32 and OspE antibodies. The other group showed stronger responses, possibly following prolonged infections or reinfections. Additionally, we assessed anti-ganglioside antibodies that could cause autoimmunity or complement dysregulation but observed that they did not correlate with neuroborreliosis in our patient cohort. The dual nature of antibody responses against the virulence factors BBK32 and OspE in neuroborreliosis patients may suggest the necessity of repeated exposures for efficient immune responses. Better protection could be achieved if the virulence factors were formulated into vaccines.
摘要：
莱姆病,由伯氏疏螺旋体引起的，是最常见的蜱传疾病。它的神经元形式，神经性伯利松病,占欧洲3％至38％的疏螺旋体病病例。疏螺旋体外表面蛋白和毒力因子，先前已报道OspE和BBK32通过促进与人宿主上皮细胞的附着和逃避补体攻击来帮助引起感染。我们评估了19名被诊断患有神经衰弱症的个体对BBK32和OspE的血清学反应，以了解是否出现了既可以靶向细菌又可以中和微生物表面毒力机制的抗体。结果评估总蛋白水平，IgG和趋化因子CXCL13，神经炎症期间B细胞募集的决定因素，患者脑脊液样本。针对BBK32和OspE的抗体水平与针对VlsE的抗体水平相关，该疾病的特征明确的诊断血清学标志物。观察到患者的双重血清学特征。K均值聚类将队列分为两个离散组，表现出不同的血清学和CNS反应。一组包含抗BBK32和OspE抗体水平较低的年轻患者。另一组表现出更强烈的反应，可能是长期感染或再感染。此外,我们评估了可能引起自身免疫或补体失调的抗神经节苷脂抗体,但在我们的患者队列中观察到它们与神经性伯利氏症无关.在神经症患者中，针对毒力因子BBK32和OspE的抗体反应的双重性质可能表明，必须反复暴露才能产生有效的免疫反应。如果将毒力因子配制到疫苗中，则可以实现更好的保护。
