Ørbæk Mathilde, Gynthersen Rosa Maja Møhring, Mens Helene, Stenør Christian, Wiese Lothar, Brandt Christian, Ostrowski Sisse Rye, Nielsen Susanne Dam, Lebech Anne-Mette
Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Front Cell Infect Microbiol. 2021 May 10;11:666037. doi: 10.3389/fcimb.2021.666037. eCollection 2021.
sensu lato complex () can cause a variety of clinical manifestations including Lyme neuroborreliosis. Following the tick-borne transmission, initially evade immune responses, later symptomatic infection is associated with occurrence of specific antibody responses. We hypothesized that induce immune hyporesponsiveness or immune suppression and aimed to investigate patients with Lyme neuroborreliosis ability to respond to immune stimulation.
An observational cohort study investigating the stimulated immune response by standardized whole blood assay (TruCulture) in adult patients with Lyme neuroborreliosis included at time of diagnosis from 01.09.2018-31.07.2020. Reference intervals were based on a 5-95% range of cytokine concentrations from healthy individuals (n = 32). Patients with Lyme neuroborreliosis and references were compared using Mann-Whitney U test. Heatmaps of cytokine responses were generated using the webtool Clustvis.
In total, 22 patients with Lyme neuroborreliosis (19 definite, 3 probable) were included. In the unstimulated samples, the concentrations of cytokines in patients with Lyme neuroborreliosis were comparable with references, except interferon (IFN)-α, interleukin (IL)-17A, IL-1β and IL-8, which were all significantly below the references. Patients with Lyme neuroborreliosis had similar concentrations of most cytokines in all stimulations compared with references. IFN-α, IFN-γ, IL-12 and IL-17A were lower than references in multiple stimulations.
In this exploratory cohort study, we found lower or similar concentrations of circulating cytokines in blood from patients with Lyme neuroborreliosis at time of diagnosis compared with references. The stimulated cytokine release in blood from patients with Lyme neuroborreliosis was in general slightly lower than in the references. Specific patterns of low IL-12 and IFN-γ indicated low Th1-response and low concentrations of IL-17A did not support a strong Th17 response. Our results suggest that patients with Lyme neuroborreliosis elicit a slightly suppressed or impaired immune response for the investigated stimulations, however, whether the response normalizes remains unanswered.
广义复合体()可引起多种临床表现,包括莱姆病神经伯氏疏螺旋体病。蜱传播后,最初逃避免疫反应,随后有症状的感染与特异性抗体反应的发生相关。我们假设诱导免疫低反应性或免疫抑制,并旨在研究莱姆病神经伯氏疏螺旋体病患者对免疫刺激的反应能力。
一项观察性队列研究,通过标准化全血检测(TruCulture)调查2018年9月1日至2020年7月31日诊断时成年莱姆病神经伯氏疏螺旋体病患者的刺激免疫反应。参考区间基于健康个体(n = 32)细胞因子浓度的5 - 95%范围。使用曼 - 惠特尼U检验比较莱姆病神经伯氏疏螺旋体病患者和参考对象。使用网络工具Clustvis生成细胞因子反应热图。
总共纳入22例莱姆病神经伯氏疏螺旋体病患者(19例确诊,3例可能)。在未刺激样本中,莱姆病神经伯氏疏螺旋体病患者的细胞因子浓度与参考对象相当,但干扰素(IFN)-α、白细胞介素(IL)-17A、IL-1β和IL-8均显著低于参考对象。与参考对象相比,莱姆病神经伯氏疏螺旋体病患者在所有刺激下大多数细胞因子的浓度相似。IFN-α、IFN-γ、IL-12和IL-17A在多次刺激下均低于参考对象。
在这项探索性队列研究中,我们发现与参考对象相比,诊断时莱姆病神经伯氏疏螺旋体病患者血液中循环细胞因子的浓度较低或相似。莱姆病神经伯氏疏螺旋体病患者血液中刺激后的细胞因子释放总体上略低于参考对象。低IL-12和IFN-γ的特定模式表明Th1反应低,IL-17A浓度低不支持强烈的Th17反应。我们的结果表明,莱姆病神经伯氏疏螺旋体病患者在研究的刺激下引发的免疫反应略有抑制或受损,然而,反应是否恢复正常仍未得到解答。