Department of Infectious Diseases, Region Jönköping County, 551 85, Jönköping, Sweden.
Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Sci Rep. 2023 Jun 15;13(1):9722. doi: 10.1038/s41598-023-36709-w.
Lyme neuroborreliosis (LNB) is associated with increased levels of pro-inflammatory cytokines and chemokines in the cerebrospinal fluid (CSF). Residual symptoms after antibiotic treatment can have deleterious effects on patients and knowledge regarding the pathogenesis linked to prolonged recovery is lacking. In this prospective follow-up study, we investigated the B cell-associated and T helper (Th) cell-associated immune responses in well-characterized patients with LNB and controls. The aims were to assess the kinetics of selected cytokines and chemokines involved in the inflammatory response and to identify potential prognostic markers. We investigated 13 patients with LNB according to a standardized clinical protocol before antibiotic treatment and after 1, 6 and 12 months of follow-up. CSF and blood samples were obtained at baseline and after 1 month. As controls, we used CSF samples from 37 patients who received spinal anesthesia during orthopedic surgery. The CSF samples were analyzed for CXCL10 (Th1-related), CCL22 (Th2-related) and IL-17A, CXCL1 and CCL20 (Th17-related), as well as for the B cell-related cytokines of a proliferation-inducing ligand (APRIL), B cell-activating factor (BAFF) and CXCL13. The CSF levels of all the cytokines and chemokines, with the exception of APRIL, were significantly higher at baseline in patients with LNB compared with controls. All the cytokines and chemokines, except for IL-17A were significantly reduced at 1-month follow-up. Patients with quick recovery (< 1 month, n = 3) had significantly lower levels of CCL20 at baseline and lower levels of IL-17A at 1-month follow-up. Patients with time of recovery > 6 months (n = 7) had significantly higher levels of IL-17A at the one-month follow-up. No other cytokines or chemokines were associated with prolonged recovery. Dominating residual symptoms were fatigue, myalgia, radiculitis and/or arthralgia. In this prospective follow-up study of patients with LNB, we found significantly lower levels of CCL20 in those who recovered rapidly, and increased levels of IL-17A in patients with delayed recovery post-treatment. Our findings indicate persistent Th17-driven inflammation in the CSF, possibly contributing to a longer convalescence, and suggest IL-17A and CCL20 as potential biomarker candidates for patients with LNB.
莱姆神经Borreliosis（LNB）与脑脊液（CSF）中促炎细胞因子和趋化因子水平升高有关。抗生素治疗后残留症状会对患者造成有害影响，而与延长恢复时间相关的发病机制知识则缺乏。在这项前瞻性随访研究中，我们研究了在经过充分特征描述的 LNB 患者和对照组中与 B 细胞相关和 T 辅助（Th）细胞相关的免疫反应。目的是评估参与炎症反应的选定细胞因子和趋化因子的动力学，并确定潜在的预后标志物。我们根据标准化临床方案，在抗生素治疗前和治疗后 1、6 和 12 个月对 13 名 LNB 患者进行了前瞻性随访。在基线和治疗后 1 个月时采集 CSF 和血液样本。作为对照组，我们使用了 37 名接受骨科手术脊髓麻醉的患者的 CSF 样本。分析了 CSF 样本中 CXCL10（Th1 相关）、CCL22（Th2 相关）和 IL-17A、CXCL1 和 CCL20（Th17 相关）以及增殖诱导配体（APRIL）、B 细胞激活因子（BAFF）和 CXCL13 的 B 细胞相关细胞因子。与对照组相比，LNB 患者的所有细胞因子和趋化因子（除 APRIL 外）在基线时均显著升高。所有细胞因子和趋化因子，除 IL-17A 外，在 1 个月时随访时均显著降低。恢复较快（<1 个月，n=3）的患者，在基线时 CCL20 水平显著降低，在 1 个月时 IL-17A 水平显著降低。恢复时间超过 6 个月（n=7）的患者，在 1 个月时随访时 IL-17A 水平显著升高。其他细胞因子或趋化因子与恢复时间延长无关。主要残留症状为疲劳、肌痛、神经根炎和/或关节炎。在这项前瞻性 LNB 患者随访研究中，我们发现快速恢复的患者 CCL20 水平显著降低，治疗后恢复时间延迟的患者 IL-17A 水平升高。我们的发现表明 CSF 中持续存在 Th17 驱动的炎症，可能导致更长的恢复期，并提示 IL-17A 和 CCL20 作为 LNB 患者潜在的生物标志物候选物。
