使用临近延伸分析方法验证脑脊髓液中白细胞介素-8 水平升高，并发现吉兰-巴雷综合征和慢性炎症性脱髓鞘性多发性神经病患者的新生物标志物。
Validation of elevated levels of interleukin-8 in the cerebrospinal fluid, and discovery of new biomarkers in patients with GBS and CIDP using a proximity extension assay.
机构信息
Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
出版信息
Front Immunol. 2023 Nov 23;14:1241199. doi: 10.3389/fimmu.2023.1241199. eCollection 2023.
BACKGROUND
Biomarkers for diagnosis of inflammatory neuropathies, assessment of prognosis, and treatment response are lacking.
METHODS
CSF and EDTA plasma from patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), healthy controls (HC) and disease controls were analyzed with Olink multiplex proximity extension assay (PEA) from two independent cohorts. Levels of interleukin-8 (IL8) were further analyzed with ELISA in patients with GBS, CIDP, paraproteinemia-related demyelinating polyneuropathy (PDN), multifocal motor neuropathy (MMN), HC and disease controls. ROC analysis was performed. Outcome was measured with the GBS-disability score (GBS-ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) score.
RESULTS
In CSF, multiplex PEA analysis revealed up-regulation of IL8 in GBS compared to CIDP and HC respectively, and CIDP compared to HC. In addition, levels of IL2RA were upregulated in GBS compared to both HC and CIDP, SELE in GBS compared to HC, and ITGAM, IL6, and NRP1 in GBS compared to CIDP. In plasma, levels of MMP3, THBD and ITGAM were upregulated in CIDP compared to HC. Validation of multiplex IL8 results using ELISA, revealed increased levels of IL8 in CSF in patients with GBS and CIDP versus HC and non-inflammatory polyneuropathies (NIP) respectively, as well as in PDN versus NIP and HC. Levels of IL8 in CSF correlated with impairment in the acute phase of GBS as well as outcome at 6-months follow up.
CONCLUSION
IL8 in CSF is validated as a diagnostic biomarker in GBS and CIDP, and a prognostic biomarker in GBS. Multiplex PEA hereby identifies several potential biomarkers in GBS and CIDP.
背景
目前缺乏用于诊断炎性神经病、评估预后和治疗反应的生物标志物。
方法
使用来自两个独立队列的 Olink 多重邻近延伸分析（PEA）分析格林-巴利综合征（GBS）、慢性炎症性脱髓鞘性多发性神经病（CIDP）、健康对照（HC）和疾病对照患者的 CSF 和 EDTA 血浆。在 GBS、CIDP、副蛋白血症相关脱髓鞘性多发性神经病（PDN）、多灶性运动神经病（MMN）、HC 和疾病对照患者中，进一步使用 ELISA 分析白细胞介素-8（IL8）的水平。进行 ROC 分析。用 GBS 残疾评分（GBS-ds）或炎症性神经病病因和治疗（INCAT）评分测量结局。
结果
在 CSF 中，与 CIDP 和 HC 相比，多聚体 PEA 分析显示 GBS 中 IL8 上调，与 HC 相比，CIDP 中 IL8 上调。此外，与 HC 和 CIDP 相比，IL2RA 在 GBS 中上调，SELE 在 GBS 中与 HC 相比上调，ITGAM、IL6 和 NRP1 在 GBS 中与 CIDP 相比上调。在血浆中，与 HC 相比，MMP3、THBD 和 ITGAM 在 CIDP 中上调。使用 ELISA 验证多聚体 IL8 结果，显示与 HC 和非炎症性多发性神经病（NIP）相比，GBS 和 CIDP 患者 CSF 中 IL8 水平升高，与 NIP 和 HC 相比，PDN 患者 CSF 中 IL8 水平升高。CSF 中 IL8 水平与 GBS 急性期的损伤以及 6 个月随访时的结局相关。
结论
CSF 中的 IL8 被验证为 GBS 和 CIDP 的诊断生物标志物，也是 GBS 的预后生物标志物。多聚体 PEA 在此确定了 GBS 和 CIDP 中的几种潜在生物标志物。
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