Changes in levels of cytokines or soluble receptors in biological fluids may provide information on immunological pathomechanisms underlying the respective diseases. Here, we studied cytokine patterns of patients with autoimmune encephalitis (AE) before and after immunosuppressive treatment in order to identify possible biomarker candidates and to look for putatively involved pathomechanisms. We performed measurements in Cerebrospinal fluid (CSF) and serum of 7 patients suffering from AE with antibodies (ab) against Leucine-rich glioma-inactivated-protein 1 (LGI1) and 9 AE patients with Contactin-associated protein-like 2 (Caspr2) ab recruited from two tertiary AE centers in Magdeburg and Berlin, Germany. In the Magdeburg samples before and after treatment were available for the measurements and in the Berlin cohort samples were collected after treatment was initiated. First, we used a human cytokine array comprising 36 cytokines or soluble receptors to screen for biomarkers in CSF samples of 8 AE (before and after treatment), 4 herpes-simplex virus meningoencephalitis patients and 4 controls without neuroinflammation. Next, CCL2, CXCl10, CXCl13, Il -6 and sICAM1 were chosen as candidates and measured in CSF and serum with specific ELISA systems in all 16 AE patients, 14 controls without neuroinflammation and 7 herpes-simplex virus meningitis patients. Clinical outcome was assessed via modified Rankin scale. LGI1 and Caspr2 abs from the Magdeburg cohort were purified by chromatography. IgG subclasses of these LGI1 or Caspr2 abs were identified by immunoblot analysis. The levels of most candidate parameters were higher in the CSF of Caspr2 than of LGI1 AE patients and controls, but there were no significant changes of cytokine concentrations before and after initiating treatment. Thus, these parameters seem unsuited as surrogate biomarkers of disease. Significantly higher levels were observed in the CSFs of Caspr2 AE patients (CXCL13 and sICAM1) as well as in the serum of Caspr2 (CXCL10) and LGI1 AE patients (CXCL13) in comparison to control samples. These results suggest that neuro-immunological pathomechanisms may differ between Caspr2 and LGI1 AE patients. Caspr2 AE seems to elicit a higher immune response than LGI1 AE, which has no correlation to the respective IgG subclass combination of AE specific abs involved in each type of disease.

中文翻译：

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血清和 CSF 细胞因子水平反映了 LGI1 和 Caspr2 脑炎患者的不同神经免疫学机制

生物体液中细胞因子或可溶性受体水平的变化可以提供有关各种疾病的免疫病理机制的信息。在这里，我们研究了免疫抑制治疗前后自身免疫性脑炎 (AE) 患者的细胞因子模式，以确定可能的生物标志物候选者并寻找可能涉及的病理机制。我们对 7 名 AE 患者的脑脊液 (CSF) 和血清进行了测量，这些患者具有针对富含亮氨酸的胶质瘤灭活蛋白 1 (LGI1) 的抗体 (ab) 和 9 名具有 Contactin 相关蛋白样 2 (Caspr2) 的 AE 患者ab 从德国马格德堡和柏林的两个三级 AE 中心招募。在治疗前后的马格德堡样本可用于测量，而在柏林队列中则在治疗开始后收集样本。首先，我们使用包含 36 种细胞因子或可溶性受体的人细胞因子阵列来筛选 8 名 AE（治疗前后）、4 名单纯疱疹病毒脑膜脑炎患者和 4 名无神经炎症的对照的 CSF 样本中的生物标志物。接下来，CCL2、CXCl10、CXCl13、Il -6 和 sICAM1 被选为候选物，并在所有 16 名 AE 患者、14 名没有神经炎症的对照和 7 名单纯疱疹病毒脑膜炎患者的脑脊液和血清中使用特定的 ELISA 系统进行测量。通过改良的Rankin量表评估临床结果。来自 Magdeburg 队列的 LGI1 和 Caspr2 abs 通过色谱法纯化。通过免疫印迹分析鉴定了这些 LGI1 或 Caspr2 abs 的 IgG 亚类。大多数候选参数在 Caspr2 的 CSF 中的水平高于 LGI1 AE 患者和对照，但在开始治疗前后细胞因子浓度没有显着变化。因此，这些参数似乎不适合作为疾病的替代生物标志物。与对照样品相比，在 Caspr2 AE 患者（CXCL13 和 sICAM1）的 CSF 以及 Caspr2（CXCL10）和 LGI1 AE 患者（CXCL13）的血清中观察到显着更高的水平。这些结果表明 Caspr2 和 LGI1 AE 患者的神经免疫病理机制可能不同。Caspr2 AE 似乎比 LGI1 AE 引发更高的免疫反应，