Piepgras Johannes, Piepgras Marlene L, Steffen Falk, Ehrhardt Laura, Schaller-Paule Martin A, Yalachkov Yavor, Zipp Frauke, Bittner Stefan
Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Mainz, Germany.
Eur J Neurol. 2025 May;32(5):e70207. doi: 10.1111/ene.70207.
Management of autoimmune encephalitis (AE) is challenging due to a lack of reliable biomarkers. We here assess the combination of glial fibrillary acid protein (GFAP) and neurofilament (NfL) as biomarkers for diagnosis and disease monitoring of AE.
GFAP and NfL CSF levels (cGFAP, cNfL) of 42 AE patients were correlated with CSF markers of neuroinflammation. NfL/GFAP ratios were compared between patients with stable and active AE, stable and active multiple sclerosis (MS), and patients undergoing diagnostic lumbar puncture without evident pathological alterations (controls).
In patients with AE, cGFAP levels showed strong correlations with albumin and IgG quotients and moderate correlations with CSF cell count; cNfL levels showed weak correlations with albumin quotients. cGFAP and cNfL levels showed no significant differences between patients with and without epileptic activity or inflammatory MRI lesions. Both sNfL and sGFAP correlated with the Clinical Assessment Scale in Autoimmune Encephalitis. Compared to NfL or GFAP alone, the NfL/GFAP ratio from CSF or serum led to a clearer separation of AE from MS patients and controls. Furthermore, serum NfL/GFAP ratios better discriminated active from stable AE.
cGFAP levels indicate intrathecal inflammatory processes in patients with active AE to a stronger degree than cNfL levels. Serum NfL/GFAP ratios recognize active AE, suggesting this ratio identifies AE patients with CNS-compartmentalized neuronal injury (autoantibody-mediated or cytotoxic) behind a relatively intact blood-brain barrier. Our findings indicate that the NfL/GFAP ratio can function as a blood-based biomarker, aiding clinicians with diagnosis and disease management of AE.
由于缺乏可靠的生物标志物，自身免疫性脑炎（AE）的管理具有挑战性。我们在此评估胶质纤维酸性蛋白（GFAP）和神经丝（NfL）联合作为AE诊断和疾病监测生物标志物的情况。
对42例AE患者的GFAP和NfL脑脊液水平（cGFAP、cNfL）与神经炎症的脑脊液标志物进行相关性分析。比较了AE病情稳定和活动期、多发性硬化（MS）病情稳定和活动期患者以及腰椎穿刺诊断但无明显病理改变的患者（对照组）之间的NfL/GFAP比值。
在AE患者中，cGFAP水平与白蛋白和IgG商数呈强相关，与脑脊液细胞计数呈中度相关；cNfL水平与白蛋白商数呈弱相关。有或无癫痫活动或炎性磁共振成像（MRI）病变的患者之间，cGFAP和cNfL水平无显著差异。血清NfL（sNfL）和血清GFAP（sGFAP）均与自身免疫性脑炎临床评估量表相关。与单独的NfL或GFAP相比，脑脊液或血清中的NfL/GFAP比值能更清晰地区分AE患者与MS患者及对照组。此外，血清NfL/GFAP比值能更好地区分活动期与稳定期AE。
cGFAP水平比cNfL水平更能强烈指示活动期AE患者的鞘内炎症过程。血清NfL/GFAP比值可识别活动期AE，表明该比值可识别血脑屏障相对完整情况下中枢神经系统存在局部神经元损伤（自身抗体介导或细胞毒性）的AE患者。我们的研究结果表明，NfL/GFAP比值可作为一种基于血液的生物标志物，有助于临床医生对AE进行诊断和疾病管理。
