血清胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）与水通道蛋白4免疫球蛋白G（AQP4-IgG）阳性视神经脊髓炎谱系障碍（NMOSD）和髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）患者脑和上颈椎磁共振成像（MRI）体积的相关性研究
Investigation of the association of serum GFAP and NfL with brain and upper cervical MRI volumes in AQP4-IgG-positive NMOSD and MOGAD.
作者信息
Schindler Patrick, Grittner Ulrike, Rust Rebekka, Asseyer Susanna, Bellmann-Strobl Judith, Schmitz-Hübsch Tanja, Scheel Michael, Jarius Sven, Wildemann Brigitte, Reindl Markus, Benkert Pascal, Kuhle Jens, Paul Friedemann, Ruprecht Klemens, Chien Claudia
机构信息
Department of Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitätsmedizin Berlin, Berlin, Germany.
出版信息
Ther Adv Neurol Disord. 2025 Jul 20;18:17562864251345792. doi: 10.1177/17562864251345792. eCollection 2025.
BACKGROUND
Serum glial fibrillary acidic protein (sGFAP) is associated with disease activity in aquaporin-4-immunoglobulin G-seropositive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSD). Serum neurofilament light chain (sNfL) is a biomarker for neuroaxonal damage. However, the association of sGFAP and sNfL with magnetic resonance imaging (MRI) volumes in AQP4-IgG+NMOSD is unclear.
OBJECTIVES
To investigate the associations of sGFAP and sNfL with brain MRI volumes in AQP4-IgG+NMOSD.
DESIGN
Monocentric, retrospective, observational study.
METHODS
In 33 clinically stable patients with AQP4-IgG+NMOSD, 17 patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and 15 healthy controls (HC), sGFAP and sNfL were measured at 2 (HC = 1) and 3-Tesla MRIs were obtained at 4 (HC = 1) yearly visits. Associations between biomarkers and MRI metrics were evaluated using linear models.
RESULTS
In AQP4-IgG+NMOSD, but not in MOGAD and HC, higher sGFAP was associated with lower hippocampus (β = -2.0 (95% confidence interval: -3.4, -0.7), = 0.004) and thalamus volumes (β = -2.5 (-4.3, -0.7), = 0.006) and higher MRI cerebrospinal fluid volume (β = 1.8 (0.7, 3.2), = 0.01), and, statistically less robust, with lower whole brain (β = -2.3 (-5.3, 0.8), = 0.15) and gray matter volumes (β = -1.8 (-4.0, 0.4), = 0.10). Furthermore, higher sGFAP (β = -0.06 (-0.11, -0.002), = 0.04), but not sNfL (β = -0.02 (-0.08, 0.03), = 0.38), was associated with percent brain volume change in AQP4-IgG+NMOSD.
CONCLUSION
The specific associations of sGFAP with brain MRI volumes corroborate sGFAP as a biomarker for disease activity in AQP4-IgG+NMOSD.
背景
血清胶质纤维酸性蛋白（sGFAP）与水通道蛋白4免疫球蛋白G血清阳性视神经脊髓炎谱系障碍（AQP4-IgG+NMOSD）的疾病活动相关。血清神经丝轻链（sNfL）是神经轴突损伤的生物标志物。然而，sGFAP和sNfL与AQP4-IgG+NMOSD磁共振成像（MRI）体积的关联尚不清楚。
目的
研究sGFAP和sNfL与AQP4-IgG+NMOSD脑MRI体积的关联。
设计
单中心、回顾性、观察性研究。
方法
在33例临床稳定的AQP4-IgG+NMOSD患者、17例髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）患者和15名健康对照者（HC）中，在2次（HC为1次）测量sGFAP和sNfL，并在4次（HC为1次）年度随访时进行3特斯拉MRI检查。使用线性模型评估生物标志物与MRI指标之间的关联。
结果
在AQP4-IgG+NMOSD中，而非在MOGAD和HC中，较高的sGFAP与较低的海马体积（β=-2.0（95%置信区间：-3.4，-0.7），P=0.004）和丘脑体积（β=-2.5（-4.3，-0.7），P=0.006）以及较高的MRI脑脊液体积（β=1.8（0.7，3.2），P=0.01）相关，但在统计学上不太显著的是，与较低的全脑体积（β=-2.3（-5.3，0.8），P=0.15）和灰质体积（β=-1.8（-4.0，0.4），P=0.10）相关。此外，在AQP4-IgG+NMOSD中，较高的sGFAP（β=-0.06（-0.11，-0.002），P=0.04），而非sNfL（β=-0.02（-0.08，0.03），P=0.38），与脑体积变化百分比相关。
结论
sGFAP与脑MRI体积的特定关联证实了sGFAP作为AQP4-IgG+NMOSD疾病活动生物标志物的作用。
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