Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Front Immunol. 2021 Mar 16;12:647618. doi: 10.3389/fimmu.2021.647618. eCollection 2021.
To evaluate the potential of serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP) as disease biomarkers in neuromyelitis optica spectrum disorder (NMOSD) with aquaporin-4 antibody (AQP4-ab) or myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD). Patients with AQP4-ab-positive NMOSD ( = 51), MOGAD ( = 42), and relapsing-remitting multiple sclerosis (RRMS) ( = 31 for sNfL and = 22 for sGFAP testing), as well as healthy controls (HCs) ( = 28), were enrolled prospectively. We assessed sNfL and sGFAP levels using ultrasensitive single-molecule array assays. Correlations of sNfL and sGFAP levels with clinical parameters were further examined in AQP4-ab-positive NMOSD and MOGAD patients. sNfL levels were significantly higher in patients with AQP4-ab-positive NMOSD (median 17.6 pg/mL), MOGAD (27.2 pg/mL), and RRMS (24.5 pg/mL) than in HCs (7.4 pg/mL, all < 0.001). sGFAP levels were remarkably increased in patients with AQP4-ab-positive NMOSD (274.1 pg/mL) and MOGAD (136.7 pg/mL) than in HCs (61.4 pg/mL, both < 0.001). Besides, sGFAP levels were also significantly higher in patients with AQP4-ab-positive NMOSD compared to those in RRMS patients (66.5 pg/mL, < 0.001). The sGFAP/sNfL ratio exhibited good discrimination among the three disease groups. sNfL levels increased during relapse in patients with MOGAD ( = 0.049) and RRMS ( < 0.001), while sGFAP levels increased during relapse in all three of the disease groups (all < 0.05). Both sNfL and sGFAP concentrations correlated positively with Expanded Disability Status Scale scores in AQP4-ab-positive NMOSD (β = 1.88, = 0.018 and β = 2.04, = 0.032) and MOGAD patients (β = 1.98, = 0.013 and β = 1.52, = 0.008). sNfL and sGFAP levels are associated with disease severity in AQP4-ab-positive NMOSD and MOGAD patients, and the sGFAP/sNfL ratio may reflect distinct disease pathogenesis.
评估血清神经丝轻链（sNfL）和血清神经胶质纤维酸性蛋白（sGFAP）作为水通道蛋白-4 抗体（AQP4-ab）或髓鞘少突胶质细胞糖蛋白抗体相关性疾病（MOGAD）相关视神经脊髓炎谱系疾病（NMOSD）的疾病生物标志物的潜力。前瞻性纳入 AQP4-ab 阳性 NMOSD（=51）、MOGAD（=42）和复发缓解型多发性硬化症（RRMS）（sNfL 检测=31，sGFAP 检测=22）患者以及健康对照者（HCs）（sNfL 检测=28，sGFAP 检测=22）。我们使用超敏单分子阵列检测评估 sNfL 和 sGFAP 水平。进一步在 AQP4-ab 阳性 NMOSD 和 MOGAD 患者中检查 sNfL 和 sGFAP 水平与临床参数的相关性。与 HCs（7.4pg/ml，均<0.001）相比，AQP4-ab 阳性 NMOSD（中位数 17.6pg/ml）、MOGAD（27.2pg/ml）和 RRMS（24.5pg/ml）患者的 sNfL 水平显著升高。与 HCs（61.4pg/ml，均<0.001）相比，AQP4-ab 阳性 NMOSD 和 MOGAD 患者的 sGFAP 水平明显升高。此外，与 RRMS 患者相比，AQP4-ab 阳性 NMOSD 患者的 sGFAP 水平也显著升高（66.5pg/ml，<0.001）。sGFAP/sNfL 比值在三组疾病中具有良好的鉴别能力。MOGAD（=0.049）和 RRMS（<0.001）患者在疾病复发期间 sNfL 水平升高，而三组疾病患者在疾病复发期间 sGFAP 水平均升高（均<0.05）。AQP4-ab 阳性 NMOSD（β=1.88，=0.018 和β=2.04，=0.032）和 MOGAD 患者的 sNfL 和 sGFAP 浓度与扩展残疾状态量表评分呈正相关。（β=1.98，=0.013 和β=1.52，=0.008）。sNfL 和 sGFAP 水平与 AQP4-ab 阳性 NMOSD 和 MOGAD 患者的疾病严重程度相关，sGFAP/sNfL 比值可能反映不同的疾病发病机制。
