Simone Marta, Palazzo Claudia, Mastrapasqua Mariangela, Bollo Luca, Pompamea Francesco, Gabellone Alessandra, Marzulli Lucia, Giordano Paola, De Giacomo Andrea, Frigeri Antonio, Ruggieri Maddalena, Margari Lucia
Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari Aldo Moro, Bari, Italy.
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy.
Front Neurol. 2021 Nov 11;12:754518. doi: 10.3389/fneur.2021.754518. eCollection 2021.
The relationship between serum neurofilament light chain (sNfL) and myelin oligodendrocyte glycoprotein antibody (MOG-Ab) status has not been yet investigated in children with the acquired demyelinating syndrome (ADS). The sNfL levels and MOG-Abs were measured by ultrasensitive single-molecule array and cell-based assay in a cohort of 37 children with ADS and negativity for serum anti-aquaporin 4 (AQP4) antibodies. The sNfL levels were compared in MOG-Ab+/MOG-Ab- and in two subgroups MOG-Ab+ with/without encephalopathy. About 40% ADS resulted in MOG-Ab+. MOG-Ab+ were younger at sampling (median = 9.8; range = 2.17-17.5 vs. 14.7/9-17; = 0.002) with lower frequency of cerebrospinal fluid oligoclonal bands positivity (27% vs. 70%; = 0.013) compared to MOG-Ab-. About 53% of MOG-Ab+ presented encephalopathy at onset, 1/22 of MOG-Ab- ( = 0.0006). Higher sNfL levels ( = 0.0001) were found in MOG-Ab+ (median/range = 11.11/6.8-1,129) and MOG-Ab- (median/range = 11.6/4.3-788) compared to age-matched controls (median/range = 2.98/1-4.53), without significant difference. MOG-Ab+ with encephalopathy resulted significantly younger at sampling (median/range: 4.5/2.17-11.17 vs. 14.16/9.8-17.5; = 0.004), had higher sNfL levels (median/range:75.24/9.1-1,129 vs. 10.22/6.83-50.53; = 0.04), and showed a trend for higher MOG-Ab titer (0.28/0.04-0.69 vs. 0.05/0.04-0.28; = 0.1) in comparison to those without encephalopathy. We confirmed high sNfL levels in pediatric ADS independently from the MOG-Ab status. Encephalopathy at onset is associated more frequently with MOG Ab+ children with higher sNfL levels and MOG titer. These findings suggest a role of acute demyelination in association with axonal damage in the pathogenesis of encephalopathy in pediatric ADS.
在获得性脱髓鞘综合征(ADS)患儿中,血清神经丝轻链(sNfL)与髓鞘少突胶质细胞糖蛋白抗体(MOG-Ab)状态之间的关系尚未得到研究。通过超灵敏单分子阵列和基于细胞的检测方法,对37例ADS患儿且血清抗水通道蛋白4(AQP4)抗体阴性的队列进行了sNfL水平和MOG-Ab检测。比较了MOG-Ab阳性/阴性组以及MOG-Ab阳性伴/不伴脑病的两个亚组中的sNfL水平。约40%的ADS患儿为MOG-Ab阳性。与MOG-Ab阴性患儿相比,MOG-Ab阳性患儿采样时年龄更小(中位数=9.8;范围=2.17-17.5岁 vs. 14.7/9-17岁;P=0.002),脑脊液寡克隆带阳性频率更低(27% vs. 70%;P=0.013)。约53%的MOG-Ab阳性患儿起病时出现脑病,MOG-Ab阴性患儿中为1/22(P=0.0006)。与年龄匹配的对照组(中位数/范围=2.98/1-4.53)相比,MOG-Ab阳性组(中位数/范围=11.11/6.8-1,129)和MOG-Ab阴性组(中位数/范围=11.6/4.3-788)的sNfL水平更高(P=0.0001),但无显著差异。与无脑病的患儿相比,起病时伴有脑病的MOG-Ab阳性患儿采样时年龄显著更小(中位数/范围:4.5/2.17-11.17岁 vs. 14.16/9.8-17.5岁;P=0.004),sNfL水平更高(中位数/范围:75.24/9.1-1,129 vs. 10.22/6.83-50.53;P=0.04),且MOG-Ab滴度有升高趋势(0.28/0.04-0.69 vs. 0.05/0.04-0.28;P=0.1)。我们证实,小儿ADS中sNfL水平升高与MOG-Ab状态无关。起病时的脑病更常见于sNfL水平和MOG滴度较高的MOG-Ab阳性患儿。这些发现提示急性脱髓鞘与轴索损伤在小儿ADS脑病发病机制中存在关联。