Horellou Philippe, Flet-Berliac Lorraine, Leroy Carole, Giorgi Laetitia, Joly Candie, Desjardins Delphine, Chrétien Pascale, Hacein-Bey-Abina Salima, Le Grand Roger, Deiva Kumaran
Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT), Université Paris-Saclay, CEA, INSERM, Le Kremlin Bicêtre 94276, France.
Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Saclay, Hôpital Kremlin-Bicêtre, Assistance Publique-Hôpitaux de Paris, Le-Kremlin-Bicêtre 94275, France.
Brain Commun. 2023 Mar 15;5(2):fcad063. doi: 10.1093/braincomms/fcad063. eCollection 2023.
Acquired demyelinating syndrome associated with myelin oligodendrocyte glycoprotein antibodies, named recently myelin oligodendrocyte glycoprotein-associated disease, represents >27% of this paediatric syndrome. Relapses occur in 40% of them, which may be associated with severe outcomes. Aiming to identify biomarker allowing to predict relapse, we measured both myelin oligodendrocyte glycoprotein antibodies and neurofilament light chain levels in blood samples of patients that are known to reflect axonal injuries in neurological diseases including demyelinating autoimmune disorders. Three groups of patients were selected: relapsing myelin oligodendrocyte glycoprotein-associated disease ( = 8), non-relapsing myelin oligodendrocyte glycoprotein-associated disease ( = 7) and control patients with non-inflammatory neurological diseases ( = 12). Neurofilament light chain concentrations were measured in plasma of these three groups of patients using the high-sensitivity single-molecule array method at onset of the disease and 6 months later. At onset of the disease, we found that levels of neurofilament light chain in blood of non-relapsing patients were significantly higher than in control patients (means: 98.36 ± 22.66 versus 12.47 ± 2.47 pg/mL, ** < 0.01, Kruskal-Wallis test). The mean neurofilament light chain value in relapsing patients (82.16 ± 38.41 pg/mL) was not significantly different from that in non-relapsing and in control patients. Plasma myelin oligodendrocyte glycoprotein antibody levels were 2.5-fold higher in relapsing than in non-relapsing patients without reaching significance (means: 15.26 ± 4.87 versus 5.96 ± 1.13; two-tailed Mann-Whitney U-test = 0.119). Plasma neurofilament light chain correlated significantly with myelin oligodendrocyte glycoprotein antibody levels in relapsing (two-tailed Spearman = 0.8, = 0.0218) but not in non-relapsing (two-tailed Spearman = 0.17, = 0.71). Interestingly, the ratio of neurofilament light chain-to-myelin oligodendrocyte glycoprotein antibodies was significantly lower in relapsing than in non-relapsing patients (means: 5.19 ± 1.61 versus 21.87 ± 6.13; two-tailed Mann-Whitney U-test = 0.014). These findings suggest that measuring both neurofilament light chain and myelin oligodendrocyte glycoprotein antibody levels in patients at onset of demyelinating disease could predict relapse of myelin oligodendrocyte glycoprotein-associated disease.
与髓鞘少突胶质细胞糖蛋白抗体相关的获得性脱髓鞘综合征,最近被命名为髓鞘少突胶质细胞糖蛋白相关疾病,占该儿科综合征的比例超过27%。其中40%会复发,这可能与严重后果相关。为了确定能够预测复发的生物标志物,我们检测了已知可反映包括脱髓鞘自身免疫性疾病在内的神经系统疾病中轴索损伤的患者血样中的髓鞘少突胶质细胞糖蛋白抗体和神经丝轻链水平。选取了三组患者:复发型髓鞘少突胶质细胞糖蛋白相关疾病患者( = 8)、非复发型髓鞘少突胶质细胞糖蛋白相关疾病患者( = 7)和非炎性神经系统疾病对照患者( = 12)。在疾病发作时及6个月后,使用高灵敏度单分子阵列法检测这三组患者血浆中的神经丝轻链浓度。在疾病发作时,我们发现非复发患者血液中的神经丝轻链水平显著高于对照患者(均值:98.36 ± 22.66对12.47 ± 2.47 pg/mL,** < 0.01,Kruskal-Wallis检验)。复发患者的神经丝轻链平均水平(82.16 ± 38.41 pg/mL)与非复发患者及对照患者相比无显著差异。复发患者的血浆髓鞘少突胶质细胞糖蛋白抗体水平比非复发患者高2.5倍,但未达到显著差异(均值:15.26 ± 4.87对5.96 ± 1.13;双尾Mann-Whitney U检验 = 0.119)。复发患者中血浆神经丝轻链与髓鞘少突胶质细胞糖蛋白抗体水平显著相关(双尾Spearman = 0.8, = 0.0218),而非复发患者中则无相关性(双尾Spearman = 0.17, = 0.71)。有趣的是,复发患者神经丝轻链与髓鞘少突胶质细胞糖蛋白抗体的比值显著低于非复发患者(均值:5.19 ± 1.61对21.87 ± 6.13;双尾Mann-Whitney U检验 = 0.014)。这些发现表明,在脱髓鞘疾病发作时检测患者的神经丝轻链和髓鞘少突胶质细胞糖蛋白抗体水平,可预测髓鞘少突胶质细胞糖蛋白相关疾病的复发。