Increased interleukin-6 correlates with myelin oligodendrocyte glycoprotein antibodies in pediatric monophasic demyelinating diseases and multiple sclerosis
Increased interleukin-6 correlates with myelin oligodendrocyte glycoprotein antibodies in pediatric monophasic demyelinating diseases and multiple sclerosis
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DOI：
10.1016/j.jneuroim.2015.10.002
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发表时间：
2015-12-15
影响因子：
3.3
通讯作者：
Deiva, Kumaran
中科院分区：
文献类型：
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作者：
Horellou, Philippe;Wang, Min;Deiva, Kumaran
儿童获得性脱髓鞘综合征 (ADS) 要么发展为单相疾病，诊断为急性脱髓鞘脑脊髓炎 (ADEM)、横贯性脊髓炎 (TM) 或视神经炎 (ON)，要么发展为多次复发的多相疾病，最常导致多发性硬化症 (MS) 或视神经脊髓炎 (NMO) 的诊断。在极少数情况下，这些神经炎症性疾病越来越多地与针对水通道蛋白 4 等蛋白质的自身抗体相关，更常见的是针对髓磷脂少突胶质细胞糖蛋白 (MUG) 的自身抗体。最近，在成年 NMO 患者中，急性加重期间脑脊液 (CSF) 中的 C5a 水平升高。我们研究了 ADS 儿童发病样本中的脑脊液过敏毒素和促炎细胞因子以及血浆 MUG 抗体的水平。纳入了 34 名首次出现 ADS 的儿童，其中 17 名单相 ADS（9 名 ADEM，4 名 TM，4 名 ON）和 17 名 MS，他们在发病时采集了配对的血液和脑脊液样本，并与 12 名其他非炎症性神经系统疾病 (OND) 患者进行了比较。通过细胞珠阵列免疫测定法测量脑脊液中的细胞因子和过敏毒素。使用表达全长人 MUG 的稳定细胞系通过流式细胞术测试血浆中的 MOG 抗体滴度。我们发现，与 OND（n = 12，p = 0.0036）和 MS（n = 17，p = 0.0371）相比，单相 ADS 患者（n = 17）的 CSF 中 C5a 水平显着增加。 MS 中的 C5a 水平高于 OND 中的水平，但未达到显着性 (p = 0.2)。与 OND (p = 0.0027) 和 MS (p = 0.0046) 相比，单相 ADS 中的 CSF IL-6 水平显着增加。单相 ADS 中 MUG 抗体血浆水平显着较高 (p
Acquired demyelinating syndromes (ADS) in children evolve either as a monophasic disease diagnosed as acute demyelinating encephalomyelitis (ADEM), transverse myelitis (TM) or optic neuritis (ON), or a multiphasic one with several relapses most often leading to the diagnosis of multiple sclerosis (MS) or neuromyelitis optica (NMO). These neuroinflammatory disorders are increasingly associated with autoantibodies against proteins such as aquaporin-4 in rare instances, and more frequently against myelin oligodendrocyte glycoprotein (MUG). Recently, in adult NMO patients, C5a levels were shown to be elevated in cerebrospinal fluid (CSF) during acute exacerbation. We investigated the CSF levels of anaphylatoxins and pro-inflammatory cytokines, and plasma MUG antibodies in onset samples from children with ADS. Thirty four children presenting with a first episode of ADS, 17 with monophasic ADS (9 with ADEM, 4 with TM and 4 with ON) and 17 with MS, who had paired blood and CSF samples at onset were included and compared to 12 patients with other non-inflammatory neurological disorders (OND). Cytokines and anaphylatoxins in CSF were measured by Cytometric Bead Array immunoassay. MOG antibody titers in plasma were tested by flow cytometry using a stable cell line expressing fulllength human MUG. We found a significant increase in C5a levels in the CSF of patients with monophasic ADS (n = 17) compared to OND (n = 12, p = 0.0036) and to MS (n = 17, p = 0.0371). The C5a levels in MS were higher than in OND without reaching significance (p = 0.2). CSF IL-6 levels were significantly increased in monophasic ADS compared to OND (p = 0.0027) and to MS (p = 0.0046). MUG antibody plasma levels were significantly higher in monophasic ADS (p