From the Department of Neurology (K.K., H.K., Y.M., N.S., N. Yamazaki, N. Yamamoto, S.U., C.N., H.O., Y.T., T.T., K.F., T.M., M.A.), Tohoku University Graduate School of Medicine, Sendai, Japan; Multiple Sclerosis and Neuromyelitis Optica Center (H.K., K.F.), Southern TOHOKU Research Institute for Neuroscience, Koriyama; Department of Multiple Sclerosis Therapeutics (H.K., K.F.), Fukushima Medical University, Fukushima, Japan; Department of Neurology (T.T.), NHO Yonezawa National Hospital, Yamagata, Japan; Division of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai, Japan; Department of Neurology (Y.H.), Japanese Redcross Maebashi Hospital; Department of Neurology (Y.H.), Mihara Memorial Hospital, Isesaki, Japan; and Center for Brain Research (H.L.), Medical University of Vienna, Austria.
Neurol Neuroimmunol Neuroinflamm. 2024 Sep;11(5):e200293. doi: 10.1212/NXI.0000000000200293. Epub 2024 Aug 12.
In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD.
CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured.
CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, = 0.044).
The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.
髓鞘少突胶质细胞糖蛋白 IgG 相关疾病（MOGAD）和水通道蛋白 4 IgG 阳性视神经脊髓炎谱系疾病（AQP4+NMOSD）中，自身抗体主要由 IgG1 组成，补体依赖性细胞毒性是 AQP4+NMOSD 的主要发病机制。本研究旨在评估 MOGAD 患者脑脊液中的补体激活情况。
在治疗前的急性期，我们测量了 12 例 MOGAD 患者、11 例 AQP4+NMOSD 患者、5 例多发性硬化症（MS）患者和 2 例非炎症性神经疾病患者的脑脊液 C3a、C4a、C5a 和 C5b-9 水平。
MOGAD（平均±标准差，5629±1079 pg/ml 和 2930±435.8 pg/ml）和 AQP4+NMOSD（6017±3937 pg/ml 和 2544±1231 pg/ml）患者的脑脊液 C3a 和 C5a 水平明显高于 MS 患者（1507±1286 pg/ml 和 193.8±0.53 pg/ml）。MOGAD 和 AQP4+NMOSD 患者的 CSF-C3a、CSF-C4a 无差异，而 MOGAD 的 CSF-C5b-9（膜攻击复合物，MAC）水平明显低于 AQP4+NMOSD（17.4±27.9 ng/ml 比 62.5±45.1 ng/ml， = 0.0019）。攻击更严重（扩展残疾状态量表 [EDSS]≥3.5）的 MOGAD 患者的 C5b-9 水平更高（34.0±38.4 ng/ml），而攻击较轻（EDSS≤3.0，0.9±0.7 ng/ml）的患者则更低（ = 0.044）。
补体途径在 MOGAD 和 AQP4+NMOSD 中均被激活，但在 MOGAD 中 MAC 的形成水平较低，特别是在攻击较轻的患者中，明显低于 AQP4+NMOSD。这些发现可能对 MOGAD 的发病机制和治疗具有重要意义。
