MOGAD和AQP4-IgG+NMOSD中C5裂解后的不同补体激活模式

IF 7.8 1区医学 Q1 CLINICAL NEUROLOGY

Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-09-01 Epub Date: 2024-08-12 DOI:10.1212/NXI.0000000000200293

Kimihiko Kaneko, Hiroshi Kuroda, Yuki Matsumoto, Naohiro Sakamoto, Naoya Yamazaki, Naoki Yamamoto, Shu Umezawa, Chihiro Namatame, Hirohiko Ono, Yoshiki Takai, Toshiyuki Takahashi, Juichi Fujimori, Ichiro Nakashima, Yasuo Harigaya, Hans Lassmann, Kazuo Fujihara, Tatsuro Misu, Masashi Aoki

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We aimed to evaluate the CSF complement activation in MOGAD.Methods: 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.Results: 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, p = 0.0019). 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引用次数: 0

摘要

研究目的在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+神经脊髓炎视谱系障碍（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的主要病理机制。我们的目的是评估 CSF 补体在 MOGAD 中的激活情况：方法：测量 MOGAD（12 例）、AQP4+NMOSD（11 例）、多发性硬化（MS）（5 例）和非炎症性神经疾病（2 例）患者治疗前急性期的 CSF-C3a、CSF-C4a、CSF-C5a 和 CSF-C5b-9 水平：结果：MOGAD（平均值±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）的CSF-C3a和CSF-C5a水平明显高于MS（1507±1286 pg/mL和193.8±0.53 pg/mL）。CSF-C3a、CSF-C4a和CSF-C5a在MOGAD和AQP4+NMOSD之间没有差异，而CSF-C5b-9（膜攻击复合物，MAC）水平在MOGAD（17.4 ± 27.9 ng/mL）显著低于AQP4+NMOSD（62.5 ± 45.1 ng/mL，p = 0.0019）。与发作较轻的患者（EDSS≤3.0，0.9 ± 0.7 ng/mL，p = 0.044）相比，发作较重（残疾状况扩展量表[EDSS]≥3.5）的 MOGAD 患者的 C5b-9 水平更高（34.0 ± 38.4 ng/m）：讨论：补体途径在 MOGAD 和 AQP4+NMOSD 中均被激活，但 MOGAD 中 MAC 的形成低于 AQP4+NMOSD，尤其是在轻度发作的患者中。这些发现可能对 MOGAD 有致病和治疗意义。

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Different Complement Activation Patterns Following C5 Cleavage in MOGAD and AQP4-IgG+NMOSD.

Objectives: 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.

Methods: 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.

Results: 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, p = 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, p = 0.044).

Discussion: 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.

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来源期刊

Neurology® Neuroimmunology & Neuroinflammation Neuroscience-Neurology

CiteScore

15.60

自引率

2.30%

发文量

219

审稿时长

8 weeks

期刊介绍： Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.