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. 2024 Sep;11(5):e200293.
doi: 10.1212/NXI.0000000000200293. Epub 2024 Aug 12.

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

Kimihiko Kaneko  1 , Hiroshi Kuroda  1 , Yuki Matsumoto  1 , Naohiro Sakamoto  1 , Naoya Yamazaki  1 , Naoki Yamamoto  1 , Shu Umezawa  1 , Chihiro Namatame  1 , Hirohiko Ono  1 , Yoshiki Takai  1 , Toshiyuki Takahashi  1 , Juichi Fujimori  1 , Ichiro Nakashima  1 , Yasuo Harigaya  1 , Hans Lassmann  1 , Kazuo Fujihara  1 , Tatsuro Misu  1 , Masashi Aoki  1
Affiliations

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

Kimihiko Kaneko et al. Neurol Neuroimmunol Neuroinflamm. 2024 Sep.

Abstract

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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Conflict of interest statement

K. Kaneko received speaker honoraria from Novartis and Biogen Japan. H. Kuroda received speaker honoraria from Alexion, Chugai, Novartis, and Otsuka. Y. Matsumoto received speaker honoraria from Novartis. N. Sakamoto has nothing to disclose. N. Yamazaki has nothing to disclose. N. Yamamoto has nothing to disclose. S. Umezawa has nothing to disclose. C. Namatame has nothing to disclose. H. Ono has nothing to disclose. Y. Takai received speaker honoraria from Alexion, Biogen, Novartis, Mitsubishi Tanabe, Chugai, and Takeda. T. Takahashi received research support from Cosmic Corporation. J. Fujimori has nothing to disclose. I. Nakashima received advisory fee from Mitsubishi Tanabe, Chugai, Alexion; honoraria for lectures from Biogen, Novartis, Mitsubishi Tanabe, Chugai, Alexion; support for attending meetings from Biogen, Novartis, Mitsubishi Tanabe, Chugai, Alexion; grants for commissioned/joint research from LSI Medience Corporation. Y. Harigaya has nothing to disclose. H. Lassman received honoraria for lectures from Novartis, Sanofi, Merck, Genzyme, Roche Biogen and Bristol-Myers Squibb. K. Fujihara received fees for consulting, speaking and serving on steering committees of AbbVie, Alexion, Asahi Kasei Medical, Biogen, Chugai/Roche, Eisai, Japan Tobacco, MedImmune/Viela Bio, Merck, Merck Biopharma, Mitsubishi-Tanabe, Novartis, Takeda, Teijin and UCB, and a Grant-in-Aid for Scientific Research from the Ministry of Health, Welfare and Labor of Japan. T. Misu received speaker honoraria from Tanabe Mitsubishi, Novartis, Alexion, Viela Bio, Teijin, Chugai, Sanofi, GE Health Care Japan, CSL Behring and Biogen Japan, and research support from Cosmic Corporation and Medical Biological Laboratories received a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Masashi Aoki received research support from Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Ministry of Health, Labour and Welfare of Japan. Go to Neurology.org/NN for full disclosures.

Figures

Figure 1
Figure 1. CSF Complement Components in MOGAD, AQP4+NMOSD, MS, and NIND
(A–E) Concentrations of activated complement components (C3a, C4a, C5a, C5b-9) and C5b-9/C5a in the CSF of patients with MOGAD, AQP4+NMOSD, MS, and NIND and (F) comparison of CSF-C5b-9 levels between patients with MOGAD with EDSS scores ≦3 and those with scores ≧3.5. AQP4+NMOSD = aquaporin-4 IgG+ neuromyelitis optica spectrum disorder, MOGAD = myelin oligodendrocyte glycoprotein IgG–associated disease, MS = multiple sclerosis, NIND = noninflammatory neurologic disease. ∗p < 0.05. Horizontal lines indicate mean values, and error bars indicate SD.
Figure 2
Figure 2. CSF-C5b-9 Levels in Relation to Clinical Phenotypes and MOG-IgG Status
AQP4+NMOSD = aquaporin-4 IgG+ neuromyelitis optica spectrum disorder, MOGAD = myelin oligodendrocyte glycoprotein IgG–associated disease.
See this image and copyright information in PMC

References

    1. Kaneko K, Sato DK, Nakashima I, et al. CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications. J Neurol Neurosurg Psychiatry. 2018;89(9):927-936. doi: 10.1136/jnnp-2018-317969 - DOI - PMC - PubMed
    1. Mariotto S, Ferrari S, Monaco S, et al. Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study. J Neurol. 2017;264(12):2420-2430. doi: 10.1007/s00415-017-8635-4 - DOI - PMC - PubMed
    1. Pittock SJ, Zekeridou A, Weinshenker BG. Hope for patients with neuromyelitis optica spectrum disorders - from mechanisms to trials. Nat Rev Neurol. 2021;17(12):759-773. doi: 10.1038/s41582-021-00568-8 - DOI - PubMed
    1. Kuroda H, Fujihara K, Takano R, et al. Increase of complement fragment C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica. J Neuroimmunol. 2013;254(1-2):178-182. doi: 10.1016/j.jneuroim.2012.09.002 - DOI - PubMed
    1. Sato DK, Callegaro D, Lana-Peixoto MA, et al. Distinction between MOG antibody positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014;82(6):474-481. doi: 10.1212/WNL.0000000000000101 - DOI - PMC - PubMed

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