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While complement inhibition significantly reduces the relapse rate in neuromyelitis optica spectrum disorders (NMOSDs), no clear consensus has been reached regarding the role of complement in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS). Therefore, we examined CNS tissues from patients with NMOSD (18 autopsies and one biopsy, median age: 56\u00a0years), MOGAD (seven autopsies and 20 biopsies, median age: 34\u00a0years) and MS (24 autopsies, median age: 54.5\u00a0years) to assess the involvement of the complement system from a histopathological perspective. To investigate complement activity at multiple steps, the tissue deposition of three different complement components (C4d, C3d, and C9neo) was examined using immunohistochemistry. In NMOSD, the typical perivascular rosette\/rim pattern of complement deposition was confirmed by the three different complement products within acute astrocyte-lytic lesions. In MOGAD, we observed C4d deposition around perivenous demyelinating lesions in 83% (20\/24 tissues). However, C9neo deposition differed between patients, with 73% (11\/15 patients with perivenous demyelination-predominant MOGAD) showing limited deposition of C9neo with relatively well-preserved oligodendrocytes (MOGAD type A), while 27% showing strong deposition accompanied by the disappearance of oligodendrocytes (MOGAD type B). The more destructive type B pathology was more frequent among deceased than living patients who, by contrast, had type A pathology in the vast majority. In MS, only C4d showed clear deposits on myelin sheaths in the peri-plaque white matter bordering the edges of the demyelinating lesions. These findings seemed to be characteristic of MS, and the extent and intensity tended to decrease in accordance with lesion activity. Complement deposition in MS lesions was linked to shorter interval between onset and death. These characteristic patterns of complement deposition in the three IDDs likely reflect the distinct pathogeneses of the diseases.<\/jats:p>","DOI":"10.1007\/s00401-026-02985-9","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T12:13:29Z","timestamp":1770639209000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characteristic patterns of complement deposition in NMOSD, MOGAD, and MS"],"prefix":"10.1007","volume":"151","author":[{"given":"Yoshiki","family":"Takai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Hametner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Riedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Misu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyoshi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norio","family":"Chihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Miyahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Iwasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Di Pauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Bramow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Laureys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda","family":"Banwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Mariotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Fujihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Bradl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Lassmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"H\u00f6ftberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"2985_CR1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/s41586-021-03892-7","volume":"597","author":"M Absinta","year":"2021","unstructured":"Absinta M, Maric D, Gharagozloo M, Garton T, Smith MD, Jin J et al (2021) A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis. 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T.M. received speaker honoraria from Alexion, Asahi Kasei Medical, GE, Mitsubishi Tanabe Pharma, Novartis, Roche\/Chugai, Sanofi, Teva Takeda Pharma, Teijin, and Viela Bio. N.C. received speaker honoraria from Alexion, Argenx, Biogen, Eisai, Kowa Company, Mitsubishi Tanabe Pharma, Novartis, Roche\/Chugai, Teva Takeda Pharma, and UCB. M.Y. received honoraria from Igaku Shoin and Eisai, and grants from Japan Agency for Medical Research and Development. F.D.P. has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations), or travel funding from Amgen, Bayer, Biogen, Celgene BMS, Horizon, Medwhizz, Merck, Neuraxpharm, Novartis, Sandoz, Sanofi-Genzyme, Teva, and Roche. S.B. received honoraria (lectures, advisory boards), or support for congress participation from Novartis, Roche, and Merck. B.B. serves as a consultant to Novartis, Roche, UCB, and UTSW. She receives grant funding from the National Institute of Health. S.M. received speaker honoraria from Alexion, Amgen, Biogen, Dynamics, Novartis, Roche, Sanofi, TSF, and UCB. K.F. received grants from the Ministry of Health, Labour and Welfare of Japan and personal fees from Amgen, Alexion, Argenx, Asahi Kasei Medical, Biogen, Cosmic Corporation, Daiichi Sankyo, Eisai, Roche\/Chugai, Mitsubishi-Tanabe, Novartis, UCB, Sanofi, Teijin, and Zenyaku. M.A. has received speaker honoraria from Eisai and Mitsubishi Tanabe Pharma.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This multi-institutional study was approved by the ethics committees of Tohoku University Graduate School of Medicine (2023\u20131-1144) and the Medical University of Vienna (EK-1067\/2024). It was conducted in accordance with internationally recognized ethical standards. In Japan, the study was conducted either after written informed consent was obtained from the participant or the surrogate or by disclosing information about the study on the website of Tohoku University Hospital; the participant or the surrogate could refuse to participate at any time.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"13"}}