{
  "abstract": "Objective\n\nAquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (AQP4+ NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and multiple sclerosis (MS) are pathophysiologically distinct neuroinflammatory disorders. Complement activation is a major mechanism of injury in AQP4+ NMOSD, whereas its role in MS is complex and in MOGAD controversial. We aimed to compare complement components and cytokines between AQP4+ NMOSD, MOGAD, and MS.Methods\n\nCSF complement components, CSF and plasma cytokines, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were measured in people with AQP4+ NMOSD (CSF: n = 19; plasma: n = 18), MOGAD (CSF: n = 29; plasma: n = 35) and MS (CSF: n = 36; plasma: n = 58) with recent disease activity. Controls included subjects with non-inflammatory conditions (CSF: n = 51) and healthy controls (plasma: n = 29).Results\n\nCSF IL-10 and TNF-a were elevated across all neuroinflammatory disease groups relative to controls. CSF IL-6 was elevated only in AQP4+ NMOSD and MOGAD. There were no significant differences in plasma cytokines between groups. Most complement components were elevated in AQP4+ NMOSD and MOGAD; only specific activation products (C2b, C3d, C4a, C5a) were elevated in MS. CSF GFAP and NfL correlated with several CSF cytokines and complement components in AQP4+ NMOSD and MOGAD. Expanded Disability Status Scale at nadir during attacks correlated with CSF BAFF, GFAP, free C1q, C1s, C1s-C1inh, C4a in AQP4+ NMOSD, and CSF IL-10, TNF-a, free C1q, C1inh, C4a in MOGAD.Interpretation\n\nOur findings suggest distinct CSF cytokine profiles in AQP4+ NMOSD, MOGAD, and MS, and widespread activation of complement pathways in AQP4+ NMOSD and MOGAD. CSF complement and cytokine profiling may help characterize neuroinflammatory disease mechanisms, although further validation of these findings in larger cohorts is needed.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.",
    "Annexon Biosciences, Brisbane, California, USA.",
    "Department of Neurological Sciences, University of Vermont School of Medicine, Burlington, Vermont, USA.",
    "Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Angeliki G Filippatou",
      "orcid": "0000-0003-0419-233X"
    },
    {
      "affs": [
        0
      ],
      "name": "Susana Dominguez-Penuela"
    },
    {
      "affs": [
        0
      ],
      "name": "David Acero-Garces",
      "orcid": "0000-0002-9717-4626"
    },
    {
      "affs": [
        0
      ],
      "name": "Georgios Gakis",
      "orcid": "0000-0002-7339-4659"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthew D Smith"
    },
    {
      "affs": [
        0
      ],
      "name": "Yasmin Resto"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Reyes-Mantilla"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiwen Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabella Hernandez"
    },
    {
      "affs": [
        0
      ],
      "name": "Yana Said",
      "orcid": "0009-0004-4350-1910"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrea Salazar-Camelo"
    },
    {
      "affs": [
        1
      ],
      "name": "Christina Huynh"
    },
    {
      "affs": [
        1
      ],
      "name": "Alessia Tassoni"
    },
    {
      "affs": [
        1
      ],
      "name": "Ted Yednock"
    },
    {
      "affs": [
        1
      ],
      "name": "Rick Artis"
    },
    {
      "affs": [
        1
      ],
      "name": "Yaisa Andrews-Zwilling"
    },
    {
      "affs": [
        0
      ],
      "name": "Scott D Newsome"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiv Saidha"
    },
    {
      "affs": [
        0
      ],
      "name": "Pavan Bhargava",
      "orcid": "0000-0002-7947-9418"
    },
    {
      "affs": [
        0
      ],
      "name": "Ellen M Mowry"
    },
    {
      "affs": [
        0
      ],
      "name": "Kathryn C Fitzgerald",
      "orcid": "0000-0003-3137-0322"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Peter A Calabresi"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Carlos A Pardo",
      "orcid": "0000-0002-4128-5335"
    },
    {
      "affs": [
        0
      ],
      "name": "Elias S Sotirchos",
      "orcid": "0000-0002-8812-1637"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8bwz9hd4bcgmh.bib",
  "cited_by": 0,
  "doi": "10.1002/acn3.70549",
  "fulltext_url": "https://europepmc.org/articles/PMC13687446",
  "id": "8bwz9hd4bcgmh",
  "issns": [
    "2328-9503"
  ],
  "landing_url": "https://europepmc.org/article/MED/42908053",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2734|Multiple Sclerosis Research Studies"
    ]
  ],
  "openalex": "W7223174189",
  "pdf_url": "https://europepmc.org/articles/PMC13687446?pdf=render",
  "pmcid": "PMC13687446",
  "pmid": "42908053",
  "published": "2026-10-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8bwz9hd4bcgmh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42908053",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42908053"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Multiple Sclerosis Research Studies",
      "subfield": "general"
    }
  ],
  "title": "Investigation of Complement Activation and Cytokine Signatures in AQP4+ NMOSD, MOGAD, and MS.",
  "title_text": "Investigation of Complement Activation and Cytokine Signatures in AQP4+ NMOSD, MOGAD, and MS.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:53Z",
  "url": "https://research.draconitic.com/paper/8bwz9hd4bcgmh",
  "venue": "Annals of clinical and translational neurology",
  "versions": []
}