Investigation of Complement Activation and Cytokine Signatures in AQP4+ NMOSD, MOGAD, and MS.

@article{filippatou2026investigation,
  title = {{Investigation of Complement Activation and Cytokine Signatures in AQP4+ NMOSD, MOGAD, and MS.}},
  author = {Angeliki G Filippatou and Susana Dominguez-Penuela and David Acero-Garces and Georgios Gakis and Matthew D Smith and Yasmin Resto and Maria Reyes-Mantilla and Haiwen Chen and Isabella Hernandez and Yana Said and Andrea Salazar-Camelo and Christina Huynh and Alessia Tassoni and Ted Yednock and Rick Artis and Yaisa Andrews-Zwilling and Scott D Newsome and Shiv Saidha and Pavan Bhargava and Ellen M Mowry and Kathryn C Fitzgerald and Peter A Calabresi and Carlos A Pardo and Elias S Sotirchos},
  journal = {Annals of clinical and translational neurology},
  year = {2026},
  month = oct,
  doi = {10.1002/acn3.70549},
  url = {https://europepmc.org/article/MED/42908053},
  note = {CC BY},
}

TY  - JOUR
TI  - Investigation of Complement Activation and Cytokine Signatures in AQP4+ NMOSD, MOGAD, and MS.
AU  - Angeliki G Filippatou
AU  - Susana Dominguez-Penuela
AU  - David Acero-Garces
AU  - Georgios Gakis
AU  - Matthew D Smith
AU  - Yasmin Resto
AU  - Maria Reyes-Mantilla
AU  - Haiwen Chen
AU  - Isabella Hernandez
AU  - Yana Said
AU  - Andrea Salazar-Camelo
AU  - Christina Huynh
AU  - Alessia Tassoni
AU  - Ted Yednock
AU  - Rick Artis
AU  - Yaisa Andrews-Zwilling
AU  - Scott D Newsome
AU  - Shiv Saidha
AU  - Pavan Bhargava
AU  - Ellen M Mowry
AU  - Kathryn C Fitzgerald
AU  - Peter A Calabresi
AU  - Carlos A Pardo
AU  - Elias S Sotirchos
PY  - 2026
DA  - 2026/10/21
JO  - Annals of clinical and translational neurology
DO  - 10.1002/acn3.70549
UR  - https://europepmc.org/article/MED/42908053
AB  - Objective  Aquaporin-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  CSF 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  CSF 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  Our 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.
SN  - 2328-9503
ER  -