ORCID: https://orcid.org/0009-0008-1190-9435; Kolotourou, Konstantina; Guranda, Mihaela; Vakrakou, Aigli G. ORCID: https://orcid.org/0000-0002-7712-7216; Franz, Jonas ORCID: https://orcid.org/0000-0001-7523-6622; Thomas, Carolina; Schmiedeknecht, Max Ulrich Heiner ORCID: https://orcid.org/0009-0001-8376-756X; Bergann, Klaus; Wrzos, Claudia; Endmayr, Verena ORCID: https://orcid.org/0000-0001-5279-5720; Tsaktanis, Thanos ORCID: https://orcid.org/0009-0002-7889-1256; Zechel, Sabrina ORCID: https://orcid.org/0000-0001-5385-2766; Ancău, Mihai ORCID: https://orcid.org/0000-0002-7454-7178; Misgeld, Thomas ORCID: https://orcid.org/0000-0001-9875-6794; Hakroush, Samy; Hametner, Simon; Rothhammer, Veit ORCID: https://orcid.org/0000-0003-0296-843X; Höftberger, Romana ORCID: https://orcid.org/0000-0002-5769-1100; Hemmer, Bernhard ORCID: https://orcid.org/0000-0001-5985-6784; Stadelmann, Christine ORCID: https://orcid.org/0000-0003-1766-5458 und Nessler, Stefan ORCID: https://orcid.org/0009-0007-8710-5233
(2026):
Complement C4d Informs the Differential Diagnosis of Inflammatory Demyelinating CNS Diseases.
In: Neurology Neuroimmunology & Neuroinflammation, Bd. 13, Nr. 2, e200528
[PDF, 1MB]
Abstract
Background and Objectives
Complement-targeting therapies are pivotal in managing neuromyelitis optica spectrum disorder (NMOSD), calling for a deeper understanding of complement activation across idiopathic inflammatory demyelinating diseases (IIDDs) of the CNS. C4d, a covalently bound complement split product, offers prolonged detectability at activation sites. This study explores whether C4d immunohistochemistry (IHC) extends the detection window for complement activation in CNS biopsies of IIDDs and evaluates its usefulness as a fluid biomarker.
Methods
Forty-four IIDD biopsies with active demyelination were analyzed for complement deposition using IHC for C9neo and C4d. C4d levels were also quantified in blood and CSF of patients with IIDDs. The persistence of C4d in CNS tissue was further evaluated in an in vivo NMOSD model.
Results
C4d IHC enhanced the sensitivity to detect complement activation, surpassing C9neo by twofold in NMOSD and by sixfold in ADEM, while remaining undetectable in MS biopsies. Exclusive C4d immunopositivity at the glia limitans distinguished NMOSD from ADEM. Furthermore, CSF C4d levels were significantly elevated in both seronegative and seropositive NMOSD compared with MS.
Discussion
C4d detection extends the window for identifying complement activation in CNS biopsies of IIDDs and emerges as a valuable CSF biomarker, enhancing diagnostic precision, autoantibody target identification, and patient stratification for complement-targeting therapies.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin > Munich Cluster for Systems Neurology (SyNergy) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| URN: | urn:nbn:de:bvb:19-epub-131235-8 |
| ISSN: | 2332-7812 |
| Sprache: | Englisch |
| Dokumenten ID: | 131235 |
| Datum der Veröffentlichung auf Open Access LMU: | 20. Jan. 2026 10:30 |
| Letzte Änderungen: | 20. Jan. 2026 10:30 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 408885537 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390729940 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 5472008 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390729940 |
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