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100 1 _ |a Landt, Carolin
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245 _ _ |a Complement C4d Informs the Differential Diagnosis of Inflammatory Demyelinating CNS Diseases.
260 _ _ |a Philadelphia, Pa.
|c 2026
|b Wolters Kluwer
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520 _ _ |a 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.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.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.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.
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650 _ 7 |a Complement C4b
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650 _ 7 |a complement C4d
|0 80295-52-9
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650 _ 7 |a Biomarkers
|2 NLM Chemicals
650 _ 7 |a Peptide Fragments
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Complement C4b: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Complement C4b: metabolism
|2 MeSH
650 _ 2 |a Complement C4b: analysis
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Middle Aged
|2 MeSH
650 _ 2 |a Adult
|2 MeSH
650 _ 2 |a Neuromyelitis Optica: diagnosis
|2 MeSH
650 _ 2 |a Diagnosis, Differential
|2 MeSH
650 _ 2 |a Biomarkers: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Biomarkers: blood
|2 MeSH
650 _ 2 |a Peptide Fragments: cerebrospinal fluid
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Demyelinating Autoimmune Diseases, CNS: diagnosis
|2 MeSH
650 _ 2 |a Complement Activation
|2 MeSH
650 _ 2 |a Young Adult
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Multiple Sclerosis: diagnosis
|2 MeSH
700 1 _ |a Held, Friederike
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700 1 _ |a Kolotourou, Konstantina
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700 1 _ |a Guranda, Mihaela
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700 1 _ |a Vakrakou, Aigli G
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700 1 _ |a Franz, Jonas
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700 1 _ |a Thomas, Carolina
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700 1 _ |a Schmiedeknecht, Max Ulrich Heiner
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700 1 _ |a Bergann, Klaus
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700 1 _ |a Wrzos, Claudia
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700 1 _ |a Endmayr, Verena
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700 1 _ |a Tsaktanis, Thanos
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700 1 _ |a Zechel, Sabrina
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700 1 _ |a Ancău, Mihai
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700 1 _ |a Höftberger, Romana
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700 1 _ |a Hemmer, Bernhard
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700 1 _ |a Stadelmann, Christine
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700 1 _ |a Nessler, Stefan
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773 _ _ |a 10.1212/NXI.0000000000200528
|g Vol. 13, no. 2, p. e200528
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|t Neurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology
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