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000283072 1001_ $$aLandt, Carolin$$b0
000283072 245__ $$aComplement C4d Informs the Differential Diagnosis of Inflammatory Demyelinating CNS Diseases.
000283072 260__ $$aPhiladelphia, Pa.$$bWolters Kluwer$$c2026
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000283072 520__ $$aComplement-targeting therapies are pivotal in managing neuromyelitis optica spectrum disorder (NMOSD), calling for a deeper understanding of complement activation across idiopathic inflammatory demyelinating diseases (IIDDs) of the CNS. C4d, a covalently bound complement split product, offers prolonged detectability at activation sites. This study explores whether C4d immunohistochemistry (IHC) extends the detection window for complement activation in CNS biopsies of IIDDs and evaluates its usefulness as a fluid biomarker.Forty-four IIDD biopsies with active demyelination were analyzed for complement deposition using IHC for C9neo and C4d. C4d levels were also quantified in blood and CSF of patients with IIDDs. The persistence of C4d in CNS tissue was further evaluated in an in vivo NMOSD model.C4d IHC enhanced the sensitivity to detect complement activation, surpassing C9neo by twofold in NMOSD and by sixfold in ADEM, while remaining undetectable in MS biopsies. Exclusive C4d immunopositivity at the glia limitans distinguished NMOSD from ADEM. Furthermore, CSF C4d levels were significantly elevated in both seronegative and seropositive NMOSD compared with MS.C4d detection extends the window for identifying complement activation in CNS biopsies of IIDDs and emerges as a valuable CSF biomarker, enhancing diagnostic precision, autoantibody target identification, and patient stratification for complement-targeting therapies.
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000283072 650_7 $$080295-50-7$$2NLM Chemicals$$aComplement C4b
000283072 650_7 $$080295-52-9$$2NLM Chemicals$$acomplement C4d
000283072 650_7 $$2NLM Chemicals$$aBiomarkers
000283072 650_7 $$2NLM Chemicals$$aPeptide Fragments
000283072 650_2 $$2MeSH$$aHumans
000283072 650_2 $$2MeSH$$aComplement C4b: cerebrospinal fluid
000283072 650_2 $$2MeSH$$aComplement C4b: metabolism
000283072 650_2 $$2MeSH$$aComplement C4b: analysis
000283072 650_2 $$2MeSH$$aFemale
000283072 650_2 $$2MeSH$$aMale
000283072 650_2 $$2MeSH$$aMiddle Aged
000283072 650_2 $$2MeSH$$aAdult
000283072 650_2 $$2MeSH$$aNeuromyelitis Optica: diagnosis
000283072 650_2 $$2MeSH$$aDiagnosis, Differential
000283072 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000283072 650_2 $$2MeSH$$aBiomarkers: blood
000283072 650_2 $$2MeSH$$aPeptide Fragments: cerebrospinal fluid
000283072 650_2 $$2MeSH$$aAged
000283072 650_2 $$2MeSH$$aDemyelinating Autoimmune Diseases, CNS: diagnosis
000283072 650_2 $$2MeSH$$aComplement Activation
000283072 650_2 $$2MeSH$$aYoung Adult
000283072 650_2 $$2MeSH$$aAnimals
000283072 650_2 $$2MeSH$$aMultiple Sclerosis: diagnosis
000283072 7001_ $$0P:(DE-2719)2813270$$aHeld, Friederike$$b1
000283072 7001_ $$aKolotourou, Konstantina$$b2
000283072 7001_ $$aGuranda, Mihaela$$b3
000283072 7001_ $$00000-0002-7712-7216$$aVakrakou, Aigli G$$b4
000283072 7001_ $$00000-0001-7523-6622$$aFranz, Jonas$$b5
000283072 7001_ $$aThomas, Carolina$$b6
000283072 7001_ $$00009-0001-8376-756X$$aSchmiedeknecht, Max Ulrich Heiner$$b7
000283072 7001_ $$aBergann, Klaus$$b8
000283072 7001_ $$aWrzos, Claudia$$b9
000283072 7001_ $$00000-0001-5279-5720$$aEndmayr, Verena$$b10
000283072 7001_ $$00009-0002-7889-1256$$aTsaktanis, Thanos$$b11
000283072 7001_ $$00000-0001-5385-2766$$aZechel, Sabrina$$b12
000283072 7001_ $$00000-0002-7454-7178$$aAncău, Mihai$$b13
000283072 7001_ $$0P:(DE-2719)2810727$$aMisgeld, Thomas$$b14$$udzne
000283072 7001_ $$aHakroush, Samy$$b15
000283072 7001_ $$aHametner, Simon$$b16
000283072 7001_ $$00000-0003-0296-843X$$aRothhammer, Veit$$b17
000283072 7001_ $$00000-0002-5769-1100$$aHöftberger, Romana$$b18
000283072 7001_ $$00000-0001-5985-6784$$aHemmer, Bernhard$$b19
000283072 7001_ $$0P:(DE-2719)9000922$$aStadelmann, Christine$$b20
000283072 7001_ $$00009-0007-8710-5233$$aNessler, Stefan$$b21
000283072 773__ $$0PERI:(DE-600)2767740-0$$a10.1212/NXI.0000000000200528$$gVol. 13, no. 2, p. e200528$$n2$$pe200528$$tNeurology: Neuroimmunology & Neuroinflammation ; official journal of the American Academy of Neurology$$v13$$x2332-7812$$y2026
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