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000276797 041__ $$aEnglish
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000276797 1001_ $$aTerroba-Navajas, Paula$$b0
000276797 245__ $$aHumoral signatures of Caspr2-antibody spectrum disorder track with clinical phenotypes and outcomes.
000276797 260__ $$aAmsterdam$$bElsevier$$c2025
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000276797 520__ $$aImmunoglobulin (Ig) G4 auto-antibodies (Abs) against contactin-associated protein-like 2 (Caspr2), a transmembrane cell adhesion protein expressed in the central and peripheral nervous system, are found in patients with a broad spectrum of neurological symptoms. While the adoptive transfer of Caspr2-specific IgG induces brain pathology in susceptible rodents, the mechanisms by which Caspr2-Abs mediate neuronal dysfunction and translate into clinical syndromes are incompletely understood.We use a systems-level approach combined with high-dimensional characterization of Ab-associated immune features to deeply profile humoral biosignatures in patients with Caspr2-Ab-associated neurological syndromes.We identify two signatures strongly associated with two major clinical phenotypes, limbic encephalitis (LE) and predominant peripheral nerve hyperexcitability without LE (non-LE). Caspr2-IgG Fc-driven pro-inflammatory features, characterized by increased binding affinities for activating Fcγ receptors (FcγRs) and C1q, along with a higher prevalence of IgG1-class Abs, in addition to IgG4, are strongly associated with LE. Both the occurrence of Caspr2-specific IgG1 and higher serum levels of interleukin (IL)-6 and IL-15, along with increased concentrations of biomarkers reflecting neuronal damage and glial cell activation, are associated with poorer clinical outcomes at 1-year follow-up.The presence of IgG1 isotypes and Fc-mediated effector functions control the pathogenicity of Caspr2-specific Abs to induce LE. Biologics targeting FcR function might potentially restrain Caspr2-Ab-induced pathology and improve clinical outcomes.This study was funded by a German-French joint research program supported by the German Research Foundation (DFG) and the Agence Nationale de la Recherche (ANR) and by the Interdisciplinary Centre for Clinical Research (IZKF) Münster.
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000276797 650_7 $$2Other$$aFc receptors
000276797 650_7 $$2Other$$aIgG1
000276797 650_7 $$2Other$$aIgG4
000276797 650_7 $$2Other$$aTranslation to patients
000276797 650_7 $$2Other$$aantibody
000276797 650_7 $$2Other$$aautoimmunity
000276797 650_7 $$2Other$$abiosignature
000276797 650_7 $$2Other$$ainnate immunity
000276797 650_7 $$2Other$$alimbic encephalitis
000276797 650_7 $$2Other$$aouctome
000276797 650_7 $$2Other$$aprecision medicine
000276797 650_7 $$2NLM Chemicals$$aCNTNAP2 protein, human
000276797 650_7 $$2NLM Chemicals$$aNerve Tissue Proteins
000276797 650_7 $$2NLM Chemicals$$aImmunoglobulin G
000276797 650_7 $$2NLM Chemicals$$aMembrane Proteins
000276797 650_7 $$2NLM Chemicals$$aAutoantibodies
000276797 650_7 $$2NLM Chemicals$$aBiomarkers
000276797 650_7 $$2NLM Chemicals$$aReceptors, IgG
000276797 650_2 $$2MeSH$$aHumans
000276797 650_2 $$2MeSH$$aNerve Tissue Proteins: immunology
000276797 650_2 $$2MeSH$$aImmunoglobulin G: blood
000276797 650_2 $$2MeSH$$aImmunoglobulin G: immunology
000276797 650_2 $$2MeSH$$aMembrane Proteins: immunology
000276797 650_2 $$2MeSH$$aAutoantibodies: blood
000276797 650_2 $$2MeSH$$aAutoantibodies: immunology
000276797 650_2 $$2MeSH$$aPhenotype
000276797 650_2 $$2MeSH$$aMale
000276797 650_2 $$2MeSH$$aFemale
000276797 650_2 $$2MeSH$$aBiomarkers: blood
000276797 650_2 $$2MeSH$$aMiddle Aged
000276797 650_2 $$2MeSH$$aReceptors, IgG: immunology
000276797 650_2 $$2MeSH$$aAdult
000276797 7001_ $$aSpatola, Marianna$$b1
000276797 7001_ $$aChuquisana, Omar$$b2
000276797 7001_ $$aJoubert, Bastien$$b3
000276797 7001_ $$ade Vries, Juna M$$b4
000276797 7001_ $$aDik, Andre$$b5
000276797 7001_ $$aMarmolejo, Laura$$b6
000276797 7001_ $$aJönsson, Friederike$$b7
000276797 7001_ $$aLauc, Gordan$$b8
000276797 7001_ $$aKovac, Stjepana$$b9
000276797 7001_ $$0P:(DE-2719)2810931$$aPrüss, Harald$$b10$$udzne
000276797 7001_ $$aWiendl, Heinz$$b11
000276797 7001_ $$aTitulaer, Maarten J$$b12
000276797 7001_ $$aHonnorat, Jérôme$$b13
000276797 7001_ $$aLünemann, Jan D$$b14
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