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| 001 | 276797 | ||
| 005 | 20250323000843.0 | ||
| 024 | 7 | _ | |a 10.1016/j.medj.2024.09.004 |2 doi |
| 024 | 7 | _ | |a pmid:39393351 |2 pmid |
| 024 | 7 | _ | |a 2666-6340 |2 ISSN |
| 024 | 7 | _ | |a 2666-6359 |2 ISSN |
| 024 | 7 | _ | |a altmetric:169243768 |2 altmetric |
| 037 | _ | _ | |a DZNE-2025-00322 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Terroba-Navajas, Paula |b 0 |
| 245 | _ | _ | |a Humoral signatures of Caspr2-antibody spectrum disorder track with clinical phenotypes and outcomes. |
| 260 | _ | _ | |a Amsterdam |c 2025 |b Elsevier |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1739955130_22768 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Immunoglobulin (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. |
| 536 | _ | _ | |a 353 - Clinical and Health Care Research (POF4-353) |0 G:(DE-HGF)POF4-353 |c POF4-353 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de |
| 650 | _ | 7 | |a Fc receptors |2 Other |
| 650 | _ | 7 | |a IgG1 |2 Other |
| 650 | _ | 7 | |a IgG4 |2 Other |
| 650 | _ | 7 | |a Translation to patients |2 Other |
| 650 | _ | 7 | |a antibody |2 Other |
| 650 | _ | 7 | |a autoimmunity |2 Other |
| 650 | _ | 7 | |a biosignature |2 Other |
| 650 | _ | 7 | |a innate immunity |2 Other |
| 650 | _ | 7 | |a limbic encephalitis |2 Other |
| 650 | _ | 7 | |a ouctome |2 Other |
| 650 | _ | 7 | |a precision medicine |2 Other |
| 650 | _ | 7 | |a CNTNAP2 protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Nerve Tissue Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Immunoglobulin G |2 NLM Chemicals |
| 650 | _ | 7 | |a Membrane Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Autoantibodies |2 NLM Chemicals |
| 650 | _ | 7 | |a Biomarkers |2 NLM Chemicals |
| 650 | _ | 7 | |a Receptors, IgG |2 NLM Chemicals |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Nerve Tissue Proteins: immunology |2 MeSH |
| 650 | _ | 2 | |a Immunoglobulin G: blood |2 MeSH |
| 650 | _ | 2 | |a Immunoglobulin G: immunology |2 MeSH |
| 650 | _ | 2 | |a Membrane Proteins: immunology |2 MeSH |
| 650 | _ | 2 | |a Autoantibodies: blood |2 MeSH |
| 650 | _ | 2 | |a Autoantibodies: immunology |2 MeSH |
| 650 | _ | 2 | |a Phenotype |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Biomarkers: blood |2 MeSH |
| 650 | _ | 2 | |a Middle Aged |2 MeSH |
| 650 | _ | 2 | |a Receptors, IgG: immunology |2 MeSH |
| 650 | _ | 2 | |a Adult |2 MeSH |
| 700 | 1 | _ | |a Spatola, Marianna |b 1 |
| 700 | 1 | _ | |a Chuquisana, Omar |b 2 |
| 700 | 1 | _ | |a Joubert, Bastien |b 3 |
| 700 | 1 | _ | |a de Vries, Juna M |b 4 |
| 700 | 1 | _ | |a Dik, Andre |b 5 |
| 700 | 1 | _ | |a Marmolejo, Laura |b 6 |
| 700 | 1 | _ | |a Jönsson, Friederike |b 7 |
| 700 | 1 | _ | |a Lauc, Gordan |b 8 |
| 700 | 1 | _ | |a Kovac, Stjepana |b 9 |
| 700 | 1 | _ | |a Prüss, Harald |0 P:(DE-2719)2810931 |b 10 |u dzne |
| 700 | 1 | _ | |a Wiendl, Heinz |b 11 |
| 700 | 1 | _ | |a Titulaer, Maarten J |b 12 |
| 700 | 1 | _ | |a Honnorat, Jérôme |b 13 |
| 700 | 1 | _ | |a Lünemann, Jan D |b 14 |
| 773 | _ | _ | |a 10.1016/j.medj.2024.09.004 |g Vol. 6, no. 2, p. 100515 - |0 PERI:(DE-600)3050845-9 |n 2 |p 100515 |t Med |v 6 |y 2025 |x 2666-6340 |
| 856 | 4 | _ | |y OpenAccess |u https://pub.dzne.de/record/276797/files/DZNE-2025-00322.pdf |
| 856 | 4 | _ | |y OpenAccess |x pdfa |u https://pub.dzne.de/record/276797/files/DZNE-2025-00322.pdf?subformat=pdfa |
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| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 10 |6 P:(DE-2719)2810931 |
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