% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{TerrobaNavajas:276797,
author = {Terroba-Navajas, Paula and Spatola, Marianna and
Chuquisana, Omar and Joubert, Bastien and de Vries, Juna M
and Dik, Andre and Marmolejo, Laura and Jönsson, Friederike
and Lauc, Gordan and Kovac, Stjepana and Prüss, Harald and
Wiendl, Heinz and Titulaer, Maarten J and Honnorat, Jérôme
and Lünemann, Jan D},
title = {{H}umoral signatures of {C}aspr2-antibody spectrum disorder
track with clinical phenotypes and outcomes.},
journal = {Med},
volume = {6},
number = {2},
issn = {2666-6340},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {DZNE-2025-00322},
pages = {100515},
year = {2025},
abstract = {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.},
keywords = {Humans / Nerve Tissue Proteins: immunology / Immunoglobulin
G: blood / Immunoglobulin G: immunology / Membrane Proteins:
immunology / Autoantibodies: blood / Autoantibodies:
immunology / Phenotype / Male / Female / Biomarkers: blood /
Middle Aged / Receptors, IgG: immunology / Adult / Fc
receptors (Other) / IgG1 (Other) / IgG4 (Other) /
Translation to patients (Other) / antibody (Other) /
autoimmunity (Other) / biosignature (Other) / innate
immunity (Other) / limbic encephalitis (Other) / ouctome
(Other) / precision medicine (Other) / CNTNAP2 protein,
human (NLM Chemicals) / Nerve Tissue Proteins (NLM
Chemicals) / Immunoglobulin G (NLM Chemicals) / Membrane
Proteins (NLM Chemicals) / Autoantibodies (NLM Chemicals) /
Biomarkers (NLM Chemicals) / Receptors, IgG (NLM Chemicals)},
cin = {AG Prüß},
ddc = {610},
cid = {I:(DE-2719)1810003},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39393351},
doi = {10.1016/j.medj.2024.09.004},
url = {https://pub.dzne.de/record/276797},
}