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Analysis of institutional authors

Spatola MCorresponding AuthorMarmolejo LAuthor
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Article

Humoral signatures of Caspr2-antibody spectrum disorder track with clinical phenotypes and outcomes.

Publicated to:Med (N Y). S2666-6340 (24): 00371-4 - 2024-10-01 S2666-6340(24), DOI: 10.1016/j.medj.2024.09.004

Authors: Terroba-Navajas P; Spatola M; Chuquisana O; Joubert B; de Vries JM; Dik A; Marmolejo L; Jönsson F; Lauc G; Kovac S; Prüss H; Wiendl H; Titulaer MJ; Honnorat J; Lünemann JD

Affiliations

CNRS & Institut Pasteur, Université Paris Cité, INSERM UMR1222, Antibodies in Therapy and Pathology, 75015 Paris, France. - Author
Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Charitéplatz 1, Berlin, Germany; German Center for Neurode - Author
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Munster, Germany. - Author
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany. Electronic address: jan.luenemann@ukmuenster.de. - Author
Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands. - Author
Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, Zagreb, Croatia; Genos, Ltd., Borongajska Cesta 83H, Zagreb, Croatia. - Author
French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Lyon, France; MeLiS - UCBL - CNRS UMR 5284 - INSERM U1314, Université de Lyon, Université Claude Bernard Lyon 1, L - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Caixa Research Institute, Barcelona, Spain. Electronic address: marianna.spatola@gmail.com. - Author
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Abstract

BackgroundImmunoglobulin (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.MethodsWe 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.FindingsWe 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.ConclusionsThe 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.FundingThis 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
AntibodyAutoimmunityBiosignatureFc receptorsIgg1Igg4Innate immunityLimbic encephalitisOuctomePrecision medicineTranslation to patients

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Med (N Y) due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 5/189, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, Research & Experimental. Notably, the journal is positioned above the 90th percentile.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-16:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 13.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 12 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 9.65.
  • The number of mentions on the social network X (formerly Twitter): 16 (Altmetric).
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Croatia; France; Germany; Netherlands.

the author responsible for correspondence tasks has been Spatola, Marianna.