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SYSTEMATIC REVIEW article

Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1491880

Antibodies against neuronal surface antigens in acute stroke: a systematic review and meta-analysis

Provisionally accepted
Matteo Paolucci Matteo Paolucci 1Andrea Zini Andrea Zini 1Luana Morelli Luana Morelli 1,2Rocco Liguori Rocco Liguori 1,2Maria Pia Giannoccaro Maria Pia Giannoccaro 1,2*
  • 1 IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
  • 2 Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Emilia-Romagna, Italy

The final, formatted version of the article will be published soon.

    Antibodies against neuronal surface antigens (NSA-Abs), particularly against the NMDA receptor (NMDAR-Ab), have been reported in acute stroke patients (ASP). However, their role in stroke is far from being understood.We conducted a systematic review and meta-analysis to investigate: 1) the frequency of NSA-Abs in patients with acute stroke compared to controls; 2) the de novo appearance of NSA-Abs after stroke; and 3) their effects on the clinical outcome.We included nine studies in the qualitative analysis and seven in the quantitative analysis.Analyses were restricted to NMDAR-Abs due to the lack of data about other NSA-Abs.Considering only studies that adopted a cell-based assay, IgA-IgM NMDAR-Abs isotypes (but not the IgG) were found more frequently in patients with acute stroke (OR 2.69, 95% CI 2.00-3.62, I 2 =4%).There was no de novo NMDAR-Abs formation after stroke.There was no statistical difference in mean discharge/day-7 NIHSS (SMD 0.21, 95% CI -1.10-1.52, I2=84%) and 3-12-month mRS (SMD 0.38, 95% CI -0.56-1.32, I2=78%) between patients with stroke with and without NMDAR-Abs seropositivity.Serum IgA/IgM NMDAR-Abs are more frequent in patients with stroke than controls. Due to several methodological issues, these findings should be interpreted cautiously.Additional, methodologically robust studies are needed to clarify the prevalence and significance of NMDAR-Abs in patients with stroke.

    Keywords: neuronal surface antigens, Nmda receptor antibodies, stroke outcome, ischemic stroke, antibody isotypes

    Received: 05 Sep 2024; Accepted: 02 Jan 2025.

    Copyright: © 2025 Paolucci, Zini, Morelli, Liguori and Giannoccaro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Maria Pia Giannoccaro, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.