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Meta-Analysis
. 2025 Jan 17:16:1491880.
doi: 10.3389/fimmu.2025.1491880. eCollection 2025.

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

Matteo Paolucci  1 , Andrea Zini  1 , Luana Morelli  2   3 , Rocco Liguori  2   3 , Maria Pia Giannoccaro  2   3
Affiliations
Meta-Analysis

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

Matteo Paolucci et al. Front Immunol. .

Abstract

Background: 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.

Methods: 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.

Results: 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, I2 = 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.

Conclusions: 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.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022241278#:~:text=https%3A//www.crd.york.ac.uk/prospero/display_record.php%3FID%3DCRD42022241278, identifier CRD42022241278.

Keywords: NMDA receptor antibodies; antibody isotypes; ischemic stroke; neuronal surface antigens; stroke outcome.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
PRISMA flow diagram.
Figure 2
Figure 2
Forest and funnel plot of the frequency of NMDAR-Abs in stroke patients and controls. (A): CBA-only studies. (B): all studies.
See this image and copyright information in PMC

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Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.