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Spontaneous cervical artery dissection is associated with a distinct peripheral immune cell signature

Title: Spontaneous cervical artery dissection is associated with a distinct peripheral immune cell signature
Authors: Beuker, Carolin; Schulte-Mecklenbeck, Andreas; Wirth, Timo; Kleffner, Ilka; Thomas, Christian; Strunk, Daniel; Schmidt-Pogoda, Antje; Gross, Catharina C.; Klotz, Luisa; Minnerup, Jens
Contributors: Tan, Xiaosheng; Deutsche Forschungsgemeinschaft
Source: PLOS One ; volume 21, issue 1, page e0340592 ; ISSN 1932-6203
Publisher Information: Public Library of Science (PLoS)
Publication Year: 2026
Collection: PLOS Publications (via CrossRef)
Description: Objectives Despite being a major cause of ischemic stroke in young adults, the biological underpinnings of cervical artery dissection (CeAD) remain poorly defined. Recent data implicate immune activation as a potential contributor. We aimed to determine whether patients with CeAD display a distinct peripheral immune signature, which may provide insights into pathogenic inflammatory processes. Methods Peripheral blood mononuclear cells (PBMCs) from patients with spontaneous CeAD (n = 7 without and n = 11 with ischemic stroke) and ten age-matched healthy controls were analyzed via multi-color flow cytometry. Immune cell composition and activation markers were assessed, and sparse partial least squares discriminant analysis (sPLS-DA) was employed to identify CeAD-associated immune features. A secondary comparison with ischemic stroke controls was included to assess the specificity of identified immune alterations. Results Compared to healthy controls, CeAD patients displayed increased frequencies of CD4 ⁺ T cells and decreased natural killer T (NKT) cells. sPLS-DA demonstrated clear separation of CeAD and control immune profiles, driven by increased CD28 expression on naïve CD8 ⁺ T cells, NKp46 on NK cells, and IL-2Rα (CD25) on myeloid dendritic cells (mDC2). Elevated granzyme K in naïve CD8 ⁺ T cells indicated enhanced cytotoxic potential, while regulatory T cells were diminished. These alterations were largely preserved when compared to ischemic stroke controls, suggesting CeAD-specific immune activation. No microbial pathogens were detected by untargeted metagenomic sequencing. Discussion CeAD is associated with a distinct peripheral immune signature characterized by enhanced cytotoxic activity and reduced regulatory features. These alterations may reflect a post-infectious autoimmune mechanism triggering CeAD or a secondary immune-inflammatory response to vascular injury. Larger, longitudinal studies are needed to clarify causality and assess whether immune modulation could serve as a therapeutic target in CeAD.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1371/journal.pone.0340592
Availability: https://doi.org/10.1371/journal.pone.0340592; https://dx.plos.org/10.1371/journal.pone.0340592
Rights: http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.80BDBC4
Database: BASE