Abstract Background and aims The immune system is increasingly recognized as a contributor to thrombus formation and outcomes in acute ischemic stroke (AIS). We aimed to characterize immune cell composition in thrombi retrieved during endovascular thrombectomy and evaluate its association with thrombus morphology, stroke etiology, and clinical outcomes. Methods Thrombi from 56 patients in the MR CLEAN-NO IV study were analyzed histologically for immune cell densities. Outcomes included thrombus volume, 90-day functional outcome (mRS ≥3), NIHSS at 24h and 7d, mortality, successful recanalization, final infarct volume, and procedure variables. Results Median age was 69 years, 33.9% female, median baseline NIHSS 17, and 51.8% received IVT. Immune cell expression was not significantly associated with thrombus morphology. However, in etiological subgroup analysis, cardioembolic (CE) thrombi exhibited higher CD68+ cell density compared with large artery atherosclerosis (p=0.016) and cryptogenic thrombi (p=0.034). In CE thrombi, CD19+ and Congo Red+ cell densities were positively correlated with thrombus volume (linear regression β=38.0, 95% CI 12.6-63.3, p=0.020; β=54.1, 95% CI 17.7-90.3, p=0.023, respectively). Furthermore, higher CD3+ and Congo Red+ cell densities were independently associated with favorable 90-day functional outcome (OR=0.37, 95% CI 0.17-0.72, p=0.006; OR=0.28, 95% CI 0.08-0.70, p=0.020, respectively). Conclusions Immune cell composition within retrieved thrombi may vary depending on the stroke etiologies and can be relevant for treatment strategy and clinical recovery. The exploratory results of this study suggest a possible role for immunothrombosis in AIS. However, further validation in larger-sample, adjusted analyses is needed before any clinical significance can be derived. Conflict of interest The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Westendorp reports receiving the Amsterdam UMC Startergrant 2024 and Amsterdam Neuroscience (PoC 2023). Dr Majoie reports grants from the CVON/Dutch Heart Foundation, the TWIN Foundation, the European Commission, Healthcare Evaluation Netherlands, Stryker, and Boehringer Ingelheim (all paid to the institution), and is a minority interest shareholder of Nicolab. Dr Dippel reports funding from the Dutch Heart Foundation, Netherlands Brain Foundation, the Netherlands Organisation for Health Research and Development, Health Holland Top Sector Life Sciences & Health, Penumbra, Stryker, Medtronic, Thrombolytic Science, and Cerenovus (all unrestricted grants for research), paid to his institution. Dr van Beusekom reports funding from the Dutch Heart Foundation and consultancy fees from Thuja Healthcare Investors. Dr van de Beek reports receiving funding from the Netherlands Scientific Organization, ItsME Foundation, and Roche. Dr Coutinho reports receiving funding from the Netherlands Thrombosis Foundation, grants from Bayer and AstraZeneca, and is co-founder and shareholder of TrianecT. The other authors report no conflicts of interest.
Wang et al. (2026) studied this question.