Article
The association of myeloperoxidase-DNA complexes and high mobility group box 1 Protein with delayed cerebral ischemia following aneurysmal subarachnoid haemorrhage
Die Assoziation von Myeloperoxidase-DNA-Komplexen und High Mobility Group Box 1 Protein mit verzögerter zerebraler Ischämie nach aneurysmatischer Subarachnoidalblutung
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Authors
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Philipp Hendrix
- Geisinger, Wilkes-Barre, PA, Vereinigte Staaten
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Jens Witsch
- University of Pennsylvania, Philadelphia, PA, Vereinigte Staaten
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Valerie Spalart
- KU Leuven, Leuven, Belgien
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Kimberly Martinod
- KU Leuven, Leuven, Belgien
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Hauke Schneider
- Universitätsklinikum Augsburg, Augsburg, Deutschland
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Joachim Oertel
- Universitätsklinikum des Saarlandes, Homburg a. d. Saar, Deutschland
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Jürgen Geisel
- Universitätsklinikum des Saarlandes, Homburg a. d. Saar, Deutschland
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Sina Hemmer
- Universitätsklinikum des Saarlandes, Homburg a. d. Saar, Deutschland
| Published: | May 25, 2022 |
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Outline
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Objective: High mobility group box 1 protein (HMGB1) acts as a key player in aseptic inflammation. Admission serum HMGB1 serves as an independent biomarker predictive of delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH). Released by leucocytes and platelets, HMGB1 has been found to induce neutrophils to release condensed chromatin and protein granules, termed neutrophil extracellular traps (NETs). Myeloperoxidase (MPO)-DNA complexes are one major NET biomarker and have been associated with arterial and venous thrombosis formation. The prevalence and role of MPO-DNA in aSAH remains to be determined.
Methods: A post-hoc analysis of a prospective, blinded, single-center biomarker observational study to investigate the role of HMGB1 was performed to explore if MPO-DNA complexes can be identified in aSAH patients, and if so, whether their titers are associated with DCI defined as new infarction on CT-scan not adjudicated to treatment. Secondary analysis was performed to explore association with clinical vasospasm. Admission and day 4 serum samples were analyzed for MPO-DNA complexes.
Results: One hundred consecutive non-traumatic spontaneous SAH patients were enrolled and 83 revealed an aneurysm on angiography. Five patients (5/83) died <48h not allowing for DCI determination per definition. MPO-DNA complexes were detected in all serum samples. HMGB1 level significantly correlated with MPO-DNA levels on admission as well as day 4 (p<0.001, r=0.606 and p<0.001, r=0.622, respectively).In 29/78 DCI patients, MPO-DNA levels significantly declined from admission to day 4 (p=0.036) whereas MPO-DNA levels remained stable in 49/78 (p=0.171). Secondary analysis showed a similar reduction in MPO-DNA levels between admission and day 4 in patients who developed clinical vasospasm (p=0.006), but not in those who did not (p=0.473).
Conclusion: MPO-DNA-complexes can be detected in aSAH patients and highly correlate with HMGB1 levels. A pronounced reduction in MPO-DNA levels in the early phase after aSAH might herald DCI. The HMGB1-NETosis axis in the context of DCI requires further exploration.
