Circulatory dipeptidyl peptidase 3 (cDPP3) is a potential biomarker for early detection of secondary brain injury after aneurysmal subarachnoid hemorrhage

Abstract

IntroductionDelayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) that can culminate in secondary brain damage. Although it remains one of the main preventable causes of aSAH-related morbidity, there is still a lack of prognostic criteria for identification of patients at risk of developing DCI. Because elevated circulatory levels of the enzyme dipeptidyl peptidase 3 (cDPP3) were recently identified as a potential biomarker for outcome prediction in critically ill patients, we evaluated the time-course of changes in cDPP3 levels after aSAH. Materials and methodscDPP3 levels were quantified in serum obtained from 96 confirmed aSAH patients during the early (EP: d1–4), critical (CP: d5–8, d9–12, d13–15) and late (LP: d16–21) phase after aSAH onset. Associations between cDPP3 levels and demographic or clinical parameters were evaluated. The relations between cDPP3 levels and DCI, DCI-related infarctions and long-term clinical outcomes were examined by receiver operating characteristics (ROC) curve analysis and multivariate logistic regression. ResultsSignificantly higher cDPP3 levels during CP (d5–8, d9–12, d13–15) were observed in patients with poor clinical (p < 0.001 to p = 0.033) or radiological (p = 0.012 to p = 0.039) status on admission, DCI (p < 0.001 to p = 0.001), DCI-related infarctions (p = 0.002 to p = 0.007), and poorer long-term outcome (p = 0.007 to p = 0.019). ROC curve analysis indicated that higher cDPP3 levels on d5–8 are predictive for a poor clinical outcome (area under the curve = 0.677, p = 0.007). In multivariate analysis, there was an independent association between cDPP3 levels on d5–8 and development of DCI-related infarctions (p = 0.038). ConclusionOur results provide first evidence that cDPP3 could serve as a promising biomarker for early diagnosis of DCI-related infarctions in poor grade aSAH patients.