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

Delayed 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.cDPP3 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.Significantly 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).Our results provide first evidence that cDPP3 could serve as a promising biomarker for early diagnosis of DCI-related infarctions in poor grade aSAH patients.