Abstract 192: Axonal Guidance Factors as Potential Pediatric AVM Urinary Biomarker
Introduction: Development of noninvasive biomarkers for pediatric arteriovenous malformations (AVMs) could improve diagnosis and identify potential therapeutic targets. The axonal guidance factor, EphrinB2, and its cognate receptor EphB4 have been implicated in AVM development. Here we report our initial experience with urinary EphrinB2 as a novel AVM-specific urinary biomarker.
Hypothesis: We hypothesize that urinary and tissue levels of EphrinB2 will be elevated in patients with AVM and distinguish AVM from other cerebrovascular disease.
Methods: Specimens were collected from 45 pediatric patients (0-21 years of age) including unruptured AVM (n=15), moyamoya (n=15) and age- and sex-matched controls (n=15), per an IRB-approved protocol. ELISA quantified levels of urinary EphrinB2. Matched AVM tissue from the same patient was subjected to immunohistochemistry to correlate source tissue expression with biomarker levels.
Results: Statistical analysis revealed a statistically significant increase in EphrinB2 and AVM-specific biomarker fingerprints capable of discerning AVM both from controls and also from other types of vascular neurosurgical disease. Compared to controls, EphrinB2 was elevated with mean EphrinB2 (0.10 pg/ug vs. 0.019 pg/ug, p<0.01) and compared to moyamoya patients mean EphrinB2 (0.10 pg/ug vs. 0.014, p<0.01). Similarly, EphrinB2 and EphB4 staining was significantly increased in AVM tissue vs. normal blood vessels matched as controls.
Conclusion: In conclusion, these data suggests potential utility of urinary biomarkers, specifically EphrinB2, as diagnostic tools for clinicians treating children with AVMs and demonstrates proof-of- principle results supporting the concept of hypothesis-driven biomarker “fingerprinting” for unique cerebrovascular disease, differentiating AVM from other vascular pathology. For the first time, these data correlate known aspects of AVM molecular biology with clinically relevant diagnostics.
Author Disclosures: K. Pricola: None. E. Smith: None.
- © 2015 by American Heart Association, Inc.