Abstract 18255: Saliva TGFβ Level as a Surrogate Therapeutic Marker in Marfan Syndrome
Objective: TGFβ antagonists such as the angiotensin II type 1 (AT1) receptor blocker losartan have shown the ability to prevent aortic aneurysm in a mouse model of Marfan syndrome (MFS). Efficient translation of such therapies to people would benefit from surrogate markers that allow the rapid assessment of dosing and efficacy. We previously showed that levels of circulating transforming growth factor beta (TGFβ) correlate with treatment status and aortic size in mice and people with MFS. Application of this method is constrained by a reluctance for serial phlebotomy in children and by the need for rapid and specialized sample processing to avoid contamination by TGFβ-rich platelets. We assessed the hypothesis that measurement of TGFβ in saliva would provide an easy and widely applicable means to monitor disease progression and response to therapy in MFS.
Patients and Methods: TGFβ-1 was measured in 44 simultaneous saliva and plasma samples from patients with MFS and matched controls using a novel electrochemoluminescence-based assay that has been optimized for saliva and plasma.
Results: In keeping with prior work, TGFβ levels in plasma were higher in MFS compared to healthy controls (7.6±2.4ng/ml vs. 1.3±0.2ng/ml, respectively; p<0.05) and patients treated with losartan had significantly lower levels than those without treatment (3.7±1.8ng/ml vs. 18.1±2.3ng/ml, respectively; p<0.005). Untreated patients had significantly higher saliva TGFβ levels than controls (109±16pg/ml vs. 60±6pg/ml, respectively; p<0.005) and patients receiving losartan therapy had significantly lower saliva TGFβ levels than those without treatment (70±8pg/ml vs. 109±16pg/ml, respectively; p<0.05). The absence of platelets in saliva likely contributed to the reduced intragroup variance in TGFβ levels, when compared to blood. Comparison of circulating TGFβ levels in matched plasma and saliva samples demonstrated a significant correlation (r=0.72, p<0.01).
Conclusion: Measuring TGFβ levels in saliva is feasible and results correlate with diagnosis and treatment status. Saliva TGFβ levels have the potential to serve as both a prognostic and therapeutic marker in MFS, allowing individualized titration of therapies.
- © 2010 by American Heart Association, Inc.