Abstract 10269: Urinary 8-hydroxy-2′-deoxyguanosine as a Novel Biomarker of Inflammatory Activity in Patients with Cardiac Sarcoidosis: Insight From Immunohistochemical Technique and 18F-FDG PET/CT
Background: Enhanced production of reactive oxygen species, capable of reducing endogenous defense levels and enhancing inflammation, is suggested to play a crucial role in the pathogenesis of cardiac sarcoidosis (SAR). We investigated whether urinary(U) 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, correlates with inflammatory activity in SAR.
Methods and Results: Immunohistochemical examination of 8-OHdG in the biopsy sample, which was selectively taken from the focus with accumulation of 18F-FDG by PET/CT, revealed positive staining for 8-OHdG in the nuclei around sarcoidosis granuloma. Serum 8-OHdG (ng/ml) was found to be significantly higher in coronary sinus(CS) than in aorta(A) only in patients with active SAR (active SAR, n=10: 0.70 ±0.11 in CS; 0.35 ± 0.10 in A; non-active SAR, n=8: 0.40±0.13 in CS; 0.35± 0.11 in A). Moreover, we measured U-8-OHdG in 30 control subjects, 30 patients with DCM (LVEF: 27±15%) and 38 patients with SAR (LVEF: 33.8±15%). All patients with SAR underwent 18F-FDG PET/CT to evaluate the inflammation status for dividing active SAR (n=20) and non-active SAR (n=18). In all patients with active SAR, U-8-OHdG were re-examined in comparison with 18F-FDG PET/CT to assess response to corticosteroids. U-8-OHdG (ng/ml creatinine) in SAR was higher than that of control subjects (Control vs. all SAR: 8.5±1.9 vs. 17.6±5.3, p<0.01). U-8-OHdG in active SAR was higher than that of non-active SAR or DCM (active SAR; 22.3±6.3 vs. non-active SAR; 12.4±4.3, DCM; 11.3±4.5, p<0.01), although there was no significant difference among these 3 groups in cardiac function (NYHA class, LVEF and serum BNP levels), as well as in other biomarkers (serum IL-6, TNFα, hs CRP, ACE). U-8-OHdG in 14 patients with active SAR, significantly decreased after corticosteroid treatment, in proportion with a decrease in the focal pathological tracer uptake in heart. In contrast, U-8-OHdG in 6 patients with active SAR, whose clinical status (i.e. ventricular tachycardia, heart failure) was worsening, increased in parallel with the accumulation of 18F-FDG.
Conclusion: These findings suggest that U-8-OHdG is a clinically useful biomarker for evaluating inflammatory activity and effectiveness to corticosteroid therapy in SAR patients.
- © 2011 by American Heart Association, Inc.