Abstract 3939: Urine 8-hydroxy-2′-deoxyguanosine as a New Biomarker of Inflammatory Activity in Patients With Cardiac Sarcoidosis
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). Here, we investigated whether or not the level of urinary 8-hydroxy-2′-deoxyguanosine (u-8-OHdG), a marker of oxidative DNA damage, correlates with inflammatory activity in SAR.
Methods: In a preliminary study, blood sampling from both coronary sinus and artery showed that cardiac tissue produced 8-OHdG in dilated cardiomyopathy (DCM) and SAR. We measured u-8-OHdG in 30 control subjects, 25 patients with DCM (NYHA I/II: 90%, LVEF: 27±15%) and 25 patients with SAR (NYHA I/II: 90%, LVEF: 28±12%). All patients with SAR underwent 18F-FDG PET/CT or 67Ga scintigraphy to evaluate inflammation status for dividing active SAR (n=12) and non-active SAR (n=13). Then, levels of u-8-OHdG were compared between control and all SAR groups as well as between the subgroups of patients with active and non-active SAR. Five patients were re-examined u-8-OHdG in comparison with 18F-FDG PET/CT or 67Ga scintigraphy to assess response to corticosteroid treatment.
Results: The levels of u-8-OHdG (ng/ml) in SAR were higher than those of control subjects (Control vs all SAR: 8.5±1.9 vs 16.8±8.2, p<0.01). Levels of U-8-OHdG in active SAR were higher than those of non-active SAR and DCM (active SAR; 21.2±7.2 vs non-active SAR; 12.5±4.2, DCM; 12.6±4.5, both p<0.01), although there was no significant difference among these 3 groups in indices of cardiac function such as NYHA class, LVEF and serum BNP levels as well as in other biomarkers such as the urine 8-isoplastane, serum IL-6, serum TNFα, high sensitive CRP, serum angiotensin-converting enzyme. Interestingly, levels of u-8-OHdG in 5 patients of active SAR group at 3– 6 months after corticosteroid treatment significantly decreased in proportion with regression of pathological tracer uptake in heart focus in comparison with before corticosteroid treatment.
Conclusion: The level of u-8-OHdG correlates with inflammatory activity in SAR, indicating that clinically useful biomarker for evaluating not only inflammatory activity, but also the response of patients with SAR treated with corticosteroid therapy.