Urinary 8-hydroxy-2'-deoxyguanosine as a novel biomarker of inflammatory activity in patients with cardiac sarcoidosis.
BACKGROUND
Inflammation and oxidative stress play a crucial role in the pathogenesis of cardiac sarcoidosis (SAR). We investigated whether urinary (U) 8-hydroxy-2'-deoxyguanosine (8-OHdG)--an oxidative DNA damage marker--was related to SAR inflammatory activity.


METHODS
U-8-OHdG levels were measured in 31 SAR patients, classified as active (n=17) or non-active (n=14) based on (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG-PET/CT), 28 dilated cardiomyopathy (DCM) patients, and 30 controls. In active SAR patients, U-8-OHdG levels were reexamined and compared with (18)F-FDG-PET/CT results at 6 months after corticosteroid treatment to assess therapeutic response.


RESULTS
Immunohistochemical examination of left ventricle (LV) autopsy samples from SAR patients revealed positive 8-OHdG staining in cardiomyocyte nuclei from LV sections showing (18)F-FDG accumulation on PET/CT, while serum 8-OHdG levels were significantly higher in the coronary sinus than in the aortic root only in active SAR patients. U-8-OHdG levels in SAR patients were higher than those in controls, and significantly higher in active SAR patients than in non-active SAR and DCM patients. U-8-OHdG was a powerful predictor of active SAR in receiver operating characteristic curve analysis (AUC, 0.98; 95% CI, 0.94-1.02; optimal cutoff value, 13.1 ng/mg creatinine), with a sensitivity of 88.2% and a specificity of 92.9%. U-8-OHdG levels in responders significantly decreased at 6 months after corticosteroid treatment initiation, in proportion with the decrease in the focal cardiac uptake of (18)F-FDG.


CONCLUSIONS
U-8-OHdG is a potentially clinically useful biomarker for evaluating inflammatory activity and monitoring the effectiveness of corticosteroid therapy in SAR patients.
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: skoba@yamaguchi-u.ac.jp.
Shigeki
S
Kobayashi
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Takeki
T
Myoren
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Seiko
S
Oda
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Makana
M
Inari
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Hironori
H
Ishiguchi
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Wakako
W
Murakami
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Masakazu
M
Fukuda
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Takeo
T
Tanaka
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Shinichi
S
Okuda
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Tomoko
T
Nao
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Masahiro
M
Doi
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Jutaro
J
Yamada
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Takayuki
T
Okamura
Department of Pathology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Yoshinobu
Y
Hoshii
Department of Radiology, St. Hill Hospital, Ube, Japan.
Kazuyoshi
K
Suga
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Masunori
M
Matsuzaki
Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Masafumi
M
Yano
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000652:urine*; D015331:Cohort Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000652:urine; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D012507:Sarcoidosis / Q000000981:diagnostic imaging* / Q000652:urine*
D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
Biomarker; Cardiac sarcoidosis; Oxidative stress