Thrombin-cleaved osteopontin is increased in urine of patients with rheumatoid arthritis.
OBJECTIVE
To measure concentrations of the thrombin-cleaved isoform of osteopontin (OPN) in urine and plasma of patients with rheumatoid arthritis (RA), and to assess whether levels of thrombin-cleaved OPN are associated with measures of RA.


METHODS
Subjects comprised 70 patients with RA, 20 patients with osteoarthritis (OA), and 46 healthy controls. RA disease activity was evaluated by tender joint count, swollen joint count, patient's global assessment of disease activity, erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), and rheumatoid factor (RF), as well as 28-joint count Disease Activity Score (DAS28). OPN levels in plasma and urine were measured by ELISA.


RESULTS
Median levels of thrombin-cleaved OPN in urine (U-half) were significantly higher in RA patients (143.5 pmol/mmol Cr) than in healthy controls (67.9 pmol/mmol Cr) or OA patients (69.8 pmol/mmol Cr). Thrombin-cleaved OPN was not detected in plasma. U-half levels correlated significantly with levels of CRP (r = 0.26, p = 0.03), ESR (r = 0.26, p = 0.03), and RF (r = 0.28, p = 0.03). Median U-half levels were significantly higher in patients with stage III (249.9 pmol/mmol Cr) and IV (251.6 pmol/mmol Cr) disease than in patients with stage I (98.6 pmol/mmol Cr) disease.


CONCLUSIONS
Our results suggest that urine levels of the thrombin-cleaved isoform of OPN may reflect the severity of active inflammatory arthritis in patients with RA.
Department of Internal Medicine II, Fukushima Medical University School of Medicine, Hikarigaoka, Fukushima, Japan.
Kiori
K
Shio
Hiroko
H
Kobayashi
Tomoyuki
T
Asano
Rie
R
Saito
Haruyo
H
Iwadate
Hiroshi
H
Watanabe
Hirofumi
H
Sakuma
Tetsuya
T
Segawa
Masahiro
M
Maeda
Hiromasa
H
Ohira
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000652:urine*; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000652:urine*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood / Q000652:urine; D053495:Osteopontin / Q000097:blood / Q000652:urine*; D010147:Pain Measurement; D020033:Protein Isoforms / Q000097:blood / Q000652:urine; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism*
D020033:Protein Isoforms; D053495:Osteopontin; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; D013917:Thrombin; D019278:Matrix Metalloproteinase 3