Soluble urokinase plasminogen activator receptor as a useful biomarker to predict the response to adalimumab in patients with rheumatoid arthritis in a Japanese population.
OBJECTIVE
To determine whether soluble urokinase plasminogen activator receptor is a useful biomarker to predict the response to adalimumab (ADA) in Japanese patients with rheumatoid arthritis.


METHODS
Rheumatoid arthritis (RA) patients administrated ADA (n=51) were classified as good responders (n=18) or nonresponders (n=9) according to the EULAR response criteria after 8 weeks of bi-weekly ADA administration. We examined the expression of cytokines and chemokines in these groups by antibody array methods. Positive results obtained by antibody array methods were further confirmed by ELISA.


RESULTS
Antibody array has identified that the macrophage migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF) and soluble urokinase plasminogen activator receptor (uPAR) decreased in the good responders to ADA whereas these changes were not observed in the non-responders. The decrement of serum uPAR was confirmed by ELISA in the good responders to ADA. Furthermore, serum uPAR at baseline was significantly high in non-responders compared with good responders.


CONCLUSIONS
An antibody array is convenient for screening the expression of proteins of interest. Examination of serum uPAR at baseline and thereafter may be useful as a predictive biomarker for primary failure toward ADA in patients with RA.
Unit of Translational Medicine, Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. tkoga@nagasaki-u.ac.jp
Tomohiro
T
Koga
Akitomo
A
Okada
Shinya
S
Kawashiri
Junko
J
Kita
Takahisa
T
Suzuki
Yoshikazu
Y
Nakashima
Mami
M
Tamai
Katsuya
K
Satoh
Tomoki
T
Origuchi
Naoki
N
Iwamoto
Satoshi
S
Yamasaki
Hideki
H
Nakamura
Kiyoshi
K
Migita
Hiroaki
H
Ida
Yukitaka
Y
Ueki
Katsumi
K
Eguchi
Atsushi
A
Kawakami
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D054316:Biomarkers, Pharmacological / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood*; D012995:Solubility; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D054316:Biomarkers, Pharmacological; D008263:Macrophage Migration-Inhibitory Factors; D055293:Receptors, Urokinase Plasminogen Activator; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; D000068879:Adalimumab