TY - JOUR
T1 - Identification of definitive serum biomarkers associated with disease activity in primary Sjögren's syndrome
AU - Nishikawa, Ayumi
AU - Suzuki, Katsuya
AU - Kassai, Yoshiaki
AU - Gotou, Yuumi
AU - Takiguchi, Maiko
AU - Miyazaki, Takahiro
AU - Yoshimoto, Keiko
AU - Yasuoka, Hidekata
AU - Yamaoka, Kunihiro
AU - Morita, Rimpei
AU - Yoshimura, Akihiko
AU - Takeuchi, Tsutomu
N1 - Funding Information:
The authors thank the patients and staff. The authors also thank DMC Corp. for editing this manuscript. This study was funded by a collaborative research grant from Takeda Pharmaceutical Co., Ltd., and internal research grants from Keio University.
Publisher Copyright:
© 2016 Nishikawa et al.
PY - 2016/5/14
Y1 - 2016/5/14
N2 - Background: In this study, we sought to identify definitive biomarkers associated with disease activity in primary Sjögren's syndrome (pSS). Methods: Serum protein concentrations in pSS patients and healthy controls (HCs) were comprehensively screened using high-throughput proteomic analysis, and differentially expressed proteins were extracted. Correlation between differentially expressed proteins and European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) scores was analyzed and disease activity-associated biomarkers were identified. These biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) in a separate pSS cohort. Results: The serum concentrations of 1100 proteins were compared between 30 pSS patients and 30 HCs, with 82 differentially expressed proteins identified as pSS-associated proteins. Of these 82 proteins, 9 were identified as disease activity-associated biomarkers. These nine biomarkers underwent validation by ELISA in a separate pSS validation cohort (n = 58), with five proteins (CXCL13, TNF-R2, CD48, B-cell activating factor (BAFF), and PD-L2) subsequently being confirmed as candidate biomarkers. Of these five candidate biomarkers, CXCL13 exhibited the most significant correlation with the lymphadenopathy, glandular, and pulmonary domains of the ESSDAI. CXCL13, TNF-R2 and CD48 exhibited a positive correlation with the biological domain of the ESSDAI. TNF-R2 exhibited the most negative correlation with uptake in the submandibular gland on technetium 99m-pertechnetate salivary gland scintigraphy. Conclusions: Our approach successfully identified serum biomarkers associated with disease activity in pSS patients. These markers might be potential therapeutic targets in pSS patients.
AB - Background: In this study, we sought to identify definitive biomarkers associated with disease activity in primary Sjögren's syndrome (pSS). Methods: Serum protein concentrations in pSS patients and healthy controls (HCs) were comprehensively screened using high-throughput proteomic analysis, and differentially expressed proteins were extracted. Correlation between differentially expressed proteins and European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) scores was analyzed and disease activity-associated biomarkers were identified. These biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) in a separate pSS cohort. Results: The serum concentrations of 1100 proteins were compared between 30 pSS patients and 30 HCs, with 82 differentially expressed proteins identified as pSS-associated proteins. Of these 82 proteins, 9 were identified as disease activity-associated biomarkers. These nine biomarkers underwent validation by ELISA in a separate pSS validation cohort (n = 58), with five proteins (CXCL13, TNF-R2, CD48, B-cell activating factor (BAFF), and PD-L2) subsequently being confirmed as candidate biomarkers. Of these five candidate biomarkers, CXCL13 exhibited the most significant correlation with the lymphadenopathy, glandular, and pulmonary domains of the ESSDAI. CXCL13, TNF-R2 and CD48 exhibited a positive correlation with the biological domain of the ESSDAI. TNF-R2 exhibited the most negative correlation with uptake in the submandibular gland on technetium 99m-pertechnetate salivary gland scintigraphy. Conclusions: Our approach successfully identified serum biomarkers associated with disease activity in pSS patients. These markers might be potential therapeutic targets in pSS patients.
KW - Biomarker
KW - Disease activity
KW - Proteomics
KW - Serum protein
KW - Sjögren's syndrome
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U2 - 10.1186/s13075-016-1006-1
DO - 10.1186/s13075-016-1006-1
M3 - Article
C2 - 27180164
AN - SCOPUS:84969242473
SN - 1478-6354
VL - 18
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 106
ER -