Identification of definitive serum biomarkers associated with disease activity in primary Sjögren's syndrome

Ayumi Nishikawa, Katsuya Suzuki, Yoshiaki Kassai, Yuumi Gotou, Maiko Takiguchi, Takahiro Miyazaki, Keiko Yoshimoto, Hidekata Yasuoka, Kunihiro Yamaoka, Rimpei Morita, Akihiko Yoshimura, Tsutomu Takeuchi

研究成果: Article

17 引用 (Scopus)

抄録

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.

元の言語English
記事番号106
ジャーナルArthritis Research and Therapy
18
発行部数1
DOI
出版物ステータスPublished - 2016 5 14

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Biomarkers
Serum
Receptors, Tumor Necrosis Factor, Type II
Proteins
Enzyme-Linked Immunosorbent Assay
B-Cell Activating Factor
Sodium Pertechnetate Tc 99m
Submandibular Gland
Technetium
Salivary Glands
Radionuclide Imaging
Proteomics
Blood Proteins
Lung

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

これを引用

Identification of definitive serum biomarkers associated with disease activity in primary Sjögren's syndrome. / Nishikawa, Ayumi; Suzuki, Katsuya; Kassai, Yoshiaki; Gotou, Yuumi; Takiguchi, Maiko; Miyazaki, Takahiro; Yoshimoto, Keiko; Yasuoka, Hidekata; Yamaoka, Kunihiro; Morita, Rimpei; Yoshimura, Akihiko; Takeuchi, Tsutomu.

:: Arthritis Research and Therapy, 巻 18, 番号 1, 106, 14.05.2016.

研究成果: Article

Nishikawa, A, Suzuki, K, Kassai, Y, Gotou, Y, Takiguchi, M, Miyazaki, T, Yoshimoto, K, Yasuoka, H, Yamaoka, K, Morita, R, Yoshimura, A & Takeuchi, T 2016, 'Identification of definitive serum biomarkers associated with disease activity in primary Sjögren's syndrome', Arthritis Research and Therapy, 巻. 18, 番号 1, 106. https://doi.org/10.1186/s13075-016-1006-1
Nishikawa, Ayumi ; Suzuki, Katsuya ; Kassai, Yoshiaki ; Gotou, Yuumi ; Takiguchi, Maiko ; Miyazaki, Takahiro ; Yoshimoto, Keiko ; Yasuoka, Hidekata ; Yamaoka, Kunihiro ; Morita, Rimpei ; Yoshimura, Akihiko ; Takeuchi, Tsutomu. / Identification of definitive serum biomarkers associated with disease activity in primary Sjögren's syndrome. :: Arthritis Research and Therapy. 2016 ; 巻 18, 番号 1.
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abstract = "Background: In this study, we sought to identify definitive biomarkers associated with disease activity in primary Sj{\"o}gren'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 Sj{\"o}gren'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.",
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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

PY - 2016/5/14

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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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