title: Identification of definitive serum biomarkers associated with disease activity in primary Sjögren's syndrome.
abstract: In this study, we sought to identify definitive biomarkers associated with disease activity in primary Sjögren's syndrome (pSS).
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our approach successfully identified serum biomarkers associated with disease activity in pSS patients. These markers might be potential therapeutic targets in pSS patients.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Nishikawa
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-26-1 Muraokahigashi, Fujisawa city, Kanagawa, 251-0012, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kassai
authors.affiliation: Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-26-1 Muraokahigashi, Fujisawa city, Kanagawa, 251-0012, Japan.
authors.forename: Yuumi
authors.initials: Y
authors.lastname: Gotou
authors.affiliation: Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-26-1 Muraokahigashi, Fujisawa city, Kanagawa, 251-0012, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Takiguchi
authors.affiliation: Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-26-1 Muraokahigashi, Fujisawa city, Kanagawa, 251-0012, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yoshimoto
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Hidekata
authors.initials: H
authors.lastname: Yasuoka
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yamaoka
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Rimpei
authors.initials: R
authors.lastname: Morita
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. tsutake@z5.keio.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods; D012859:Sjogren's Syndrome / Q000097:blood*
chemical_list: D015415:Biomarkers
keywords: Biomarker; Disease activity; Proteomics; Serum protein; Sjögren’s syndrome