title: Increased serum GP88 (Progranulin) concentrations in rheumatoid arthritis.
abstract: GP88 (Progranulin; PGRN) is a secreted glycosylated protein with important functions in several processes, including immune response and cancer growth. Recent reports have shown that PGRN is a therapeutic target for rheumatoid arthritis (RA) because of its capability to bind with tumor necrosis factor receptor (TNFR). However, the serum PGRN level in RA patients has not been investigated. We used enzyme-linked immunosorbent assay (ELISA) to quantify the serum levels of PGRN in 417 healthy subjects, 56 patients with RA and 31 patients with osteoarthritis (OA). In RA patients, we also measured the serum TNF-α and sTNFR concentration. Immunohistochemical staining of PGRN was performed using synovectomy tissue of RA patients. The serum PGRN normal range was established as 40.1 ± 8.7 ng/ml. PGRN levels were not influenced by sex or age. A significant increase in serum PGRN levels was observed in RA (50.2 ± 11.1 ng/ml) and OA (45.4 ± 6.6 ng/ml) groups compared to those in age-matched healthy controls (40.4 ± 9.9 ng/ml) (p<0.05, Tukey). Further, PGRN levels in the synovial fluid of RA patients (68.4 ± 3.4 ng/ml) were found to be significantly higher than those in OA patients (35.9 ± 16.8 ng/ml). Immunohistochemical staining of PGRN revealed that the highest positive signal was detected in macrophages. Circulating PGRN in RA patients was weakly associated with TNF-α and sTNFR 2 concentration. Furthermore, PGRN/TNF-α ratio was correlated the stage of the disease in RA patients. The concentrations of serum PGRN in RA were found to be significantly higher than those in age-matched healthy controls, although it remains to be clarified how blood PGRN is related to the pathogenesis of RA. Our results showed that the serum PGRN may be a useful approach to monitor the disease activity in RA patients.
authors.affiliation: Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto, 606-8507, Japan, yamamoto.yasuko.5x@kyoto-u.ac.jp.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masao
authors.initials: M
authors.lastname: Takemura
authors.forename: Ginette
authors.initials: G
authors.lastname: Serrero
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
authors.forename: Binbin
authors.initials: B
authors.lastname: Yue
authors.forename: Aya
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Hisako
authors.initials: H
authors.lastname: Kubo
authors.forename: Takashi
authors.initials: T
authors.lastname: Mitsuhashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Mannami
authors.forename: Masao
authors.initials: M
authors.lastname: Sato
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Matsunami
authors.forename: Yushi
authors.initials: Y
authors.lastname: Matuo
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000077153:Progranulins; D055815:Young Adult
chemical_list: D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins