Increased Serum GP88 (Progranulin) Concentrations in Rheumatoid Arthritis

Yasuko Yamamoto, Masao Takemura, Ginette Serrero, Jun Hayashi, Binbin Yue, Aya Tsuboi, Hisako Kubo, Takashi Mitsuhashi, Kenji Mannami, Masao Sato, Hidetoshi Matsunami, Yushi Matuo, Kuniaki Saito

研究成果: Article査読

44 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1806-1813
ページ数8
ジャーナルInflammation
37
5
DOI
出版ステータスPublished - 24-09-2014
外部発表はい

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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