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Increased Serum GP88 (Progranulin) Concentrations in Rheumatoid Arthritis

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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.

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Key Message

The serum PGRN normal range was established as 40.1 ± 8.7 ng/ml. In the serum and synovial fluid of RA patients, PGRN levels were higher than those in OA patients. Serum PGRN levels may be a useful biomarker in RA disease.

Conflict of Interest

The authors declare that there are no conflicts of interest.

Funding Statements

This works was supported by Grant-in-Aid from the Ministry of Education, Science and Culture of Japan (to K. Saito 23390149) and (to Y. Yamamoto 23790621).

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Correspondence to Yasuko Yamamoto.

ELECTRONIC SUPPLEMENTARY MATERIAL

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Supplemental Table 1

Correlation between PGRN and various clinical parameters in healthy individuals. (PDF 19 kb)

Supplemental Table 2

Correlation between PGRN and clinical characteristics of RA. (PDF 6 kb)

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Yamamoto, Y., Takemura, M., Serrero, G. et al. Increased Serum GP88 (Progranulin) Concentrations in Rheumatoid Arthritis. Inflammation 37, 1806–1813 (2014). https://doi.org/10.1007/s10753-014-9911-4

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