Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis.

Lucie Andrés Cerezo,David Veigl,Markéta Kuklová,Hana Hulejová,Karel Pavelka,Ladislav Šenolt,Nikola Kaspříková,Zdeňka Vernerová,Jiří Vencovský

doi:10.1155/2015/740357

Lucie Andrés Cerezo, David Veigl + Show 7 more

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https://doi.org/10.1155/2015/740357

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Abstract

Objective. Progranulin (PGRN) is implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to assess the relationship between PGRN and disease activity in RA. Methods. PGRN levels were evaluated in patients with RA (n = 47) and OA (n = 42) and healthy controls (n = 41). Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP), disease activity score (DAS28-CRP), and health assessment questionnaire (HAQ) was studied. Results. Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1 ± 100.2 and 221.5 ± 102.5 versus 128.1 ± 34.7 ng/mL; P < 0.001). Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5 ± 275.3 versus 241.4 ± 165.2 ng/mL; P = 0.002). PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r = 0.327, P = 0.049) and HAQ score (r = 0.323, P = 0.032), while synovial fluid PGRN correlated only with HAQ (r = 0.310, P = 0.043) in patients with RA. PGRN levels were not associated with CRP or autoantibodies. Conclusions. This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA.

Highlights

Progranulin (PGRN), known as granulin epithelin precursor (GEP), PC-cell-derived growth factor (PCDGF), proepithelin, or acrogranin, is an 80 kDa glycoprotein originally identified as an autocrine growth factor for cancer cells and fibroblasts [1]
PGRN inhibits, whereas granulins stimulate, the production of neutrophil attracting chemokines, which is neutralized by its degradation on granulins by serine proteases NE and PR3 released by neutrophils and macrophages [5, 6]
The expression of PGRN was detected in both rheumatoid arthritis (RA) and OA synovial tissues; the staining intensity was significantly enhanced in patients with RA (Figure 1)

Summary

Introduction

Progranulin (PGRN), known as granulin epithelin precursor (GEP), PC-cell-derived growth factor (PCDGF), proepithelin, or acrogranin, is an 80 kDa glycoprotein originally identified as an autocrine growth factor for cancer cells and fibroblasts [1]. PGRN is abundantly expressed in rapidly cycling epithelial cells, leukocytes, chondrocytes, and neurons [2] and is involved in biological processes such as embryogenesis [2], tumorigenesis [1, 3] and wound healing [4], inflammation [5, 6], host defense [7], and cartilage development and degradation [8,9,10]. PGRN inhibits, whereas granulins stimulate, the production of neutrophil attracting chemokines, which is neutralized by its degradation on granulins by serine proteases NE and PR3 released by neutrophils and macrophages [5, 6]. Mice lacking PGRN respond to infection with exaggerated inflammation and PGRN-deficient macrophages challenged with microbial LPS upregulate the production of proinflammatory cytokines [7]

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