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. 2015:2015:740357.
doi: 10.1155/2015/740357. Epub 2015 Aug 3.

Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis

Lucie Andrés Cerezo  1 , Markéta Kuklová  1 , Hana Hulejová  1 , Zdeňka Vernerová  2 , Nikola Kaspříková  3 , David Veigl  4 , Karel Pavelka  5 , Jiří Vencovský  5 , Ladislav Šenolt  5
Affiliations

Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis

Lucie Andrés Cerezo et al. Mediators Inflamm. 2015.

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.

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Figures

Figure 1
Figure 1
Detection of progranulin (PGRN) protein in rheumatoid arthritis (RA) synovial tissues (a1) and osteoarthritis synovial tissues (b1). Strong staining intensity for PGRN was observed in the lining layer and particularly in the mononuclear cell infiltrates of the sublining layer of RA synovial tissue. Vessels and capillaries were positive for PGRN in both RA and OA synovial tissues. Mouse IgG was used as an isotype control (a2, b2). The original magnification is 200x.
Figure 2
Figure 2
Progranulin (PGRN) levels in the synovial fluid, but not in the serum, were significantly higher in rheumatoid arthritis (RA) compared with osteoarthritis (OA) patients. Serum PGRN was significantly elevated in RA and OA patients compared to healthy controls (HC). The concentration of PGRN in patients with RA was significantly higher in synovial fluid compared to serum. Data are expressed as mean. ∗ P < 0.01, ∗∗ P < 0.001.
Figure 3
Figure 3
Association of serum PGRN levels with DAS28-CRP (a) and HAQ (b) in patients with rheumatoid arthritis (RA). DAS28: Disease Activity Score; HAQ: Health Assessment Questionnaire score.
See this image and copyright information in PMC

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