Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis.
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.
Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic.
Lucie Andrés
LA
Cerezo
Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic.
Markéta
M
Kuklová
Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic.
Hana
H
Hulejová
Department of Pathology, Third Faculty of Medicine, Charles University, Šrobárova 50, 100 34 Prague 10, Czech Republic.
Zdeňka
Z
Vernerová
Institute of Biophysics and Informatics, First Faculty of Medicine, Charles University, Salmovská 1, 120 00 Prague 2, Czech Republic.
Nikola
N
Kaspříková
First Orthopaedic Clinic, First Faculty of Medicine, Charles University, V Úvalu 84, 150 06 Prague 5, Czech Republic.
David
D
Veigl
Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic ; Department of Rheumatology, First Faculty of Medicine, Charles University, Na Slupi 4, 128 50 Prague 2, Czech Republic.
Karel
K
Pavelka
Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic ; Department of Rheumatology, First Faculty of Medicine, Charles University, Na Slupi 4, 128 50 Prague 2, Czech Republic.
Jiří
J
Vencovský
Institute of Rheumatology, Na Slupi 4, 12850 Prague 2, Czech Republic ; Department of Rheumatology, First Faculty of Medicine, Charles University, Na Slupi 4, 128 50 Prague 2, Czech Republic.
Ladislav
L
Šenolt
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000077153:Progranulins; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D002097:C-Reactive Protein