Local Synovial Engagement of Angiogenic TIE‐2 Is Associated With the Development of Persistent Erosive Rheumatoid Arthritis in Patients With Early Arthritis. Issue 12 (December 2013)

• Record Type: Journal Article
• Authors: van de Sande, Marleen G. H.; de Launay, Daphne; de Hair, Maria J. H.; García, Samuel; van de Sande, Gijs P. M.; Wijbrandts, Carla A.; Gerlag, Danielle M.; Reedquist, Kris A.; Tak, Paul P.
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 12(2013:Dec.)
• Page Start: 3073
• Page End: 3083
• Publication Date: 2013-12
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.38128
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38128-sec-0001" sec-type="section"> <title>Objective</title> <p>To examine the role of vascular endothelial growth factor (VEGF) and angiopoietin signaling in the diagnosis and disease outcome of patients with early arthritis.</p> </sec> <sec id="art38128-sec-0002" sec-type="section"> <title>Methods</title> <p>Fifty patients with early arthritis (disease duration <1 year) who had not been treated with disease‐modifying antirheumatic drugs (DMARDs) were monitored prospectively and were classified at baseline and after 2 years as having undifferentiated arthritis (UA), rheumatoid arthritis (RA), or spondyloarthritis (SpA). All patients underwent arthroscopic synovial biopsy at baseline. Synovial expression of VEGF, VEGF receptor, angiopoietin 1 (Ang‐1), Ang‐2, TIE‐2, and activated p–TIE‐2 was evaluated by immunohistochemistry. Serum levels of VEGF, Ang‐1, and Ang‐2 were measured by enzyme‐linked immunosorbent assay. Secreted products of macrophages stimulated with Ang‐1 and Ang‐2 were measured using a multiplex system.</p> </sec> <sec id="art38128-sec-0003" sec-type="section"> <title>Results</title> <p>Expression of Ang‐1 was comparable between the patients with RA at baseline and patients with UA who fulfilled the criteria for RA over time (UA/RA), and it was significantly higher in patients with RA (<italic>P</italic> < 0.05) or UA/RA (<italic>P</italic> < 0.005) than in patients with SpA. TIE‐2 and p–TIE‐2 were more highly expressed in patients with RA (<italic>P</italic> < 0.005) or UA/RA (<italic>P</italic> < 0.05) than in patients with SpA. Ang‐1 significantly enhanced the tumor necrosis factor–dependent macrophage production of cytokines and chemokines that are known to be elevated in the synovial fluid of patients with early RA. In RA, relative TIE‐2 activation predicted the development of erosive disease (R<sup>2</sup> = 0.35, <italic>P</italic> < 0.05).</p> </sec> <sec id="art38128-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Local engagement of synovial TIE‐2 is observed during the earliest phases of RA, suggesting that TIE‐2 signaling may contribute to disease development and progression or may indicate an attempt to protect against these processes. Early therapeutic targeting of TIE‐2 signaling may be useful in improving outcome in arthritis.</p> </sec> </abstract>