PTX3 in small-vessel vasculitides: An independent indicator of disease activity produced at sites of inflammation
✍ Scribed by Fausto Fazzini; Giuseppe Peri; Andrea Doni; Giacomo Dell'Antonio; Elena Dal Cin; Enrica Bozzolo; Francesca D'Auria; Luisa Praderio; Gianfranco Ciboddo; Maria Grazia Sabbadini; Angelo A. Manfredi; Alberto Mantovani; Patrizia Rovere Querini
- Book ID
- 102681708
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 907 KB
- Volume
- 44
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Objective. To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis.
Methods. Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples.
Results. Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions.
Conclusion. PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis.
Small-vessel vasculitis encompasses a group of disorders characterized by inflammatory damage within or through the vessel wall, accompanied by widespread systemic inflammation. In most cases, inflammation is due to immunopathogenic mechanisms (1-3) and primary proinflammatory cytokines. Tumor necrosis factor ␣ (TNF␣) and interleukin-1 (IL-1) in particular contribute to the inflammatory lesions (4), initiating or promoting the activation of endothelial cell and circulating leukocytes. These events in turn impinge on the permeability barrier and the homeostatic function of the vascular endothelium (5), promoting the firm adhesion and the transmigration of leukocytes and the eventual impairment of blood flow and of vessel and tissue integrity. Accordingly, levels of proinflammatory cytokines and their antagonists are elevated in the blood of patients with systemic vasculitis (6,7).
Most patients experience active or quiescent phases during the course of vasculitis. Changes in the erythrocyte sedimentation rate (ESR) and blood concentrations of the short pentraxin C-reactive protein (CRP) are used to monitor the activity of vasculitis. Furthermore, elevations in the ESR and CRP levels