Selective up-regulation of the soluble pattern-recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: Relevance for recent optic nerve ischemia

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 64; no. 3; pp. 854 - 865
• Main Authors: Baldini, Mattia, Maugeri, Norma, Ramirez, Giuseppe A., Giacomassi, Chiara, Castiglioni, Alessandra, Prieto-González, Sergio, Corbera-Bellalta, Marc, Comite, Gabriele Di, Papa, Ilenia, Dell'Antonio, Giacomo, Ammirati, Enrico, Cuccovillo, Ivan, Vecchio, Viviana, Mantovani, Alberto, Rovere-Querini, Patrizia, Sabbadini, Maria Grazia, Cid, Maria C., Manfredi, Angelo A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2012; Wiley; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; C-Reactive Protein - analysis; C-Reactive Protein - biosynthesis; Cytokines - metabolism; Diseases of the osteoarticular system; Diseases of visual field, optic nerve, optic chiasma and optic tracts; Female; Giant Cell Arteritis - complications; Giant Cell Arteritis - diagnosis; Giant Cell Arteritis - metabolism; Humans; Interferon; Ischemia; Male; Medical sciences; Middle Aged; Ophthalmology; Optic nerve; Optic Neuropathy, Ischemic - diagnosis; Optic Neuropathy, Ischemic - etiology; Optic Neuropathy, Ischemic - metabolism; Proteins; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Serum Amyloid P-Component - analysis; Serum Amyloid P-Component - biosynthesis; Temporal Arteries - metabolism; Temporal Arteries - pathology; Up-Regulation; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - blood; Vascular disease; Eye disease; Nervous system diseases; Cranial nerve disease; Vasculitis; Vascular endothelium growth factor; Systemic disease; Rheumatology; Cardiovascular disease; Giant cell arteritis; Optic nerve ischemia
• ISSN: 0004-3591; 2326-5191; 1529-0131; 2326-5205
• DOI: 10.1002/art.33411

Objective
To assess local expression and plasma levels of pentraxin 3 (PTX3) in patients with giant cell arteritis (GCA).
Methods
Plasma and serum samples were obtained from 75 patients with GCA (20 of whom had experienced optic nerve ischemia in the previous 3 weeks and 24 of whom had experienced symptom onset in the previous 6 months and had no history of optic nerve ischemia) and 63 controls (35 age‐matched healthy subjects, 15 patients with rheumatoid arthritis, and 13 patients with chronic stable angina). In 9 patients in whom GCA was recently diagnosed, circulating levels of interleukin‐1β (IL‐1β), IL‐2, IL‐4, IL‐6, IL‐7, IL‐8, IL‐10, IL‐12p70, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1α (MIP‐1α), CCL4/MIP‐1β, CCL11/eotaxin, CXCL9/monokine induced by interferon‐γ, CXCL10/interferon‐γ–inducible 10‐kd protein, tumor necrosis factor α (TNFα), interferon‐γ, vascular endothelial growth factor (VEGF), granulocyte–macrophage colony‐stimulating factor, and FasL were measured via a multiplexed cytometric assay. PTX3 and VEGF concentrations were assessed by enzyme‐linked immunosorbent assay. PTX3 and CD68 expression were determined by immunohistochemistry and immunofluorescence on temporal artery samples.
Results
GCA patients with very recent optic nerve ischemia had significantly higher PTX3 and VEGF levels compared to other GCA patients and controls. GCA patients with a disease duration of <6 months had significantly higher PTX3 levels compared to other GCA patients and controls. Immunohistochemistry revealed selective PTX3 expression in the wall of inflamed arteries.
Conclusion
Our findings indicate that local expression of PTX3 is a feature of vascular inflammation in GCA; elevated circulating levels of PTX3 identify patients with very recent optic nerve ischemia or a recent diagnosis. Optic nerve ischemia is also associated with increased circulating VEGF levels.