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

Abstract

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-1␤ (IL-1␤), IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12p70, CCL2/monocyte chemotactic protein 1, CCL3/macrophage inflammatory protein 1␣ (MIP-1␣), CCL4/MIP-1␤, CCL11/eotaxin, CXCL9/ monokine induced by interferon-␥, CXCL10/interferon-␥-inducible 10-kd protein, tumor necrosis factor ␣ (TNF␣), interferon-␥, vascular endothelial growth factor (VEGF), granulocyte-macrophage colonystimulating 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.

Is vascular endothelial growth factor a useful biomarker in giant cell arteritis?

“…This was surprising given that Baldini et al reported a sixfold upregulation of pentraxin-3 in GCA compared with healthy controls or controls with rheumatoid arthritis. 8 Concentration of pentraxin-3 in controls for this study (3.35 ng/mL) was similar to Baldini et al (3.97 ng/mL) but concentration in GCA patients (5.48 ng/mL) was significantly lower than in Baldini et al (23.3 ng/mL). This suggests that the groups of GCA patients in the two studies are different.…”

“…15 The main source of VEGF is CD68 macrophages and giant cells within the vessel wall, 15 16 and this local production of VEGF is mirrored by raised serum levels of VEGF in patients with GCA compared with controls. 8 Furthermore, allelic variants in VEGF confer different susceptibility to development of GCA 17 18 and certain polymorphisms are associated with increased risk of ischaemic complications. 18 19 VEGF may function in GCA either to compensate for ischaemia in the thickened artery, 20 or to drive inflammation by increasing new blood vessels which are the primary expressers of adhesion molecules involved in recruitment of inflammatory cells.…”

“…8 Pentraxins are members of the acute phase reactant superfamily. Pentraxin-3 is synthesised in response to vascular injury, 9 and levels correlate with disease activity in small-vessel vasculitides.…”

Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients

“…The number of patients diagnosed with GCA by 2050 is projected to be over 3 million in Europe, North America, and Oceania, representing a significant clinical and financial challenge [8]. Several previous reports have described potential serological markers for GCA [9][10][11][12][13][14][15][16][17][18], among them cytokines, chemokines, growth factors, cell adhesion molecules, and matrix metalloproteinases (MMPs). In 2000, Weyand et al emphasized that interleukin (IL)-6 may act as a biological marker of GCA activity in untreated and treated GCA patients [19].…”

T Cell–Macrophage Interactions and Granuloma Formation in Vasculitis

“…Accordingly, serum IL-6 and IL-1β levels have been found strongly increased in patients with active GCA (74, 99) and associated with disease activity (100, 101). While the precise cellular source of the excess IL-6 and IL-1β has not been determined, highly activated macrophages and DC in the vasculitic lesions emerge as the likely producers (102).…”