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

Abstract

ObjectivesTo assess the performance of circulating vascular endothelial growth factor (VEGF) levels as a tool for diagnosing giant cell arteritis (GCA) in a cohort of patients referred for assessment of suspected GCA.MethodsWe selected 298 patients recruited to the multicentre study Temporal Artery Biopsy versus Ultrasound in diagnosis of suspected GCA (TABUL). In a random subset of 26 biopsy-proven GCA cases and 26 controls, serum from weeks 0, 2 and 26 was analysed for VEGF concentration using ELISA. VEGF concentration at week 0 was used to generate a receiver-operating characteristic curve and thereby identify a cut-off for an abnormal result which was used to analyse the full patient cohort. Sections of paraffin-embedded temporal artery were stained by immunohistochemistry for VEGF.ResultsThe mean (95% CI) VEGF concentration at week 0 was 873 pg/mL (631 to 1110) in 26 patients versus 476 pg/mL (328 to 625) in 26 controls (p=0.017). This difference was not observed at any other time point. The optimal cut-off of 713 pg/mL was applied to the whole patient cohort (n=298), yielding sensitivity of 32% and specificity of 85%. This was not improved by combination with any clinical parameters. When patients with biopsy-proven GCA were compared with controls, sensitivity was 58% and specificity remained 85%. Sections of biopsy from biopsy-positive GCA showed intense staining in the adventitia which was not seen in controls.ConclusionsSerum VEGF concentration predicts biopsy positivity but is not useful for differentiating clinical cases of GCA from controls. Further studies into VEGF as a prognostic marker and therapeutic target are warranted.Trial registration numberNCT00974883; Post-results.

Limited utility of novel serological biomarkers in patients newly suspected of having giant cell arteritis

“…Pentraxin 3 has been proposed as a useful biomarker in GCA due to the fact that it is both an acute phase reactant and is elevated in non‐inflammatory vascular injury states and atherosclerosis 14,24 . Our negative results are in keeping with the findings of Goodfellow et al which required serum to be collected within 7 days of corticosteroids 9 . It contrasts with the positive findings of an earlier cohort of long‐term GCA patients where pentraxin 3 levels were higher for GCA than healthy controls and rheumatoid arthritis patients 14 …”

“…A number of studies have found VEGF to be elevated in GCA patients and those with rheumatic diseases 25 compared with normal controls 9,14 . VEGF is a growth factor that stimulates angiogenesis in chronic inflammatory states and promotes the migration of monocytes and lymphocytes into the extracellular matrix 8,26 .…”

“…These stimulate and/or are released from endothelial and vascular smooth muscle cells in response to vascular injury or chronic inflammation 8 . They include vascular endothelial growth factor (VEGF), 9 von Willebrand factor (vWF), 10‐12 soluble intra‐cellular adhesion molecule (ICAM)1 13 and pentraxin 3 14 …”

Markers of angiogenesis and macrophage products for predicting disease course and monitoring vascular inflammation in giant cell arteritis

“…Our findings highlight the importance of new vessel formation at the site of inflammation in GCA to fuel the ongoing inflammatory process and are in line with previous studies reporting on elevated levels of VEGF in GCA. However, these studies did not investigate this marker in longitudinal follow-up studies [25, 30, 31].…”

“…During inflammation, monocytes/macrophages also release calprotectin, sCD163 and YKL-40 [22–24]. Inflamed GCA vessels are characterized by new vessel formation involving VEGF, angiopoietin-1 and -2 and sTie2 as key regulators in this process [25–27].…”