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

Nicola Goodfellow, Julien Morlet, Surjeet Singh, Afsie Sabokbar, Andrew Hutchings, Vanshika Sharma, Jana Vaskova, Shauna Masters, Allahdad Zarei, Raashid Luqmani, Nicola Goodfellow, Julien Morlet, Surjeet Singh, Afsie Sabokbar, Andrew Hutchings, Vanshika Sharma, Jana Vaskova, Shauna Masters, Allahdad Zarei, Raashid Luqmani

Abstract

Objectives: To 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.

Methods: We 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.

Results: The 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.

Conclusions: Serum 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 number: NCT00974883; Post-results.

Keywords: Giant Cell Arteritis; Inflammation; Systemic vasculitis.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Distribution of patients amongst diagnostic groups in this study. TAB=temporal artery biopsy, US=temporal artery ultrasound, +=positive result compatible with GCA, −=negative result.
Figure 2
Figure 2
A. Serum VEGF is raised in patients with biopsy-proven GCA compared to controls at week 0, but this is not seen at any other time-point; B. Serum VEGF concentration is not dependent on duration of glucocorticoid therapy at the point of serum sampling. Graphs show mean ±SEM, significance tested with Mann-Whitney U test with Bonferroni correction; C. The receiver-operating characteristic curve for VEGF concentration at week 0 generates an optimal cut off of 713pg/ml
Figure 3
Figure 3
VEGF concentration at week 0 is significantly raised in biopsy-proven GCA (TAB+) but not in Ultrasound-positive (US+) GCA or in clinical diagnoses of GCA. Graph shows mean ± 95% CI. Significance tested with Mann-Whitney U test with Bonferroni correction.
Figure 4
Figure 4
Mild or moderate positive correlation between measurements of A. VEGF and ESR, B. VEGF and CRP at week 0.
Figure 5
Figure 5
VEGF is upregulated in the arterial wall of patients with biopsy-proven GCA but not in controls. Representative images of VEGF immunohistochemistry, all taken at 10× magnification. A–C from control patient; A. H&E, B. control IgG, C. αVEGF; arrow=tunica adventitia. D–F from GCA patient; D. H&E, E. control IgG, F. αVEGF; arrow=internal elastic lamina
Figure 6
Figure 6
Pentraxin 3 concentrations in the plasma of biopsy-positive GCA patients and controls are indistinguishable at weeks 0, 2, and 26. Graph shows mean ± SEM.

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