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Original article
Is vascular endothelial growth factor a useful biomarker in giant cell arteritis?
  1. Nicola Goodfellow1,
  2. Julien Morlet1,
  3. Surjeet Singh2,
  4. Afsie Sabokbar1,
  5. Andrew Hutchings3,
  6. Vanshika Sharma1,
  7. Jana Vaskova1,
  8. Shauna Masters1,
  9. Allahdad Zarei4 and
  10. Raashid Luqmani1
  11. the TABUL Investigators
    1. 1Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
    2. 2Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
    3. 3London School of Hygiene and Tropical Medicine, London, UK
    4. 4Botnar Research Centre, University of Oxford, Oxford, UK
    1. Correspondence to Professor Raashid Luqmani; raashid.luqmani{at}ndorms.ox.ac.uk

    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.

    • Giant Cell Arteritis
    • Systemic vasculitis
    • Inflammation

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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    Footnotes

    • Collaborators TABUL Investigators; Ellen Lee; Amanda Loban; Christopher Ellis; Mike Gillett; Mike Bradburn; Wolfgang Schmidt; Bhaskar Dasgupta; Andreas Diamantopoulos; Eugene McNally; Jennifer Piper; Wulf Forrester-Barker; Willie Hamilton; Brendan McDonald; Colin Pease; John Salmon; Allan Wailoo; Konrad Wolfe; Keri Fathers; Leo Marcus-Wan; Nicola Farrar; Varun Manhas; Connor Scott; Nicky Sullivan; Denise Brown; Gareth Bicknell; Karolina Kliskey; David Gray; Samiya Mahmood; Ann-Marie Morgan; Ifzal Ahmed; Michael Ehrenstein; Bleddyn Davies; Karim Raza; David Mant; Lyn Williamson; Kate Gilbert; Simon Travis; Jonathan Sterne; Colin Pease; David Carruthers; Rainer Klocke; Vadivelu Saravanan; Damodar Makkuni; Ruth Geraldes; Andreas Diamantopoulos; Thomas Neumann; Adrian Pendleton; Khalid Ahmed; Richard Hull; Kuntal Chakravarty; Peter Lanyon; Antoni Chan; Nicholas Raj; Frances Borg; Eamonn Molloy; Malgorzata Magliano; David Wright.

    • Contributors NG designed, executed and analysed the ELISA work and prepared the manuscript. JM conducted pilot experiment upon which the work is based and executed the immunohistochemistry with AZ. SS was the trial coordinator for the parent TABUL study. AS supervised JM and provided scientific design and expertise, and edited the manuscript. AH was the statistician for parent TABUL study, also helped with statistics for this study. VS helped to coordinate sample collection and storage. JV took over from SS as TABUL trial coordinator. SM was the research nurse for parent TABUL study, and helped coordinate sample collection and storage. AZ helped JM with immunohistochemistry. RL was the principal investigator for TABUL, was supervisor for NG, and was involved in design of work and editing of manuscript.

    • Funding This work was supported by the HTA (grant number 08/64/01 to RL), the Oxfordshire Health Research Services Committee (grant number 1175 to NG) and the NIHR (Academic Clinical Fellowship to NG).

    • Competing interests None declared.

    • Ethics approval Ethics approval was obtained from Berkshire Research Ethics Committee (09/H0505/132).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement No additional data are available.

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