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Disease Markers
Volume 24, Issue 1, Pages 1-10

Circulating VEGF As a Biological Marker in Patients with Rheumatoid Arthritis? Preanalytical and Biological Variability in Healthy Persons and in Patients

Merete Lund Hetland,1 Ib Jarle Christensen,2 Tine Lottenburger,3 Julia Sidenius Johansen,4 Mads Nordahl Svendsen,2 Kim Hørslev-Petersen,3 Lone Nielsen,5 and Hans Jørgen Nielsen2

1Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark
2Department of Surgical Gastroenterology, Copenhagen University Hospital, Hvidovre, Denmark
3Rheumatism Hospital, University of Southern Denmark, Gråsten, Denmark
4Department of Rheumatology, Copenhagen University Hospital, Herlev, Denmark
5Department of Clinical Immunology, Nykøbing Falster Hospital, Denmark

Received 21 November 2007; Accepted 21 November 2007

Copyright © 2008 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background: Soluble vascular endothelial growth factor (VEGF) is a promising biomarker in monitoring rheumatoid arthritis (RA), but studies of pre-analytical and biologic variability are few.

Methods: VEGF was measured by ELISA methods in serum and plasma from healthy persons and RA patients. Pre-analytical factors were investigated. A reference interval for VEGF was established in serum and plasma from 306 healthy persons. Diurnal, day-to-day, week-to-week, long-term variability, and impact of exercise were evaluated.

Results: Delayed processing time, room temperature, low centrifugal force and contamination of plasma with cellular elements lead to significant increases in VEGF levels, whereas storage for up to 2 years at −80°C or up to 10 freeze/thaw cycles did not affect VEGF levels. Serum VEGF levels were 7–10 fold higher than plasma VEGF levels. Reference intervals for VEGF (plasma: 45 pg/ml (range: non-detectable to 352); serum: 328 pg/ml (53–1791)) were independent of gender and age. Short- and long-term biologic variability included diurnal variation (sampling should take place after 7 AM) and impact of exercise (increased VEGF immediately after bicycling normalised within 1 hour).

Conclusions: Pre-analytical factors and biologic variability including diurnal variation and impact of exercise should be accounted for in future studies that include circulating VEGF as a biological marker.