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Article type: Research Article
Authors: Hetland, Merete Lund | Christensen, Ib Jarle | Lottenburger, Tine | Johansen, Julia Sidenius | Svendsen, Mads Nordahl | Hørslev-Petersen, Kim | Nielsen, Lone | Jørgen Nielsen, Hans
Affiliations: Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark | Department of Surgical Gastroenterology, Copenhagen University Hospital, Hvidovre, Denmark | Rheumatism Hospital, University of Southern Denmark, Gråsten, Denmark | Department of Rheumatology, Copenhagen University Hospital, Herlev, Denmark | Department of Clinical Immunology, Nykøbing Falster Hospital, Denmark
Note: [] Corresponding author: Merete Lund Hetland, MD, PHD, Department of Rheumatology 232, Copenhagen University Hospital at Hvidovre, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. Tel.: +45 36322277; Fax: +45 36471410; E-mail: merete.hetland@dadlnet.dk
Abstract: 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.
Keywords: Rheumatoid arthritis, vascular endothelial growth factor, exercise, biological marker
Journal: Disease Markers, vol. 24, no. 1, pp. 1-10, 2008
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