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Biomarkers of Inflammation in Patients with Unclassified Polyarthritis and Early Rheumatoid Arthritis. Relationship to Disease Activity and Radiographic Outcome

LENE S. KNUDSEN, METTE KLARLUND, HENRIK SKJØDT, TRINE JENSEN, MIKKEL ØSTERGAARD, KARL ERIK JENSEN, MICHAEL S. HANSEN, MERETE L. HETLAND, HANS J. NIELSEN, and JULIA S. JOHANSEN

ABSTRACT.

Objective. To determine plasma interleukin 6 (pIL-6), plasma vascular endothelial growth factor (pVEGF), and serum (s) YKL-40 in patients with early rheumatoid arthritis (RA) and unclassified polyarthritis (PA), and investigate their relationship with radiographic outcome.

Methods. pIL-6 and pVEGF were determined by ELISA and sYKL-40 by an in-house radioimmunoassay in 51 patients with early RA and 21 with PA. Patients were followed with clinical and biochemical measurement every month for 2 years. Conventional radiographs of hands, wrists, and forefeet were scored according to the Larsen method, and magnetic resonance imaging of 2nd to 5th metacarpophalangeal joints of the dominant hand were evaluated for presence or absence of bone erosions.

Results. Baseline pIL-6, pVEGF, sYKL-40, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were elevated in RA patients compared to healthy persons (p < 0.001), but were not in patients with PA. Patients with early RA had higher pIL-6 (p = 0.007), pVEGF (p = 0.02), and sYKL-40 (p = 0.024) compared to PA patients. pIL-6, sYKL-40, CRP, and ESR but not pVEGF decreased in patients that responded to treatment after 2 years. The mean value of pIL-6 during the first and second year were higher in patients with early RA with progression in bone erosions (n = 14) compared to early RA patients without progression (n = 30; first year 8.4 vs 2.8 ng/l, p = 0.04; second year 6.1 vs 3.6 ng/l, p = 0.03).

Conclusion. Plasma IL-6 was the only biomarker related to treatment response and progressive erosive disease in patients with early RA, but it may not give additional information compared to CRP in relation to disease activity and treatment response. (First Release June 15 2008; J Rheumatol 2008;35:1277–87)

Key Indexing Terms:

BIOMARKERS
EARLY RHEUMATOID ARTHRITIS
INTERLEUKIN 6
YKL-40
UNCLASSIFIED POLYARTHRITIS
VASCULAR ENDOTHELIAL GROWTH FACTOR

From the Department of Rheumatology, Herlev Hospital, University of Copenhagen; Departments of Rheumatology and Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen; and Department of Radiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Supported by grants from Dagmar Marshalls Foundation, The Danish Rheumatism Association, Direktør Jacob Madsens and Hustru Olga Madsens Fond, Direktør Jens Aage Sørensens og Hustru Edith Ingeborg Sørensens Mindefond, Foundation for the Advancement of Medical Science, Karen Marie Jørgensen and datters legat, Michaelsen Fonden, and The Research Foundation of Copenhagen Council.

L.S. Knudsen, MD; M. Klarlund, MD, PhD, Department of Rheumatology, Herlev Hospital; T. Jensen, MD, PhD, Department of Rheumatology, Hvidovre Hospital; M. Østergaard, MD, PhD, DMSc, Professor, Department of Rheumatology, Herlev Hospital, Department of Rheumatology, Hvidovre Hospital; K.E. Jensen, MD, DMSc, Department of Radiology, Rigshospitalet; M.S. Hansen, MD, PhD, Department of Rheumatology, Herlev Hospital; M.L. Hetland, MD, PhD, Department of Rheumatology, Hvidovre Hospital; H.J. Nielsen, MD, DMSc, Professor, Department of Surgical Gastroenterology, Hvidovre Hospital; H. Skjødt, MD, PhD, Department of Rheumatology, Hvidovre Hospital; J.S. Johansen, MD, DMSc, Department of Rheumatology, Herlev Hospital.

Address reprint requests to Dr. L.S. Knudsen, Department of Rheumatology Q107, Herlev Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. E-mail: surland@dadlnet.dk

Accepted for publication January 30, 2008.