Elsevier

Joint Bone Spine

Volume 68, Issue 6, December 2001, Pages 493-498
Joint Bone Spine

ORIGINAL ARTICLE
Does vascular endothelial growth factor in the rheumatoid synovium predict joint destruction? A clinical, radiological, and pathological study in 12 patients monitored for 10 years

https://doi.org/10.1016/S1297-319X(01)00313-XGet rights and content

Abstract

Objective. Synovial angiogenesis is at the epicenter of rheumatoid pannus development and is largely dependent on vascular endothelial growth factor (VEGF). We sought to determine whether the VEGF level in rheumatoid synovial tissue is a marker for disease severity. Patients and methods. Twelve patients with rheumatoid arthritis (RA) underwent a clinical and radiological evaluation at the time of a synovial biopsy done during joint surgery required by RA progression (T1) and, on average, 10 years later (T2). Immunohistochemistry was used to detect and quantitate VEGF in the synovial biopsy taken at T1. Results. VEGF labeling was seen on endothelial cells and macrophages in all 12 synovial biopsies. The amount of endothelial-cell VEGF labeling (assessed semi-quantitatively) was significantly correlated with Larsen score progression during the 10-year follow-up. The amounts of endothelial cell or macrophage VEGF labeling was not correlated with the joint count, radiological stage of the biopsied joint or progression of this stage, Larsen scores at T1 or T2, presence of rheumatoid factor, or presence of extra-articular manifestations. Conclusion. Our results suggest that the amount of VEGF in the rheumatoid synovium may be a marker for joint destruction in patients with RA.

Section snippets

Study design

We retrospectively reviewed clinical, radiological, and pathological data from 12 RA patients from whom synovial membrane biopsies had been harvested during surgery for rheumatoid joint lesions (at time-point T1). These biopsies were preserved. A technique for detecting intrasynovial VEGF became available about 10 years later. This technique was used to examine the biopsies (time-point T2).

Patients

All 12 patients met American College of Rheumatology criteria for RA. There were ten women and two men,

Results

Table I reports all findings at T1 and T2.

The joint count and radiological score increased from T1 to T2 in all patients. Mean increases were 8 for the joint count and 48.2 for the Larsen score (see table I). All synovial biopsies (collected at T1) showed florid, active synovitis typical of progressive RA (figure 1). VEGF labeling of macrophages and endothelial cells was a consistent finding (figure 3 and 4). All specimens in the ‘diffuse macrophage labeling’ category showed strong endothelial

Discussion

VEGF (or vascular permeability factor, VPF) is a pro-angiogenic factor that has been studied in many angiogenesis-dependent conditions. VEGF is produced by various cell types including macrophages, mastocytes, fibroblasts, keratinocytes, and smooth muscle cells. Neutrophils contain VEGF stores available for immediate release 〚5〛. Endothelial cells do not produce VEGF but carry receptors for VEGF. VEGF production is increased by hypoxia and by certain cytokines, including angiogenesis growth

References (28)

  • M. De Bandt et al.

    Suppression of arthritis and protection from bone destruction by treatment with TNP-470/AGM1470 in a transgenic mouse model of rheumatoid arthritis

    Arthritis Rheum

    (2000)
  • E.M. Paleolog et al.

    Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis

    Arthritis Rheum

    (1998)
  • M. Harada et al.

    Vascular endothelial growth factor in patients with rheumatoid arthritis

    Scand J Rheumatol

    (1998)
  • K. Kikuchi et al.

    Serum concentrations of vascular endothelial growth factor in collagen diseases

    Br J Dermatol

    (1998)
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