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. 1998 Aug;57(8):480–486. doi: 10.1136/ard.57.8.480

A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers

D Elewaut 1, F De Keyser 1, N De Wever 1, D Baeten 1, N Van Damme 1, G Verbruggen 1, C Cuvelier 1, E Veys 1
PMCID: PMC1752727  PMID: 9797554

Abstract

OBJECTIVES—(1)To analyse the in situ expression of adhesion molecules in rheumatoid nodules. (2) To compare the endothelial expression of adhesion molecules in synovial tissue and subcutaneous nodules obtained from the same patients. (3) To compare the expression of adhesion molecules and activation markers on T cell lines from nodules and synovium.
METHODS—(1) Immunohistochemical analysis by APAAP technique of E selectin, CD44, ICAM-1, PECAM-1, and VCAM-1 was performed on 10 rheumatoid nodules from seven patients with rheumatoid arthritis (RA); nodules and synovium were simultaneously analysed from three patients. (2) T cell lines were generated from RA nodules (n=7) and synovium (n=7) by interleukin 2 expansion, and subsequently characterised by flow cytometry for surface expression of αEβ7, α4β7, CD44, L selectin, LFA-1a, PECAM-1, and CD30.
RESULTS—(1) In rheumatoid nodules, the palisading layer strongly stains for ICAM-1 and PECAM-1, but less pronounced for CD44. VCAM-1 staining was usually negative. ICAM-1 is upregulated in the vessels surrounding the central zone of fibrinoid necrosis. The immunohistological picture in different nodules derived from the same patient was similar. (2) The endothelial expression of adhesion molecules is comparable in RA nodules and synovium on an individual level, except for E selectin, which is overexpressed in nodule endothelium. (3) T cell lines from nodules and synovium display similar adhesion molecule profiles. However, the expression of CD30, a T cell activation marker linked with Th2 subsets, is higher in nodules compared with synovium.
CONCLUSION—These data support a recirculation hypothesis of T cells between articular and extra-articular manifestations in RA, although the activation state of the T cells in each of these localisations may differ.

 Keywords: T cells; adhesion molecules; rheumatoid nodules; rheumatoid synovium

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Figure 1  .

Figure 1  

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Immunostaining of an early onset rheumatoid nodule (removal two weeks after appearance) for PECAM-1. Note impressive vascularisation in the absence of fibrinoid necrosis. Bar=100 µm.

Figure 2  .

Figure 2  

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Rheumatoid nodules stained for PECAM-1 (A), ICAM-1 (B), E-selectin (C), VCAM-1 (D,E), and CD44 (F). Single staining using APAAP technique counterstained with haematoxylin. A-D: bar=200 µm; E-F: bar=100 µm.

Figure 3  .

Figure 3  

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Endothelial expression of PECAM-1 (A, C) and ICAM-1 (B, D) in a rheumatoid nodule (A, B) and rheumatoid synovium (C, D). Single staining using APAAP technique counterstained with haematoxylin. Bar=100 µm.

Figure 4  .

Figure 4  

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Endothelial expression of E-selectin (A) and VCAM-1 (B) in a rheumatoid nodule. Single staining using APAAP technique counterstained with haematoxylin. Bar=100 µm.

Figure 5  .

Figure 5  

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Endothelial expression of adhesion molecules in simultaneously obtained rheumatoid nodules and rheumatoid synovium of three patients with rheumatoid arthritis. Data represent semiquantitative scores on endothelium.

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