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. 2004 May;63(5):489–493. doi: 10.1136/ard.2003.012302

Tumour necrosis factor α independent disease mechanisms in rheumatoid arthritis: a histopathological study on the effect of infliximab on rheumatoid nodules

D Baeten 1, F De Keyser 1, E Veys 1, Y Theate 1, F Houssiau 1, P Durez 1
PMCID: PMC1754984  PMID: 15082477

Abstract

Background: It has been suggested that the immunopathology of rheumatoid nodules parallels that of inflamed synovium in rheumatoid arthritis (RA).

Objective: To analyse the effect of infliximab on the immunopathology of rheumatoid nodules in order to provide new insights into the relationship between synovial inflammation and rheumatoid nodules.

Materials and methods: Nodules were present at baseline in six patients with RA and after infliximab treatment in five patients, including paired nodules before and after treatment in three patients. In one patient, the nodule appeared during treatment. Paraffin sections were used for histological analysis. Frozen sections were stained by immunohistochemistry for cellular markers (CD3, CD4, CD8, CD16, CD20, CD68), blood vessels (CD146, vWF, αvß3), and adhesion molecules (E-selectin, VCAM-1, ICAM-1).

Results: No manifest immunopathological differences were found between the nodules before and after infliximab treatment. All nodules depicted the classical structure with a central necrotic zone, surrounding the palisade layer, and an outer connective tissue zone. Immunohistochemistry showed the presence of CD68+ and CD16+ macrophages in the palisade and the connective tissue zone, as well as a small number of CD3+, CD4+ T lymphocytes in the perivascular areas. Small vessels were seen in the connective tissue and were sometimes positive for the neovascularisation marker αvß3. They expressed no VCAM-1, E-selectin weakly, but ICAM-1 strongly. ICAM-1 was also strongly expressed on palisade cells.

Conclusions: Despite an improvement of articular symptoms, infliximab treatment had no distinct effect on the histopathology of rheumatoid nodules, suggesting that different pathogenetic mechanisms mediate the two disease manifestations in RA.

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Figure 1 .

Figure 1

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Immunohistochemical analysis of the effect of infliximab on cellular markers, blood vessels, and adhesion molecules in rheumatoid nodules. The nodules were obtained after 6–24 months of infliximab treatment. (A) Central necrotic zone with palisade layer (original magnification x160); (B) palisade layer with radially orientated mononuclear cells and occasional multinucleated giant cells (original magnification x160); (C) outer connective tissue zone with small blood vessels and perivascular infiltration with lymphocyte-like mononuclear cells (original magnification x160); (D) anti-CD3 staining (original magnification x320); (E) anti-CD68 staining (original magnification x160); (F) anti-CD16 staining (original magnification x160); (G) anti-vWF staining (original magnification x160); (H) anti-αVß3 staining (original magnification x160); (I) anti-ICAM-1 staining (original magnification x160); (J) anti-ICAM-1 staining (original magnification x320).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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