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TNF-alpha independent disease mechanisms in RA: a histopathological study on the effect of Remicade on rheumatoid nodules

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Ann Rheum Dis. 2004 May;63(5):489-493.

Tumour necrosis factor {alpha} independent disease mechanisms in

rheumatoid arthritis: a histopathological study on the effect of

infliximab on rheumatoid nodules.

Baeten D, De Keyser F, Veys EM, Theate Y, Houssiau FA, Durez P.

Department of Rheumatology, 0K12IB, Ghent University Hospital, De

Pintelaan 185, 9000 Gent, Belgium. dominique.baeten@...

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, alphavbeta3), 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 alphavbeta3. 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.

PMID: 15082477

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Mayo Clinic in Rochester

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s Hopkins Medicine

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