Benvenuti ad Adobe GoLive 6

Inflammatory cell infiltrate and RANKL/OPG expression in rheumatoid synovium: Comparison with other inflammatory arthropathies and correlation with outcome

J.E. Fonseca^1,2, N. Cortez-Dias², A. Francisco², M. Sobral², H. Canhão¹, C. Resende¹, W. Castelão¹, C. Macieira¹, G. Sequeira¹, F. Saraiva¹, J.A. Pereira da Silva¹, M. Carmo-Fonseca², M. Viana Queiroz¹

¹Rheumatology Department, Santa Maria Hospital, Lisbon; ²Rheumatoid Arthritis Unit, Institute
of Molecular Medicine, Faculty of Medicine, University of Lisbon; Lisbon, Portugal.

ABSTRACT
Objectives
To evaluate if the immunofluorescence analysis of synovial tissue (ST) using antibodies against RANKL/OPG, conjugated with the immunophenotyping of lymphocytes and macrophages, could be of diagnostic and prognostic value in rheumatoid arthritis (RA) patients.

Methods
3-year prospective study of 103 consecutive patients submitted to closed needle biopsy for diagnostic purposes. ST was analyzed with routine histologic techniques and immunofluorescence, using monoclonal antibodies against RANKL, OPG, CD163, CD68, CD4, CD8, interferon-g and CD19. Patients were prospectively evaluated with a clinical, laboratorial and radiological protocol. At the end of the follow-up patients were divided according to the final diagnosis. Results of the initial histologic evaluation were compared between the main diagnostic groups and in RA patients histologic data was correlated with clinical and radiologic outcome measures.

Results
The RANKL/OPG ratio and the inflammatory infiltrate were significatively higher in RA (n = 25) as compared to the same ratio observed in other inflammatory joint diseases (OIJD, n = 48) and in osteoarthritis (n = 17). The difference between RA and OIJD was specifically confirmed when the comparison involved spondyloarthropathy (n = 26). Final HAQ score and radiologic outcome were correlated with the density of intimal CD68+ macrophages. Radiologic progression was correlated with subintimal CD4+ lymphocytes and CD68+ macrophages and intimal CD68 and CD163+ macrophages.

Conclusion
The quantification of the RANKL/OPG ratio and of the number of lymphocytes in the ST might be useful to differentiate RA from other inflammatory joint diseases. The ST number of CD4+ lymphocytes and macrophages are probable predictors of radiologic progression in RA patients.

Key words
Rheumatoid arthritis, synovial tissue, RANKL, OPG, prognosis, diagnosis.

This work was supported by a grant from Comissão de Fomento da Investigação em Cuidados da Saúde, Ministério da Saúde P.I. nº 163/01 and by Programa Operacional Ciência Tecnologia Inovação (POCTI), financed by the EU and by national funds of the MCES.
Please address correspondence to: Prof. Dr. J.E. Fonseca, Rheumatoid Arthritis Unit, Institute of Molecular Medicine, Edifício Egas Moniz, Faculty of Medicine, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
E-mail: jefonseca@netcabo.pt