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Published Online First: 25 October 2005. doi:10.1136/ard.2005.037465
Annals of the Rheumatic Diseases 2006;65:713-720
Copyright © 2006 BMJ Publishing Group Ltd & European League Against Rheumatism.

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Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor {alpha} in two patients with early disease and transforming growth factor ß in three more advanced cases

R J François1, L Neure2, J Sieper2, J Braun3

1 Arthritis Research Unit, Queen Astrid Military Hospital, Brussels, Belgium
2 Department of Rheumatology, Berlin Free University, Berlin, Germany
3 Rheumazentrum Ruhrgebiet, Herne, and Ruhr-Universität Bochum, Germany

Correspondence to:
Professor J Braun
Rheumazentrum Ruhrgebiet, Landgrafenstr.15, 44652 Herne, Germany; J.Braun{at}rheumazentrum-ruhrgebiet.de

Objective: To characterise the immunohistological features of sacroiliitis in ankylosing spondylitis (AS) at different disease stages.

Methods: Biopsy samples from sacroiliac joints (SIJs) of five patients with AS, two with early, three with advanced changes and samples from age matched controls from one necropsy SIJ and two iliac bone marrow (BM) biopsies were studied. Paraffin sections were immunostained in triplicate for T cells (CD3, CD8), macrophages (CD68), and the cytokines tumour necrosis factor {alpha} (TNF{alpha}), interferon {gamma}, interleukin (IL) 1ß, IL6, IL10, and transforming growth factor ß1 (TGFß1). Stained cells were counted over one entire high power field (x400) per section in BM, cartilage, and other connective tissue (CT). Results are the mean of three sections.

Results: CD3+ T cells were numerous in the BM of early AS, and in the CT of one patient with early and one with late AS, with variable proportions of CD8+ T cells. All patients with AS had more CD68+ macrophages than controls in BM and CT; in cartilage, one patient with early and one with late AS had increased CD68+ cells, some being osteoclasts. The patient with very early AS had large numbers of TNF{alpha} cells in the three tissular areas; for the other patient with early disease they were found only in CT and cartilage. IL6 was seen in 4/4 patients with AS in most areas. Patients with early disease had more T cells, TNF{alpha}, and IL6, and patients with advanced AS more TGFß1.

Conclusion: The immunohistological findings of a limited sample suggest a role for BM in sacroiliitis, for TNF{alpha} and IL6 in early, active lesions, and for TGFß1 at the time of secondary cartilage and bone proliferation.

Abbreviations: AS, ankylosing spondylitis; BM, bone marrow; CT, connective tissue; IFN{gamma}, interferon {gamma}; IL, interleukin; RA, rheumatoid arthritis; rh, recombinant human; SIJs, sacroiliac joints; SpA, spondyloarthritis; TNF{alpha}, tumour necrosis factor {alpha}, TGFß, transforming growth factor ß

Keywords: ankylosing spondylitis; sacroiliitis; immunohistology; tumour necrosis factor {alpha}; transforming growth factor ß


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