Abstract
OBJECTIVE—To determine which inflammatory cell types are present in entheses from patients with spondyloarthropathy (SpA) compared with patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS—Enthesis specimens were obtained during orthopaedic procedures in eight patients with SpA, four with RA, and three with OA. After decalcification, the lymphocyte subsets (CD3, CD4, CD8, CD20) in the bone marrow component of each enthesis were measured by an immunohistochemical technique. RESULTS—Oedema and an inflammatory infiltrate were present in all the SpA specimens, being clearly predominant in the bone marrow component of the entheses. The density of all cell types in the bone marrow was significantly higher in the SpA group than in the two other groups. The cell type CD3+ showed the greatest difference between the SpA and RA groups, being increased fivefold in the SpA group. Within the SpA group, CD3+ cells were considerably more numerous than CD20+ cells—a difference from the RA group—and the predominant T cells were CD8+. CONCLUSION—Persistent oedema with an inflammatory infiltrate composed predominantly of CD8+ cells was noted in the entheses of patients with SpA, being predominant in the bone marrow. These results suggest that CD8+ cells may have a key role in local inflammation in SpAs.
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Figure 1 .
Serial sections of an erosive lesion of a vastus lateralis enthesis in a patient with ankylosing spondylitis (patient 5). (A) Haematoxylin, eosin, and saffron staining. Osteoclastic hyperresorption of osseous areas of the enthesis associated with oedema and lymphocytic infiltration of the underlying bone marrow. B= bone; F = tendinous fibrosis; M = bone marrow; single arrow = osteoclasts; double arrows = lymphocytes; * = oedema. (B) Immunostaining with anti-CD68 antibody. Visualisation of the osteoclasts as CD68+ cells (arrow). (c) Immunostaining with anti-CD8 antibody showing sparse CD8 lymphocytes (arrow) in the bone marrow part of the same enthesis. (A), (B), (C) Original magnification ×100.
Figure 2 .
Vastus lateralis enthesis from a patient with ankylosing spondylitis (patient 7). Bone marrow oedema (single arrow) with scattered mononuclear cell infiltrates (double arrows). Hyperplasia of the enthesis fibrocartilage (*). Haematoxylin, eosin, and saffron staining. Original magnification ×100.
Figure 3 .
Serial immunohistochemistry sections of a cruciate ligament enthesis from a patient with ankylosing spondylitis (patient 4). (A) Anti-CD3+ antibody. Sparse (single arrow) or nodular (double arrows) CD3+ cell infiltrates of the bone marrow around a congestive vascular sinus (*). (B and C) Anti-CD4 and anti-CD8 antibodies, respectively. The CD3+ cell infiltrate contains both CD4+ and CD8+ cells, with an apparent predominance of CD8+ cells, which was confirmed by the cell count. Original magnification ×250.
Selected References
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- Allen R. L., Gillespie G. M., Hall F., Edmonds S., Hall M. A., Wordsworth B. P., McMichael A. J., Bowness P. Multiple T cell expansions are found in the blood and synovial fluid of patients with reactive arthritis. J Rheumatol. 1997 Sep;24(9):1750–1757. [PubMed] [Google Scholar]
- Altman R., Asch E., Bloch D., Bole G., Borenstein D., Brandt K., Christy W., Cooke T. D., Greenwald R., Hochberg M. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039–1049. doi: 10.1002/art.1780290816. [DOI] [PubMed] [Google Scholar]
- Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
- Arnett F. C. Seronegative spondylarthropathies. Bull Rheum Dis. 1987;37(1):1–12. [PubMed] [Google Scholar]
- Aufdermaur M. Pathogenesis of square bodies in ankylosing spondylitis. Ann Rheum Dis. 1989 Aug;48(8):628–631. doi: 10.1136/ard.48.8.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ball J. Enthesopathy of rheumatoid and ankylosing spondylitis. Ann Rheum Dis. 1971 May;30(3):213–223. doi: 10.1136/ard.30.3.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braun J., Bollow M., Neure L., Seipelt E., Seyrekbasan F., Herbst H., Eggens U., Distler A., Sieper J. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum. 1995 Apr;38(4):499–505. doi: 10.1002/art.1780380407. [DOI] [PubMed] [Google Scholar]
- Cawley M. I., Chalmers T. M., Kellgren J. H., Ball J. Destructive lesions of vertebral bodies in ankylosing spondylitis. Ann Rheum Dis. 1972 Sep;31(5):345–358. doi: 10.1136/ard.31.5.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Costello P., Bresnihan B., O'Farrelly C., FitzGerald O. Predominance of CD8+ T lymphocytes in psoriatic arthritis. J Rheumatol. 1999 May;26(5):1117–1124. [PubMed] [Google Scholar]
- Cunnane G., Bresnihan B., FitzGerald O. Immunohistologic analysis of peripheral joint disease in ankylosing spondylitis. Arthritis Rheum. 1998 Jan;41(1):180–182. doi: 10.1002/1529-0131(199801)41:1<180::AID-ART24>3.0.CO;2-V. [DOI] [PubMed] [Google Scholar]
- Dougados M., van der Linden S., Juhlin R., Huitfeldt B., Amor B., Calin A., Cats A., Dijkmans B., Olivieri I., Pasero G. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 1991 Oct;34(10):1218–1227. doi: 10.1002/art.1780341003. [DOI] [PubMed] [Google Scholar]
- Duke O., Panayi G. S., Janossy G., Poulter L. W. An immunohistological analysis of lymphocyte subpopulations and their microenvironment in the synovial membranes of patients with rheumatoid arthritis using monoclonal antibodies. Clin Exp Immunol. 1982 Jul;49(1):22–30. [PMC free article] [PubMed] [Google Scholar]
- Kidd B. L., Moore K., Walters M. T., Smith J. L., Cawley M. I. Immunohistological features of synovitis in ankylosing spondylitis: a comparison with rheumatoid arthritis. Ann Rheum Dis. 1989 Feb;48(2):92–98. doi: 10.1136/ard.48.2.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGonagle D., Gibbon W., O'Connor P., Green M., Pease C., Emery P. Characteristic magnetic resonance imaging entheseal changes of knee synovitis in spondylarthropathy. Arthritis Rheum. 1998 Apr;41(4):694–700. doi: 10.1002/1529-0131(199804)41:4<694::AID-ART17>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
- McGonagle D., Khan M. A., Marzo-Ortega H., O'Connor P., Gibbon W., Emery P. Enthesitis in spondyloarthropathy. Curr Opin Rheumatol. 1999 Jul;11(4):244–250. doi: 10.1097/00002281-199907000-00004. [DOI] [PubMed] [Google Scholar]
- Paolaggi J. B., Durigon M., Pie Pou P., Struz P., Le Parc J. M. Etude anatomo-pathologique des enthésopathies des spondyloarthropathies inflammatoires. Rev Rhum Mal Osteoartic. 1987 Mar;54(3):249–253. [PubMed] [Google Scholar]
- Pileri S. A., Roncador G., Ceccarelli C., Piccioli M., Briskomatis A., Sabattini E., Ascani S., Santini D., Piccaluga P. P., Leone O. Antigen retrieval techniques in immunohistochemistry: comparison of different methods. J Pathol. 1997 Sep;183(1):116–123. doi: 10.1002/(SICI)1096-9896(199709)183:1<116::AID-PATH1087>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
- Sieper J., Braun J. Pathogenesis of spondylarthropathies. Persistent bacterial antigen, autoimmunity, or both? Arthritis Rheum. 1995 Nov;38(11):1547–1554. doi: 10.1002/art.1780381105. [DOI] [PubMed] [Google Scholar]
- Smeets T. J., Dolhain R. J., Breedveld F. C., Tak P. P. Analysis of the cellular infiltrates and expression of cytokines in synovial tissue from patients with rheumatoid arthritis and reactive arthritis. J Pathol. 1998 Sep;186(1):75–81. doi: 10.1002/(SICI)1096-9896(199809)186:1<75::AID-PATH142>3.0.CO;2-B. [DOI] [PubMed] [Google Scholar]
- van der Linden S., Valkenburg H. A., Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984 Apr;27(4):361–368. doi: 10.1002/art.1780270401. [DOI] [PubMed] [Google Scholar]