Skip to main content
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1994 Jan;53(1):39–44. doi: 10.1136/ard.53.1.39

Synovial tissue macrophages and joint erosion in rheumatoid arthritis.

G Yanni 1, A Whelan 1, C Feighery 1, B Bresnihan 1
PMCID: PMC1005241  PMID: 8311554

Abstract

OBJECTIVES--To analyse the mononuclear cell populations in synovial membrane biopsies obtained before treatment from patients with rheumatoid arthritis (RA) and to correlate the findings with the degree of joint damage occurring over one year. METHODS--Multiple needle biopsy specimens were obtained from inflamed knee joints on entry to the study. The tissue samples were examined using immunohistochemical techniques. The degree of joint damage was estimated using the Larsen radiological index. RESULTS--Twelve patients were studied. It was observed that there was a significant correlation between the number of synovial tissue macrophages and the degree of joint erosion over one year (r = 0.66; p = 0.04). The synovial lining layer contained large numbers of macrophages and the cellularity of the lining layer correlated significantly with the number of macrophages infiltrating the sublining areas (r = 0.65; p = 0.01). Finally, the cellularity of the lining layer correlated with the synovial fluid levels of interleukin-6 (r = 0.66; p = 0.04). The radiological course did not correlate with infiltrating T or B lymphocyte populations, but did correlate with other previously identified indicators of the clinical course, including a high index of disease activity and IgA rheumatoid factors levels. CONCLUSION--This study suggests that synovial tissue macrophages play a critical role in the pathogenesis of joint erosion in RA.

Full text

PDF
39

Selected References

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

  1. Aarden L. A., De Groot E. R., Schaap O. L., Lansdorp P. M. Production of hybridoma growth factor by human monocytes. Eur J Immunol. 1987 Oct;17(10):1411–1416. doi: 10.1002/eji.1830171004. [DOI] [PubMed] [Google Scholar]
  2. Aarden L. A., De Groot E. R., Schaap O. L., Lansdorp P. M. Production of hybridoma growth factor by human monocytes. Eur J Immunol. 1987 Oct;17(10):1411–1416. doi: 10.1002/eji.1830171004. [DOI] [PubMed] [Google Scholar]
  3. Arnason J. A., Jónsson T., Brekkan A., Sigurjónsson K., Valdimarsson H. Relation between bone erosions and rheumatoid factor isotypes. Ann Rheum Dis. 1987 May;46(5):380–384. doi: 10.1136/ard.46.5.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Astaldi G. C., Janssen M. C., Lansdorp P., Willems C., Zeijlemaker W. P., Oosterhof F. Human endothelial culture supernatant (HECS): a growth factor for hybridomas. J Immunol. 1980 Oct;125(4):1411–1414. [PubMed] [Google Scholar]
  6. Bhardwaj N., Santhanam U., Lau L. L., Tatter S. B., Ghrayeb J., Rivelis M., Steinman R. M., Sehgal P. B., May L. T. IL-6/IFN-beta 2 in synovial effusions of patients with rheumatoid arthritis and other arthritides. Identification of several isoforms and studies of cellular sources. J Immunol. 1989 Oct 1;143(7):2153–2159. [PubMed] [Google Scholar]
  7. Cats A., Hazevoet H. M. Significance of positive tests for rheumatoid factor in the prognosis of rheumatoid arthritis. A follow-up study. Ann Rheum Dis. 1970 May;29(3):254–260. doi: 10.1136/ard.29.3.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dawes P. T., Fowler P. D., Jackson R., Collins M., Shadforth M. F., Stone R., Scott D. L. Prediction of progressive joint damage in patients with rheumatoid arthritis receiving gold or D-penicillamine therapy. Ann Rheum Dis. 1986 Nov;45(11):945–949. doi: 10.1136/ard.45.11.945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eberhardt K. B., Truedsson L., Pettersson H., Svensson B., Stigsson L., Eberhardt J. L., Wollheim F. A. Disease activity and joint damage progression in early rheumatoid arthritis: relation to IgG, IgA, and IgM rheumatoid factor. Ann Rheum Dis. 1990 Nov;49(11):906–909. doi: 10.1136/ard.49.11.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eggelmeijer F., Otten H. G., de Rooy H. H., Daha M. R., Breedveld F. C. Significance of rheumatoid factor isotypes in seronegative rheumatoid arthritis. Rheumatol Int. 1990;10(1):43–46. doi: 10.1007/BF02274780. [DOI] [PubMed] [Google Scholar]
  11. Faith A., Pontesilli O., Unger A., Panayi G. S., Johns P. ELISA assays for IgM and IgG rheumatoid factors. J Immunol Methods. 1982 Dec 17;55(2):169–177. doi: 10.1016/0022-1759(82)90029-1. [DOI] [PubMed] [Google Scholar]
  12. Feigenbaum S. L., Masi A. T., Kaplan S. B. Prognosis in rheumatoid arthritis. A longitudinal study of newly diagnosed younger adult patients. Am J Med. 1979 Mar;66(3):377–384. doi: 10.1016/0002-9343(79)91055-6. [DOI] [PubMed] [Google Scholar]
  13. Field M., Chu C., Feldmann M., Maini R. N. Interleukin-6 localisation in the synovial membrane in rheumatoid arthritis. Rheumatol Int. 1991;11(2):45–50. doi: 10.1007/BF00291144. [DOI] [PubMed] [Google Scholar]
  14. Firestein G. S., Alvaro-Gracia J. M., Maki R., Alvaro-Garcia J. M. Quantitative analysis of cytokine gene expression in rheumatoid arthritis. J Immunol. 1990 May 1;144(9):3347–3353. [PubMed] [Google Scholar]
  15. Firestein G. S., Zvaifler N. J. How important are T cells in chronic rheumatoid synovitis? Arthritis Rheum. 1990 Jun;33(6):768–773. doi: 10.1002/art.1780330602. [DOI] [PubMed] [Google Scholar]
  16. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Guerne P. A., Zuraw B. L., Vaughan J. H., Carson D. A., Lotz M. Synovium as a source of interleukin 6 in vitro. Contribution to local and systemic manifestations of arthritis. J Clin Invest. 1989 Feb;83(2):585–592. doi: 10.1172/JCI113921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Harris E. D., Jr Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990 May 3;322(18):1277–1289. doi: 10.1056/NEJM199005033221805. [DOI] [PubMed] [Google Scholar]
  19. Hirano T., Matsuda T., Turner M., Miyasaka N., Buchan G., Tang B., Sato K., Shimizu M., Maini R., Feldmann M. Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988 Nov;18(11):1797–1801. doi: 10.1002/eji.1830181122. [DOI] [PubMed] [Google Scholar]
  20. Horii Y., Muraguchi A., Suematsu S., Matsuda T., Yoshizaki K., Hirano T., Kishimoto T. Regulation of BSF-2/IL-6 production by human mononuclear cells. Macrophage-dependent synthesis of BSF-2/IL-6 by T cells. J Immunol. 1988 Sep 1;141(5):1529–1535. [PubMed] [Google Scholar]
  21. Houssiau F. A., Devogelaer J. P., Van Damme J., de Deuxchaisnes C. N., Van Snick J. Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum. 1988 Jun;31(6):784–788. doi: 10.1002/art.1780310614. [DOI] [PubMed] [Google Scholar]
  22. Iguchi T., Ziff M. Electron microscopic study of rheumatoid synovial vasculature. Intimate relationship between tall endothelium and lymphoid aggregation. J Clin Invest. 1986 Feb;77(2):355–361. doi: 10.1172/JCI112312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ishikawa H., Ziff M. Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane. Arthritis Rheum. 1976 Jan-Feb;19(1):1–14. doi: 10.1002/art.1780190101. [DOI] [PubMed] [Google Scholar]
  24. Jirik F. R., Podor T. J., Hirano T., Kishimoto T., Loskutoff D. J., Carson D. A., Lotz M. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol. 1989 Jan 1;142(1):144–147. [PubMed] [Google Scholar]
  25. Kohase M., Henriksen-DeStefano D., May L. T., Vilcek J., Sehgal P. B. Induction of beta 2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation. Cell. 1986 Jun 6;45(5):659–666. doi: 10.1016/0092-8674(86)90780-4. [DOI] [PubMed] [Google Scholar]
  26. Larsen A., Thoen J. Hand radiography of 200 patients with rheumatoid arthritis repeated after an interval of one year. Scand J Rheumatol. 1987;16(6):395–401. doi: 10.3109/03009748709165409. [DOI] [PubMed] [Google Scholar]
  27. Lotz M., Jirik F., Kabouridis P., Tsoukas C., Hirano T., Kishimoto T., Carson D. A. B cell stimulating factor 2/interleukin 6 is a costimulant for human thymocytes and T lymphocytes. J Exp Med. 1988 Mar 1;167(3):1253–1258. doi: 10.1084/jem.167.3.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mallya R. K., Mace B. E. The assessment of disease activity in rheumatoid arthritis using a multivariate analysis. Rheumatol Rehabil. 1981 Feb 1;20(1):14–17. doi: 10.1093/rheumatology/20.1.14. [DOI] [PubMed] [Google Scholar]
  29. Masi A. T., Maldonado-Cocco J. A., Kaplan S. B., Feigenbaum S. L., Chandler R. W. Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome. Semin Arthritis Rheum. 1976 May;4(4):299–326. doi: 10.1016/0049-0172(76)90013-5. [DOI] [PubMed] [Google Scholar]
  30. Mason D. Y., Cordell J. L., Abdulaziz Z., Naiem M., Bordenave G. Preparation of peroxidase: antiperoxidase (PAP) complexes for immunohistological labeling of monoclonal antibodies. J Histochem Cytochem. 1982 Nov;30(11):1114–1122. doi: 10.1177/30.11.6183312. [DOI] [PubMed] [Google Scholar]
  31. Miyasaka N., Sato K., Hashimoto J., Kohsaka H., Yamamoto K., Goto M., Inoue K., Matsuda T., Hirano T., Kishimoto T. Constitutive production of interleukin 6/B cell stimulatory factor-2 from inflammatory synovium. Clin Immunol Immunopathol. 1989 Aug;52(2):238–247. doi: 10.1016/0090-1229(89)90175-x. [DOI] [PubMed] [Google Scholar]
  32. Möttönen T. T. Prediction of erosiveness and rate of development of new erosions in early rheumatoid arthritis. Ann Rheum Dis. 1988 Aug;47(8):648–653. doi: 10.1136/ard.47.8.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Noma T., Mizuta T., Rosén A., Hirano T., Kishimoto T., Honjo T. Enhancement of the interleukin 2 receptor expression on T cells by multiple B-lymphotropic lymphokines. Immunol Lett. 1987 Jul;15(3):249–253. doi: 10.1016/0165-2478(87)90032-0. [DOI] [PubMed] [Google Scholar]
  34. Ottèn H. G., Daha M. R., van Laar J. M., de Rooy H. H., Breedveld F. C. Subclass distribution and size of human IgA rheumatoid factor at mucosal and nonmucosal sites. Arthritis Rheum. 1991 Jul;34(7):831–839. doi: 10.1002/art.1780340708. [DOI] [PubMed] [Google Scholar]
  35. Panayi G. S., Lanchbury J. S., Kingsley G. H. The importance of the T cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. Arthritis Rheum. 1992 Jul;35(7):729–735. doi: 10.1002/art.1780350702. [DOI] [PubMed] [Google Scholar]
  36. Poulter L. W., Duke O., Hobbs S., Janossy G., Panayi G. Histochemical discrimination of HLA-DR positive cell populations in the normal and arthritic synovial lining. Clin Exp Immunol. 1982 May;48(2):381–388. [PMC free article] [PubMed] [Google Scholar]
  37. Rasker J. J., Cosh J. A. The natural history of rheumatoid arthritis: a fifteen year follow-up study. The prognostic significance of features noted in the first year. Clin Rheumatol. 1984 Mar;3(1):11–20. doi: 10.1007/BF02715690. [DOI] [PubMed] [Google Scholar]
  38. Ritchie D. M., Boyle J. A., McInnes J. M., Jasani M. K., Dalakos T. G., Grieveson P., Buchanan W. W. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med. 1968 Jul;37(147):393–406. [PubMed] [Google Scholar]
  39. Rooney M., Condell D., Quinlan W., Daly L., Whelan A., Feighery C., Bresnihan B. Analysis of the histologic variation of synovitis in rheumatoid arthritis. Arthritis Rheum. 1988 Aug;31(8):956–963. doi: 10.1002/art.1780310803. [DOI] [PubMed] [Google Scholar]
  40. Rooney M., Whelan A., Feighery C., Bresnihan B. The immunohistologic features of synovitis, disease activity and in vitro IgM rheumatoid factor synthesis by blood mononuclear cells in rheumatoid arthritis. J Rheumatol. 1989 Apr;16(4):459–467. [PubMed] [Google Scholar]
  41. Sawada T., Hirohata S., Inoue T., Ito K. Correlation between rheumatoid factor and IL-6 activity in synovial fluids from patients with rheumatoid arthritis. Clin Exp Rheumatol. 1991 Jul-Aug;9(4):363–368. [PubMed] [Google Scholar]
  42. Soden M., Rooney M., Whelan A., Feighery C., Bresnihan B. Immunohistological analysis of the synovial membrane: search for predictors of the clinical course in rheumatoid arthritis. Ann Rheum Dis. 1991 Oct;50(10):673–676. doi: 10.1136/ard.50.10.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Strober S., Holoshitz J. Mechanisms of immune injury in rheumatoid arthritis: evidence for the involvement of T cells and heat-shock protein. Immunol Rev. 1990 Dec;118:233–255. doi: 10.1111/j.1600-065x.1990.tb00818.x. [DOI] [PubMed] [Google Scholar]
  44. Takai Y., Wong G. G., Clark S. C., Burakoff S. J., Herrmann S. H. B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes. J Immunol. 1988 Jan 15;140(2):508–512. [PubMed] [Google Scholar]
  45. Teitsson I., Withrington R. H., Seifert M. H., Valdimarsson H. Prospective study of early rheumatoid arthritis. I. Prognostic value of IgA rheumatoid factor. Ann Rheum Dis. 1984 Oct;43(5):673–678. doi: 10.1136/ard.43.5.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tosato G., Pike S. E. Interferon-beta 2/interleukin 6 is a co-stimulant for human T lymphocytes. J Immunol. 1988 Sep 1;141(5):1556–1562. [PubMed] [Google Scholar]
  47. Van Damme J., Cayphas S., Opdenakker G., Billiau A., Van Snick J. Interleukin 1 and poly(rI).poly(rC) induce production of a hybridoma growth factor by human fibroblasts. Eur J Immunol. 1987 Jan;17(1):1–7. doi: 10.1002/eji.1830170102. [DOI] [PubMed] [Google Scholar]
  48. Waage A., Kaufmann C., Espevik T., Husby G. Interleukin-6 in synovial fluid from patients with arthritis. Clin Immunol Immunopathol. 1989 Mar;50(3):394–398. doi: 10.1016/0090-1229(89)90146-3. [DOI] [PubMed] [Google Scholar]
  49. Wood N. C., Symons J. A., Dickens E., Duff G. W. In situ hybridization of IL-6 in rheumatoid arthritis. Clin Exp Immunol. 1992 Feb;87(2):183–189. doi: 10.1111/j.1365-2249.1992.tb02972.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Young A., Corbett M., Winfield J., Jaqueremada D., Williams P., Papasavvas G., Hay F., Roitt I. A prognostic index for erosive changes in the hands, feet, and cervical spines in early rheumatoid arthritis. Br J Rheumatol. 1988 Apr;27(2):94–101. doi: 10.1093/rheumatology/27.2.94. [DOI] [PubMed] [Google Scholar]
  51. van Zeben D., Hazes J. M., Zwinderman A. H., Cats A., van der Voort E. A., Breedveld F. C. Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study. Ann Rheum Dis. 1992 Sep;51(9):1029–1035. doi: 10.1136/ard.51.9.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. van der Heijde D. M., van Riel P. L., van Leeuwen M. A., van 't Hof M. A., van Rijswijk M. H., van de Putte L. B. Prognostic factors for radiographic damage and physical disability in early rheumatoid arthritis. A prospective follow-up study of 147 patients. Br J Rheumatol. 1992 Aug;31(8):519–525. doi: 10.1093/rheumatology/31.8.519. [DOI] [PubMed] [Google Scholar]
  53. van der Heijde D. M., van Riel P. L., van Rijswijk M. H., van de Putte L. B. Influence of prognostic features on the final outcome in rheumatoid arthritis: a review of the literature. Semin Arthritis Rheum. 1988 May;17(4):284–292. doi: 10.1016/0049-0172(88)90013-3. [DOI] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES