Synovial tissue macrophage populations and articular damage in rheumatoid arthritis.

OBJECTIVE To examine the relative contribution of individual synovial cell populations to polyarticular destruction in rheumatoid arthritis (RA). METHODS Serial measurements of disease activity and articular destruction, obtained prospectively in 28 RA patients followed for a mean of 5.8 years, were correlated with synovial cell populations quantified using immunohistochemical techniques. RESULTS The mean radiologic score worsened (from 37 to 86; P = 0.0001) despite significant improvement in disease activity. Synovial lining layer cell depth and sublining layer macrophage, but no lymphocyte, cell counts correlated significantly with radiologic course. Detailed analysis of 11 patients demonstrated reduced synovial lining expression of CD14 compared with CD68 (P = 0.003), whereas sublining expression of CD14 and CD68 was equivalent. CONCLUSION Synovial macrophage numbers correlated with articular destruction in RA. In addition, the study results provided further evidence that lining layer macrophages may represent a distinct subpopulation that is of importance in this process. These findings have implications for the development of new therapies for RA.

[1]  J. Woody,et al.  Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis , 1994, The Lancet.

[2]  F. Wolfe,et al.  Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study. , 1994, Arthritis and rheumatism.

[3]  G. Firestein,et al.  Pannus and pannocytes , 1994 .

[4]  G. Panayi,et al.  Intramuscular gold decreases cytokine expression and macrophage numbers in the rheumatoid synovial membrane. , 1994, Annals of the rheumatic diseases.

[5]  G. Firestein,et al.  Mechanisms of methotrexate action in rheumatoid arthritis. Selective decrease in synovial collagenase gene expression. , 1994, Arthritis and rheumatism.

[6]  B. Bresnihan,et al.  Synovial tissue macrophages and joint erosion in rheumatoid arthritis. , 1994, Annals of the rheumatic diseases.

[7]  F. Breedveld,et al.  Chimeric CD4 monoclonal antibody cM-T412 as a therapeutic approach to rheumatoid arthritis. , 1993, Arthritis and rheumatism.

[8]  G. Panayi.  The pathogenesis of rheumatoid arthritis: from molecules to the whole patient. , 1993, British journal of rheumatology.

[9]  Bucy Rp,et al.  Use of a chimeric monoclonal anti-CD4 antibody in patients with refractory rheumatoid arthritis. , 1993, Arthritis and rheumatism.

[10]  F. Emmrich,et al.  Reduction of monocyte‐macrophage activation markers upon anti‐CD4 treatment. Decreased levels of IL‐1, IL‐6, neopterin and soluble CD14 in patients with rheumatoid arthritis , 1993, Clinical and experimental immunology.

[11]  K. Elkon,et al.  The SCID mouse as a vehicle to study autoimmunity. , 1993, British journal of rheumatology.

[12]  A. Pitsillides,et al.  Light microscopic characterization of the fibroblast-like synovial intimal cell (synoviocyte). , 1992, Arthritis and rheumatism.

[13]  M. Feldmann,et al.  Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair. , 1992, British journal of rheumatology.

[14]  J. Isaacs,et al.  Humanised monoclonal antibody therapy for rheumatoid arthritis , 1992, The Lancet.

[15]  F. Thien,et al.  Chimeric CD7 monoclonal antibody therapy in rheumatoid arthritis. , 1992, The Journal of rheumatology.

[16]  G. Firestein,et al.  Stromelysin and tissue inhibitor of metalloproteinases gene expression in rheumatoid arthritis synovium. , 1992, The American journal of pathology.

[17]  J. Symons,et al.  In situ hybridization of interleukin-1 in CD14-positive cells in rheumatoid arthritis. , 1992, Clinical immunology and immunopathology.

[18]  G. Panayi.  The immunopathogenesis of rheumatoid arthritis. , 1979, Clinical and experimental rheumatology.

[19]  H. Stein,et al.  Ber-MAC3: new monoclonal antibody that defines human monocyte/macrophage differentiation antigen. , 1991, Journal of clinical pathology.

[20]  B. Bresnihan,et al.  Immunohistological analysis of the synovial membrane: search for predictors of the clinical course in rheumatoid arthritis. , 1991, Annals of the rheumatic diseases.

[21]  M. Bayliss,et al.  The synovium-cartilage junction of the normal human knee. Implications for joint destruction and repair. , 2010, Arthritis and rheumatism.

[22]  M. Tocci,et al.  Analysis of IL-1 and TNF-alpha gene expression in human rheumatoid synoviocytes and normal monocytes by in situ hybridization. , 1990, Journal of immunology.

[23]  J. McGee,et al.  Labelling of cells of the mononuclear phagocyte system in routinely processed archival biopsy specimens with monoclonal antibody EBM/11. , 1990, Journal of clinical pathology.

[24]  J. Sany,et al.  Radiologic progression during intramuscular methotrexate treatment of rheumatoid arthritis. , 1990, The Journal of rheumatology.

[25]  L. Wilkinson,et al.  Immunohistological reassessment of accessory cell populations in normal and diseased human synovium. , 1990, British journal of rheumatology.

[26]  G. Firestein,et al.  How important are T cells in chronic rheumatoid synovitis? , 1990, Arthritis and rheumatism.

[27]  F. Epstein,et al.  Rheumatoid arthritis. Pathophysiology and implications for therapy. , 1990, The New England journal of medicine.

[28]  P. Lydyard,et al.  The prevalence and distribution of macrophages bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in synovium. , 1990, Scandinavian journal of rheumatology.

[29]  B. Bresnihan,et al.  Lymphoid irradiation in intractable rheumatoid arthritis. Long-term followup of patients treated with 750 rads or 2,000 rads. , 1989, Arthritis and rheumatism.

[30]  B. Bresnihan,et al.  Changes in lymphocyte infiltration of the synovial membrane and the clinical course of rheumatoid arthritis. , 1989, Arthritis and rheumatism.

[31]  B. Bresnihan,et al.  The immunohistologic features of synovitis, disease activity and in vitro IgM rheumatoid factor synthesis by blood mononuclear cells in rheumatoid arthritis. , 1989, The Journal of rheumatology.

[32]  O. Söder,et al.  Stimulation of chondrocyte DNA synthesis by interleukin-1. , 1988, British journal of rheumatology.

[33]  Dawes Pt.  Radiological assessment of outcome in rheumatoid arthritis. , 1988 .

[34]  G. Firestein,et al.  Down regulation of human monocyte differentiation antigens by interferon gamma. , 1987, Cellular immunology.

[35]  M. T. Walters,et al.  An investigation of the action of disease modifying antirheumatic drugs on the rheumatoid synovial membrane: reduction in T lymphocyte subpopulations and HLA-DP and DQ antigen expression after gold or penicillamine therapy. , 1987, Annals of the rheumatic diseases.

[36]  L. Poulter,et al.  Macrophage-like cells of the pannus area in rheumatoid arthritic joints. , 1987, Scandinavian journal of rheumatology.

[37]  R. Hoppe,et al.  Long-term followup of rheumatoid arthritis patients treated with total lymphoid irradiation. , 1987, Arthritis and rheumatism.

[38]  G. Janossy,et al.  Discrimination of Human Macrophages and Dendritic Cells by Means of Monoclonal Antibodies , 1986, Scandinavian journal of immunology.

[39]  D. Scott,et al.  Long term progression of joint damage in rheumatoid arthritis. , 1986, Annals of the rheumatic diseases.

[40]  N. Hogg,et al.  Mononuclear phagocytes of normal and rheumatoid synovial membrane identified by monoclonal antibodies. , 1985, Immunology.

[41]  P. Bacon,et al.  Progression of radiological changes in rheumatoid arthritis. , 1984, Annals of the rheumatic diseases.

[42]  R. Winchester,et al.  Identification of Three Major Synovial Lining Cell Populations by Monoclonal Antibodies Directed to Ia Antigens and Antigens Associated with Monocytes/Macrophages and Fibroblasts , 1983, Scandinavian journal of immunology.

[43]  G. Janossy,et al.  Histochemical discrimination of HLA-DR positive cell populations in the normal and arthritic synovial lining. , 1982, Clinical and experimental immunology.

[44]  L. Klareskog,et al.  Appearance of Anti‐HLA‐DR‐Reactive Cells in Normal and Rheumatoid Synovial Tissue , 1981, Scandinavian journal of immunology.

[45]  R. Mallya,et al.  The assessment of disease activity in rheumatoid arthritis using a multivariate analysis. , 1981, Rheumatology and rehabilitation.

[46]  H. Paulus,et al.  Lymphocyte Involvement in Rheumatoid Arthritis , 1977 .

[47]  A. Larsen,et al.  Radiographic Evaluation of Rheumatoid Arthritis and Related Conditions by Standard Reference Films , 1977, Acta radiologica: diagnosis.

[48]  H. Ishikawa,et al.  Electron microscopic observations of immunoreactive cells in the rheumatoid synovial membrane. , 1976, Arthritis and rheumatism.

[49]  M. Ziff,et al.  Electron microscopic studies of the cartilage-pannus junction in rheumatoid arthritis. , 1975, Arthritis and rheumatism.

[50]  K. Muirden,et al.  Do Lymphocytes Protect the Rheumatoid Joint? , 1971, British medical journal.

[51]  W. Buchanan,et al.  Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. , 1968, The Quarterly journal of medicine.