T-cell responses to versican in ankylosing spondylitis

详细信息    查看全文

• 作者：Tae-Jong Kim (1)
  Tae-Hwan Kim (2)
  Hyun-Joo Lee (2)
  Bitnara Lee (2)
  A. Robin Poole (3)
  Robert D. Inman (4)
  
• 关键词：Ankylosing spondylitis ; T cell ; Proteoglycan ; Versican
• 刊名：Rheumatology International
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：31
• 期：2
• 页码：191-195
• 全文大小：361KB
• 参考文献：1. Carette S, Graham D, Little H, Rubenstein J, Rosen P (1983) The natural disease course of ankylosing spondylitis. Arthritis Rheum 26:186-90 CrossRef
  2. Sieper J, Braun J (1995) Pathogenesis of spondylarthropathies. Persistent bacterial antigen, autoimmunity, or both? Arthritis Rheum 38:1547-554 CrossRef
  3. Bollow M, Fischer T, Reisshauer H, Backhaus M, Sieper J, Hamm B, Braun J (2000) Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis-cellularity correlates with the degree of enhancement detected by magnetic resonance imaging. Ann Rheum Dis 59:135-40 CrossRef
  4. Duchmann R, Lambert C, May E, Hohler T, Marker-Hermann E (2001) CD4+ and CD8+ clonal T cell expansions indicate a role of antigens in ankylosing spondylitis; a study in HLA-B27+ monozygotic twins. Clin Exp Immunol 123:315-22 CrossRef
  5. Marker-Hermann E, Meyer zum Buschenfelde KH, Wildner G (1997) HLA-B27-derived peptides as autoantigens for T lymphocytes in ankylosing spondylitis. Arthritis Rheum 40:2047-054 CrossRef
  6. Poole AR (1998) The histopathology of ankylosing spondylitis: are there unifying hypotheses? Am J Med Sci 316:228-33 CrossRef
  7. Shi S, Ciurli C, Cartman A, Pidoux I, Poole AR, Zhang Y (2003) Experimental immunity to the G1 domain of the proteoglycan versican induces spondylitis and sacroiliitis, of a kind seen in human spondylarthropathies. Arthritis Rheum 48:2903-915 CrossRef
  8. Leroux JY, Guerassimov A, Cartman A, Delaunay N, Webber C, Rosenberg LC, Banerjee S, Poole AR (1996) Immunity to the G1 globular domain of the cartilage proteoglycan aggrecan can induce inflammatory erosive polyarthritis and spondylitis in BALB/c mice but immunity to G1 is inhibited by covalently bound keratan sulfate in vitro and in vivo. J Clin Invest 97:621-32 CrossRef
  9. Jobanputra P, Choy EH, Kingsley GH, Sieper J, Palacios-Boix AA, Heinegard D, Panayi GS (1992) Cellular immunity to cartilage proteoglycans: relevance to the pathogenesis of ankylosing spondylitis. Ann Rheum Dis 51:959-62 CrossRef
  10. Glant TT, Mikecz K, Arzoumanian A, Poole AR (1987) Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthritis Rheum 30:201-12 CrossRef
  11. van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361-68 CrossRef
  12. Thiel A, Wu P, Lauster R, Braun J, Radbruch A, Sieper J (2000) Analysis of the antigen-specific T cell response in reactive arthritis by flow cytometry. Arthritis Rheum 43:2834-842 CrossRef
  13. Chou CT, Huo AP, Chang HN, Tsai CY, Chen WS, Wang HP (2007) Cytokine production from peripheral blood mononuclear cells in patients with ankylosing spondylitis and their first-degree relatives. Arch Med Res 38:190-95 CrossRef
  14. Suni MA, Picker LJ, Maino VC (1998) Detection of antigen-specific T cell cytokine expression in whole blood by flow cytometry. J Immunol Methods 212:89-8 CrossRef
  15. Yin Z, Siegert S, Neure L, Grolms M, Liu L, Eggens U, Radbruch A, Braun J, Sieper J (1999) The elevated ratio of interferon gamma-/interleukin-4-positive T cells found in synovial fluid and synovial membrane of rheumatoid arthritis patients can be changed by interleukin-4 but not by interleukin-10 or transforming growth factor beta. Rheumatology (Oxford) 38:1058-067 CrossRef
  16. Zou J, Zhang Y, Thiel A, Rudwaleit M, Shi SL, Radbruch A, Poole R, Braun J, Sieper J (2003) Predominant cellular immune response to the cartilage autoantigenic G1 aggrecan in ankylosing spondylitis and rheumatoid arthritis. Rheumatology (Oxford) 42:846-55 CrossRef
  17. Keeney TS, Nomura LE, Maecker HT, Sastry KJ (2003) Flow cytometric analysis of macaque whole blood for antigen-specific intracellular cytokine production by T lymphocytes. J Med Primatol 32:23-0 CrossRef
  18. Laloux L, Voisin MC, Allain J, Martin N, Kerboull L, Chevalier X, Claudepierre P (2001) Immunohistological study of entheses in spondyloarthropathies: comparison in rheumatoid arthritis and osteoarthritis. Ann Rheum Dis 60:316-21 CrossRef
  19. Boyle LH, Goodall JC, Opat SS, Gaston JS (2001) The recognition of HLA-B27 by human CD4(+) T lymphocytes. J Immunol 167:2619-624
  20. Braun J, Bollow M, Neure L, Seipelt E, Seyrekbasan F, Herbst H, Eggens U, Distler A, Sieper J (1995) Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 38:499-05 CrossRef
  21. Boyle LH, Goodall JC, Gaston JS (2004) The recognition of abnormal forms of HLA-B27 by CD4?+?T cells. Curr Mol Med 4:51-8 CrossRef
  22. Zhang Y, Guerassimov A, Leroux JY, Cartman A, Webber C, Lalic R, de Miguel E, Rosenberg LC, Poole AR (1998) Arthritis induced by proteoglycan aggrecan G1 domain in BALB/c mice. Evidence for t cell involvement and the immunosuppressive influence of keratan sulfate on recognition of T and B cell epitopes. J Clin Invest 101:1678-686 CrossRef
  23. Mikecz K, Glant TT, Poole AR (1987) Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis Rheum 30:306-18 CrossRef
  
• 作者单位：Tae-Jong Kim (1)
  Tae-Hwan Kim (2)
  Hyun-Joo Lee (2)
  Bitnara Lee (2)
  A. Robin Poole (3)
  Robert D. Inman (4)
  
  1. Department of Rheumatology, Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, Gwangju, South Korea
  2. Department of Rheumatology, The Hospital for Rheumatic Diseases, Hanyang University College of Medicine, 17 Haengdang-Dong, Sungdong-Gu, Seoul, 133-792, Korea
  3. Joint Diseases Laboratory, Shriners Hospitals for Children, McGill University, Montreal, Canada
  4. Department of Rheumatology, Toronto Western Hospital, The University of Toronto, Toronto, Canada
  

文摘

The objective of our study was to undertake a systematic analysis of the T-cell response to the proteoglycan versican G1-globular domain (VG1) in ankylosing spondylitis (AS) as immunity to VG1 in mice can induce a pathology closely resembling AS. Peripheral blood lymphocytes from 36 AS patients and 33 healthy controls were incubated with recombinant human VG1 in culture for 6?h. T-cell responses were assessed by FACS analyses using mAb against surface expression of the activation marker CD69 and against the intracellular cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha. T cells activated by exposure to versican were determined by assessing the percentage of CD4+ or CD8+ T cells that were CD69/cytokine double-positive cells as compared to isotype control staining. In the AS patients, exposure to VG1 resulted in increased expression by CD4+ T cells of IFN-gamma in 55.6% of patients and of TNF-alpha in 52.8% of patients. In the controls, only 36.4% of subjects demonstrated an IFN-gamma response and 36.4% demonstrated a TNF-alpha response (P value 0.148, 0.227, respectively). With respect to CD8+ T-cell responses, versican stimulation enhanced IFN-gamma expression in 44.4% of AS patients and 39.4% of controls, and enhanced TNF-alpha response in 50.0% of AS patients and 39.4% of controls (P value 0.620, 0.327, respectively). Although, there was no statistically significant difference in the magnitude of the IFN-γ or TNF secretion by CD4+ T cells and CD8+ T cells between AS and controls, our results demonstrate an enhanced T-cell response to VG1 in AS.