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Advances in the Immunopathogenesis of Behçet’s Disease

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Behçet’s Disease

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Abstract

The international effort over the past 30 years to define Behçet’s disease (BD), with its mucosal, cutaneous, ocular, CNS, vascular and joint manifestations, has resulted in significant advances in the understanding of this disease. The Eighth International Conference on BD in Reggio Emilia brought together expertise on the basic issues of the causes and development of the disease. This review summarizes recent advances in the immunopathogenesis of BD. The progress reported adds not only to our understanding of BD but also enables us to develop novel strategies in the treatment of this intractable disease. In this overview four major aspects of the immunopathogenesis are considered.

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References

  1. Ohno S, Nakayama E, Sugiura S, Itakura K, Aoki K, Aizawa M (1975) Specific histocompatibihty antigens associated with Behçet’s disease. J Rheumatol 3: 1

    Google Scholar 

  2. Mizuki N, Inoko H, Ando H, Nakamura S, Kashiwase K, Akaza T, Fujino Y, Masuda K, Takiguchi M, Ohno S (1993) Behçet’s disease associated with one of the HLA-B51 subantigens, HLA-B 5101. Am J Ophthalmol 116: 406–409

    PubMed  CAS  Google Scholar 

  3. Yazici H, Akokan G, Yalcin B, Muftuoglu A (1977) The high prevalence of HLA-B5 in Behçet’s disease. Clin Exp Immunol 30: 259–261

    PubMed  CAS  Google Scholar 

  4. Godeau P, Torre D, Campinchi R, Bloch-Michel E, Schmid M, Nunez-Roldan A, Hors J, Dausset J (1977) HLA and Behçet’s disease. Rev Fr Transfus Immunochematol 20: 43–46

    Article  CAS  Google Scholar 

  5. Lehner T, Batchelor JR, Challacombe SJ, Kennedy L (1979) An immunogenetic basis for the tissue involvement of Behçet’s Syndrome. Immunology 37: 895–900

    PubMed  CAS  Google Scholar 

  6. Hirohata S, Oka H, Mizushima Y (1992) Streptococcalrelated antigens stimulate production of IL-6 and interferon-gamma by T cells from patients with Behçet’s disease. Cell Immunol 140: 410–419

    Article  PubMed  CAS  Google Scholar 

  7. Takeno M, Kariyone A, Yamashita N, Takiguchi M, Mizushima Y, Kaneka H, Sakane T (1995) Excessive function of peripheral blood neutrophils from patients with Behçet’s diseases and from HLA-B51 transgenic mice. Arthritis Rheum 38: 426–433

    Article  PubMed  CAS  Google Scholar 

  8. Pervin K, Childerstone A, Shinnick T, Mizushima Y, Zee R van der, Hasan A, Vaughan R, Lehner T (1993) T-cell epitope expression of mycobacterial and homologous human 65-kilodalton heat shock protein peptides in short term cell Unes from patients with Behçet’s disease. J Immunol 151:2273–2282

    PubMed  CAS  Google Scholar 

  9. Hasan A, Fortune F, Wilson A, Warr K, Shinnick T, Mizushima Y, Zee R van der, Stanford MR, Sanderson J, Lehner T (1996) Role of y5 T cells in pathogenesis and diagnosis of Behçet’s disease. Lancet 347: 789–794

    Article  PubMed  CAS  Google Scholar 

  10. Bahram S, Bresnahan M, Geraghty DE, Spies T (1994) A second lineage of mammaUan major histocompatibility complex class I genes. Proc Natl Acad. Sci USA 91: 6259–6263

    Article  PubMed  CAS  Google Scholar 

  11. Fodil N, Laloux L, Wanner V, Pellet P, Hauptmann G, Mizuki N, Inoko H, Spies T, Theodorou I, Bahram S (1996) Allelic repertoire of the human MHC class 1 MICA gene. Immunogenetics 44: 351–357

    Article  PubMed  CAS  Google Scholar 

  12. Morimoto M, Furukawa H, Kaneoka Miki T, Aikawa E, Sakane T (1993) Autocrine cytokine-production of neutrophils in Behçet’s disease. Annual Report of Behçet’s Disease Research Committee of Japan. Ministry of Health and Weifare, Tokyo, p 208

    Google Scholar 

  13. Groh V, Bahram S, Bauer S, Harman A, Beauchamp M, Spies T (1996) Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA 93: 12445–12450

    Article  PubMed  CAS  Google Scholar 

  14. Steinle A, Groh V, Spies T (1998) Diversification, expression and gamma delta T cell recognition of evolutionarily distant members of the MIC family of major histocompatibility complex class I-related molecules. Proc Natl Acad Sci USA 95: 12510–12515

    Article  PubMed  CAS  Google Scholar 

  15. Mizuki N, Ota M, Kimura M, Ohno S, Ando H, Katsuyama Y, Yamazaki M, Watanabe K, Goto K, Nakamura S, Bahram S, Inoko H (1997) Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behçet’s disease. Proc Natl Acad Sci USA 94: 1298–1303

    Article  PubMed  CAS  Google Scholar 

  16. Amoura Z, Caillat-Zucman S, Wechsler B, Cacoub P, Piette J.C, Sciamak B (1998) Eighth International Congress on Behçet’s Disease. Reggio Emilia, October. p12

    Google Scholar 

  17. Ohno S, Goto K (1998) HLA association in Behçet’s disease. Eighth International Congress on Behçet’s Disease. Reggio Emilia, p 44

    Google Scholar 

  18. Denman AM, Fialkow PJ, Pelton BK, Salo AC, Appleford DJ (1979) Attempts to establish a viral aetiology for Behçet’s Syndrome. In: Lehner T, Barnes CG (eds) Behçet’s Syndrome. Academic Press, London, pp 91–105

    Google Scholar 

  19. Eglin RP, Lehner T, Subak-Sharpe JH (1982) Detection of RNA complimentary to herpes-simplex virus in mononuclear cells from patients with Behçet’s Syndrome and recurrent oral ulcers. Lancet 2: 1356–1361

    Article  PubMed  CAS  Google Scholar 

  20. Bonass WA, Bird-Stewart JA, Chamberlain MA, Haliburton IW (1986) Molecular studies in Behçet’s Syndrome. In: Lehner T, Barnes CG (eds) Recent advances in Behçet’s Syndrome. Royal Society of Medicine Services, London, pp 37–41

    Google Scholar 

  21. Studd M, McCance DJ, Lehner T (1991) Detection of HSV-1 DNA in patients with Behçet’s Syndrome and in patients with recurrent oral ulcers by the ploymerase chain reaction. J Med Microbiol 34: 39–43

    Article  PubMed  CAS  Google Scholar 

  22. Sohn S (1997) Etiopathology of Behçet’s disease: herpes simplex virus infection and animal model. Yonsei Med J 38: 359–364

    PubMed  CAS  Google Scholar 

  23. Graykowski EA, Barile MF, Lee WB, Stanley HR (1996) Recurrent aphthous Stomatitis. Clinical, therapeutic, histopathologic complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA 93: 12445–12450

    Article  Google Scholar 

  24. Donatsky O (1976) A leucocyte migration study on the cell-mediated immunity against adult human oral mueosa and streptococcal antigens on patients with recurrent aphthous Stomatitis. Acta Pathol Microbiol Scand 84: 227–234

    CAS  Google Scholar 

  25. Kaneko F, Takahashi Y, Muramatsu Y, Miura Y (1985) Immunological studies on aphthous ulcers and erythema nodosum-like eruptions in Behçet’s disease. Br J Dermatol 113: 303–312

    Article  PubMed  CAS  Google Scholar 

  26. Mizushima Y (1989) Skin hypersensitivity to streptococcal antigens and the induction of systemic Symptoms by the antigens in Behçet’s disease — a muhicentre study. J Rheumatol 16: 506–511

    Google Scholar 

  27. Oshima Y, Shimizy T, Yokohari R, Matsumoto T, Kano K, Kagami T, Nagaya H (1963) Clinical studies on Behçet’s Syndrome. Ann Rheum Dis 22: 36–45

    Article  PubMed  CAS  Google Scholar 

  28. Lehner T (1964) Recurrent aphthous ulceration and autoimmunity. Lancet ii: 1134–1155

    Google Scholar 

  29. Lehner T (1967) Behçet’s Syndrome and autoimmunity. BMJ 1:465–467

    Article  PubMed  CAS  Google Scholar 

  30. Rogers RD, Sams WJ, Shorter RG (1974) Lymphotoxicity in recurrent aphthous Stomatitis. Lymphotoxicity for oral epithelial cells in recurrent aphthous Stomatitis and Behçet’s Syndrome. Arch Dermatol 109: 361–363

    Article  PubMed  Google Scholar 

  31. Lehner T, Lavery E, Smith R, Zee R van der, Mizushima Y, Shinnick T (1991) Association between the 65-kildalton heat shock protein, Streptococcus sanguis, and the corresponding antibodies in Behçet’s Syndrome. Infect Immun 59:1434–1441

    PubMed  CAS  Google Scholar 

  32. Jindal S, Dudani AK, Singh B, Harley CB, Gupta RS (1989) Primary structure of a human mitochondrial protein homologous to the bacterial and plant chaparonins and to the 65-kilodalton mycobacterial antigen. Mol Cell Biol 9:2279–2283

    PubMed  CAS  Google Scholar 

  33. Suzuki N, Sakane T (1996) Characterisation of heat shock protein specific T cells in patients with Behçet’s disease. Rev Rhum 63: 531

    Google Scholar 

  34. Sakane T, Suzuki N, Taneko M (1998) Innate and acquired immunity in Behçet’s disease. Eighth International Congress on Behçet’s Disease. Reggio Emilia, L14

    Google Scholar 

  35. Direskeneli H, Hasan A. Shinnick T, Mizushima Y, Zee R van der, Fortune F, Stanford MR, Lehner T (1996) Recognition of B-cell epitopes of the 65 kDa HSP in Behçet’s disease. Scand J Immunol 43: 464–471

    Article  PubMed  CAS  Google Scholar 

  36. Ergun T, Ince U, Demiralp E, Direskeneli H, Gurbuz P, Gurses L, Akoglu T (1998) Expression of heat shock protein in mueocutaneous lesions of Behçet’s disease. Eighth International Congress on Behçet’s Disease. Reggio Emilia, P52

    Google Scholar 

  37. Tasci B, Direskeneh H, Serdarogul P, Akman-Demir G, Eraksoy M, Saruhan-DireskeneH G (1998) Humoralimmune response to mycobacterial heat shock proteins (hsp) 65 in the cerebrospinal fluid of neuro-Behçet’s patients. Clin Exp Immunol 113: 100–104

    Article  PubMed  CAS  Google Scholar 

  38. Stanford MR, Kasp E, Whiston R, Hasan A, Todryk S, Shinnick T, Mizushima Y, Dumonde DC, Zee R van der, Lehner T (1994) Heat shock protein peptides reactive in patients with Behçet’s disease are uveitogenic in Lewis rats. Clin Exp Immunol 97: 226–231

    Article  PubMed  CAS  Google Scholar 

  39. Hu W, Hason A, Wilson A, Stanford MR, Li-Yang Y, Todryk S, Whiston R, Shinnick T, Mizushima Y, Zee R van der, Hasan, Lehner T (1998) Experimental mucosal induction of Uveitis with the 60Kd HSP derived peptide aa336-351. Eur J Immunol 28: 2444–2455

    Article  PubMed  CAS  Google Scholar 

  40. Poulter LW, Lehner T (1989) Immunohistology of oral lesions from patients with recurrent oral ulcers and Behçet’s Syndrome. Clin Exp Immunol 78: 189

    PubMed  CAS  Google Scholar 

  41. Kansu R (1998) Endothehal cell dysfunction in Behçet’s disease. Eighth International Congress on Behçet’s Disease. Reggio Emilia, October, LI7

    Google Scholar 

  42. Kansu E, Sabin G, Sabin F, Siviri B, Sayek L, Batman F (1986) Impaired procyclin synthesis by vessel walls in Behçet’s Disease. Lancet 15: 1154

    Article  Google Scholar 

  43. Inaba G, Kaku H, Suemarau J, Ujihara H, Miyanaga Y (1998) Plasma levels of thrombomodulin, intracellular adhesion molecule-1 and von Willebrand factor antigen in patients with Behçet’s disease in relation to their disease activities. Eighth International Congress on Behçet’s Disease. Reggio Emiha, P62

    Google Scholar 

  44. Ural AU, Yalcin A, Beyan C, Isimer A, Bayham H (1994) Plasma endothelin-1 concentrations in patients with Behçet’s disease. Scand J Rheumatol 23: 322–325

    Article  PubMed  CAS  Google Scholar 

  45. Chambers J, Kooner J, Haskard D (1998) Endothelial dysfunction in patients with Behçet’s Syndrome. Eighth International Congress on Behçet’s Disease. Reggio Emiha, October. P60

    Google Scholar 

  46. Cervera R, Navarro M, Lopez-Soto A, Cid M-C, Font J, Esparza J, Reverter JC, Monteagudo J, Ingelmo M, Urbano-Marquez A (1994) Antibodies to endothelial cells in Behçet’s disease: cell-binding heterogeneity and association with clinieal activity. Ann Rheum Dis 53: 265–267

    Article  PubMed  CAS  Google Scholar 

  47. Direskeneli H, Keser G, D’Cruz D, Khamashta MA, Akoglu T, Yazici H, Yurdakul S, Hamuryudan V, Ozgun S, Goral AJ (1995) Anti-endothehal cell antibodies, endothehal proliferation and von Willebrand factor antigen in Behçet’s disease. Clin Rheumatol 14: 55–61

    Article  PubMed  CAS  Google Scholar 

  48. Uslu T, Erem C, Tosum M, Deger O (1997) Plasma endothelin-1 levels in Behçet’s disease. Clin Rheumatol 16: 59–61

    Article  PubMed  CAS  Google Scholar 

  49. Lee KH, Chung H-S, Bang D, Lee S (1998) The effect of the serum from patients with Behçet’s disease on the expression of endothelial cell adhesion molecules and the adhesion of T-lymphoeytes to vascular endothelial cells. Eighth International Congress on Behçet’s Disease. Reggio Emiha, P65

    Google Scholar 

  50. Rizzi R, Numo R, Bruno S, Stellaeci C, Dammaeco R (1998) Anti-endothelial cell autoantibodies in patients with Behçet’s disease. Eighth International Congress on Behçet’s Disease. Reggio Emiha, P69

    Google Scholar 

  51. Yamashita N, Nagafuchi H, Ueda Y, Mizoguchi M, Sakane T (1996) Cytokine profiles and expression of heat shock protein (hsp) 60 in skin biopsy speeimens in patients with Behçet’s disease. Annual Report of Behçet’s Disease Research Committee of Japan. Ministry of Health and Welfare of Japan, Tokyo, p 208

    Google Scholar 

  52. Parronchi P, Sampognaro S, Marchione T, Brugnolo F, LiGobbi F, Emmi L, Maggi E, Romagnani S (1996) Phenotypic and functional characterization of T-cell clones derived from cerebrospinal fluid in neuro-Behçet. Rev Rhum 63: 552

    Google Scholar 

  53. Alper G, Ozsan H, Girgin F, Buyukkececi F, Onat T (1998) Antiphospholoid antibodies in Behçet’s disease. Eighth International Congress on Behçet’s Disease. Reggio Emilla, October. P58

    Google Scholar 

  54. Al-Dalaan A, Al-Shaikh A, Bahabri S, Khan B, Al-Mayouf S, Elkhalifa M (1998) Study of HLA class 2 antigens allele distribution in Behçet’s disease among small populations. Eighth International Congress on Behçet’s Disease. Reggio Emilia, P11

    Google Scholar 

  55. Mochizuki M, Suzuki N, Takeno M, Nagafuchi H, Harada T, Kandeka H, Yamashita N, Hirayzma K, Nakajima T, Mizushima Y, Yamamoto S, Sakane T (1994) Fine antigen specificity of human gd T cell lines (Vg9+) established by repetitive Stimulation with a serotype (KTH-1) of a gram-positive bacterium, Streptococcus sanguis. Eur J Immunol 24:1536–1543

    Article  PubMed  CAS  Google Scholar 

  56. Frassanito MA, Dammaeco R, Silvestris N, Axxohni C, Numo R (1998) Tbl polarization of immune response in Behçet’s disease. Eighth International Congress on Behçet’s Disease. Reggio Emilha, P41

    Google Scholar 

  57. Aydintug AO, Tokgoz G, Ozoran K, Duzgun N, Gurler A, Tutkak H (1995) Elevated levels of soluble intracellular adhesion molecule-1 eorrelate with disease activity in Behçet’s disease. Rheumatol Int 15: 75–78

    Article  PubMed  CAS  Google Scholar 

  58. Ketteier R, Treudler R, Orfanos CE, Zoubouhs CHC (1998) Induction of lL-8 secretion and ICAM-1 expression by serum of patients with Adamantiades-Behçet’s disease in immortahzed human dermal microvascular endothehal dells in vitro is not regulated by IL-ß or TNF-a. Eighth International Congress on Behçet’s Disease. Reggio Emiha, p63

    Google Scholar 

  59. Yoshizaki K, Aoki C, Nishimoto N, Shima Y, Kishimoto T (1995) Serum levels of TNF-a and IL-6 in Behçet’s disease. Annual Report of Behçet’s Disease Research Committee of Japan. Ministry of Health and Weifare of Japan, Tokyo, p 208

    Google Scholar 

  60. Erken E, Gunesacar R, Soylu M (1996) Correlation between IL-8 and soluble GMP-140 levels in Behçet’s disease. Rev Rhum 63: 529

    Google Scholar 

  61. Treudler R, Ketteier R, Orfanos CE, Zouboulis ChC (1996) Increased serum levels of interleukin (IL) 1-beta and basic Fibroblast growth factor (bFGF) in severe Adamantiades Behçet’s disease. Rev Rhum 63: 529

    Google Scholar 

  62. Mege JL, Dillen N, Sanguedolce V, Gul A, Bongrand P, Roux H, Oeal L, Inanc M, Capo C (1993) Over-production of monocyte derived tumor necrosis factor alpha interleukin (IL) 6, IL-8 and increased neutrophil Superoxide generation in Behçet’s disease. A comparative study with famihal Mediterranean fever and heahhy subjects. J Rheumatol 20: 1544–1549

    PubMed  CAS  Google Scholar 

  63. Nishikawa M, Furukawa H, Kaneoka Miki T, Aikawa E, Sakane T (1993) Autocrine cytokine-production of neutrophils in Behçet’s disease. Annual Report of Behçet’s Disease Research Committee of Japan. Ministry of Health and Welfare of Japan, Tokyo, p 208

    Google Scholar 

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Lehner, T. (2001). Advances in the Immunopathogenesis of Behçet’s Disease. In: Behçet’s Disease. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56455-0_1

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  • DOI: https://doi.org/10.1007/978-3-642-56455-0_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63094-1

  • Online ISBN: 978-3-642-56455-0

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