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Ann Rheum Dis. Nov 2001; 60(11): 996–1002.
PMCID: PMC1753405

Behçet's disease: infectious aetiology, new autoantigens, and HLA-B51

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Selected References

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  • Sakane T, Takeno M, Suzuki N, Inaba G. Behçet's disease. N Engl J Med. 1999 Oct 21;341(17):1284–1291. [PubMed]
  • Mege JL, Dilsen N, Sanguedolce V, Gul A, Bongrand P, Roux H, Ocal L, Inanç M, Capo C. Overproduction 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 familial Mediterranean fever and healthy subjects. J Rheumatol. 1993 Sep;20(9):1544–1549. [PubMed]
  • Pronai L, Ichikawa Y, Nakazawa H, Arimori S. Enhanced superoxide generation and the decreased superoxide scavenging activity of peripheral blood leukocytes in Behçet's disease--effects of colchicine. Clin Exp Rheumatol. 1991 May-Jun;9(3):227–233. [PubMed]
  • Carletto A, Pacor ML, Biasi D, Caramaschi P, Zeminian S, Bellavite P, Bambara LM. Changes of neutrophil migration without modification of in vitro metabolism and adhesion in Behçet's disease. J Rheumatol. 1997 Jul;24(7):1332–1336. [PubMed]
  • Takeno M, Kariyone A, Yamashita N, Takiguchi M, Mizushima Y, Kaneoka H, Sakane T. Excessive function of peripheral blood neutrophils from patients with Behçet's disease and from HLA-B51 transgenic mice. Arthritis Rheum. 1995 Mar;38(3):426–433. [PubMed]
  • Tüzün B, Tüzün Y, Yurdakul S, Hamuryudan V, Yazici H, Ozyazgan Y. Neutrophil chemotaxis in Behçet's syndrome. Ann Rheum Dis. 1999 Oct;58(10):658–658. [PMC free article] [PubMed]
  • Sahin S, Akoğlu T, Direskeneli H, Sen LS, Lawrence R. Neutrophil adhesion to endothelial cells and factors affecting adhesion in patients with Behçet's disease. Ann Rheum Dis. 1996 Feb;55(2):128–133. [PMC free article] [PubMed]
  • Hallett MB, Lloyds D. Neutrophil priming: the cellular signals that say 'amber' but not 'green'. Immunol Today. 1995 Jun;16(6):264–268. [PubMed]
  • Direskeneli H, Eksioglu-Demiralp E, Kibaroglu A, Yavuz S, Ergun T, Akoglu T. Oligoclonal T cell expansions in patients with Behçet's disease. Clin Exp Immunol. 1999 Jul;117(1):166–170. [PMC free article] [PubMed]
  • Suzuki Y, Hoshi K, Matsuda T, Mizushima Y. Increased peripheral blood gamma delta+ T cells and natural killer cells in Behçet's disease. J Rheumatol. 1992 Apr;19(4):588–592. [PubMed]
  • Freysdottir J, Lau S, Fortune F. Gammadelta T cells in Behçet's disease (BD) and recurrent aphthous stomatitis (RAS). Clin Exp Immunol. 1999 Dec;118(3):451–457. [PMC free article] [PubMed]
  • Sugi-Ikai N, Nakazawa M, Nakamura S, Ohno S, Minami M. Increased frequencies of interleukin-2- and interferon-gamma-producing T cells in patients with active Behçet's disease. Invest Ophthalmol Vis Sci. 1998 May;39(6):996–1004. [PubMed]
  • Frassanito MA, Dammacco R, Cafforio P, Dammacco F. Th1 polarization of the immune response in Behçet's disease: a putative pathogenetic role of interleukin-12. Arthritis Rheum. 1999 Sep;42(9):1967–1974. [PubMed]
  • Mantaş C, Direskeneli H, Ekşioglu-Demiralp E, Akoglu T. Serum levels of Th2 cytokines IL-4 and IL-10 in Behçet's disease. J Rheumatol. 1999 Feb;26(2):510–512. [PubMed]
  • Raziuddin S, al-Dalaan A, Bahabri S, Siraj AK, al-Sedairy S. Divergent cytokine production profile in Behçet's disease. Altered Th1/Th2 cell cytokine pattern. J Rheumatol. 1998 Feb;25(2):329–333. [PubMed]
  • Yazici H. The place of Behçet's syndrome among the autoimmune diseases. Int Rev Immunol. 1997;14(1):1–10. [PubMed]
  • Suzuki N, Sakane T, Ueda Y, Tsunematsu T. Abnormal B cell function in patients with Behçet's disease. Arthritis Rheum. 1986 Feb;29(2):212–219. [PubMed]
  • Direskeneli H, Keser G, D'Cruz D, Khamashta MA, Akoğlu T, Yazici H, Yurdakul S, Hamuryudan V, Ozgün S, Goral AJ, et al. Anti-endothelial cell antibodies, endothelial proliferation and von Willebrand factor antigen in Behçet's disease. Clin Rheumatol. 1995 Jan;14(1):55–61. [PubMed]
  • Matsui T, Kurokawa M, Kobata T, Oki S, Azuma M, Tohma S, Inoue T, Yamamoto K, Nishioka K, Kato T. Autoantibodies to T cell costimulatory molecules in systemic autoimmune diseases. J Immunol. 1999 Apr 1;162(7):4328–4335. [PubMed]
  • Tokay S, Direskeneli H, Yurdakul S, Akoglu T. Anticardiolipin antibodies in Behçet's disease: a reassessment. Rheumatology (Oxford) 2001 Feb;40(2):192–195. [PubMed]
  • Ekşioglu-Demiralp E, Kibaroglu A, Direskeneli H, Yavuz S, Karsli F, Yurdakul S, Yazici H, Akoglu T. Phenotypic characteristics of B cells in Behçet's disease: increased activity in B cell subsets. J Rheumatol. 1999 Apr;26(4):826–832. [PubMed]
  • SEZER FN. The isolation of a virus as the cause of Behcet's diseases. Am J Ophthalmol. 1953 Mar;36(3):301–315. [PubMed]
  • Lehner T. The role of heat shock protein, microbial and autoimmune agents in the aetiology of Behçet's disease. Int Rev Immunol. 1997;14(1):21–32. [PubMed]
  • Sohn S, Lee ES, Kwon HJ, Lee SI, Bang D, Lee S. Expression of Th2 cytokines decreases the development of and improves Behçet's disease-like symptoms induced by herpes simplex virus in mice. J Infect Dis. 2001 Apr 15;183(8):1180–1186. [PubMed]
  • Calgüneri M, Kiraz S, Ertenli I, Benekli M, Karaarslan Y, Celik I. The effect of prophylactic penicillin treatment on the course of arthritis episodes in patients with Behçet's disease. A randomized clinical trial. Arthritis Rheum. 1996 Dec;39(12):2062–2065. [PubMed]
  • Hirohata S, Oka H, Mizushima Y. Streptococcal-related antigens stimulate production of IL6 and interferon-gamma by T cells from patients with Behcet's disease. Cell Immunol. 1992 Apr;140(2):410–419. [PubMed]
  • Mochizuki M, Suzuki N, Takeno M, Nagafuchi H, Harada T, Kaneoka H, Yamashita N, Hirayama K, Nakajima T, Mizushima Y, et al. Fine antigen specificity of human gamma delta T cell lines (V gamma 9+) established by repetitive stimulation with a serotype (KTH-1) of a gram-positive bacterium, Streptococcus sanguis. Eur J Immunol. 1994 Jul;24(7):1536–1543. [PubMed]
  • Nagvekar N, Jacobson LW, Willcox N, Vincent A. Epitopes expressed in myasthenia gravis (MG) thymomas are not recognized by patients' T cells or autoantibodies. Clin Exp Immunol. 1998 Apr;112(1):17–20. [PMC free article] [PubMed]
  • Lamb JR, Young DB. T cell recognition of stress proteins. A link between infectious and autoimmune disease. Mol Biol Med. 1990 Aug;7(4):311–321. [PubMed]
  • Lehner T, Lavery E, Smith R, van der Zee R, Mizushima Y, Shinnick T. Association between the 65-kilodalton heat shock protein, Streptococcus sanguis, and the corresponding antibodies in Behçet's syndrome. Infect Immun. 1991 Apr;59(4):1434–1441. [PMC free article] [PubMed]
  • Pervin K, Childerstone A, Shinnick T, Mizushima Y, van der Zee R, Hasan A, Vaughan R, Lehner T. T cell epitope expression of mycobacterial and homologous human 65-kilodalton heat shock protein peptides in short term cell lines from patients with Behçet's disease. J Immunol. 1993 Aug 15;151(4):2273–2282. [PubMed]
  • Direskeneli H, Hasan A, Shinnick T, Mizushima R, van der Zee R, Fortune F, Stanford MR, Lehner T. Recognition of B-cell epitopes of the 65 kDa HSP in Behçet's disease. Scand J Immunol. 1996 Apr;43(4):464–471. [PubMed]
  • Hasan A, Fortune F, Wilson A, Warr K, Shinnick T, Mizushima Y, van der Zee R, Stanford MR, Sanderson J, Lehner T. Role of gamma delta T cells in pathogenesis and diagnosis of Behcet's disease. Lancet. 1996 Mar 23;347(9004):789–794. [PubMed]
  • Kaneko S, Suzuki N, Yamashita N, Nagafuchi H, Nakajima T, Wakisaka S, Yamamoto S, Sakane T. Characterization of T cells specific for an epitope of human 60-kD heat shock protein (hsp) in patients with Behcet's disease (BD) in Japan. Clin Exp Immunol. 1997 May;108(2):204–212. [PMC free article] [PubMed]
  • Direskeneli H, Ekşioglu-Demiralp E, Yavuz S, Ergun T, Shinnick T, Lehner T, Akoglu T. T cell responses to 60/65 kDa heat shock protein derived peptides in Turkish patients with Behçet's disease. J Rheumatol. 2000 Mar;27(3):708–713. [PubMed]
  • Tanaka T, Yamakawa N, Koike N, Suzuki J, Mizuno F, Usui M. Behçet's disease and antibody titers to various heat-shock protein 60s. Ocul Immunol Inflamm. 1999 Jun;7(2):69–74. [PubMed]
  • Taşi B, Direskeneli H, Serdaroglu P, Akman-Demir G, Eraksoy M, Saruhan-Direskeneli G. Humoral immune response to mycobacterial heat shock protein (hsp)65 in the cerebrospinal fluid of neuro-Behçet patients. Clin Exp Immunol. 1998 Jul;113(1):100–104. [PMC free article] [PubMed]
  • Stanford MR, Kasp E, Whiston R, Hasan A, Todryk S, Shinnick T, Mizushima Y, Dumonde DC, van der Zee R, Lehner T. Heat shock protein peptides reactive in patients with Behçet's disease are uveitogenic in Lewis rats. Clin Exp Immunol. 1994 Aug;97(2):226–231. [PMC free article] [PubMed]
  • Hu W, Hasan A, Wilson A, Stanford MR, Li-Yang Y, Todryk S, Whiston R, Shinnick T, Mizushima Y, van der Zee R, et al. Experimental mucosal induction of uveitis with the 60-kDa heat shock protein-derived peptide 336-351. Eur J Immunol. 1998 Aug;28(8):2444–2455. [PubMed]
  • van Eden W, van der Zee R, Paul AG, Prakken BJ, Wendling U, Anderton SM, Wauben MH. Do heat shock proteins control the balance of T-cell regulation in inflammatory diseases? Immunol Today. 1998 Jul;19(7):303–307. [PubMed]
  • de Graeff-Meeder ER, van Eden W, Rijkers GT, Prakken BJ, Kuis W, Voorhorst-Ogink MM, van der Zee R, Schuurman HJ, Helders PJ, Zegers BJ. Juvenile chronic arthritis: T cell reactivity to human HSP60 in patients with a favorable course of arthritis. J Clin Invest. 1995 Mar;95(3):934–940. [PMC free article] [PubMed]
  • Bajramović JJ, Lassmann H, van Noort JM. Expression of alphaB-crystallin in glia cells during lesional development in multiple sclerosis. J Neuroimmunol. 1997 Sep;78(1-2):143–151. [PubMed]
  • Celet B, Akman-Demir G, Serdaroğlu P, Yentür SP, Taşci B, van Noort JM, Eraksoy M, Saruhan-Direskeneli G. Anti-alpha B-crystallin immunoreactivity in inflammatory nervous system diseases. J Neurol. 2000 Dec;247(12):935–939. [PubMed]
  • Gül A, Inanç M, Ocal L, Aral O, Koniçe M. Familial aggregation of Behçet's disease in Turkey. Ann Rheum Dis. 2000 Aug;59(8):622–625. [PMC free article] [PubMed]
  • Ohno S, Ohguchi M, Hirose S, Matsuda H, Wakisaka A, Aizawa M. Close association of HLA-Bw51 with Behçet's disease. Arch Ophthalmol. 1982 Sep;100(9):1455–1458. [PubMed]
  • Gül A, Hajeer AH, Worthington J, Barrett JH, Ollier WE, Silman AJ. Evidence for linkage of the HLA-B locus in Behçet's disease, obtained using the transmission disequilibrium test. Arthritis Rheum. 2001 Jan;44(1):239–240. [PubMed]
  • Verity DH, Marr JE, Ohno S, Wallace GR, Stanford MR. Behçet's disease, the Silk Road and HLA-B51: historical and geographical perspectives. Tissue Antigens. 1999 Sep;54(3):213–220. [PubMed]
  • Yazici H, Akokan G, Yalçin B, Müftüoğlu A. The high prevalence of HLA-B5 in Behçet's disease. Clin Exp Immunol. 1977 Nov;30(2):259–261. [PMC free article] [PubMed]
  • Yurdakul S, Günaydin I, Tüzün Y, Tankurt N, Pazarli H, Ozyazgan Y, Yazici H. The prevalence of Behçet's syndrome in a rural area in northern Turkey. J Rheumatol. 1988;15(5):820–822. [PubMed]
  • Falk K, Rötzschke O, Takiguchi M, Gnau V, Stevanović S, Jung G, Rammensee HG. Peptide motifs of HLA-B51, -B52 and -B78 molecules, and implications for Behćet's disease. Int Immunol. 1995 Feb;7(2):223–228. [PubMed]
  • Mizuki N, Inoko H, Ohno S. Pathogenic gene responsible for the predisposition of Behçet's disease. Int Rev Immunol. 1997;14(1):33–48. [PubMed]
  • Mizuki N, Ohno S. Immunogenetic studies of Behçet's disease. Rev Rhum Engl Ed. 1996 Jul-Sep;63(7-8):520–527. [PubMed]
  • Mizuki N, Ota M, Katsuyama Y, Yabuki K, Ando H, Goto K, Nakamura S, Bahram S, Ohno S, Inoko H. Association analysis between the MIC-A and HLA-B alleles in Japanese patients with Behçet's disease. Arthritis Rheum. 1999 Sep;42(9):1961–1966. [PubMed]
  • Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999 Jul 30;285(5428):727–729. [PubMed]
  • Zwirner NW, Dole K, Stastny P. Differential surface expression of MICA by endothelial cells, fibroblasts, keratinocytes, and monocytes. Hum Immunol. 1999 Apr;60(4):323–330. [PubMed]
  • de Smet MD, Yamamoto JH, Mochizuki M, Gery I, Singh VK, Shinohara T, Wiggert B, Chader GJ, Nussenblatt RB. Cellular immune responses of patients with uveitis to retinal antigens and their fragments. Am J Ophthalmol. 1990 Aug 15;110(2):135–142. [PubMed]
  • Yamamoto JH, Minami M, Inaba G, Masuda K, Mochizuki M. Cellular autoimmunity to retinal specific antigens in patients with Behçet's disease. Br J Ophthalmol. 1993 Sep;77(9):584–589. [PMC free article] [PubMed]
  • Wildner G, Thurau SR. Cross-reactivity between an HLA-B27-derived peptide and a retinal autoantigen peptide: a clue to major histocompatibility complex association with autoimmune disease. Eur J Immunol. 1994 Nov;24(11):2579–2585. [PubMed]
  • Baum H, Davies H, Peakman M. Molecular mimicry in the MHC: hidden clues to autoimmunity? Immunol Today. 1996 Feb;17(2):64–70. [PubMed]
  • Chicz RM, Urban RG, Gorga JC, Vignali DA, Lane WS, Strominger JL. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J Exp Med. 1993 Jul 1;178(1):27–47. [PMC free article] [PubMed]
  • Kurhan-Yavuz S, Direskeneli H, Bozkurt N, Ozyazgan Y, Bavbek T, Kazokoglu H, Eksioglu-Demiralp E, Wildner G, Diedrichs-Möhring M, Akoglu T. Anti-MHC autoimmunity in Behçet's disease: T cell responses to an HLA-B-derived peptide cross-reactive with retinal-S antigen in patients with uveitis. Clin Exp Immunol. 2000 Apr;120(1):162–166. [PMC free article] [PubMed]
  • Thurau SR, Diedrichs-Möhring M, Fricke H, Burchardi C, Wildner G. Oral tolerance with an HLA-peptide mimicking retinal autoantigen as a treatment of autoimmune uveitis. Immunol Lett. 1999 Jun 1;68(2-3):205–212. [PubMed]
  • Ehrlich GE. Vasculitis in Behçet's disease. Int Rev Immunol. 1997;14(1):81–88. [PubMed]
  • Gül A, Aslantas AB, Tekinay T, Koniçe M, Ozçelik T. Procoagulant mutations and venous thrombosis in Behçet's disease. Rheumatology (Oxford) 1999 Dec;38(12):1298–1299. [PubMed]
  • Chambers JC, Haskard DO, Kooner JS. Vascular endothelial function and oxidative stress mechanisms in patients with Behçet's syndrome. J Am Coll Cardiol. 2001 Feb;37(2):517–520. [PubMed]
  • Yazici H, Başaran G, Hamuryudan V, Hizli N, Yurdakul S, Mat C, Tüzün Y, Ozyazgan Y, Dimitriyadis I. The ten-year mortality in Behçet's syndrome. Br J Rheumatol. 1996 Feb;35(2):139–141. [PubMed]
  • Yazici H, Mat C, Deniz S, Iscimen A, Yurdakul S, Tuzun Y, Hekim N, Yazici Y. Sebum production is increased in Behçet's syndrome and even more so in rheumatoid arthritis. Clin Exp Rheumatol. 1987 Oct-Dec;5(4):371–374. [PubMed]
  • Miyamoto N, Mandai M, Suzuma I, Suzuma K, Kobayashi K, Honda Y. Estrogen protects against cellular infiltration by reducing the expressions of E-selectin and IL-6 in endotoxin-induced uveitis. J Immunol. 1999 Jul 1;163(1):374–379. [PubMed]
  • Buyon JP, Korchak HM, Rutherford LE, Ganguly M, Weissmann G. Female hormones reduce neutrophil responsiveness in vitro. Arthritis Rheum. 1984 Jun;27(6):623–630. [PubMed]
  • Ehrlich GE. Behçet disease and the emergence of thalidomide. Ann Intern Med. 1998 Mar 15;128(6):494–495. [PubMed]
  • Hamuryudan V, Mat C, Saip S, Ozyazgan Y, Siva A, Yurdakul S, Zwingenberger K, Yazici H. Thalidomide in the treatment of the mucocutaneous lesions of the Behçet syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998 Mar 15;128(6):443–450. [PubMed]
  • Bläss S, Engel JM, Burmester GR. The immunologic homunculus in rheumatoid arthritis. Arthritis Rheum. 1999 Dec;42(12):2499–2506. [PubMed]

Figures and Tables

Figure 1
Role of bacterial and human heat shock protein (HSP) 60/65 as T cell antigens in Behçet's disease. APC = antigen presenting cells.
Figure 2
An immunological model for the role of cross reactive retinal-S antigen (S-Ag) and HLA-B27/51 derived peptides in chronic posterior uveitis of Behçet's disease.

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