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Published in: Rheumatology International 3/2013

01-03-2013 | Original Article

Behçet’s disease: immunological relevance with arthritis of ankylosing spondylitis

Authors: Esin Aktas Cetin, Fulya Cosan, Umut Can Kucuksezer, Sema Bilgic, Yonca Cagatay, Ahmet Gul, Gunnur Deniz

Published in: Rheumatology International | Issue 3/2013

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Abstract

Behçet’s disease (BD) is a multi-system inflammatory disorder, in which cytokine balance is polarized to Th1. In this study, the cell surface molecule expression, Th1/Th2, inflammatory cytokine levels in blood, and synovial fluid of CD3+ T lymphocytes in BD were investigated. The study group consisted of 10 BD, 10 ankylosing spondylitis (AS) patients with peripheral arthritis, and 10 healthy subjects. Expression of cell surface molecules, intracellular IL-2, IL-5, IL-8, IL-10, IL-12, IFN-γ, and TNF-α levels in CD3+ T lymphocytes were determined by flow cytometry in synovial and peripheral blood mononuclear cells (PBMCs). Synovial and plasma cytokine levels were measured by ELISA and CBA. In PBMCs, CD4, CD25, HLA-DR expression and intracellular IL-12, and TNF-α levels of CD3+ T lymphocytes were statistically increased in BD patients compared to healthy subjects. Compare to AS patients, CD25 and HLA-DR surface expression and intracellular IFN-γ and TNF-α levels in T cells were significantly elevated in BD patients. In BD patients, there was an increase in IL-8 secretion; however, in AS patients, both Th1- and Th2-type cytokines were increased compare to healthy subjects. Intracellular cytokine expression did not show any difference in BD patients; however, IL-12 content of synovial fluid was significantly increased compared to AS patients. Our findings revealed that Th1 polarization occurred in both peripheral blood and synovial fluid of BD patients with arthritis. It is found no difference between synovial fluid analysis of BD and AS patients, showing the similarities in the pathogenesis of both diseases.
Literature
1.
go back to reference The International Study Group for Behçet’s Disease (1992) Evaluation of diagnostic (‘classification’) criteria in Behçet’s disease—towards internationally agreed criteria. Br J Rheumatol 31:299–308CrossRef The International Study Group for Behçet’s Disease (1992) Evaluation of diagnostic (‘classification’) criteria in Behçet’s disease—towards internationally agreed criteria. Br J Rheumatol 31:299–308CrossRef
2.
go back to reference Kaneko F, Togashi A, Saito S et al (2011) Behçet’s disease (Adamantiades-Behçet’s disease). Clin Dev Immunol 2011:681956PubMedCrossRef Kaneko F, Togashi A, Saito S et al (2011) Behçet’s disease (Adamantiades-Behçet’s disease). Clin Dev Immunol 2011:681956PubMedCrossRef
3.
go back to reference Esin S, Gül A, Hodara V, Jeddi-Tehrani M, Dilsen N, Koniçe M, Andersson R, Wigzell H (1997) Peripheral blood T cell expansions in patients with Behcet’s disease. Clin Exp Immunol 107:520–527PubMedCrossRef Esin S, Gül A, Hodara V, Jeddi-Tehrani M, Dilsen N, Koniçe M, Andersson R, Wigzell H (1997) Peripheral blood T cell expansions in patients with Behcet’s disease. Clin Exp Immunol 107:520–527PubMedCrossRef
4.
go back to reference Kim J, Park JA, Lee EY, Lee YJ, Song YW, Lee EB (2010) Imbalance of Th17 to Th1 cells in Behçet’s disease. Clin Exp Rheumatol 28:S16–S19PubMed Kim J, Park JA, Lee EY, Lee YJ, Song YW, Lee EB (2010) Imbalance of Th17 to Th1 cells in Behçet’s disease. Clin Exp Rheumatol 28:S16–S19PubMed
5.
go back to reference Ilhan F, Demir T, Türkçüoğlu P, Turgut B, Demir N, Gödekmerdan A (2008) Th1 polarization of the immune response in uveitis in Behçet’s disease. Can J Ophthalmol 43:105–108PubMedCrossRef Ilhan F, Demir T, Türkçüoğlu P, Turgut B, Demir N, Gödekmerdan A (2008) Th1 polarization of the immune response in uveitis in Behçet’s disease. Can J Ophthalmol 43:105–108PubMedCrossRef
6.
go back to reference Rose NR, Bona C (1993) Defining criteria for autoimmune diseases (Witebsky’s postulates revisited). Immunol Today 14:426–430PubMedCrossRef Rose NR, Bona C (1993) Defining criteria for autoimmune diseases (Witebsky’s postulates revisited). Immunol Today 14:426–430PubMedCrossRef
7.
go back to reference Harrington LE, Hatton RD, Mangan PR et al (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132PubMedCrossRef Harrington LE, Hatton RD, Mangan PR et al (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132PubMedCrossRef
8.
go back to reference Moll C, Bogas M, Gómez-Puerta JA et al (2009) Macroscopic features of knee synovitis in early untreated Behçet disease and psoriatic arthritis. Clin Rheumatol 28:1053–1057PubMedCrossRef Moll C, Bogas M, Gómez-Puerta JA et al (2009) Macroscopic features of knee synovitis in early untreated Behçet disease and psoriatic arthritis. Clin Rheumatol 28:1053–1057PubMedCrossRef
9.
go back to reference Cañete JD, Celis R, Noordenbos T et al (2009) Distinct synovial immunopathology in Behçet disease and psoriatic arthritis. Arthritis Res Ther 11:R17PubMedCrossRef Cañete JD, Celis R, Noordenbos T et al (2009) Distinct synovial immunopathology in Behçet disease and psoriatic arthritis. Arthritis Res Ther 11:R17PubMedCrossRef
10.
go back to reference Amberger M, Groll S, Günaydin I, Deuter C, Vonthein R, Kötter I (2007) Intracellular cytokine patterns in Behçet’s disease in comparison to ankylosing spondylitis–influence of treatment with interferon-alpha2a. Clin Exp Rheumatol 25:S52–S57PubMed Amberger M, Groll S, Günaydin I, Deuter C, Vonthein R, Kötter I (2007) Intracellular cytokine patterns in Behçet’s disease in comparison to ankylosing spondylitis–influence of treatment with interferon-alpha2a. Clin Exp Rheumatol 25:S52–S57PubMed
11.
go back to reference Dalghous AM, Freysdottir J, Fortune F (2006) Expression of cytokines, chemokines, and chemokine receptors in oral ulcers of patients with Behcet’s disease (BD) and recurrent aphthous stomatitis is Th1-associated, although Th2-association is also observed in patients with BD. Scand J Rheumatol 35:472–475PubMedCrossRef Dalghous AM, Freysdottir J, Fortune F (2006) Expression of cytokines, chemokines, and chemokine receptors in oral ulcers of patients with Behcet’s disease (BD) and recurrent aphthous stomatitis is Th1-associated, although Th2-association is also observed in patients with BD. Scand J Rheumatol 35:472–475PubMedCrossRef
12.
go back to reference Charteris DG, Barton K, McCartney AC, Lightman SL (1992) CD4+ lymphocyte involvement in ocular Behçet’s disease. Autoimmunity 12:201–206PubMedCrossRef Charteris DG, Barton K, McCartney AC, Lightman SL (1992) CD4+ lymphocyte involvement in ocular Behçet’s disease. Autoimmunity 12:201–206PubMedCrossRef
13.
go back to reference Mochizuki M, Morita E, Yamamoto S, Yamana S (1997) Characteristics of T cell lines established from skin lesions of Behçet’s disease. J Dermatol Sci 15:9–13PubMedCrossRef Mochizuki M, Morita E, Yamamoto S, Yamana S (1997) Characteristics of T cell lines established from skin lesions of Behçet’s disease. J Dermatol Sci 15:9–13PubMedCrossRef
14.
go back to reference Gül A, Esin S, Dilsen N, Koniçe M, Wigzell H, Biberfeld P (1995) Immunohistology of skin pathergy reaction in Behçet’s disease. Br J Dermatol 132:901–907PubMedCrossRef Gül A, Esin S, Dilsen N, Koniçe M, Wigzell H, Biberfeld P (1995) Immunohistology of skin pathergy reaction in Behçet’s disease. Br J Dermatol 132:901–907PubMedCrossRef
15.
go back to reference Sugi-Ikai N, Nakazawa M, Nakamura S, Ohno S, Minami M (1998) Increased frequencies of interleukin-2- and interferon-gamma-producing T cells in patients with active Behçet’s disease. Invest Ophthalmol Vis Sci 39:996–1004PubMed Sugi-Ikai N, Nakazawa M, Nakamura S, Ohno S, Minami M (1998) Increased frequencies of interleukin-2- and interferon-gamma-producing T cells in patients with active Behçet’s disease. Invest Ophthalmol Vis Sci 39:996–1004PubMed
16.
go back to reference Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75:163–189PubMedCrossRef Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75:163–189PubMedCrossRef
17.
go back to reference Akdis M, Burgler S, Crameri R et al (2011) Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. J Allergy Clin Immunol 127(3):701-21.e1-70 Akdis M, Burgler S, Crameri R et al (2011) Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases. J Allergy Clin Immunol 127(3):701-21.e1-70
18.
go back to reference Raziuddin S, al-Dalaan A, Bahabri S, Siraj AK, al-Sedairy S (1998) Divergent cytokine production profile in Behçet’s disease. Altered Th1/Th2 cell cytokine pattern. J Rheumatol 25:329–333PubMed Raziuddin S, al-Dalaan A, Bahabri S, Siraj AK, al-Sedairy S (1998) Divergent cytokine production profile in Behçet’s disease. Altered Th1/Th2 cell cytokine pattern. J Rheumatol 25:329–333PubMed
19.
go back to reference Sayinalp N, Ozcebe OI, Ozdemir O, Haznedaroğlu IC, Dündar S, Kirazli S (1996) Cytokines in Behçet’s disease. J Rheumatol 23:321–322PubMed Sayinalp N, Ozcebe OI, Ozdemir O, Haznedaroğlu IC, Dündar S, Kirazli S (1996) Cytokines in Behçet’s disease. J Rheumatol 23:321–322PubMed
20.
go back to reference Evereklioglu C, Er H, Türköz Y, Cekmen M (2002) Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet’s disease. Mediators Inflamm 11:87–93PubMedCrossRef Evereklioglu C, Er H, Türköz Y, Cekmen M (2002) Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet’s disease. Mediators Inflamm 11:87–93PubMedCrossRef
21.
go back to reference Alpsoy E, Cayirli C, Er H, Yilmaz E (1998) The levels of plasma interleukin-2 and soluble interleukin-2R in Behçet’s disease: a marker of disease activity. J Dermatol 25:513–516PubMed Alpsoy E, Cayirli C, Er H, Yilmaz E (1998) The levels of plasma interleukin-2 and soluble interleukin-2R in Behçet’s disease: a marker of disease activity. J Dermatol 25:513–516PubMed
22.
go back to reference Ertenli I, Kiraz S, Calgüneri M et al (2001) Synovial fluid cytokine levels in Behçet’s disease. Clin Exp Rheumatol 19:S37–S41PubMedCrossRef Ertenli I, Kiraz S, Calgüneri M et al (2001) Synovial fluid cytokine levels in Behçet’s disease. Clin Exp Rheumatol 19:S37–S41PubMedCrossRef
23.
go back to reference Aridogan BC, Yildirim M, Baysal V, Inaloz HS, Baz K, Kaya S (2003) Serum Levels of IL-4, IL-10, IL-12, IL-13 and IFN-gamma in Behçet’s disease. J Dermatol 30:602–607PubMed Aridogan BC, Yildirim M, Baysal V, Inaloz HS, Baz K, Kaya S (2003) Serum Levels of IL-4, IL-10, IL-12, IL-13 and IFN-gamma in Behçet’s disease. J Dermatol 30:602–607PubMed
24.
go back to reference Nagalakshmi ML, Murphy E, McClanahan T, de Waal Malefyt R (2004) Expression patterns of IL-10 ligand and receptor gene families provide leads for biological characterization. Int Immunopharmacol 4:577–592PubMedCrossRef Nagalakshmi ML, Murphy E, McClanahan T, de Waal Malefyt R (2004) Expression patterns of IL-10 ligand and receptor gene families provide leads for biological characterization. Int Immunopharmacol 4:577–592PubMedCrossRef
25.
go back to reference de Waal Malefyt R, Haanen J, Spits H et al (1991) Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174:915–924PubMedCrossRef de Waal Malefyt R, Haanen J, Spits H et al (1991) Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174:915–924PubMedCrossRef
26.
go back to reference Mizuki N, Meguro A, Ota M et al (2010) Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci. Nat Genet 42:703–706PubMedCrossRef Mizuki N, Meguro A, Ota M et al (2010) Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci. Nat Genet 42:703–706PubMedCrossRef
27.
go back to reference Remmers EF, Cosan F, Kirino Y et al (2010) Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet’s disease. Nat Genet 42:698–702PubMedCrossRef Remmers EF, Cosan F, Kirino Y et al (2010) Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet’s disease. Nat Genet 42:698–702PubMedCrossRef
28.
go back to reference Mukaida N (2000) Interleukin-8: an expanding universe beyond neutrophil chemotaxis and activation. Int J Hematol 72:391–398PubMed Mukaida N (2000) Interleukin-8: an expanding universe beyond neutrophil chemotaxis and activation. Int J Hematol 72:391–398PubMed
29.
go back to reference Durmazlar SP, Ulkar GB, Eskioglu F, Tatlican S, Mert A, Akgul A (2009) Significance of serum interleukin-8 levels in patients with Behcet’s disease: high levels may indicate vascular involvement. Int J Dermatol 48:259–264PubMedCrossRef Durmazlar SP, Ulkar GB, Eskioglu F, Tatlican S, Mert A, Akgul A (2009) Significance of serum interleukin-8 levels in patients with Behcet’s disease: high levels may indicate vascular involvement. Int J Dermatol 48:259–264PubMedCrossRef
30.
go back to reference Freire Ade L, Bertolo MB, de Pinho AJ, Samara AM Jr, Fernandes SR (2004) Increased serum levels of interleukin-8 in polyarteritis nodosa and Behçet’s disease. Clin Rheumatol 23:203–205PubMedCrossRef Freire Ade L, Bertolo MB, de Pinho AJ, Samara AM Jr, Fernandes SR (2004) Increased serum levels of interleukin-8 in polyarteritis nodosa and Behçet’s disease. Clin Rheumatol 23:203–205PubMedCrossRef
31.
go back to reference Zouboulis CC, Katsantonis J, Ketteler R et al (2000) Adamantiades-Behçet’s disease: interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells. Arch Dermatol Res 292:279–284PubMedCrossRef Zouboulis CC, Katsantonis J, Ketteler R et al (2000) Adamantiades-Behçet’s disease: interleukin-8 is increased in serum of patients with active oral and neurological manifestations and is secreted by small vessel endothelial cells. Arch Dermatol Res 292:279–284PubMedCrossRef
32.
go back to reference Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV, Boldin MP (1999) Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 17:331–367PubMedCrossRef Wallach D, Varfolomeev EE, Malinin NL, Goltsev YV, Kovalenko AV, Boldin MP (1999) Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 17:331–367PubMedCrossRef
33.
go back to reference Ahn JK, Yu HG, Chung H, Park YG (2006) Intraocular cytokine environment in active Behçet uveitis. Am J Ophthalmol 142:429–434PubMedCrossRef Ahn JK, Yu HG, Chung H, Park YG (2006) Intraocular cytokine environment in active Behçet uveitis. Am J Ophthalmol 142:429–434PubMedCrossRef
34.
go back to reference Oztas MO, Onder M, Gurer MA, Bukan N, Sancak B (2005) Serum interleukin 18 and tumour necrosis factor-alpha levels are increased in Behcet’s disease. Clin Exp Dermatol 30:61–63PubMedCrossRef Oztas MO, Onder M, Gurer MA, Bukan N, Sancak B (2005) Serum interleukin 18 and tumour necrosis factor-alpha levels are increased in Behcet’s disease. Clin Exp Dermatol 30:61–63PubMedCrossRef
35.
go back to reference Pay S, Erdem H, Pekel A et al (2006) Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet’s disease. Does interleukin-1beta play a major role in Behçet’s synovitis? Rheumatol Int 26:608–613PubMedCrossRef Pay S, Erdem H, Pekel A et al (2006) Synovial proinflammatory cytokines and their correlation with matrix metalloproteinase-3 expression in Behçet’s disease. Does interleukin-1beta play a major role in Behçet’s synovitis? Rheumatol Int 26:608–613PubMedCrossRef
36.
go back to reference Turan B, Pfister K, Diener PA et al (2008) Soluble tumour necrosis factor receptors sTNFR1 and sTNFR2 are produced at sites of inflammation and are markers of arthritis activity in Behçet’s disease. Scand J Rheumatol 37:135–141PubMedCrossRef Turan B, Pfister K, Diener PA et al (2008) Soluble tumour necrosis factor receptors sTNFR1 and sTNFR2 are produced at sites of inflammation and are markers of arthritis activity in Behçet’s disease. Scand J Rheumatol 37:135–141PubMedCrossRef
Metadata
Title
Behçet’s disease: immunological relevance with arthritis of ankylosing spondylitis
Authors
Esin Aktas Cetin
Fulya Cosan
Umut Can Kucuksezer
Sema Bilgic
Yonca Cagatay
Ahmet Gul
Gunnur Deniz
Publication date
01-03-2013
Publisher
Springer-Verlag
Published in
Rheumatology International / Issue 3/2013
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-012-2446-9

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