Cytokines of the Th1 and Th2 type in sera of rheumatoid arthritis patients; correlations with anti-Hsp40 immune response and diagnostic markers

• Autorzy: Tukaj S. , Kotlarz A. , Jozwik A. , Smolenska Z. , Bryl E. , Witkowski J. M. , Lipinska B.
• Języki publikacji: EN

Abstrakty

EN

 Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease which affects approximately 1 % of the population worldwide. Recent research on the role of heat shock proteins (Hsps) in RA development indicates that they may have pro- or anti-inflammatory effect, most probably via modulating cytokine secretion. We investigated type Th1 (INFγ, TNFα, IL-2) and type Th2 (IL-10, IL-6, IL-4) cytokine levels in sera of RA patients and healthy controls, using flow cytometric bead array assay, and searched for correlations between the cytokine levels and serum antibodies against bacterial (DnaJ) and human (Hdj1, Hdj2 and Hdj3) Hsp40 proteins, as well as clinical and laboratory parameters. The levels of all cytokines studied were significantly increased in RA patients; the highest increase relative to healthy controls (7-fold) was observed for IL-6 and its levels correlated positively with the antibodies directed to DnaJ and to the C-terminal domain of Hdj2, and with diagnostic parameters (DAS 28, Steinbrocker RTG criteria, ARA/7, ESR, TEN, SW and GH). INFγ levels correlated negatively with DAS 28, ESR, TEN and SW. No correlations were found for TNFα, IL-2 or IL-4. Our results support the hypothesis of Hsp40 involvement in RA as well as indicate that IL-6 serum level is a good marker of the RA activity.

Słowa kluczowe

EN

cytokine; serum; human disease; rheumatoid arthritis; patient; heat shock protein; chronic disease; immune response; diagnostic marker; etiology; autoimmune disease; pathogenesis; diagnostic parameter

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2010
• Tom: 57
• Numer: 3
• Opis fizyczny: p.327-332,fig.,ref.

Twórcy

autor

Tukaj S.

• Department of Biochemistry, University of Gdansk, Gdansk, Poland

autor

Kotlarz A.

autor

Jozwik A.

autor

Smolenska Z.

autor

Bryl E.

autor

Witkowski J. M.

autor

Lipinska B.

Bibliografia

• Albani S, Keystone EC, Nelson JL, Ollier WE, La Cava A, Montemayor AC, Weber DA, Montecucco C, Martini A, Carson DA (1995) Positive selection in autoimmunity: abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis. Nat Med 1: 448-452. 
• Albani S, Carson DA (1996) A multistep molecular mimicry hypothesis for the pathogenesis of rheumatoid arthritis. Immunol Today 17: 466-470. 
• Altomonte L, Zoli A, Mirone L, Scolieri P, Magaró M (1992) Serum levels of interleukin-1b, tumour necrosis factor-α and interleukin-2 in rheumatoid arthritis. Correlation with disease activity. Clin Rheumatol 11: 202-205. 
• Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al. (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31: 315-324. 
• Billiau A (1996) Interferon-γ: biology and role in pathogenesis. Adv Immunol 62: 61-130. 
• Bryl E, Daca A, Jóźwik A, Witkowski JM (2009) Human CD4(low)CD25(high) regulatory T cells indiscriminately kill autologous activated T cells. Immunology doi: 10.1111/j.1365-2567.20081.x  
• Cheetham ME, Caplan AJ (1998) Structure, function and evolution of DnaJ: conservation and adaptation of chaperone function. Cell Stress Chaperones 3: 28-36. 
• De Benedetti F, Massa M, Pignatti P, Albani S, Novick D, Martini AJ (1994) Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 93: 2114-2119. 
• van Eden W, van der Zee R, Prakken B (2005) Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5: 318-330. 
• van Eden W, Wick G, Albani S, Cohen I (2007) Stress, heat shock proteins, and autoimmunity: how immune responses to heat shock proteins are to be used for the control of chronic inflammatory diseases. Ann N Y Acad Sci 1113: 217-237. 
• Funauchi M, Sugishima H, Minoda M, Horiuchi A (1991) Serum level of interferon-gamma in autoimmune diseases. Tohoku J Exp Med 164: 259-267. 
• Fournier C (2005) Where do T cells stand in rheumatoid arthritis? Joint Bone Spine 72: 527-532.  
• Fröde TS, Tenconi P, Debiasi MR, Medeiros YS (2002) Tumour necrosis factor-alpha, interleukin-2 soluble receptor and different inflammatory parameters in patients with rheumatoid arthritis. Mediators Inflamm 11: 345-349.  
• Groux H, Cottrez F, Houssiau FA, Devogelaer JP, Van Damme J., de Deuxchaisnes CN, Van Snick J (2003) The complex role of interleukin-10 in autoimmunity. J Autoimmun 20: 281-285. 
• Houssiau FA, Devogelaer JP, Van Damme J, de Deuxchaisnes CN, Van Snick J (1988) Interleukin-6 in synovial fluid and serum of patients with rheumatoid arthritis and other inflammatory arthritides. Arthritis Rheum 31: 784-788. 
• Kampinga HH, Hageman J, Vos MJ, Kubota H, Tanguay RM, Bruford EA, Cheetham ME, Chen B, Hightower LE (2009) Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones 14: 105-111. 
• Kamphuis S, Kuis W, de Jager W, Teklenburg G, Massa M, Gordon G, Boerhof M, Rijkers GT, Uiterwaal CS, Otten HG, Sette A, Albani S, Prakken BJ (2005) Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis. Lancet 366: 50-56. 
• Klareskog L, Catrina AI, Paget S (2009) Rheumatoid arthritis. Lancet 373: 659-672. 
• Krzewski K, Kunikowska D, Wysocki J, Kotlarz A, Thompkins P, Ashraf W, Lindsey N, Picksley S, Glosnicka R, Lipinska B (2003) Characterization of the anti-DnaJ monoclonal antibodies and their use to compare immunological properties of DnaJ and its human homologue HDJ-1. Cell Stress Chaperones 8: 8-17. 
• Lacki JK, Klama K, Mackiewicz SH, Mackiewicz U, Müller W (1995) Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: preliminary report. Inflamm Res 44: 24-26. 
• Lacki JK, Samborski W, Mackiewicz SH (1997) Interleukin-10 and interleukin-6 in lupus erythematosus and rheumatoid arthritis, correlations with acute phase proteins. Clin Rheumatol 16: 275-278. 
• Lee DM, Weinblatt ME (2001) Rheumatoid arthritis. Lancet 358: 903-911. 
• Machold KP, Neumann K, Smolen JS (1992) Recombinant human interferon gamma in the treatment of rheumatoid arthritis: double blind placebo controlled study. Ann Rheum Dis 51: 1039-1043. 
• Massa M, Passalia M, Manzoni SM, Campanelli R, Ciardelli L, Yung GP, Kamphuis S, Pistorio A, Meli V, Sette A, Prakken B, Martini A, Albani S (2007) Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis. Arthritis Rheum 56: 1648-1657. 
• Minami R, Sakai K, Miyamura T, Yamamoto M, Suematsu E (2006) The role of CD4+CD25+regulatory T cells in patients with rheumatoid Arthritis. Nihon Rinsho Meneki Gakkai Kaishi 29: 37-42. 
• Prakken B, Kuis W, van Eden W, Albani S (2002a) Heat shock proteins in juvenile idiopathic arthritis: keys for understanding remitting arthritis and candidate antigens for immune therapy. Curr Rheumatol Rep 4: 466-473. 
• Prakken BJ, Roord S, van Kooten PJ, Wagenaar JP, van Eden W, Albani S, Wauben MH (2002b) Inhibition of adjuvant-induced arthritis by interleukin-10-driven regulatory cells induced via nasal administration of a peptide analog of an arthritis-related heat-shock protein 60 T cell epitope. Arthritis Rheum 46: 1937-1946. 
• Prakken BJ, Samodal R, Le TD, Giannoni F, Yung GP, Scavulli J, Amox D, Roord S, de Kleer I, Bonnin D, Lanza P, Berry C, Massa M, Billetta R, Albani S (2004) Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc Natl Acad Sci USA 101: 4228-4233.  
• Raziuddin S, Bahabri S, Al-Dalaan A, Siraj AK, Al-Sedairy S (1998) A mixed Th1/Th2 cell cytokine response predominates in systemic onset juvenile rheumatoid arthritis: immunoregulatory IL-10 function. Clin Immunol Immunopathol 86: 192-198. 
• Rivas D, Mozo L, Zamorano J, Gayo A, Torre-Alonso JC, Rodríguez A, Gutiérrez CJ (1995) Upregulated expression of IL-4 receptors and increased levels of IL-4 in rheumatoid arthritis patients. J Autoimmun 8: 587-600. 
• Schulze-Koops H, Kalden JR (2001) The balance of Th1/Th2 cytokines in rheumatoid arthritis. Best Pract Res Clin Rheumatol 15: 677-6791. 
• Shahrara S, Huang Q, Mandelin AM, Pope RM (2008) TH-17 cells in rheumatoid arthritis. Arthritis Res Ther 10: R93. 
• Skapenko A, Leipe J, Lipsky PE, Schulze-Koops H (2005) The role of the T cell in autoimmune inflammation. Arthritis Res Ther 7: S4-14.  
• Terada K, Mori M (2000) Human DnaJ homologs dj2 and dj3, and bag-1 are positive cochaperones of hsc70. J Biol Chem 275: 24728-24734. 
• Tukaj S, Kotlarz A, Jozwik A, Smolenska Z, Bryl E, Witkowski JM, Lipinska B (2010) Hsp40 proteins modulate humoral and cellular immune response in rheumatoid arthritis patients. Cell Stress Chaperones. 15: 555-566. Epub 2010 Feb 2. 
• Uchiyama Y, Yoshida H, Koike N, Hayakawa N, Sugita A, Nishimura T, Mihara M (2008) Anti-IL-6 receptor antibody increases blood IL-6 level via the blockade of IL-6 clearance, but not via the induction of IL-6 production. Int Immunopharmacol 8: 1595-601.  
• Verhoef C (2001) T1/T2 cell balance in rheumatoid arthritis. Clin Appl Immunol Rev 1: 153-161.
• Wieten L, Broere F, van der Zee R, Koerkamp EK, Wagenaar J, van Eden W (2007) Cell stress induced HSP are targets of regulatory T cells: a role for HSP inducing compounds as anti-inflammatory immuno-modulators? FEBS Lett 581: 3716-3722.  
• Zlacka D, Vavrincova P, Hien Nguyen TT, Hromadnikova I (2006) Frequency of anti-hsp60, -65 and -70 antibodies in sera of patients with juvenile idiopathic arthritis. J Autoimmun 27: 81-88. 
• Zylicz M, Yamamoto T, McKittrick N, Sell S, Georgopoulos C (1985) Purification and properties of the dnaJ replication protein of Escherichia coli. J Biol Chem 260: 7591-758.