Circulating Heat Shock Protein 90 (HSP90) in patients with rheumatoid arthritis and axial spondylarthritis


Authors: L. Procházková 1;  J. Hulejová 2;  P. Němec 1;  L. Šenolt 2
Authors‘ workplace: Revmatologie, II. interní klinika, FN u sv. Anny, Brno 1;  Revmatologický ústav a Revmatologická klinika, 1. LF UK, Praha 2
Published in: Čes. Revmatol., 21, 2013, No. 4, p. 164-169.
Category: Original Papers

Overview

Introduction:
Heat Shock Protein 90 (HSP90) is involved in the regulation of immunological and inflammatory responses, and its inhibition has been effectively used in the treatment of several animal models of autoimmune diseases. The role of HSP90 in rheumatic diseases is not precisely known. The aim of our study was to analyze the levels of HSP90 in the serum of patients with rheumatoid arthritis (RA) and compare them with those in patients with axial spondylarthritis (AxSpA) and in healthy volunteers and to evaluate the association of these findings with disease activity.

Methods:
HSP90 was analyzed in peripheral blood of 58 patients with RA, 68 patients with AxSpA and 30 healthy volunteers. Disease activity in patients with RA was assessed by the DAS28 score and in patients with AxSPA by BASDAI index. The concentration of serum C-reactive protein (CRP), autoantibodies (rheumatoid factors, anti-cyclic citrullinated peptides) and the presence of HLA-B27 were measured by standard methods.

Results:
Although the serum levels of HSP90 were not different between the groups of patients and healthy controls, patients with RA treated with anti-TNF therapy had significantly lower HSP90 serum levels compared with those without this treatment (6.03, 95% CI 3,77-12,00 vs. 8.46, 95% CI 4.26 to 18.78 ng/ml, p = 0.016). No relationship between serum HSP90 and clinical activity of both diseases was observed, however, in RA patients a positive correlation between serum HSP90 and CRP was found (p = 0.017). Circulating HSP90 had no relationship to autoantibody activity in RA.

Conclusion:
The results of this study highlight the potential significance of HSP90 in the regulation of the inflammatory process in rheumatoid arthritis.

Key words:
Rheumatoid arthritis, axial spondylarthritis, Heat Shock Proteins, disease activity


Sources

1. Middleton GD. Prospects for Stopping the Runaway Train by Reintroduction of tolerance. J Clin Cell Immunol 2012; S6: 004 .

2. Keijzer C, Wieten L, van Herwijnen M et al. Heat shock proteins are therapeutic targets in autoimmune diseases and other chronic inflammatory conditions. Expert Opin Ther Targets. 2012 Sep; 16(9): 849–57.

3. Shield A M, Panayi G S, Corrigall V M, A new-age for biologic therapies: long therm drug free therapy with Bip? Frontiers in imunology 2012; 3: 17.

4. Srivastava P. Roles of heat-shock proteins in innate and adaptive immunity. Nature Reviews Immunology, 2002; 2(3): 185–194.

5. Barreto A, Gonzalez JM, Kabingu E, et al. Stress-induced release of HSC70 from human tumors. Cellular Immunology, 2003; 222(2): 97–104.

6. Calderwood SK, Stevenson MA, Murshid A. Heat shock proteins, autoimmunity, and cancer treatment. Autoimmune Dis. 2012; 2012: 486069.

7. Růčková E, Müller P, Vojtěšek B. Hsp90 – a Target for Anticancer Therapy Klin Onkol 2011; 24(5): 329–337.

8. Tsan MF, Gao B. Heat shock protein and innate immunity. Cellular & Molecular Immunology, 2004; 1(4): 274–279.

9. Bae J, Munshi A, Li C, Samur M, et al. Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells. J Immunol. 2013; 190(3): 1360–71.

10. Shimp SK 3rd, Parson CD, Regna NL, et al. HSP90 inhibition by 17-DMAG reduces inflammation in J774 macrophages through suppression of Akt and nuclear factor-κB pathways. Inflamm Res. 2012; 61(5): 521–33.

11. Rice JW, Veal JM, Fadden RP, et al. Small Molecule Inhibitors of Hsp90 potently affect inflammatory disease pathways and exhibit activity in models of rheumatoid arthritis. Arthritis Rheum 2008; 581(12): 3765–3775.

12. Han JM, Kwon NH, Lee JY, et al. Identification of gp96 as a novel target for treatment of autoimmune disease in mice. PLoS One. 2010 Mar 23; 5(3): e9792.

13. Tomcik M, Zerr P, Pitkowski J, et al. Heat shock protein 90 (Hsp90) inhibition targets canonical TGF-β signalling to prevent fibrosis. Ann Rheum Dis. 2013 May 9. [Epub ahead of print].

14. Schoof N, von Bonin F, Trümper, L et al. HSP90 is essential for Jak-STAT signaling in classical Hodgkin lymphoma cells. Cell Communication and Signaling 2009; 7: 17.

15. Huang QQ, Sobkoviak R, Jockheck-Clark AR, et al. Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling. J Immunol. 2009; 182(8): 4965–73.

16. Hayem G, Bandt MD, Palazzo E, et al. Anti-heat shock protein 70 kDa and 90 kDa antibodiest in serum of patients with rheumatoid arthritis. Ann Rheum Dis 1999; 58: 291–296.

17. Hashiramoto A, Murata M, Kawazoe T, et al. Heat shock protein 90 maintains the tumour-like character of rheumatoid synovial cells by stabilizing integrin-linked kinase, extracellular signal-regulated kinase and protein kinase B. Rheumatology (Oxford). 2011; 50(5): 852–61.

18. Harlow L, Rosas IO, Gochuico BR, et al. Identification of citrullinated hsp90 isoforms as novel autoantigens in rheumatoid arthritis-associated interstitial lung disease. Arthritis Rheum. 2013; 65(4): 869–79.

19. Tomasello G, Sciumè C, et al. Hsp10, Hsp70, and Hsp90 immunohistochemical levels change in ulcerative colitis after therapy. Eur J Histochem. 2011 October 19; 55(4): e38.

20.Tukaj S, Kleszczyński K, Vafia K, et al. Aberrant expression and secretion of heat shock protein 90 in patients with bullous pemphigoid. PLoS One. 2013; 8(7): e70496.

Labels
Dermatology & STDs Paediatric rheumatology Rheumatology
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account