Increased Plasma Levels of Hsp90 Are Associated with More Severe Organ Involvement in Patients with Systemic Sclerosis

Hana Storkanova¹, Sabina Oreska¹, Maja Spiritovic^1,2, Karel Pavelka¹, Jiri Vencovsky¹, Jörg Distler³, Ladislav Senolt¹, Radim Becvar¹ and Michal Tomcik¹, ¹Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, Prague, Czech Republic, ²Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic, Prague, Czech Republic, ³Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, Erlangen, Germany

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: fibrosis, heat-shock proteins and systemic sclerosis

Session Information

Date: Sunday, November 5, 2017

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Pathogenesis, Animal Models and Genetics Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Our previous study demonstrated that Heat shock protein 90 (Hsp90) is overexpressed in the skin of patients with systemic sclerosis (SSc), in cultured SSc fibroblasts and preclinical models of SSc in a TGF-β dependent manner. We showed that Hsp90 is a new regulator of canonical TGF-β signalling and its inhibition prevents the stimulatory effects of TGF-β on collagen synthesis and dermal fibrosis in three preclinical models of SSc¹. The aim of this study was to evaluate Hsp90 in the circulation of SSc patients and characterize its potential association with skin changes and SSc-related features.

Methods: A total of 91 patients (78 females; mean age 52.7; disease duration 6.0 years; diffuse cutaneous (dc)SSc / limited cutaneous (lc)SSc = 38/53) who met the ACR/EULAR 2013 classification criteria for SSc and 85 age- and sex- matched healthy individuals were included. Plasma Hsp90 levels were measured by ELISA (eBioscience, Vienna, Austria). SSc-related manifestations were obtained from the Czech Registry of SSc patients. Skin changes were assessed using the modified Rodnan skin score (mRSS) and EUSTAR SSc activity score was determined. Data are presented as median (IQR, 25. – 75. percentile).

Results: Plasma Hsp90 levels were increased in SSc patients compared to healthy controls [12.5 (9.6–17.9) vs. 9.9 (7.9–12.6) ng/mL, p = 0.001], but no difference between (lc)SSc and (dc)SSc were detected [13.1 (9.4–18.1) vs. 11.5 (9.5–17.5) ng/mL, p = 0.316]. Hsp90 levels in all patients positively correlated with CRP (r = 0.313, p = 0.006). Furthermore, Hsp90 concentrations were increased in patients with interstitial lung disease (ILD) compared to those without ILD [12.8 (10.2–17.9) vs. 10.3 (8.6–16.6) ng/mL, p = 0.045] and were negatively associated with functional parameters of ILD: FVC (r = -0.299, p = 0.011), FEV1 (r = -0.256, p = 0.031), DLCO (r = -0.303, p = 0.009) and SpO₂ (r = -0.317, p = 0.038). In addition, only in patients with dcSSc, Hsp90 levels positively correlated with the mRSS (r = 0.437, p = 0.006). Concentrations of extracellular Hsp90 were not significantly affected by other main clinical parameters of SSc.

Conclusion: We demonstrated higher plasma levels of Hsp90 in SSc patients compared to healthy controls. Concentrations of extracellular Hsp90 increase with higher inflammatory activity, with deteriorated lung functions in ILD and also with the extent and severity of the skin involvement in patients with diffuse cutaneous SSc. These data further highlight the role of Hsp90 as a significant regulator of fibroblast activation and tissue fibrosis in SSc.

References: ¹Tomcik M et al., Ann Rheum Dis.2014;73(6):1215-22.

Acknowledgement: Supported by AZV – 16-33542A and SVV – 260373.

Disclosure: H. Storkanova, None; S. Oreska, None; M. Spiritovic, None; K. Pavelka, None; J. Vencovsky, Samsung Bioepis Co., Ltd., Biogen, 5; J. Distler, 4D Science, 1,Anamar Medical, Active Biotech, Array Biopma, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, GSK, Novartis, Sanofi-Aventis, UCB, 2,Actelion Pharmaceuticals US, Active Biotech, Anamar, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi, UCB, 5; L. Senolt, None; R. Becvar, None; M. Tomcik, None.

To cite this abstract in AMA style:

Storkanova H, Oreska S, Spiritovic M, Pavelka K, Vencovsky J, Distler J, Senolt L, Becvar R, Tomcik M. Increased Plasma Levels of Hsp90 Are Associated with More Severe Organ Involvement in Patients with Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/increased-plasma-levels-of-hsp90-are-associated-with-more-severe-organ-involvement-in-patients-with-systemic-sclerosis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-plasma-levels-of-hsp90-are-associated-with-more-severe-organ-involvement-in-patients-with-systemic-sclerosis/