Session Title: Systemic Sclerosis & Related Disorders – Clinical Poster III
Session Type: Poster Session (Tuesday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Our previous study demonstrated that 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 signaling and its inhibition prevents the stimulatory effects of TGF-β on collagen synthesis and dermal fibrosis1. The aim of this study was to evaluate plasma Hsp90 of SSc patients and characterize its potential association with skin changes and SSc-related features.
Methods: A total of 92 patients (79 females; mean age 52.7; disease duration 6.0 years; diffuse cutaneous (dc)SSc / limited cutaneous (lc)SSc = 38/54) and 92 age- and sex- matched healthy individuals were included. Plasma Hsp90 levels were measured by ELISA (eBioscience, Vienna, Austria). Data are presented as median.
Results: Plasma Hsp90 levels were increased in SSc patients compared to healthy controls [12.5 (9.6–17.9) vs. 9.8 (7.7–12.4) ng/mL, p=0.0001]. Hsp90 levels in all patients positively correlated with CRP (r=0.271, p=0.015). Furthermore, Hsp90 concentrations were negatively associated with functional parameters of ILD: FVC (r=-0.291, p=0.013), FEV1 (r=-0.248, p=0.036), DLCO (r=-0.290, p=0.012) and SpO2 (r=-0.317, p=0.038). When adjusted for CRP, these correlations still remained significant in multivariate analysis. Higher Hsp90 concentrations were associated with presence of synovitis [17.6 (15.4 – 24.0) vs. 12.2 (9.3 – 17.3), p=0.039]. In addition, only in patients with dcSSc, Hsp90 levels positively correlated with the mRSS (r=0.437, p=0.006). In a prospective analysis of patients with progressive SSc-ILD treated with 6 (n=21 patients) or 12 (n=14 patients) monthly i.v. pulses of cyclophosphamide (CPA, 10 mg/kg) we did not observe any significant differences between the baseline sample (month 0) and blood drawn after 1, 6 and 12 months. However, baseline Hsp90 was able to predict long-term response after one year of CPA treatment (DLCOm12-m0; r=-0.494, p=0.037). Moreover, change in Hsp90 after one month of CPA treatment (Hsp90m1-m0) was able to predict the short-term inflammatory response (CRPm3-m0, r=-0.495, p=0.019; ESR m3-m0, r=-0.496, p=0.031). 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. In addition, Hsp90 could become a predictor of treatment response.
References: 1Tomcik M et al., Ann Rheum Dis.2014;73(6):1215-22.
Acknowledgement: Supported by AZV-16-33542A, MHCR 023728 and SVV – 260373.
To cite this abstract in AMA style:Storkanova H, Oreska S, Spiritovic M, Hermankova B, Bubova K, Komarc M, Pavelka K, Vencovsky J, Distler J, Senolt L, Becvar R, Tomcik M. Hsp90 as a Potential Biomarker of Lung and Skin Involvement in Patients with Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/hsp90-as-a-potential-biomarker-of-lung-and-skin-involvement-in-patients-with-systemic-sclerosis/. Accessed April 17, 2021.
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