Plasma Hsp90 levels in patients with systemic sclerosis and relation to lung and skin involvement: a cross-sectional and longitudinal study

Sci Rep. 2021 Jan 7;11(1):1. doi: 10.1038/s41598-020-79139-8.


Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / metabolism
  • Carbon Monoxide / metabolism
  • Case-Control Studies
  • Cross-Sectional Studies
  • Cyclophosphamide / therapeutic use
  • Dermatitis / metabolism
  • Female
  • HSP90 Heat-Shock Proteins / blood*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Longitudinal Studies
  • Lung / physiopathology
  • Lung Diseases, Interstitial / blood*
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / etiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Diffusing Capacity / drug effects
  • Scleroderma, Systemic / blood*
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / drug therapy
  • Skin / physiopathology
  • Vital Capacity / drug effects


  • HSP90 Heat-Shock Proteins
  • Immunosuppressive Agents
  • Carbon Monoxide
  • Cyclophosphamide
  • C-Reactive Protein