Association of extracellular Hsp70 with the severity of chronic obstructive pulmonary disease

Abstract

Heat-shock protein 70 (Hsp70) acts as a damage-associated molecular pattern (DAMP) in extracellular compartment and might induce secretion of pro-inflammatory cytokines and trigger innate immunity. The aim of the study was to assess whether its concentration is increased in plasma of patients with stable chronic obstructive pulmonary disease (COPD) and to explore its association with smoking status, severity of airflow obstruction, symptoms and exacerbations history. Blood samples were collected from 137 COPD patients and 95 healthy volunteers matched by age and sex. COPD patients were subdivided based on FEV₁-based severity (stages 1-4) and symptoms severity (ABCD assessment), as recommended by Global Initiative for Chronic Obstructive Lung Disease (GOLD). Concentration of extracellular Hsp70 (eHsp70) was measured by the commercially available ELISA kit. Concentration of eHsp70 was increased in COPD patients in comparison to control group (p<0.001). It was also increasing with the severity of airflow obstruction throughout GOLD 2-4 stages (P<0.001) as well as with symptoms severity and exacerbations frequency throughout GOLD A-D groups (P<0.001). There were no differences in eHsp70 concentrations among COPD patients based on smoking status (non-smokers, former smokers, smokers), yet eHsp70 was increased in healthy smokers compared to healthy non-smokers (P<0.05). Moreover, eHsp70 showed significant negative correlation with FEV₁ (r=-0.708, p<0.001) and FEV₁/FVC (r=-0.644, P<0.001), while its odds ratio (OR) was 7.63 (95% CI = 3.68 – 15.82, P<0.001). eHsp70 may contribute to COPD inflammation associated with disease progression and could become prognostic biomarker for disease severity.