Heat-shock protein 90α in plasma reflects severity of fatigue in patients with Crohn's disease

Heat-shock proteins (HSPs) are evolutionarily conserved proteins with important cellular homeostasis functions during harmful conditions, including inflammation. Some HSPs are secreted extracellularly and act on distant cells by down-regulating inflammation and increasing cellular stress defence mechanisms. HSP90 alpha has been postulated to signal fatigue in chronic inflammation. We investigated whether HSP90 alpha is associated with fatigue in patients with Crohn's disease. Fifty-three patients with newly diagnosed Crohn's disease were included in a cross-sectional study. Data on demographics and disease distribution were obtained. Fatigue was measured by the fatigue visual analogue scale (fVAS). Disease activity was assessed by the Simple Endoscopic Score for Crohn's disease and Harvey Bradshaw Index. C-reactive protein, faecal calprotectin and HSP90 alpha were also measured. The median fVAS score was 52 mm, indicating significant fatigue. HSP90 alpha scores correlated significantly with fVAS (r = 0.31, P = 0.03). In a multivariate regression model, HSP90 alpha was the only significant contributor to fVAS scores (beta = 0.31, P = 0.03). When patients were dichotomised into groups with high and low HSP90 alpha concentrations, significantly higher fVAS scores were demonstrated in the group with high HSP90 alpha (M = 62.4, confidence interval 53.0-71.8 vs. 43.3, 31.6-55.0; P = 0.01). Thus, HSP90 alpha may contribute to fatigue generation and/or modulation in patients with Crohn's disease.