Proteomics-based monitoring of heatstroke recovery identifies molecular signatures of organ stress

Background: Global warming exacerbates heatstroke, increasing its severity and associated health risks, including fatal kidney damage. Predicting post-heatstroke organ injury remains difficult, delaying timely medical intervention. This study aims to identify potential blood biomarkers that reflect organ stress and recovery status following heatstroke. Methods: Plasma samples (n = 12) from clinically diagnosed classical (non-exertional) heatstroke patients were collected at diagnosis and recovery. Two-dimensional gel electrophoresis was used to analyze protein expression, identifying 359 protein spots. Selected proteins showing differential expression were validated by Western blotting. Results: Here, five proteins—alpha-1 antitrypsin, alpha-1 microglobulin/bikunin precursor, apolipoprotein A-IV, clusterin, and complement component 2—show significant changes between the two timepoints. These proteins are linked to inflammatory, coagulation, and lipid metabolism pathways. Alpha-1 antitrypsin, alpha-1 microglobulin, and complement component 2 may reflect the resolution of inflammation, while apolipoprotein A-IV and clusterin indicate renal stress. The alpha-1 microglobulin–IgA complex may exert anti-inflammatory effects. Complement component 2, an initiator of the complement cascade, has not been previously reported to be associated with heat stress. Conclusions: The findings suggest that these proteins may serve as blood biomarkers to assess heatstroke severity and monitor recovery. Their clinical application could improve early detection of organ damage and guide intervention strategies.