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

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. 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. 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. 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. Heatstroke is becoming more common due to rising global temperatures. It can cause serious damage to organs such as the kidneys, but doctors often struggle to predict how well someone will recover. We looked at blood samples from people with heatstroke occurring during hot conditions, rather than that caused by strenuous physical activity, to find proteins that change during heatstroke and recovery. We found five specific proteins that may show whether a patient is recovering or still at risk of organ damage. These proteins could serve as early warning signals in the blood, helping doctors to respond sooner and more effectively. This research could lead to a simple blood test that could help monitor patients with heatstroke, making treatment safer and more personalized in the future. Jin et al. investigate protein expression changes in plasma from non-exertional heatstroke patients using 2D gel electrophoresis. Five proteins (A1AT, A1M, APOA4, clusterin, and C2) are identified that are linked to inflammation, coagulation, and renal stress.