Reduced Circulating Angiopoietin-Like Protein Levels in Crimean-Congo Hemorrhagic Fever

Abstract

Crimean-Congo Hemorrhagic Fever (CCHF) is a life-threatening zoonotic viral disease characterized by endothelial dysfunction, coagulopathy, and systemic inflammation. Angiopoietin-like proteins (ANGPTLs) regulate vascular integrity, lipid metabolism, and inflammatory responses; however, their roles in the pathogenesis of CCHF remain unclear. In this prospective case–control study, serum levels of ANGPTL1, ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL6, and ANGPTL8 were measured by enzyme-linked immunosorbent assay (ELISA) in 60 patients with laboratory-confirmed CCHF and 30 healthy controls. Standard laboratory parameters were recorded, and correlations between ANGPTLs and inflammatory, coagulation, and metabolic markers were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess diagnostic performance and exploratory mortality-discrimination ability. All measured ANGPTL levels were significantly lower in CCHF patients than in healthy controls. However, no statistically significant differences in ANGPTL1, ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL6, or ANGPTL8 levels were observed between survivors and non-survivors. Although ANGPTL2 and ANGPTL3 yielded statistically significant area under the curve (AUC) values for mortality, the small number of fatal cases limits the strength of this finding. Overall, reduced ANGPTL levels were associated with disease-related inflammatory, endothelial, coagulation-related, and metabolic alterations, but these findings do not support their role as prognostic markers for mortality or establish a causal role in CCHF pathogenesis.