Serum decoy receptor 3 (DcR3) concentrations and associations with clinical parameters in Plasmodium vivax and Plasmodium falciparum malaria

Abstract

Decoy receptor (DcR3) is a soluble member of the tumor necrosis factor receptor superfamily with immunomodulatory properties that is elevated in several inflammatory and infectious diseases. However, its role in malaria remains poorly understood. This study investigated serum DcR3 concentrations in patients with Plasmodium vivax and Plasmodium falciparum malaria and evaluate the associations between DcR3 concentrations and clinical parameters. This retrospective secondary analysis utilized archived serum samples and associated clinical data from two previously conducted malaria cohort studies. Seventy-six malaria patients were included: P. vivax (n = 36), uncomplicated P. falciparum (n = 30), and severe P. falciparum (n = 10), together with 20 healthy controls. Serum DcR3 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) at hospital admission (Day 0) and after treatment (Day 7). Differences in DcR3 concentrations, associations with clinical parameters, and longitudinal changes across malaria groups were evaluated. At admission, serum DcR3 concentrations were significantly elevated in all malaria groups compared with healthy controls, with the highest concentrations observed in patients with severe P. falciparum malaria. Following treatment, DcR3 concentrations declined significantly in all malaria groups. Longitudinal analysis demonstrated no statistical evidence of differences in DcR3 decline patterns among malaria groups. However, DcR3 concentrations remained elevated in patients with severe P. falciparum malaria compared with healthy controls at Day 7. DcR3 concentrations correlated positively with parasite density in uncomplicated and severe P. falciparum malaria and inversely with platelet count in P. vivax malaria. Serum DcR3 concentrations were elevated during acute malaria infection and decreased following treatment. Patients with severe P. falciparum malaria had higher DcR3 concentrations compared with other malaria groups; however, the longitudinal decline in DcR3 concentrations was comparable among groups. These findings are exploratory due to the retrospective study design and limited number of patients with severe malaria and require validation in larger prospective cohorts.