Osteoprotegerin (OPG) and its ligands RANKL and TRAIL in falciparum, vivax and knowlesi malaria: correlations with disease severity, and B cell production of OPG
Year: 2024
Type: preprint
Abstract: ABSTRACT Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of NF-ƙB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL), and is increasingly recognised as a marker of poor prognosis in a number of diseases. Here we demonstrate that in Malaysian adults with falciparum and vivax malaria, OPG is increased, and its ligands TRAIL and RANKL decreased, in proportion to disease severity. In volunteers experimentally infected with P. falciparum and P. vivax , RANKL was suppressed, while TRAIL was unexpectedly increased, suggesting binding of OPG to RANKL prior to TRAIL. We also demonstrate that P. falciparum stimulates B cells to produce OPG in vitro , and that B cell OPG production is increased ex vivo in patients with falciparum, vivax and knowlesi malaria. Our findings provide further evidence of the importance of the OPG/RANKL/TRAIL pathway in pathogenesis of diseases involving systemic inflammation, and may have implications for adjunctive therapies. Further evaluation of the role of B cell production of OPG in host responses to malaria and other inflammatory diseases is warranted.
Source: medRxiv
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Addressing the threat of emerging zoonotic malaria in our region, Malaria volunteer infection studies for the advancement of antimalarial therapeutics, Translational studies in infectious diseases, Comparative incidence and clinical spectrum of Plasmodium knowlesi malaria, a longitudinal study in Sabah, Malaysia, Tropical Disease - immunity, pathogenesis and vaccine development: global translation, Targeting acute kidney injury in knowlesi malaria, Comparative pathophysiology of severe knowlesi and falciparum malaria
OpenAlex ID: W4400915634