Secreted extracellular heat shock protein gp96 and inflammatory cytokines are markers of severe malaria outcome

Malaria caused by Plasmodium spp., is a major public health issue in sub-Saharan Africa. The fight against malaria has stalled due to increasing resistance to treatments and insecticides. There is an urgent need to focus on new therapeutic targets to combat malaria effectively. This study aimed to measure the secreted heat shock protein gp96 levels in both malaria patients and controls. Indeed, gp96 plays a crucial role in parasite survival within the host and in establishing a successful infection. Therefore, gp96 could be a promising target for antimalarial drugs. In our study, we included 60 malaria patients, 30 with severe malaria (SM) and 30 with uncomplicated malaria (UM). Additionally, 28 controls were included. Using the ELISA method, we measured gp96 levels in the participants' blood samples. We then used the Mann-Whitney or analyse of variance tests to calculate descriptive statistics and determined the correlation between gp96 level and parasitemia using Spearman's rank correlation test. The study found that gp96 levels in the plasma significantly increased in malaria patients (23.86 ng/mL) compared to control (5.88 ng/mL), with a P < 0.0001. Interestingly, there was a significant difference between SM (27.56 ng/mL) and UM (13.9 ng/mL), with a P-value of 0.001. These findings are accompanied by significantly higher parasitemia and elevated proinflammatory cytokines such as IL-17A and IL-1β levels in SM patients compared to UM and controls. Furthermore, there was no significant positive correlation between gp96 levels and parasitemia/proinflammatory cytokines. Our research has revealed, for the first time, that individuals with SM have significantly higher levels of gp96 in the context of high parasitemia and proinflammatory cytokines. Our preliminary results will be taken further to evaluate gp96 as a valuable biomarker for the diagnosis of SM and a potential target for antimalarial drug discovery.