Thiam Fatou, Djoumoi Djibaba, Mbaye Mame Ndew, Fall Aminata, Diouara Abou Abdallah Malick, Diop Mamadou, Nguer Cheikh Momar, Mbengue Babacar, Diop Gora, Kohli Evelyne, Dieye Alioune
Groupe de Recherche Biotechnologies Appliquees & Bioprocedes Environnementaux, Ecole Superieure Polytechnique, Universite Cheikh Anta Diop de Dakar, 5085 Dakar-Fann, Senegal.
Groupe de Recherche Biotechnologies Appliquees & Bioprocedes Environnementaux, Ecole Superieure Polytechnique, Universite Cheikh Anta Diop de Dakar, 5085 Dakar-Fann, Senegal.
Cell Stress Chaperones. 2025 Feb;30(1):48-56. doi: 10.1016/j.cstres.2024.12.004. Epub 2024 Dec 26.
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.
由疟原虫属引起的疟疾是撒哈拉以南非洲的一个主要公共卫生问题。由于对治疗方法和杀虫剂的耐药性不断增加，抗击疟疾的工作陷入了停滞。迫切需要关注新的治疗靶点以有效对抗疟疾。本研究旨在测量疟疾患者和对照组中分泌型热休克蛋白gp96的水平。事实上，gp96在寄生虫在宿主体内的存活以及建立成功感染方面起着关键作用。因此，gp96可能是抗疟药物的一个有前景的靶点。在我们的研究中，我们纳入了60名疟疾患者，其中30名患有重症疟疾（SM），30名患有非重症疟疾（UM）。此外，还纳入了28名对照组。使用酶联免疫吸附测定（ELISA）方法，我们测量了参与者血液样本中的gp96水平。然后我们使用曼-惠特尼检验或方差分析来计算描述性统计量，并使用斯皮尔曼等级相关检验确定gp96水平与寄生虫血症之间的相关性。研究发现，与对照组（5.88纳克/毫升）相比，疟疾患者血浆中的gp96水平显著升高（23.86纳克/毫升），P值<0.0001。有趣的是，SM组（27.56纳克/毫升）和UM组（13.9纳克/毫升）之间存在显著差异，P值为0.001。这些发现伴随着与UM组和对照组相比，SM患者中显著更高的寄生虫血症以及促炎细胞因子如白细胞介素-17A和白细胞介素-1β水平的升高。此外，gp96水平与寄生虫血症/促炎细胞因子之间没有显著的正相关。我们的研究首次揭示，在高寄生虫血症和促炎细胞因子的背景下，患有SM的个体的gp96水平显著更高。我们的初步结果将进一步用于评估gp96作为SM诊断的有价值生物标志物以及抗疟药物发现的潜在靶点。
