title: Inflammatory cytokine and humoral responses to Plasmodium falciparum glycosylphosphatidylinositols correlates with malaria immunity and pathogenesis.
abstract: Pro-inflammatory cytokines induced by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum contribute to malaria pathogenesis and hence, the naturally acquired anti-GPI antibody thought to provide protection against severe malaria (SM) by neutralizing the stimulatory activity of GPIs. In previous studies, the anti-GPI antibody levels increased with age in parallel with the development of acquired immunity, and high levels of anti-GPI antibodies were associated with mild malaria (MM) cases. In the present study, the relationship between the levels of pro-inflammatory cytokines and anti-GPI IgG antibody responses, parasitemia, and the clinical outcomes were evaluated in SM and mild malaria (MM) patients. Sera from a total of 110 SM and 72 MM cases after excluding of ineligible patients were analyzed for the levels of anti-GPI antibodies, IgG subclasses, and cytokine responses by ELISA. While the total anti-GPI antibody levels were similar in overall SM and MM groups, they were significantly higher in surviving SM patients than in fatal SM cases. In the case of cytokines, the TNF-α and IL-6 levels were significantly higher in SM compared to MM, whereas the IL-10 levels were similar in both groups. The data presented here demonstrate that high levels of the circulatory pro-inflammatory, TNF-α, and IL-6, are indicators of malaria severity, whereas anti-inflammatory cytokine IL-10 level does not differentiate SM and MM cases. Further, among SM patients, relatively low levels of anti-GPI antibodies are indicators of fatal outcomes compared to survivors, suggesting that anti-GPI antibodies provide some level of protection against SM fatality.
authors.affiliation: Service d'Immunologie Université Cheikh Anta Diop de DakarUCADDakarSenegal; Unité d'ImmunogénétiqueInstitut Pasteur de Dakar, IPDDakarSenegal.
authors.forename: Babacar
authors.initials: B
authors.lastname: Mbengue
authors.affiliation: Service de Réanimation Hôpital Principal de Dakar, HPD Dakar Senegal.
authors.forename: Birahim
authors.initials: B
authors.lastname: Niang
authors.affiliation: Service d'Immunologie Université Cheikh Anta Diop de Dakar UCAD Dakar Senegal.
authors.forename: Maguette Sylla
authors.initials: MS
authors.lastname: Niang
authors.affiliation: Unité d'Immunologie Institut Pasteur de Dakar, IPD Dakar Senegal.
authors.forename: Marie Louise
authors.initials: ML
authors.lastname: Varela
authors.affiliation: Fédération des laboratoires Hôpital Principal de Dakar, HPD Dakar Senegal.
authors.forename: Becaye
authors.initials: B
authors.lastname: Fall
authors.affiliation: Service de Réanimation Hôpital Principal de Dakar, HPD Dakar Senegal.
authors.forename: Mouhamadou Mansour
authors.initials: MM
authors.lastname: Fall
authors.affiliation: Unité d'Immunogénétique Institut Pasteur de Dakar, IPD Dakar Senegal.
authors.forename: Rokhaya Ndiaye
authors.initials: RN
authors.lastname: Diallo
authors.affiliation: Service de Réanimation Hôpital Principal de Dakar, HPD Dakar Senegal.
authors.forename: Bacary
authors.initials: B
authors.lastname: Diatta
authors.affiliation: Department of Biochemistry and Molecular Biology Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center Pennsylvania Hershey USA.
authors.forename: D Channe
authors.initials: DC
authors.lastname: Gowda
authors.affiliation: Service d'Immunologie Université Cheikh Anta Diop de DakarUCADDakarSenegal; Unité d'ImmunogénétiqueInstitut Pasteur de Dakar, IPDDakarSenegal.
authors.forename: Alioune
authors.initials: A
authors.lastname: Dieye
authors.affiliation: Unité d'Immunologie Institut Pasteur de Dakar, IPD Dakar Senegal.
authors.forename: Ronald
authors.initials: R
authors.lastname: Perraut
keywords: IgG; Plasmodium falciparum GPIs; cytokines; parasitemia; severe malaria