Browsing by Author "Cazenave, P.A."
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- Clusters of cytokines determine malaria severity in Plasmodium falciparum - Infected patients from endemic areas of central IndiaPublication . Prakash, D.; Fesel, C.; Jain, R.; Cazenave, P.A.; Mishra, G.C.; Pied, S.We investigated the role of interferon (IFN)- gamma , interleukin (IL)-1 beta , IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)- alpha , and transforming growth factor (TGF)- beta in clinically well-defined groups of Plasmodium falciparum-infected patients manifesting mild malaria (MM), severe noncerebral malaria (SM), or cerebral malaria (CM) and in control subjects from Gondia, a malaria-endemic site in India, as well as in healthy subjects from non-malaria-endemic areas. Two-way coupled cluster analysis revealed 2 clusters of cytokines relevant to clinical subgroups of disease. The first cluster was composed of IFN- gamma , IL-2, IL-5, IL-6, and IL-12, the levels of which were significantly increased during infection but were predominant in patients with MM and allowed us to distinguish them from patients with SM or CM. The second cluster was composed of TGF- beta , TNF- alpha , IL-10, and IL-1 beta , the levels of which were highly correlated with each other in the different clinical groups of patients and significantly increased with disease severity, particularly in CM. Discriminant analyses allowed us to propose a minimal model. Levels of cytokines such as IL-5, IL-1 beta , IL-10, and IL-2 increase with infection. Levels of IL-12, IL-5, and IL-6 discriminate severe forms of malaria from MM. Finally, levels of IL-1 beta , IL-12, and IFN- gamma are relevant for the discrimination of CM from SM: high IL-1 beta levels are associated with CM, and high IL-12 and IFN- gamma levels are associated with SM
- IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central IndiaPublication . Bansal, D.; Herbert, F.; Lim, P.; Deshpande, P.; Becavin, C.; Guiyedi, V.; de Maria, I.; Rousselle, J.C.; Namane, A.; Jain, R.; Cazenave, P.A.; Mishra, G.C.; Ferlini, C.; Fesel, C.; Benecke, A.; Pied, S.We investigated the significance of these self-reactive antibodies in clinically well-defined groups of P. falciparum infected patients manifesting mild malaria (MM), severe non-cerebral malaria (SM), or cerebral malaria (CM) and in control subjects from Gondia, a malaria epidemic site in central India using quantitative immunoprinting and multivariate statistical analyses. A two-fold complete-linkage hierarchical clustering allows classifying the different patient groups and to distinguish the CM from the others on the basis of their profile of IgG reactivity to brain proteins defined by PANAMA Blot. We identified beta tubulin III (TBB3) as a novel discriminant brain antigen in the prevalence of CM. In addition, circulating IgG from CM patients highly react with recombinant TBB3. Overall, correspondence analyses based on singular value decomposition show a strong correlation between IgG anti-TBB3 and elevated concentration of cluster-II cytokine (IFNγ, IL1β, TNFα, TGFβ) previously demonstrated to be a predictor of CM in the same population
- Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese childrenPublication . Guiyedi, V.; Chanseaud, Y.; Fesel, C.; Snounou, G.; Rousselle, J.C.; Lim, P.; Koko, J.; Namane, A.; Cazenave, P.A.; Kombila, M.; Pied, S.Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFα), with the manifestation of CM in Gabonese children
- Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical statusPublication . Duarte, J.; Deshpande, P.; Guiyedi, V.; Mecheri, S.; Fesel, C.; Cazenave, P.A.; Mishra, G.C.; Kombila, M.; Pied, S.Blood samples were collected from controls and P. falciparum-infected patients before treatment on the day of hospitalization (day 0) in India and, in addition, on days 7 and 30 after treatment in Gabon. Total IgE levels were determined by ELISA and functional P. falciparum-specific IgE were estimated using a mast cell line RBL-2H3 transfected with a human Fcε RI α-chain that triggers degranulation upon human IgE cross-linking. Mann Whitney and Kruskall Wallis tests were used to compare groups and the Spearman test was used for correlations. Total IgE levels were confirmed to increase upon infection and differ with level of transmission and age but were not directly related to the disease phenotype. All studied groups exhibited functional parasite-specific IgEs able to induce mast cell degranulation in vitro in the presence of P. falciparum antigens. Plasma IgE levels correlated with those of IL-10 in uncomplicated malaria patients from Gabon. In Indian patients, plasma IFN-γ , TNF and IL-10 levels were significantly correlated with IgE concentrations in all groups.