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      Total and functional parasite specific IgE responses in Plasmodium falciparum-infected patients exhibiting different clinical status

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          Abstract

          Background

          There is an increase of serum levels of IgE during Plasmodium falciparum infections in individuals living in endemic areas. These IgEs either protect against malaria or increase malaria pathogenesis. To get an insight into the exact role played by IgE in the outcome of P. falciparum infection, total IgE levels and functional anti-parasite IgE response were studied in children and adults, from two different endemic areas Gabon and India, exhibiting either uncomplicated malaria, severe non cerebral malaria or cerebral malaria, in comparison with control individuals.

          Methodology and results

          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.

          Conclusion

          Circulating levels of total IgE do not appear to correlate with protection or pathology, or with anti-inflammatory cytokine pattern bias during malaria. On the contrary, the P. falciparum-specific IgE response seems to contribute to the control of parasites, since functional activity was higher in asymptomatic and uncomplicated malaria patients than in severe or cerebral malaria groups.

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          Most cited references42

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          Human malaria parasites in continuous culture.

          Plasmodium falciparum can now be maintained in continuous culture in human erythrocytes incubated at 38 degrees C in RPMI 1640 medium with human serum under an atmosphere with 7 percent carbon dioxide and low oxygen (1 or 5 percent). The original parasite material, derived from an infected Aotus trivirgatus monkey, was diluted more than 100 million times by the addition of human erythrocytes at 3- or 4-day intervals. The parasites continued to reproduce in their normal asexual cycle of approximately 48 hours but were no longer highly synchronous. The have remained infective to Aotus.
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            Allergy, parasites, and the hygiene hypothesis.

            The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.
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              Allergy assessment of foods or ingredients derived from biotechnology, gene-modified organisms, or novel foods.

              The introduction of novel proteins into foods carries a risk of eliciting allergic reactions in individuals sensitive to the introduced protein and a risk of sensitizing susceptible individuals. No single predictive test exists to perform a hazard assessment in relation to allergenic properties of newly expressed proteins in gene-modified organisms (GMOs). Instead, performance of a weighted risk analysis based on the decision tree approach has been suggested. The individual steps of this analysis comprise sequence homology to known allergens, specific or targeted serum screens for immunoglobulin E (IgE) cross-reactions to known allergens, digestability studies of the proteins in simulated gastric and/or intestinal fluids, and animal studies. These steps are discussed and five examples of risk evaluation of GMOs or novel foods are presented. These include ice-structuring protein derived from fish, microbial transglutaminase, GMO-soybeans, amylase and the Nangai nut.
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                Author and article information

                Journal
                Malar J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                2007
                4 January 2007
                : 6
                : 1
                Affiliations
                [1 ]Instituto Gulbenkian de Ciencia, LEA CNRS-IGC, Oeiras, Portugal
                [2 ]National Centre for Cell Sciences, Pune, India
                [3 ]Unité d'Immunophysiopathologie Infectieuse, Institut Pasteur, 25 rue du Docteur Roux, 75 724, Paris Cedex 15, France
                [4 ]Département de Parasitologie-Mycologie-Médecine Tropicale, Faculté de Médecine de Libreville, Gabon
                [5 ]Unité des Réponses Immunes Précoces aux Parasites, Institut Pasteur Paris, France
                Article
                1475-2875-6-1
                10.1186/1475-2875-6-1
                1781948
                17204149
                6d899071-cd6b-4df2-8cc0-3c3228ac8f4c
                Copyright © 2007 Duarte et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 October 2006
                : 4 January 2007
                Categories
                Research

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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