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      Changes Related to Age in Natural and Acquired Systemic Self-IgG Responses in Malaria

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          Abstract

          Background. Absence of acquired protective immunity in endemic areas children leads to higher susceptibility to severe malaria. To investigate the involvement of regulatory process related to self-reactivity, we evaluated potent changes in auto-antibody reactivity profiles in children and older subjects living in malaria-endemic zones comparatively to none-exposed healthy controls. Methods. Analysis of IgG self-reactive footprints was performed using Western blotting against healthy brain antigens. Plasmas of 102 malaria exposed individuals (MEIs) from endemic zone, with or without cerebral malaria (CM) were compared to plasmas from non-endemic controls (NECs). Using linear discriminant and principal component analysis, immune footprints were compared by counting the number, the presence or absence of reactive bands. We identified the most discriminant bands with respect to age and clinical status. Results. A higher number of bands were recognized by IgG auto-antibodies in MEI than in NEC. Characteristic changes in systemic self-IgG-reactive repertoire were found with antigenic bands that discriminate Plasmodium falciparum infections with or without CM according to age. 8 antigenic bands distributed in MEI compared with NEC were identified while 6 other antigenic bands were distributed within MEI according to the age and clinical status. Such distortion might be due to evolutionary processes leading to pathogenic/protective events.

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          Gamma-globulin and acquired immunity to human malaria.

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            A unified hypothesis for the genesis of cerebral malaria: sequestration, inflammation and hemostasis leading to microcirculatory dysfunction.

            A unifying hypothesis for the genesis of cerebral malaria proposes that parasite antigens (released by replication in blood, surface molecules on parasitized erythrocytes, or merozoites) activate platelets that, in turn, contribute to the activation of the inflammatory response and increased levels of endothelial cell adhesion molecules (eCAMs). Increased levels of eCAMs result in further parasitized-erythrocyte sequestration and marked local inflammation that might disrupt the brain microvasculature, which cannot be repaired by the hemostasis system because of its procoagulant state. Disruption of the brain microvasculature can result in vascular leak and/or hemorrhaging into the brain; similar processes can occur in other vascular beds, including the lung. The blockage of functional capillaries by parasitized and/or unparasitized erythrocytes with decreased deformability or rosettes is also a key interaction between hemostasis and mechanical obstruction leading to pathogenesis. The events resulting in the development of cerebral malaria complications are multi-factorial, encompassing a dynamic interaction between three processes, thereby explaining the complexity of this deadly syndrome.
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              Antibodies that protect humans against Plasmodium falciparum blood stages do not on their own inhibit parasite growth and invasion in vitro, but act in cooperation with monocytes

              IgG extracted from the sera of African adults immune to malaria were injected intravenously into eight Plasmodium falciparum-infected nonimmune Thai patients. Clinical and parasitological improvement was reproducibly obtained in each case. After the disappearance of the transferred Ig, recrudescent parasites were equally susceptible to the same Ig preparation. High levels of antibodies to most parasite proteins were detected by Western blots in the receivers' sera (taken before transfer) as in the donors' Ig, thus indicating that the difference was qualitative rather than quantitative between donors and receivers. In vitro, the clinically effective Ig had no detectable inhibitory effect on either penetration or intra-erythrocytic development of the parasite. On the contrary, they sometimes increased parasite growth. In contrast, these IgG, as the receivers' Ig collected 4 d after transfer, but not those collected before transfer, proved able to exert an antibody-dependent cellular inhibitory (ADCI) effect in cooperation with normal blood monocytes. Results were consistent among the seven isolates studied in vitro, as with the recrudescent parasites. Thus, the results obtained in the ADCI assay correlate closely with clinical and parasitological observations.
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                Author and article information

                Journal
                Interdiscip Perspect Infect Dis
                IPID
                Interdisciplinary Perspectives on Infectious Diseases
                Hindawi Publishing Corporation
                1687-708X
                1687-7098
                2011
                29 December 2011
                : 2011
                : 462767
                Affiliations
                1Laboratoire d'Immunologie EA 2686, IMPRT-IFR 114, Faculté de Médecine Pôle Recherche, Université Lille 2, 1 Place de Verdun, 59045 Lille Cedex, France
                2Laboratoire d'Immunologie et Hématologie du CHU-Cocody, Abidjan, Cote D'Ivoire
                3Laboratoire de Parasitologie et de Mycologie, Institute de Biologie et Pathologie, CHRU de Lille 59037 Lille, France
                4Service de Neurologie D, Hôpital Roger Salengro, 59037 Lille Cedex, France
                Author notes

                Academic Editor: Jose G. Estrada-Franco

                Article
                10.1155/2011/462767
                3255176
                22253622
                e41d9fca-b96b-4dba-9984-b08ea9fb9d42
                Copyright © 2011 Romuald Dassé et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 July 2011
                : 23 September 2011
                Categories
                Research Article

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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