title: Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3.
abstract: BACKGROUND
  Mechanisms of acquired protection to malaria in asymptomatic Plasmodium falciparum carriers are only partially understood. Among them, the role plays by the self-reactive antibodies has not been clarified yet. In this study, the relationship between repertoires of circulating self-reactive and parasite-specific immunoglobulin G (IgG), their correlation with cytokine levels, and their association with protection against malaria was investigated in asymptomatic Plasmodium falciparum-infected Gabonese children.
  
  
  METHODS
  The diversity of P. falciparum-specific antibody repertoire was analysed using a protein micro-array immunoassay, the total auto-antibody repertoire by quantitative immunoblotting and circulating cytokine levels were measured by ELISA in endemic controls (EC) and P. falciparum-infected children from Gabon with asymptomatic (AM) or mild malaria (MM). The association of self- and parasite-specific antibody repertoires with circulating cytokines was evaluated using single linkage hierarchical clustering, Kruskal-Wallis tests and Spearman's rank correlation.
  
  
  RESULTS
  Children with AM exhibited an IgG response to merozoite surface protein 3 (MSP3) but not to MSP1-19, although their levels of total P. falciparum-specific IgG were similar to those in the MM group. Moreover, the asymptomatic children had increased levels of autoantibodies recognising brain antigens. In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children. These two groups also exhibited significant correlations between plasma levels of IL-10 and IFN-γ with age and with total plasma IgG levels. IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM.
  
  
  CONCLUSIONS
  Altogether, these results indicate that a self-reactive polyclonal response associated with increased IgG to MSP3 and high plasma levels of IL-10 and IFN-γ may contribute to protective immune mechanisms triggered in asymptomatic P. falciparum infection in Gabonese children.
authors.affiliation: CIIL-Centre for Infection and Immunity of Lille, INSERM U1019 - CNRS UMR 8204, Lille University, Institut Pasteur de Lille, 1, rue du Professeur Calmette, Cedex 59019, Lille, France. guidyvin@hotmail.com.|Département de Parasitologie-Mycologie-Médecine Tropicale, Faculté de Médecine de Libreville, Université des Sciences de la Santé, Owendo, Gabon. guidyvin@hotmail.com.
authors.forename: Vincent
authors.initials: V
authors.lastname: Guiyedi
authors.affiliation: Département de Biologie Cellulaire et Infection, Institut Pasteur, Unité des Interactions Bactéries-Cellules, F-75015, Paris, France. christophe.becavin@pasteur.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bécavin
authors.affiliation: CIIL-Centre for Infection and Immunity of Lille, INSERM U1019 - CNRS UMR 8204, Lille University, Institut Pasteur de Lille, 1, rue du Professeur Calmette, Cedex 59019, Lille, France. fabien.herbert@pasteur-lille.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Herbert
authors.affiliation: Department of Biological Sciences, London Imperial College, London, UK. julian.c.gray@gmail.com.
authors.forename: Julian
authors.initials: J
authors.lastname: Gray
authors.affiliation: CIIL-Centre for Infection and Immunity of Lille, INSERM U1019 - CNRS UMR 8204, Lille University, Institut Pasteur de Lille, 1, rue du Professeur Calmette, Cedex 59019, Lille, France. cazenave@pasteur.fr.
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Cazenave
authors.affiliation: Département de Parasitologie-Mycologie-Médecine Tropicale, Faculté de Médecine de Libreville, Université des Sciences de la Santé, Owendo, Gabon. kombila.maryvonne@gmail.com.
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Kombila
authors.affiliation: Department of Biological Sciences, London Imperial College, London, UK. a.crisanti@imperial.ac.uk.
authors.forename: Andrea
authors.initials: A
authors.lastname: Crisanti
authors.affiliation: Instituto Gulbenkian de Ciência, Oeiras, Portugal. cfesel@igc.gulbenkian.pt.
authors.forename: Constantin
authors.initials: C
authors.lastname: Fesel
authors.affiliation: CIIL-Centre for Infection and Immunity of Lille, INSERM U1019 - CNRS UMR 8204, Lille University, Institut Pasteur de Lille, 1, rue du Professeur Calmette, Cedex 59019, Lille, France. sylviane.pied@pasteur-lille.fr.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Pied
mesh_terms: D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D058345:Asymptomatic Infections; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood*; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005681:Gabon; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000097:blood*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D001323:Autoantibodies; C508609:IL10 protein, human; D015800:Protozoan Proteins; C089133:merozoite surface protein 3, Plasmodium; D016753:Interleukin-10