title: IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central India.
abstract: BACKGROUND
  The main processes in the pathogenesis of cerebral malaria caused by Plasmodium falciparum involved sequestration of parasitized red blood cells and immunopathological responses. Among immune factors, IgG autoantibodies to brain antigens are increased in P. falciparum infected patients and correlate with disease severity in African children. Nevertheless, their role in the pathophysiology of cerebral malaria (CM) is not fully defined. We extended our analysis to an Indian population with genetic backgrounds and endemic and environmental status different from Africa to determine if these autoantibodies could be either a biomarker or a risk factor of developing CM.
  
  
  RESULTS
  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 (IFNgamma, IL1beta, TNFalpha, TGFbeta) previously demonstrated to be a predictor of CM in the same population.
  
  
  CONCLUSIONS
  Collectively, these findings validate the relationship between antibody response to brain induced by P. falciparum infection and plasma cytokine patterns with clinical outcome of malaria. They also provide significant insight into the immune mechanisms associated to CM by the identification of TBB3 as a new disease-specific marker and potential therapeutic target.
authors.affiliation: Equipe PIME CNRS, Inserm U547, Institut Pasteur de Lille, Pôle Universitaire Nord, France.
authors.forename: Devendra
authors.initials: D
authors.lastname: Bansal
authors.forename: Fabien
authors.initials: F
authors.lastname: Herbert
authors.forename: Pharath
authors.initials: P
authors.lastname: Lim
authors.forename: Prakash
authors.initials: P
authors.lastname: Deshpande
authors.forename: Christophe
authors.initials: C
authors.lastname: Bécavin
authors.forename: Vincent
authors.initials: V
authors.lastname: Guiyedi
authors.forename: Ilaria
authors.initials: I
authors.lastname: de Maria
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Rousselle
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Namane
authors.forename: Rajendra
authors.initials: R
authors.lastname: Jain
authors.forename: Pierre-André
authors.initials: PA
authors.lastname: Cazenave
authors.forename: Gyan Chandra
authors.initials: GC
authors.lastname: Mishra
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ferlini
authors.forename: Constantin
authors.initials: C
authors.lastname: Fesel
authors.forename: Arndt
authors.initials: A
authors.lastname: Benecke
authors.forename: Sylviane
authors.initials: S
authors.lastname: Pied
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000953:Antigens, Protozoan / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001921:Brain / Q000276:immunology* / Q000469:parasitology; D002648:Child; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D003710:Demography; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007194:India; D016779:Malaria, Cerebral / Q000097:blood / Q000145:classification / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000276:immunology; D013045:Species Specificity; D014404:Tubulin / Q000276:immunology*; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014404:Tubulin