IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central India

Devendra Bansal, Fabien Herbert, Pharath Lim, Prakash Deshpande, Christophe Bécavin, Vincent Guiyedi, Ilaria de Maria, Jean Claude Rousselle, Abdelkader Namane, Rajendra Jain, Pierre André Cazenave, Gyan Chandra Mishra, Cristiano Ferlini, Constantin Fesel, Arndt Benecke, Sylviane Pied

Research output: Contribution to journalArticle

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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. Methods/Principal Findings: 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 (IFNc, IL1b, TNFa, TGFb) previously demonstrated to be a predictor of CM in the same population. Conclusions/Significance: 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.

Original languageEnglish
Article numbere8245
JournalPLoS One
Volume4
Issue number12
DOIs
Publication statusPublished - 1 Dec 2009
Externally publishedYes

Fingerprint

Cerebral Malaria
autoantibodies
Tubulin
tubulin
Autoantibodies
India
Brain
cytokines
Immunoglobulin G
Cytokines
brain
Malaria
Plasmodium falciparum
malaria
Antigens
Antibodies
Immunologic Factors
Biomarkers
Singular value decomposition
Blood

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central India. / Bansal, Devendra; Herbert, Fabien; Lim, Pharath; Deshpande, Prakash; Bécavin, Christophe; Guiyedi, Vincent; de Maria, Ilaria; Rousselle, Jean Claude; Namane, Abdelkader; Jain, Rajendra; Cazenave, Pierre André; Mishra, Gyan Chandra; Ferlini, Cristiano; Fesel, Constantin; Benecke, Arndt; Pied, Sylviane.

In: PLoS One, Vol. 4, No. 12, e8245, 01.12.2009.

Research output: Contribution to journalArticle

Bansal, D, Herbert, F, Lim, P, Deshpande, P, Bécavin, C, Guiyedi, V, de Maria, I, Rousselle, JC, Namane, A, Jain, R, Cazenave, PA, Mishra, GC, Ferlini, C, Fesel, C, Benecke, A & Pied, S 2009, 'IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central India', PLoS One, vol. 4, no. 12, e8245. https://doi.org/10.1371/journal.pone.0008245
Bansal, Devendra ; Herbert, Fabien ; Lim, Pharath ; Deshpande, Prakash ; Bécavin, Christophe ; Guiyedi, Vincent ; de Maria, Ilaria ; Rousselle, Jean Claude ; Namane, Abdelkader ; Jain, Rajendra ; Cazenave, Pierre André ; Mishra, Gyan Chandra ; Ferlini, Cristiano ; Fesel, Constantin ; Benecke, Arndt ; Pied, Sylviane. / IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central India. In: PLoS One. 2009 ; Vol. 4, No. 12.
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AU - Bansal, Devendra

AU - Herbert, Fabien

AU - Lim, Pharath

AU - Deshpande, Prakash

AU - Bécavin, Christophe

AU - Guiyedi, Vincent

AU - de Maria, Ilaria

AU - Rousselle, Jean Claude

AU - Namane, Abdelkader

AU - Jain, Rajendra

AU - Cazenave, Pierre André

AU - Mishra, Gyan Chandra

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AU - Fesel, Constantin

AU - Benecke, Arndt

AU - Pied, Sylviane

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