IgG autoantibody to brain beta tubulin III associated with cytokine cluster-II discriminate cerebral malaria in central India.
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.
Bansal
Devendra
D
Equipe PIME CNRS, Inserm U547, Institut Pasteur de Lille, Pôle Universitaire Nord, France.
Herbert
Fabien
F
Lim
Pharath
P
Deshpande
Prakash
P
Bécavin
Christophe
C
Guiyedi
Vincent
V
de Maria
Ilaria
I
Rousselle
Jean Claude
JC
Namane
Abdelkader
A
Jain
Rajendra
R
Cazenave
Pierre-André
PA
Mishra
Gyan Chandra
GC
Ferlini
Cristiano
C
Fesel
Constantin
C
Benecke
Arndt
A
Pied
Sylviane
S
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
D000953:Antigens, Protozoan; D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014404:Tubulin