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Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children.

Guiyedi V, Chanseaud Y, Fesel C, Snounou G, Rousselle JC, Lim P, Koko J, Namane A, Cazenave PA, Kombila M, Pied S - PLoS ONE (2007)

Bottom Line: Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups.We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain.These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM.

View Article: PubMed Central - PubMed

Affiliation: Unité d'Immunophysiopathologie Infectieuse, URA CNRS 1961, Université Pierre et Marie Curie Paris, Institut Pasteur, Paris, France.

ABSTRACT

Background: Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFalpha), with the manifestation of CM in Gabonese children.

Methodology: To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFalpha concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM.

Results/conclusion: The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFalpha concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM.

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Total reactivity to brain proteins and intensity of IgG reacting to band-0 as a function of plasma TNFα levels in children older than 1 year.A. Positive correlation between PCA factor 1 and TNFα concentrations in the CM group, indicated by dashed regression line. B. Positive correlation between unadjusted reactivity to band 0 and TNFα levels. C. High band-0 reactivity was observed most frequently in CM patients with TNFα levels above 100 pg/mL (indicated as high-TNFα in a separate group on the right). Horizontal bars indicate medians. Only children over the age of 1 year are shown.
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pone-0000389-g007: Total reactivity to brain proteins and intensity of IgG reacting to band-0 as a function of plasma TNFα levels in children older than 1 year.A. Positive correlation between PCA factor 1 and TNFα concentrations in the CM group, indicated by dashed regression line. B. Positive correlation between unadjusted reactivity to band 0 and TNFα levels. C. High band-0 reactivity was observed most frequently in CM patients with TNFα levels above 100 pg/mL (indicated as high-TNFα in a separate group on the right). Horizontal bars indicate medians. Only children over the age of 1 year are shown.

Mentions: We assessed whether IgG autoantibody response and the type of disease were associated with cytokines concentrations in P. falciparum-infected patients. Plasma IFNγ and IL-10 concentrations were not associated with reactivity in the various groups. In the adjusted assay, reactivity to brain antigens, as measured by PCA factor 1 score, was positively correlated with TNFα concentration. This correlation was significant for children over the age of one year (RSpearman = +0.41, p = 0.02) (figure 7a). Factor 1 score was particularly high in the CM patients with the highest plasma TNFα concentrations (>100 pg/ml). The intensity of the unadjusted (but not of the adjusted) reactivity with band-0 was also correlated with TNFα concentrations (in all children: RSpearman = +0.35, p = 0.008; children aged over 1 year: RSpearman = +0.54, p = 0.002) (Figure 7b). Reactivity with band-0 was significantly stronger for the CM patients with the highest plasma TNFα concentrations (>100 pg/ml) than for SNCM and UM patients (p = 0.0006 and p = 0.003, respectively) (figure 7c).


Self-reactivities to the non-erythroid alpha spectrin correlate with cerebral malaria in Gabonese children.

Guiyedi V, Chanseaud Y, Fesel C, Snounou G, Rousselle JC, Lim P, Koko J, Namane A, Cazenave PA, Kombila M, Pied S - PLoS ONE (2007)

Total reactivity to brain proteins and intensity of IgG reacting to band-0 as a function of plasma TNFα levels in children older than 1 year.A. Positive correlation between PCA factor 1 and TNFα concentrations in the CM group, indicated by dashed regression line. B. Positive correlation between unadjusted reactivity to band 0 and TNFα levels. C. High band-0 reactivity was observed most frequently in CM patients with TNFα levels above 100 pg/mL (indicated as high-TNFα in a separate group on the right). Horizontal bars indicate medians. Only children over the age of 1 year are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1851099&req=5

pone-0000389-g007: Total reactivity to brain proteins and intensity of IgG reacting to band-0 as a function of plasma TNFα levels in children older than 1 year.A. Positive correlation between PCA factor 1 and TNFα concentrations in the CM group, indicated by dashed regression line. B. Positive correlation between unadjusted reactivity to band 0 and TNFα levels. C. High band-0 reactivity was observed most frequently in CM patients with TNFα levels above 100 pg/mL (indicated as high-TNFα in a separate group on the right). Horizontal bars indicate medians. Only children over the age of 1 year are shown.
Mentions: We assessed whether IgG autoantibody response and the type of disease were associated with cytokines concentrations in P. falciparum-infected patients. Plasma IFNγ and IL-10 concentrations were not associated with reactivity in the various groups. In the adjusted assay, reactivity to brain antigens, as measured by PCA factor 1 score, was positively correlated with TNFα concentration. This correlation was significant for children over the age of one year (RSpearman = +0.41, p = 0.02) (figure 7a). Factor 1 score was particularly high in the CM patients with the highest plasma TNFα concentrations (>100 pg/ml). The intensity of the unadjusted (but not of the adjusted) reactivity with band-0 was also correlated with TNFα concentrations (in all children: RSpearman = +0.35, p = 0.008; children aged over 1 year: RSpearman = +0.54, p = 0.002) (Figure 7b). Reactivity with band-0 was significantly stronger for the CM patients with the highest plasma TNFα concentrations (>100 pg/ml) than for SNCM and UM patients (p = 0.0006 and p = 0.003, respectively) (figure 7c).

Bottom Line: Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups.We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain.These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM.

View Article: PubMed Central - PubMed

Affiliation: Unité d'Immunophysiopathologie Infectieuse, URA CNRS 1961, Université Pierre et Marie Curie Paris, Institut Pasteur, Paris, France.

ABSTRACT

Background: Hypergammaglobulinemia and polyclonal B-cell activation commonly occur in Plasmodium sp. infections. Some of the antibodies produced recognize self-components and are correlated with disease severity in P. falciparum malaria. However, it is not known whether some self-reactive antibodies produced during P. falciparum infection contribute to the events leading to cerebral malaria (CM). We show here a correlation between self-antibody responses to a human brain protein and high levels of circulating TNF alpha (TNFalpha), with the manifestation of CM in Gabonese children.

Methodology: To study the role of self-reactive antibodies associated to the development of P. falciparum cerebral malaria, we used a combination of quantitative immunoblotting and multivariate analysis to analyse correlation between the reactivity of circulating IgG with a human brain protein extract and TNFalpha concentrations in cohorts of uninfected controls (UI) and P. falciparum-infected Gabonese children developing uncomplicated malaria (UM), severe non-cerebral malaria (SNCM), or CM.

Results/conclusion: The repertoire of brain antigens recognized by plasma IgGs was more diverse in infected than in UI individuals. Anti-brain reactivity was significantly higher in the CM group than in the UM and SNCM groups. IgG self-reactivity to brain antigens was also correlated with plasma IgG levels and age. We found that 90% of CM patients displayed reactivity to a high-molecular mass band containing the spectrin non-erythroid alpha chain. Reactivity with this band was correlated with high TNFalpha concentrations in CM patients. These results strongly suggest that an antibody response to brain antigens induced by P. falciparum infection may be associated with pathogenic mechanisms in patients developing CM.

Show MeSH
Related in: MedlinePlus