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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.

Guiyedi V, Bécavin C, Herbert F, Gray J, Cazenave PA, Kombila M, Crisanti A, Fesel C, Pied S - Malar. J. (2015)

Bottom Line: In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children.IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Relationship between auto-antibody response and Plasmodium falciparum-specific antibody response. (A) Relationship of the auto-antibody response to anti-P. falciparum IgG response in the EC, AM and MM groups, and division of response patterns into three sub-groups: α (anti-P. falciparum IgG <3 pg/ml; F1 > 1.5), β (anti-falciparum IgG >3 pg/ml; F1 < 1.5), δ anti-falciparum IgG <3 pg/ml; F1 < 1.5). (B) Frequencies of patients in α and β sub-groups in the EC, AM and MM groups.
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Fig4: Relationship between auto-antibody response and Plasmodium falciparum-specific antibody response. (A) Relationship of the auto-antibody response to anti-P. falciparum IgG response in the EC, AM and MM groups, and division of response patterns into three sub-groups: α (anti-P. falciparum IgG <3 pg/ml; F1 > 1.5), β (anti-falciparum IgG >3 pg/ml; F1 < 1.5), δ anti-falciparum IgG <3 pg/ml; F1 < 1.5). (B) Frequencies of patients in α and β sub-groups in the EC, AM and MM groups.

Mentions: The subjects were grouped according to anti-brain (PCA-1 score > +1.5) and anti-P. falciparum (>3 pg/mL) IgG reactivity. With the exception of two, all study participants fell into three sub-groups: α) high self-reactive IgG and low P. falciparum-specific IgG; β) low self-reactive IgG and high P. falciparum-specific IgG; and, δ) low self-reactive IgG and low P. falciparum-specific IgG (Figure 4A). Participants were unequally distributed between sub-groups. AM individuals were over-represented in sub-group α (40 AM versus 12% EC and 4% MM; χ2 = 15.3; p = 0.0004) (Figure 4B). Conversely, sub-group β contained more MM (33% MM versus 10% AM and 6% EC, χ2 = 7.4; p = 0.02) (Figure 4B). Most EC children were classified into sub-group δ. These data clearly suggest that AM is associated with a predominant self-antibody response against brain antigens and low parasite-specific IgG while MM is associated with low self-reactive antibodies but high parasite-specific response.Figure 4


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.

Guiyedi V, Bécavin C, Herbert F, Gray J, Cazenave PA, Kombila M, Crisanti A, Fesel C, Pied S - Malar. J. (2015)

Relationship between auto-antibody response and Plasmodium falciparum-specific antibody response. (A) Relationship of the auto-antibody response to anti-P. falciparum IgG response in the EC, AM and MM groups, and division of response patterns into three sub-groups: α (anti-P. falciparum IgG <3 pg/ml; F1 > 1.5), β (anti-falciparum IgG >3 pg/ml; F1 < 1.5), δ anti-falciparum IgG <3 pg/ml; F1 < 1.5). (B) Frequencies of patients in α and β sub-groups in the EC, AM and MM groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4419484&req=5

Fig4: Relationship between auto-antibody response and Plasmodium falciparum-specific antibody response. (A) Relationship of the auto-antibody response to anti-P. falciparum IgG response in the EC, AM and MM groups, and division of response patterns into three sub-groups: α (anti-P. falciparum IgG <3 pg/ml; F1 > 1.5), β (anti-falciparum IgG >3 pg/ml; F1 < 1.5), δ anti-falciparum IgG <3 pg/ml; F1 < 1.5). (B) Frequencies of patients in α and β sub-groups in the EC, AM and MM groups.
Mentions: The subjects were grouped according to anti-brain (PCA-1 score > +1.5) and anti-P. falciparum (>3 pg/mL) IgG reactivity. With the exception of two, all study participants fell into three sub-groups: α) high self-reactive IgG and low P. falciparum-specific IgG; β) low self-reactive IgG and high P. falciparum-specific IgG; and, δ) low self-reactive IgG and low P. falciparum-specific IgG (Figure 4A). Participants were unequally distributed between sub-groups. AM individuals were over-represented in sub-group α (40 AM versus 12% EC and 4% MM; χ2 = 15.3; p = 0.0004) (Figure 4B). Conversely, sub-group β contained more MM (33% MM versus 10% AM and 6% EC, χ2 = 7.4; p = 0.02) (Figure 4B). Most EC children were classified into sub-group δ. These data clearly suggest that AM is associated with a predominant self-antibody response against brain antigens and low parasite-specific IgG while MM is associated with low self-reactive antibodies but high parasite-specific response.Figure 4

Bottom Line: In addition, a correlation between IL-10 levels and parasite load was found in AM and MM children.IL-10 and IFN-γ levels were also associated with auto-antibody responses in AM.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus