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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

Repertoire of Plasmodium falciparum antigenic diversity recognized by infected children in Gabon. (A) Percentage of individuals in the study population that recognized at least one P. falciparum antigen. (B) Antibody patterns and percentage of positive patients for each of the 20 P. falciparum-specific antigens tested in the total study population. (C) Kruskal-Wallis analysis of the antibody responses against the 20 parasite antigens in all groups. (D) Plasma levels (pg/mL) of anti-P. falciparum MSP3-3D7 antibodies in EC, AM and MM. (E) Single linkage hierarchical clustering of the antibody response against the 20 P. falciparum antigens tested in the different groups. (F) Heat map representing fold change of the antibody response and Mann–Whitney p-value comparing the different groups: AM vs MM, AM vs EC, and EC vs MM. Antigens: MSP1 block 2 PA repeats; MSP1 block 2 3D7 Wellcome repeats; MSP1 block 2 3D7 full length; MSP1 block 2 3D7 Wellcome full length; MSP1 block 2 MAD20 full length; MSP1 block 2 RO33 full length; MSP1 block 2 K1 super repeats; MSP1 block 2 K1 flanking; MSP1 block 2 MAD20 repeats; MSP1 block 2 3D7 repeats; MSP3 3D7; MBP; MSP3 K1; MSP2 3D7; MSP2 FC27; AMA-1; GST; MSP1-19 GST; PfEMP1; NANP.
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Fig2: Repertoire of Plasmodium falciparum antigenic diversity recognized by infected children in Gabon. (A) Percentage of individuals in the study population that recognized at least one P. falciparum antigen. (B) Antibody patterns and percentage of positive patients for each of the 20 P. falciparum-specific antigens tested in the total study population. (C) Kruskal-Wallis analysis of the antibody responses against the 20 parasite antigens in all groups. (D) Plasma levels (pg/mL) of anti-P. falciparum MSP3-3D7 antibodies in EC, AM and MM. (E) Single linkage hierarchical clustering of the antibody response against the 20 P. falciparum antigens tested in the different groups. (F) Heat map representing fold change of the antibody response and Mann–Whitney p-value comparing the different groups: AM vs MM, AM vs EC, and EC vs MM. Antigens: MSP1 block 2 PA repeats; MSP1 block 2 3D7 Wellcome repeats; MSP1 block 2 3D7 full length; MSP1 block 2 3D7 Wellcome full length; MSP1 block 2 MAD20 full length; MSP1 block 2 RO33 full length; MSP1 block 2 K1 super repeats; MSP1 block 2 K1 flanking; MSP1 block 2 MAD20 repeats; MSP1 block 2 3D7 repeats; MSP3 3D7; MBP; MSP3 K1; MSP2 3D7; MSP2 FC27; AMA-1; GST; MSP1-19 GST; PfEMP1; NANP.

Mentions: The repertoires of parasite antigens recognized by EC, AM and MM were compared using a protein micro-array consisting of 20 antigens, including 13 variants of MSP1, MSP2 and MSP3 from P. falciparum 3D7 and FC27 clones, AMA1, PfEMP1, and NANP-4. The results showed that 80% of the studied population, including EC, recognized at least one of the P. falciparum antigens tested while 20% had any reactivity (Figure 2A). In addition, 75% of MM recognized the highest number of P. falciparum antigens when compared to 15% in AM and 10% in EC. When grouped together, 60% of the studied population had IgG to MSP2, 75% IgG to MSP1-19 IgG and less than 40% had IgG to at least one the other tested antigens (Figure 2B). It is worthy to note that no reactivity was observed against AMA1, PfEMP1, GST and NANP-4. The most significant difference between the groups was observed by Kruskal-Wallis for MSP3-3D7 (Figure 2C; p = 0.034). Plasma levels (pg/mL) of circulating anti-MSP3-3D7 IgG was higher in the AM group than in the MM and EC groups (Figure 2D; p = 0.03). It is also noteworthy that 55% of AM compared to 12% EN and 19% MM produced IgG anti-MSP3-3D7. Conversely, the level of anti-MSP1-19 antibody was significantly higher in the MM than in AM and EC [see Additional file 1]. In the same patient group, IgG to MSP2-3D7 or MSP2-FC27 detected in some MM patients on day 0 persisted with the same intensity until day 30, even after treatment [see Additional file 2A]. However, for some of the antigens, such as MSP1-19, reactivity increased between days 0 and 7 or between days 0 and 30 [see Additional file 2B].Figure 2


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)

Repertoire of Plasmodium falciparum antigenic diversity recognized by infected children in Gabon. (A) Percentage of individuals in the study population that recognized at least one P. falciparum antigen. (B) Antibody patterns and percentage of positive patients for each of the 20 P. falciparum-specific antigens tested in the total study population. (C) Kruskal-Wallis analysis of the antibody responses against the 20 parasite antigens in all groups. (D) Plasma levels (pg/mL) of anti-P. falciparum MSP3-3D7 antibodies in EC, AM and MM. (E) Single linkage hierarchical clustering of the antibody response against the 20 P. falciparum antigens tested in the different groups. (F) Heat map representing fold change of the antibody response and Mann–Whitney p-value comparing the different groups: AM vs MM, AM vs EC, and EC vs MM. Antigens: MSP1 block 2 PA repeats; MSP1 block 2 3D7 Wellcome repeats; MSP1 block 2 3D7 full length; MSP1 block 2 3D7 Wellcome full length; MSP1 block 2 MAD20 full length; MSP1 block 2 RO33 full length; MSP1 block 2 K1 super repeats; MSP1 block 2 K1 flanking; MSP1 block 2 MAD20 repeats; MSP1 block 2 3D7 repeats; MSP3 3D7; MBP; MSP3 K1; MSP2 3D7; MSP2 FC27; AMA-1; GST; MSP1-19 GST; PfEMP1; NANP.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4419484&req=5

Fig2: Repertoire of Plasmodium falciparum antigenic diversity recognized by infected children in Gabon. (A) Percentage of individuals in the study population that recognized at least one P. falciparum antigen. (B) Antibody patterns and percentage of positive patients for each of the 20 P. falciparum-specific antigens tested in the total study population. (C) Kruskal-Wallis analysis of the antibody responses against the 20 parasite antigens in all groups. (D) Plasma levels (pg/mL) of anti-P. falciparum MSP3-3D7 antibodies in EC, AM and MM. (E) Single linkage hierarchical clustering of the antibody response against the 20 P. falciparum antigens tested in the different groups. (F) Heat map representing fold change of the antibody response and Mann–Whitney p-value comparing the different groups: AM vs MM, AM vs EC, and EC vs MM. Antigens: MSP1 block 2 PA repeats; MSP1 block 2 3D7 Wellcome repeats; MSP1 block 2 3D7 full length; MSP1 block 2 3D7 Wellcome full length; MSP1 block 2 MAD20 full length; MSP1 block 2 RO33 full length; MSP1 block 2 K1 super repeats; MSP1 block 2 K1 flanking; MSP1 block 2 MAD20 repeats; MSP1 block 2 3D7 repeats; MSP3 3D7; MBP; MSP3 K1; MSP2 3D7; MSP2 FC27; AMA-1; GST; MSP1-19 GST; PfEMP1; NANP.
Mentions: The repertoires of parasite antigens recognized by EC, AM and MM were compared using a protein micro-array consisting of 20 antigens, including 13 variants of MSP1, MSP2 and MSP3 from P. falciparum 3D7 and FC27 clones, AMA1, PfEMP1, and NANP-4. The results showed that 80% of the studied population, including EC, recognized at least one of the P. falciparum antigens tested while 20% had any reactivity (Figure 2A). In addition, 75% of MM recognized the highest number of P. falciparum antigens when compared to 15% in AM and 10% in EC. When grouped together, 60% of the studied population had IgG to MSP2, 75% IgG to MSP1-19 IgG and less than 40% had IgG to at least one the other tested antigens (Figure 2B). It is worthy to note that no reactivity was observed against AMA1, PfEMP1, GST and NANP-4. The most significant difference between the groups was observed by Kruskal-Wallis for MSP3-3D7 (Figure 2C; p = 0.034). Plasma levels (pg/mL) of circulating anti-MSP3-3D7 IgG was higher in the AM group than in the MM and EC groups (Figure 2D; p = 0.03). It is also noteworthy that 55% of AM compared to 12% EN and 19% MM produced IgG anti-MSP3-3D7. Conversely, the level of anti-MSP1-19 antibody was significantly higher in the MM than in AM and EC [see Additional file 1]. In the same patient group, IgG to MSP2-3D7 or MSP2-FC27 detected in some MM patients on day 0 persisted with the same intensity until day 30, even after treatment [see Additional file 2A]. However, for some of the antigens, such as MSP1-19, reactivity increased between days 0 and 7 or between days 0 and 30 [see Additional file 2B].Figure 2

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