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The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children.

Vigan-Womas I, Lokossou A, Guillotte M, Juillerat A, Bentley G, Garcia A, Mercereau-Puijalon O, Migot-Nabias F - Malar. J. (2010)

Bottom Line: Antibody responses were compared in the clinical groups.They were essentially stable, although levels tended to decrease with time.The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, F-75015 Paris, France.

ABSTRACT

Background: The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting) is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic P. falciparum infection.

Methods: Serum was collected from Beninese children with severe malaria, uncomplicated malaria or P. falciparum asymptomatic infection (N = 65, 37 and 52, respectively) and from immune adults (N = 30) living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTS-DBL1α1, CIDRγ and DBL2βC2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children.

Results: Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100%) and asymptomatic children (92.3%) but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively). The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL1α1. None of the children sera, including those with surface-reactive antibodies possessed anti-VarO-rosetting activity, and few adults had rosette-disrupting antibodies.

Conclusions: Children with severe and uncomplicated malaria had similar responses. The higher prevalence and level of VarO-reactive antibodies in asymptomatic children compared to children with malaria is consistent with a protective role for anti-VarO antibodies against clinical falciparum malaria. The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play.

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Correlation between S-IFA and antibody-reactivity to the NTS-DBL1α1 protein: linear regression of ln(S-IFA) [ordinate] as a function of NTS-DBL1α1 IgG levels (AU) [abscissa] in HA, AP, UM and SM groups.
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Figure 5: Correlation between S-IFA and antibody-reactivity to the NTS-DBL1α1 protein: linear regression of ln(S-IFA) [ordinate] as a function of NTS-DBL1α1 IgG levels (AU) [abscissa] in HA, AP, UM and SM groups.

Mentions: For all four groups, the strongest correlations involving VarO-surface reactive antibodies were observed with total IgG to NTS-DBL1α1 (Rho from 0.38 to 0.67, all P < 0.006) (Figure 5). A similar observation was valuable for the CM sub-group (Rho = 0.37, P = 0.02). Less numerous and strong correlations were observed between VarO-surface reactive antibodies and IgG1 or IgG3 levels to varO-domains. Antibodies to the VarO-IE crude extract correlated to none of the antibody level to the individual varO-domains in the HA and AP groups (all Rho < 0.06, all P > 0.18).


The humoral response to Plasmodium falciparum VarO rosetting variant and its association with protection against malaria in Beninese children.

Vigan-Womas I, Lokossou A, Guillotte M, Juillerat A, Bentley G, Garcia A, Mercereau-Puijalon O, Migot-Nabias F - Malar. J. (2010)

Correlation between S-IFA and antibody-reactivity to the NTS-DBL1α1 protein: linear regression of ln(S-IFA) [ordinate] as a function of NTS-DBL1α1 IgG levels (AU) [abscissa] in HA, AP, UM and SM groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2959068&req=5

Figure 5: Correlation between S-IFA and antibody-reactivity to the NTS-DBL1α1 protein: linear regression of ln(S-IFA) [ordinate] as a function of NTS-DBL1α1 IgG levels (AU) [abscissa] in HA, AP, UM and SM groups.
Mentions: For all four groups, the strongest correlations involving VarO-surface reactive antibodies were observed with total IgG to NTS-DBL1α1 (Rho from 0.38 to 0.67, all P < 0.006) (Figure 5). A similar observation was valuable for the CM sub-group (Rho = 0.37, P = 0.02). Less numerous and strong correlations were observed between VarO-surface reactive antibodies and IgG1 or IgG3 levels to varO-domains. Antibodies to the VarO-IE crude extract correlated to none of the antibody level to the individual varO-domains in the HA and AP groups (all Rho < 0.06, all P > 0.18).

Bottom Line: Antibody responses were compared in the clinical groups.They were essentially stable, although levels tended to decrease with time.The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut Pasteur, Unité d'Immunologie Moléculaire des Parasites, F-75015 Paris, France.

ABSTRACT

Background: The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting) is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic P. falciparum infection.

Methods: Serum was collected from Beninese children with severe malaria, uncomplicated malaria or P. falciparum asymptomatic infection (N = 65, 37 and 52, respectively) and from immune adults (N = 30) living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTS-DBL1α1, CIDRγ and DBL2βC2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children.

Results: Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100%) and asymptomatic children (92.3%) but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively). The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL1α1. None of the children sera, including those with surface-reactive antibodies possessed anti-VarO-rosetting activity, and few adults had rosette-disrupting antibodies.

Conclusions: Children with severe and uncomplicated malaria had similar responses. The higher prevalence and level of VarO-reactive antibodies in asymptomatic children compared to children with malaria is consistent with a protective role for anti-VarO antibodies against clinical falciparum malaria. The mechanism of such protection seems independent of rosette-disruption, suggesting that the cytophilic properties of antibodies come into play.

Show MeSH
Related in: MedlinePlus