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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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Prevalence rates of IgG to VarO-IE crude extract, and of IgG, IgG1 and IgG3 to varO recombinant NTS-DBL1α1, CIDRγ and DBL2βC2 in healthy adults (dots) and the children recruited in 2006, AP (grey), UM (white), SM (criss-cross). Bars denote the 95% confidence interval. Asterisks indicate P values estimated using the χ2 test as follows: ***, P < 0.0001; **, P < 0.001; *, P < 0.01.
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Figure 3: Prevalence rates of IgG to VarO-IE crude extract, and of IgG, IgG1 and IgG3 to varO recombinant NTS-DBL1α1, CIDRγ and DBL2βC2 in healthy adults (dots) and the children recruited in 2006, AP (grey), UM (white), SM (criss-cross). Bars denote the 95% confidence interval. Asterisks indicate P values estimated using the χ2 test as follows: ***, P < 0.0001; **, P < 0.001; *, P < 0.01.

Mentions: In none of the assays did UM and SM children, as well as UM and CM children, display a statistically different response (Figure 3). Total IgG seroprevalence to the recombinant antigens and the crude extract was similarly high in HA adults and AP children. Seroprevalence to the crude extract was lower in UM children. Total IgG and IgG1 seroprevalence to the three recombinant domains was higher in AP children than in UM and/or SM children. Similar results were observed for IgG3 except for seroprevalence to NTS-DBL1α1 which was higher in AP children than UM children but not different from SM children (Figure 3).


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)

Prevalence rates of IgG to VarO-IE crude extract, and of IgG, IgG1 and IgG3 to varO recombinant NTS-DBL1α1, CIDRγ and DBL2βC2 in healthy adults (dots) and the children recruited in 2006, AP (grey), UM (white), SM (criss-cross). Bars denote the 95% confidence interval. Asterisks indicate P values estimated using the χ2 test as follows: ***, P < 0.0001; **, P < 0.001; *, P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Prevalence rates of IgG to VarO-IE crude extract, and of IgG, IgG1 and IgG3 to varO recombinant NTS-DBL1α1, CIDRγ and DBL2βC2 in healthy adults (dots) and the children recruited in 2006, AP (grey), UM (white), SM (criss-cross). Bars denote the 95% confidence interval. Asterisks indicate P values estimated using the χ2 test as follows: ***, P < 0.0001; **, P < 0.001; *, P < 0.01.
Mentions: In none of the assays did UM and SM children, as well as UM and CM children, display a statistically different response (Figure 3). Total IgG seroprevalence to the recombinant antigens and the crude extract was similarly high in HA adults and AP children. Seroprevalence to the crude extract was lower in UM children. Total IgG and IgG1 seroprevalence to the three recombinant domains was higher in AP children than in UM and/or SM children. Similar results were observed for IgG3 except for seroprevalence to NTS-DBL1α1 which was higher in AP children than UM children but not different from SM children (Figure 3).

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