Acquisition of naturally acquired antibody response to Plasmodium falciparum erythrocyte membrane protein 1-DBLα and differential regulation of IgG subclasses in severe and uncomplicated malaria

Objectives:To explore whether individuals infected with Plasmodium falciparum (P.falciparum) develop antibodies directed against PfEMP1-DBLα,and to assess their IgG subclass distribution in severe and uncomplicated malaria.Methods:The anti-PfDBLα IgG and their IgG subclass distributions in plasma of severe (SM) and uncomplicated malaria (UCM) were assessed by enzyme-linked immunoabsorbent assay.The antibody profiles to P.falciparum blood stage antigens were evaluated.CD36 binding ability was determined by static receptor-binding assays.Rosette formation was performed by staining with acridine orange.Results:Significantly higher number of UCM (86.48％) than SM (57.78％) plasma contained total acquisition of specific IgG to P.falciparum antigens (P =0.000).Similar manners were seen in response to P.falciparum DBLα with significant difference (UCM,59.46％ vs SM,40.00％;P =0.014).Anti-PfDBLα-IgG1 and-IgG3 were the predominant subclasses.Similar percentage of UCM (31.82％) and SM (33.33％) plasma contained only IgG1,while 13.64％ of UCM and 27.78％ of SM plasma contained only IgG3.AntiPfTDBLα-IgG1 coexpressed with more than one subclass was noted (UCM,27.27％;SM,16.67％).Obviously,IgG1 coexpressed with IgG3 (9.09％) was observed in only UCM plasma.IgG1 was coexpressed with IgG2 in UCM (9.09％) and SM (11.11％) plasma,while IgG1 was coexpressed with IgG4 only in UCM plasma (4.55％).IgG subclasses to P.falciparum antigens were distributed in a similar manner.Only the levels of IgG1,but not IgG3 were significantly higher in UCM than in SM.Conclusions:These data suggest that individuals infected with P.falciparum can develop the anti-PfEMP1 antibodies with the major contribution of specific IgG subclasses.The balance and the levels of anti-PfDBLα IgG subclasses play a crucial role in antibody mediated protection against severe malaria.

Acquisition of naturally acquired antibody response to Plasmodium falciparum erythrocyte membrane protein 1-DBLα and differential regulation of IgG subclasses in severe and uncomplicated malaria

Objectives To explore whether individuals infected with Plasmodium falciparum (P. falciparum) develop antibodies directed against PfEMP1-DBLα and to assess their IgG subclass distribution in severe and uncomplicated malaria. Methods The anti-PfDBLα IgG and their IgG subclass distributions in plasma of severe (SM) and uncomplicated malaria (UCM) were assessed by enzyme-linked immunoabsorbent assay. The antibody profiles to P. falciparum blood stage antigens were evaluated. CD36 binding ability was determined by static receptor-binding assays. Rosette formation was performed by staining with acridine orange. Results Significantly higher number of UCM (86.48%) than SM (57.78%) plasma contained total acquisition of specific IgG to P. falciparum antigens (P = 0.000). Similar manners were seen in response to P. falciparum DBLα with significant difference (UCM, 59.46% vs SM, 40.00%; P = 0.014). Anti-PfDBLα-IgG1 and -IgG3 were the predominant subclasses. Similar percentage of UCM (31.82%) and SM (33.33%) plasma contained only IgG1, while 13.64% of UCM and 27.78% of SM plasma contained only IgG3. Anti-PfDBLα-IgG1 coexpressed with more than one subclass was noted (UCM, 27.27%; SM, 16.67%). Obviously, IgG1 coexpressed with IgG3 (9.09%) was observed in only UCM plasma. IgG1 was coexpressed with IgG2 in UCM (9.09%) and SM (11.11%) plasma, while IgG1 was coexpressed with IgG4 only in UCM plasma (4.55%). IgG subclasses to P. falciparum antigens were distributed in a similar manner. Only the levels of IgG1, but not IgG3 were significantly higher in UCM than in SM. Conclusions These data suggest that individuals infected with P. falciparum can develop the anti-PfEMP1 antibodies with the major contribution of specific IgG subclasses. The balance and the levels of anti-PfDBLα IgG subclasses play a crucial role in antibody mediated protection against severe malaria.

Antibody recognition of Plasmodium falciparum infected red blood cells by symptomatic and asymptomatic individuals in the Brazilian Amazon

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms. .