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

Abstract

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. Keywords: Plasmodium falciparum, PfEMP1-DBLα, Antibody, Severe malaria, Uncomplicated malaria