63167

Does complement protection come at a cost? Role of complement-fixing antibodies in the pathogenesis of severe malaria anaemia of P. vivax infection

Damian Adithya Oyong ; Enny Kenangalem 1 ; Jeanne Rini Poespoprodjo 2 ; Nicholas M. Anstey 3 ; Ric N. Price 4 ; Michelle J. Boyle 5
Favorite this paper

Background: The complement system acts as an essential component of defence mechanism against malaria parasite invasion however may contribute to the immunopathogenesis of severe malarial anaemia.Increase in complement activation by functional antibodies and the removal of complement regulatory proteins (CRPs) by Plasmodium infection may exacerbate the destruction of red blood cells (RBCs), althoughthis interaction has yet to be formally tested.We investigated the relationship of complement-fixing antibodies with the removal of CRPsand the degree to which this makes RBCs vulnerable to complement attack and ultimately results in anaemiain both P. vivax and P. falciparum infection. Materials and Methods: Blood samples from 120 patients with uncomplicated and severe P. vivax (n=60) and P. falciparum (n=60) malaria were collected from patients enrolled in Papua, Indonesia and categorised as: anaemic (<8 Hb), mild anaemic (8-12 Hb), and non-anaemic (>12Hb). Indirect fluorescence staining was used to measure levels of CRPs(CD35/CR1, CD55/DAF, CD47, and CD59) on the surface of RBCs.The magnitude of complement activation (C3a and C5a) and complement-fixing antibodies targeting P. vivax merozoite antigens was measured by ELISA. Results and Conclusions: Expression levels of CR1 and DAF on uninfected RBCs inanaemic patients were significantly lower compared to non-anaemic individuals,in both P. vivax(CR1; p=0.003, DAF; p=0.005) and P.falciparum (CR1; p=0.008, DAF; p<0.001) infection. Expression of CD47,a marker that reduces phagocytosis, was 1.5 fold higher in anaemic individuals infected with P. vivax(p=0.048). The relationship between complement-fixing antibodies, complement activation, and CRPs will be presented. This studyis the first to investigate complement-associated immunopathogenesis in P. vivax,and the interaction between complement activation, complement fixing antibodies and CRP loss. Loss of CRPs on uninfected RBCs may account for uninfected RBC loss in both P. vivax and P. falciparum malaria, and may contribute to anaemia in both species.