Malarial anaemia : the potential involvement of Plasmodium falciparum rhoptry proteins

Abstract: Malaria remains a challenging health problem in malaria endemic regions. Infection with malaria invariably leads to anaemia. The groups at risk of developing malarial anaemia include children below the age of five years and pregnant women, especially primigravidae. Several factors have been suggested to be responsible for its aetiology, including increased destruction of infected and normal red blood cells together with bone marrow suppression. However, until recently, the molecular mechanisms involved have remained elusive. The aim of the work presented herein was to investigate the mechanisms responsible for the destruction of normal red blood cells in anaemia, and more specifically to define the role of the ring surface protein (RSP/RAP) -2 and other members of the low molecular weight rhoptry associated protein (RAP) complex, RAP-1 and -3. In the first study we showed that antibodies to the RAP complex could mediate the destruction of RSP-2 tagged erythroid cells by phagocytosis or by complement activation and then lysis. In addition, antibodies to RAP-1 and RAP-2 could induce the death of RSP-2/RAP-2 tagged erythroblasts. We further investigated the frequency and functionality of naturally occurring RSP-2/RAP-2 antibodies in the sera of anaemic and non-anaemic Cameroonian children. We found that all sera investigated contained RSP-2/RAP-2 reactive antibodies by both immunoflorescence and flow cytometry. The anaemic group of children had significantly higher levels of antibodies of the IgG isotype than the non-anaemic individuals, while the levels of IgM were similar in both groups. With respect to IgG subclasses, low levels of IgG1 and -3 antibodies were detected. Higher levels of IgG3 were seen in the non-anaemic individuals as compared to anaemic subjects. With regards to antibody functionality, the non-anaemic individuals recognised a greater proportion of RSP-2/RAP-2 tagged erythrocytes and activated complement to a greater extent than the anaemic individuals. From our findings, we can conclude that antibodies to the RAP complex are potentially involved in erythroid cell destruction during malaria which may result in anaemia, and that high levels of such antibodies may be detrimental to the host.