Abstract
BackgroundAnaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. However, little is known about loss of CRPs on RBCs during mild malarial anaemia and in low-density infection.MethodsThe expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated.ResultsCRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM.ConclusionsRemoval of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.
Highlights
Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation
Reduced CR1, CD55, and CD59 on uninfected normocytes and reticulocytes in Malaysian malaria patients with mild anaemia To establish whether changes in complement regulatory protein (CRP) expression on RBC and reticulocyte was a feature of mild anaemia during malaria in low transmission settings, RBC samples were examined from P. falciparum and P. vivax-infected patients living in Sabah, Malaysia
Consistent with previous studies demonstrating that CRP loss is associated with severe malarial anaemia [11, 19], the current results show that the expression of CRPs on RBC is reduced in individuals with mild malarial anaemia associated with either falciparum or vivax malaria
Summary
Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. Conclusions: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia. Destruction of RBCs by complement attack is mediated through the removal of complement regulatory proteins (CRPs) on the RBC surface and consequent complement deposition [11,12,13]. Activation of the complement system can occur under the classical, alternative, and lectin cascade pathway, all of which are regulated by CRPs. Membrane-bound CRPs are expressed on the surface of cells, including RBC, and serve to protect from complement attack [14]. A recent study shown that the loss of CRPs during malaria is mainly restricted to uninfected RBCs, rather than parasitized RBCs [19]
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