IgGs como mediadoras da eritrofagocitose: possível contribuição na anemia em infecções por Plasmodium vivax e influência dos grupos sanguíneos do sistema ABO

Abstract

The removal of non-parasitized erythrocytes is a major cause of anemia in Plasmodium vivax infection. However, the main pathophysiological mechanisms involved in their destruction are still unknown. Studies conducted with Plasmodium falciparum have suggested that phagocytosis of non-infected red blood cells by splenic macrophages is one of the main mechanisms that could explain such removal, but little is known with regard to infection caused P. vivax. It has been shown that erythrophagocytosis of non-parasitized erythrocytes, as well as senescent erythrocytes is related to changes in the membrane of these cells by several factors, including the immunoglobulinss deposition. During the malarial infection an increase in the production of antibodies, mainly IgG occurs. Thus, the aim of this study was to investigate the role of such immunoglobulins purified from sera from individuals with different clinical status in inducing phagocytosis of uninfected erythrocytes as well as to establish possible associations between the different phenotypes of the ABO blood system and anemia in vivax malaria. Erythrophagocytosis assays were performed in vitro, using THP-1 cells and red blood cells obtained from healthy individuals of different blood types. IgGs purified from sera of anemic or non-anemic infected patients were used to conduct in vitro experiments. There was a greater erythrophagocytosis rate for erythrocyte opsonized with IgG purified from anemic patients compared to erythrocytes sensitized with IgGs non-anemic patients, and also compared to the negative control (IgGs from healthy donor). Using two different multivariate analyses (NMDS and GLM) we demonstrated that red cells of blood group O were more susceptible to erythrophagocytosis when compared to groups A or B. We also investigated the relationship between erythrophagocytosis and the disease severity. Thus, inactivated sera from patients hospitalized with a severe outcome and also sera from patients without severe clinical manifestations were used to opsonize erythrocytes in vitro. There was an inverse correlation between the erythrophagocytosis rates and hemoglobin or hematocrit levels of those patients suggesting that erythrophagocytosis could be considered an important factor in the genesis of anemia. Finally, the effect of erythrophagocytosis on the disease severity was examined by a principal component analysis confirming that erythrophagocytosis could be considered as an important biomarker of severity in vivax malaria. Our findings extend our understanding of the mechanisms involved in anemia and may contribute to improve the control strategies to this important disease.