Autoimmune Anemia in Malaria

Abstract

Severe anemia is a major cause of death by malaria. The loss of uninfected erythrocytes is an important contributor to malarial anemia; however, the mechanisms underlying this pathology are not well understood. Malaria-induced anemia is related to autoimmune antibodies against the membrane lipid phosphatidylserine (PS). In mice, these antibodies induce the clearance of uninfected erythrocytes after binding to PS exposed in their membrane. In human malaria patients there is a strong correlation between anemia and anti-PS antibodies. During malaria, anti-PS antibodies are produced by atypical B cells, whose levels correlate with the development of anemia in patients. Autoimmune responses, which are documented frequently in different infections, contribute to the pathogenesis of malaria by inducing the clearance of uninfected erythrocytes.

Keywords: Plasmodium falciparum; Plasmodium vivax; antiphosphatidylserine antibodies; atypical B cells; autoantibodies; autoimmunity.

Figure 1, Key Figure.. Proposed model for differentiation of atypical B cells secreting anti-PS antibodies and their roles in erythrocyte clearance during malaria.

During malaria, naïve B cells would encounter phosphatidylserine (PS), parasite DNA and IFN-γ which result in the activation of the B-cell receptor (BCR), TLR-9 and IFN-γ receptor, respectively. Activation of these receptors results in the differentiation of atypical B cells producing anti-PS antibodies. These antibodies bind uninfected erythrocytes that expose PS in their surface during malaria and facilitate their clearance by complement-mediated lysis or opsonization, promoting anemia in malaria patients.