Anti-band 3 and anti-spectrin antibodies are increased in Plasmodium vivax infection and are associated with anemia

Abstract

Clearance of non-infected red blood cells (nRBCs) is one of the main components of anemia associated with Plasmodium vivax malaria. Recently, we have shown that anemic patients with P. vivax infection had elevated levels of anti-RBCs antibodies, which could enhance in vitro phagocytosis of nRBCs and decrease their deformability. Using immunoproteomics, here we characterized erythrocytic antigens that are differentially recognized by autoantibodies from anemic and non-anemic patients with acute vivax malaria. Protein spots exclusively recognized by anemic P. vivax-infected patients were identified by mass spectrometry revealing band 3 and spectrin as the main targets. To confirm this finding, antibody responses against these specific proteins were assessed by ELISA. In addition, an inverse association between hemoglobin and anti-band 3 or anti-spectrin antibodies levels was found. Anemic patients had higher levels of IgG against both band 3 and spectrin than the non-anemic ones. To determine if these autoantibodies were elicited because of molecular mimicry, we used in silico analysis and identified P. vivax proteins that share homology with human RBC proteins such as spectrin, suggesting that infection drives autoimmune responses. These findings suggest that band 3 and spectrin are potential targets of autoantibodies that may be relevant for P. vivax malaria-associated anemia.

Rosettes integrity protects Plasmodium vivax of being phagocytized

“…P. vivax rosetting has been previously associated with anemia during pregnancy . Even though the mechanisms that are driving anemia in vivax malaria are not completely elucidate, there are evidences that the presence of autoantibodies are increased during acute P. vivax infection [22][23][24][25] .…”

Effects of IgG and IgM autoantibodies on non-infected erythrocytes is related to ABO blood group in Plasmodium vivax malaria and is associated with anemia

“…These subjects were examined by an experienced physician, who applied a questionnaire to collect demographic and epidemiological data. A detailed description of the characteristics of the studied population has been published elsewhere [12]. Blood samples were collected upon admission and analyzed for hemoglobin level.…”

Atypical memory B-cells and autoantibodies correlate with anemia during Plasmodium vivax complicated infections

“…The mechanisms underlying the loss of uninfected erythrocytes are not clear yet, but malariainduced anemia was recently related to autoimmune responses in patients [10]. Malaria, as other highly inflammatory infectious diseases, induces a strong autoimmune response characterized by the generation of anti-self antibodies with different specificities [11][12][13]. Studies in mice models of malaria showed that antibodies recognizing the lipid phosphatidylserine (PS) exposed on the surface of uninfected erythrocytes promote their clearance contributing to anemia [14].…”