Nonimmune IgM, but not IgG binds to the surface of Plasmodium falciparum-infected erythrocytes and correlates with rosetting and severe malaria

Recent work suggests that IgG and IgM from nonimmune human serum (natural antibodies) bind to the surface of Plasmodium falciparum-infected erythrocytes and contribute to rosette formation by stabilizing the interaction between infected and uninfected erythrocytes. Here we show, in both laboratory clones and field isolates, that only IgM but not IgG is detected on the surface of infected cells. In field isolates, there was a strong positive correlation between IgM binding and rosette formation (Spearman's rank correlation coefficient rho = 0.804, P < 0.001). Both rosette formation and IgM binding were associated with severe malaria, although statistical analysis indicates that rosette formation is the more strongly associated variable. Rosette formation, but not IgM binding, was also associated with malarial anemia. We conclude that IgM is the predominant class of natural antibodies binding to the surface of infected erythrocytes. However, we could not confirm previous suggestions that infected erythrocytes are coated with nonimmune IgG, which could lead to their interaction with host Fcgamma receptors.