Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia

Cell Host Microbe. 2016 Feb 10;19(2):194-203. doi: 10.1016/j.chom.2016.01.009.


Plasmodium species, the parasitic agents of malaria, invade erythrocytes to reproduce, resulting in erythrocyte loss. However, a greater loss is caused by the elimination of uninfected erythrocytes, sometimes long after infection has been cleared. Using a mouse model, we found that Plasmodium infection induces the generation of anti-self antibodies that bind to the surface of uninfected erythrocytes from infected, but not uninfected, mice. These antibodies recognize phosphatidylserine, which is exposed on the surface of a fraction of uninfected erythrocytes during malaria. We find that phosphatidylserine-exposing erythrocytes are reticulocytes expressing high levels of CD47, a "do-not-eat-me" signal, but the binding of anti-phosphatidylserine antibodies mediates their phagocytosis, contributing to anemia. In human patients with late postmalarial anemia, we found a strong inverse correlation between the levels of anti-phosphatidylserine antibodies and plasma hemoglobin, suggesting a similar role in humans. Inhibition of this pathway may be exploited for treating malarial anemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / etiology*
  • Animals
  • Antibodies, Protozoan / immunology*
  • Erythrocytes / immunology*
  • Erythrocytes / parasitology
  • Female
  • Humans
  • Malaria, Falciparum / complications*
  • Malaria, Falciparum / immunology
  • Male
  • Mice
  • Phagocytosis
  • Phosphatidylserines / immunology*
  • Plasmodium falciparum / physiology*


  • Antibodies, Protozoan
  • Phosphatidylserines