Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia

Juan L Rivera-Correa's picture
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TitleAnti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia
Publication TypeJournal Article
Year of Publication2016
AuthorsFernandez-Arias, C, Rivera-Correa, J, Gallego-Delgado, J, Rudlaff, R, Fernandez, C, Roussel, C, Gotz, A, Gonzalez, S, Mohanty, A, Mohanty, S, Wassmer, S, Buffet, P, Ndour, PA, Rodriguez, A
JournalCell Host MicrobeCell Host Microbe
Volume19
Pagination194-203
Date PublishedFeb 10
ISBN Number1934-6069 (Electronic)<br/>1931-3128 (Linking)
Accession Number26867178
KeywordsAnemia/*etiology, Animals, Antibodies, Protozoan/*immunology, Erythrocytes/*immunology/parasitology, Female, Humans, Malaria, Falciparum/*complications/immunology, Male, Mice, Phagocytosis, Phosphatidylserines/*immunology, Plasmodium falciparum/*physiology
AbstractPlasmodium 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.