title: Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia.
abstract: 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.
authors: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Cristina
authors: C
authors: Fernandez-Arias
authors: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Juan
authors: J
authors: Rivera-Correa
authors: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Julio
authors: J
authors: Gallego-Delgado
authors: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Rachel
authors: R
authors: Rudlaff
authors: Universidad Carlos III, 28911 Madrid, Spain.
authors: Clemente
authors: C
authors: Fernandez
authors: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Paris 6, Laboratoire d'excellence du Globule Rouge (Labex GR-EX), 75000 Paris, France.
authors: Camille
authors: C
authors: Roussel
authors: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Anton
authors: A
authors: Götz
authors: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Sandra
authors: S
authors: Gonzalez
authors: Institute of Life Sciences Laboratory, Bubhaneswar and Anusandhan Laboratory, Rourkela, Orissa, India.
authors: Akshaya
authors: A
authors: Mohanty
authors: Ispat General Hospital, Rourkela Steel Plant, Rourkela, Orissa, India.
authors: Sanjib
authors: S
authors: Mohanty
authors: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
authors: Samuel
authors: S
authors: Wassmer
authors: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Paris 6, Laboratoire d'excellence du Globule Rouge (Labex GR-EX), 75000 Paris, France.
authors: Pierre
authors: P
authors: Buffet
authors: Centre d'Immunologie et des Maladies Infectieuses de Paris, U 1135 INSERM/Université Paris 6, Laboratoire d'excellence du Globule Rouge (Labex GR-EX), 75000 Paris, France.
authors: Papa Alioune
authors: PA
authors: Ndour
authors: Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: ana.rodriguez@nyumc.org.
authors: Ana
authors: A
authors: Rodriguez
mesh_terms: D000740:Anemia / Q000209:etiology*; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000150:complications* / Q000276:immunology; D008297:Male; D051379:Mice; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000276:immunology*; D010963:Plasmodium falciparum / Q000502:physiology*
chemical_list: D000913:Antibodies, Protozoan; D010718:Phosphatidylserines