What Causes Malaria-Induced Anemia?

Anemia is a common and sometimes deadly complication of malaria infections. While the immune system must destroy red blood cells infected with the malaria parasite to clear the infection, a study published today in eLife suggests that the infection can trigger an ongoing autoimmune attack on uninfected red blood cells, ultimately causing anemia.

Previous studies in mice with malaria showed that autoimmune antibodies attach to a molecule called phosphatidylserine (PS) on uninfected cells, marking them for destruction by the immune system. These autoimmune antibodies were also found in patients with malaria-induced anemia, suggesting that they may be the cause of red blood cell loss.

However, it has been difficult to study these immune processes in patients living in areas where malaria is endemic since they may experience repeated infections. To address this, the team decided to study the immune response in people from Germany who were exposed to malaria for the first time while traveling in Africa.

“Studying the immune cells that produce these autoantibodies during new malaria infections in European travelers represented a unique opportunity,” says first author Juan Rivera-Correa of NYU.

In their experiments, the team identified the production of an unusual type of B cell—the FcRL5+T-bet+ B cell—that increases anti-PS antibody production associated with the development of anemia in these patients. These immune cells also developed and produced anti-PS antibodies in blood drawn from uninfected people that was then exposed to broken remnants of malaria-infected red blood cells in the laboratory.

“Our results provide the first mechanistic evidence of autoimmune-mediated anemia in malaria patients and highlight these atypical immune cells as major promoters of this complication,” Rivera-Correa says.

Senior author Ana Rodriguez of NYU adds, “There is a great need for novel targeted treatments for malaria-induced anemia, which is common and can be fatal for many malaria patients. The unique phenotype and specificity of these immune B cells could allow them to be used as a biomarker for anemia or as a target for new therapies.”