A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria

Ian A Cockburn, Margaret J Mackinnon, Angela O'Donnell, Stephen J Allen, Joann M Moulds, Moses Baisor, Moses Bockarie, John C Reeder, J Alexandra Rowe

Research output: Contribution to journalArticlepeer-review

Abstract

Parasitized red blood cells (RBCs) from children suffering from severe malaria often adhere to complement receptor 1 (CR1) on uninfected RBCs to form clumps of cells known as "rosettes." Despite a well documented association between rosetting and severe malaria, it is controversial whether rosetting is a cause or a correlate of parasite virulence. CR1-deficient RBC show greatly reduced rosetting; therefore, we hypothesized that, if rosetting is a direct cause of malaria pathology, CR1-deficient individuals should be protected against severe disease. In this study, we show that RBC CR1 deficiency occurs in up to 80% of healthy individuals from the malaria-endemic regions of Papua New Guinea. This RBC CR1 deficiency is associated with polymorphisms in the CR1 gene and, unexpectedly, with alpha-thalassemia, a common genetic disorder in Melanesian populations. Analysis of a case-control study demonstrated that the CR1 polymorphisms and alpha-thalassemia independently confer protection against severe malaria. We have therefore identified CR1 as a new malaria resistance gene and provided compelling evidence that rosetting is an important parasite virulence phenotype that should be a target for drug and vaccine development.
Original languageEnglish
Pages (from-to)272-7
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume101
Issue number1
DOIs
Publication statusPublished - 2004

Fingerprint

Dive into the research topics of 'A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria'. Together they form a unique fingerprint.

Cite this