Natural Protection Against Severe Plasmodium falciparum Malaria Due to Impaired Rosette Formation

Genes for two lethal diseases, thalassemia and sickle cell anemia, are favored by evolution because, in their heterozygous form, they protect against cerebral malaria. Rosette formation, the binding of uninfected red cells (RBCs) to Plasmodium falciparum-infected RBCs (PRBCs), has previously been fo...

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Published inBlood Vol. 84; no. 11; pp. 3909 - 3914
Main Authors Carlson, Johan, Nash, Gerard B., Gabutti, Vilma, Al-Yaman, Fadwa, Wahlgren, Mats
Format Journal Article
LanguageEnglish
Published Washington, DC Elsevier Inc 01.12.1994
The Americain Society of Hematology
Subjects
alpha-Thalassemia - blood
Anemia, Sickle Cell - blood
Animals
Biological and medical sciences
Cerebrovascular Circulation
Erythrocyte Volume
Erythrocytes, Abnormal - parasitology
Human protozoal diseases
Humans
Immunity, Innate - genetics
Infectious diseases
Malaria
Malaria, Cerebral - physiopathology
Malaria, Falciparum - blood
Medical sciences
Microcirculation
Parasitic diseases
Plasmodium falciparum
Protozoal diseases
Rosette Formation
Sickle Cell Trait - blood
Thalassemia - blood
Infection
Human
Protozoa
Plasmodium falciparum
Protozoal disease
Malaria
Rosette test
Red blood cell
Parasitosis
Sporozoa
Protection
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Summary:Genes for two lethal diseases, thalassemia and sickle cell anemia, are favored by evolution because, in their heterozygous form, they protect against cerebral malaria. Rosette formation, the binding of uninfected red cells (RBCs) to Plasmodium falciparum-infected RBCs (PRBCs), has previously been found to be associated with cerebral malaria, the most important severe manifestation of P falciparum malaria. We show here that thalassemic RBCs and, under certain conditions, even hemoglobin S (HbS)-containing RBCs possess an impaired ability to bind to PRBCs, forming small and weak erythrocyte rosettes compared with rosettes formed by normal RBCs. This decreased rosetting ability is associated with the small size of the thalassemic RBCs and with distortion of the mechanical properties of HbS-containing RBCs. The impairment of rosette formation may hinder the development of cerebral malaria by abatement of sequestration.
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ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V84.11.3909.bloodjournal84113909