HbS PROTECTION FROM MALARIA: A REAPPRAISAL

• Main Author: Sandro Eridani
• Format: Article
• Language: English
• Published: PAGEPress Publications 2014-08-01
• Series: Mediterranean Journal of Hematology and Infectious Diseases
• Subjects: Malaria; Sickle Cell Disease; Red Cell Membrane
• Online Access: https://mjhid.org/index.php/mjhid/article/view/1684

A protective effect by some Hbpathies against incidence and severity of malaria has been known for long time. Recent investigations have highlighted possible mechanisms for this effect, with special regard to Haemoglobin S ( HbS) and related clinical forms. Some protection is afforded by genetic changes preventing plasmodium falciparum to survive and proliferate within the red cell : such changes may include variants of the “basigin” receptor for the parasite antigens and inhibition by HbS of parasite-induced red cell remodelling. Genetic factors specifically interacting with the development of the infection are the sickle cell trait ( an example of negative epistasis), the presence of foetal Haemoglobin ( HbF) , particularly in its pancellular distribution, and a few genes, identified by genome-wide linkage studies, associated with malaria resistance. A special role in protection from malaria is played by molecular mediators, particularly a sequence involving haeme-oxygenase( HMO-1), which appears up-regulated in transgenic sickle cell mice : the action of HMO-1 prevents the cytotoxic effect of free heme and is in turn mediated by carbon monoxide , which inhibits Hb oxidation and further release of haeme from haemoglobin. Immunological factors are also important, as shown by the development of children immunity to malaria, a rapid process in the early years of age ( anti-disease immunity) and a slower one later ( anti-parasite immunity) : a relevant role is played by antibodies to variant surface antigens (VSA) expressed by the parasite : an association was actually found between carriage of HbAS and the presence of IgG anti-VSA responses . Among other mechanisms of protection, it has been recently found that an unwelcome event in severe malaria, like the sequestration of parasite –invaded red cells in many tissues and organs , including the brain, can be inhibited by protein extracts from HbS and HbC , which prevent actin polymerization in vitro. A minor role is played by phagocytosis and removal of ring-parasitized infected red cells, a process present in subjects with glucose-6-phosphate- dehydrogenase (G-6PD) deficiency, but also enhanced in the presence of HbS. There is therefore ample evidence that, among many factors operating in the induction of protection from malaria, the presence of HbS and other Hb variants plays a very significant role, which is now in the process of being gradually elucidated.