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Conclusive evidence exists on the protective role against clinical Plasmodium falciparum malaria of Haemoglobin S (beta 6Glu-->Val) and HbC (HbC; beta 6Glu-->Lys), both occurring in sub-Saharan Africa. However, the mechanism/s of the protection exerted remain/s debated for both haemoglobin variants, HbC and HbS. Recently, an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, was reported on HbAC and HbCC infected erythrocytes that showed reduced cytoadhesion and impaired rosetting in vitro. On this basis it has been proposed that HbC protection might be attributed to the reduced PfEMP1-mediated adherence of parasitized erythrocytes in the microvasculature. Furthermore, impaired cytoadherence was observed in HbS carriers suggesting for the first time a convergence in the protection mechanism of these two haemoglobin variants. We investigated the impact of this hypothesis on the development of acquired immunity against P. falciparum variant surface antigens (VSA) encoding PfEMP1 in HbC and HbS carriers in comparison with HbA of Burkina Faso. Higher immune response against a VSA panel and several malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the beta-globin genotype. Thus, these findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. We reviewed the hypothesized mechanisms so far proposed in light of these recent results.

Type

Journal

Parassitologia

Publication Date

12/2007

Volume

49

Pages

209 - 213

Addresses

Dipartimento di Scienze di Sanità Pubblica, Sezione di Parassitologia, Università degli Studi di Roma "La Sapienza", Roma, Italy. federica.verra@uniroma1.it

Keywords

Erythrocytes, Animals, Humans, Plasmodium falciparum, Malaria, Falciparum, Genetic Predisposition to Disease, Hemoglobin C, Hemoglobin, Sickle, Immunoglobulin G, Antibodies, Protozoan, Antigens, Protozoan, Selection (Genetics), Genotype, Models, Immunological, Adult, Child, Africa South of the Sahara, Host-Parasite Interactions