Haemoglobin C and S Role in Acquired Immunity against Plasmodium falciparum Malaria

Autor: David J. Conway, Thomas N. Williams, Kevin K. A. Tetteh, Kevin Marsh, Federica Verra, Tevis Howard, Pamela Avellino, Germana Bancone, Jacques Simpore, Isa Blot, Peter C. Bull, Greg Fegan, Faith H. A. Osier, George M. Warimwe, David Modiano
Rok vydání: 2007
Předmět:
Hemoglobin
Sickle

Protozoan Proteins
lcsh:Medicine
Cell Separation
0302 clinical medicine
Microbiology/Parasitology
Malaria
Falciparum

lcsh:Science
Genetics and Genomics/Genetics of Disease
Genetics and Genomics/Medical Genetics
0303 health sciences
Multidisciplinary
Hemoglobin C
Toxoid
virus diseases
Flow Cytometry
Acquired immune system
Microbiology/Immunity to Infections
3. Good health
Evolutionary Biology/Human Evolution
Research Article
Genotype
Plasmodium falciparum
030231 tropical medicine
Antigens
Protozoan

Enzyme-Linked Immunosorbent Assay
Molecular Biology/Molecular Evolution
Biology
03 medical and health sciences
Immune system
Antigen
Immunology/Immunity to Infections
Malaria Vaccines
parasitic diseases
medicine
Antigenic variation
Animals
Humans
030304 developmental biology
lcsh:R
Infectious Diseases/Protozoal Infections
medicine.disease
biology.organism_classification
Virology
digestive system diseases
Immune System
Immunoglobulin G
Immunology
lcsh:Q
Hematology/Hemoglobinopathies
Malaria
Zdroj: PLoS ONE, Vol 2, Iss 10, p e978 (2007)
PLoS ONE
ISSN: 1932-6203
Popis: A recently proposed mechanism of protection for haemoglobin C (HbC; β6Glu←Lys) links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA) encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i) total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS); ii) total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii) total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not assodated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and 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 β-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria. © 2007 Verra et al.
Databáze: OpenAIRE