Human Leukocyte Antigen (HLA) part 64

MALARIA

The best example of this resistence is the association of specific HLA class I and class II alleles with protection against severe malaria in sub-Saharan Africa. In the Gambia, infection with Plassmodium falciparum, which causes malaria, is extremely common, although the mortality  rate among children with malarial anaemia or cerebral malaria is low. Both complications are believed to be the consequence of a failure to clear the parasites from the blood, leading to increase  haemolysis and blockage of cerebral blood vessels  by parasitized erythrocytes. HLA typing of the relevant population revealed the presence of the HLA-B*53 allele at a frequency  of approximately  25%  among  healthy people  or children with mild malaria (the allele is rare in non-African populations). By contrast, the frequency of HLA-B*53 among patients with severe   malaria was approximately 15%. The comparison suggests that possesion of the HLA-B*53 molecules bind very effeciently  certain peptides produced by processing the malarial circumsporozoite protein and  present them to CD8 T cells, who progeny attact  the liver-stage parasites. Such cytotoxic  T cells  have indeed been found in patients with malaria, and circumsporozoite peptides  have been eluted  from the HLA-B*53 molecules of these  patients. Protection against severe malarial anaemia is also afforded  by possession of the class II HLA-DRB1*1302/DQB1*0501 haplotype.