Open AccessAssociation of HLA alleles with Plasmodium falciparum severity in Malian children
Author(s) -
Lyke K. E.,
FernándezViňa M. A.,
Cao K.,
Hollenbach J.,
Coulibaly D.,
Kone A. K.,
Guindo A.,
Burdett L. A.,
Hartzman R. J.,
Wahl A. R.,
Hildebrand W. H.,
Doumbo O. K.,
Plowe C. V.,
Sztein M. B.
Publication year - 2011
Publication title -
tissue antigens
Language(s) - English
Resource type - Journals
eISSN - 1399-0039
pISSN - 0001-2815
DOI - 10.1111/j.1399-0039.2011.01661.x
Subject(s) - allele , cerebral malaria , malaria , plasmodium falciparum , human leukocyte antigen , biology , immunology , major histocompatibility complex , odds ratio , antigen , hla b antigens , haplotype , allele frequency , genetics , gene , medicine
Pre‐erythrocytic immunity to Plasmodium falciparum malaria is likely to be mediated by T‐cell recognition of malaria epitopes presented on infected host cells via class I and II major histocompatibility complex (MHC) antigens. To test for associations of human leukocyte antigen (HLA) alleles with disease severity, we performed high‐resolution typing of HLA class I and II loci and compared the distributions of alleles of HLA‐A, ‐B, ‐C and ‐DRB1 loci in 359 Malian children of Dogon ethnicity with uncomplicated or severe malaria. We observed that alleles A*30:01 and A*33:01 had higher frequency in the group of patients with cerebral disease compared to patients with uncomplicated disease [A*30:01: gf = 0.2031 vs gf = 0.1064, odds ratio (OR) = 3.17, P = 0.004, confidence interval (CI) (1.94–5.19)] and [A*33:01: gf = 0.0781 vs gf = 0.0266, 4.21, P = 0.005, CI (1.89–9.84)], respectively. The A*30:01 and A*33:01 alleles share some sequence motifs and A*30:01 appears to have a unique peptide binding repertoire compared to other A*30 group alleles. Computer algorithms predicted malaria peptides with strong binding affinity for HLA‐A*30:01 and HLA‐A*33:01 but not to closely related alleles. In conclusion, we identified A*30:01 and A*33:01 as potential susceptibility factors for cerebral malaria, providing further evidence that polymorphism of MHC genes results in altered malaria susceptibility.