Association of HLA alleles with Plasmodium falciparum severity in Malian children.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lyke, KE; Fernández-Vi┼ła, MA; Cao, K; Hollenbach, J; Coulibaly, D; Kone, AK; Guindo, A; Burdett, LA; Hartzman, RJ; Wahl, AR; Hildebrand, WH; Doumbo, OK; Plowe, CV; Sztein, MB

Published Date

  • June 2011

Published In

Volume / Issue

  • 77 / 6

Start / End Page

  • 562 - 571

PubMed ID

  • 21447146

Pubmed Central ID

  • 21447146

Electronic International Standard Serial Number (EISSN)

  • 1399-0039

International Standard Serial Number (ISSN)

  • 0001-2815

Digital Object Identifier (DOI)

  • 10.1111/j.1399-0039.2011.01661.x

Language

  • eng