title: Association of HLA alleles with Plasmodium falciparum severity in Malian children.
abstract: 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.
authors: Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: K E
authors: KE
authors: Lyke
authors: M A
authors: MA
authors: Fernández-Viňa
authors: K
authors: K
authors: Cao
authors: J
authors: J
authors: Hollenbach
authors: D
authors: D
authors: Coulibaly
authors: A K
authors: AK
authors: Kone
authors: A
authors: A
authors: Guindo
authors: L A
authors: LA
authors: Burdett
authors: R J
authors: RJ
authors: Hartzman
authors: A R
authors: AR
authors: Wahl
authors: W H
authors: WH
authors: Hildebrand
authors: O K
authors: OK
authors: Doumbo
authors: C V
authors: CV
authors: Plowe
authors: M B
authors: MB
authors: Sztein
mesh_terms: D000293:Adolescent; D000465:Algorithms; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease; D015234:HLA-A Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000166:cytology; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology*; D008302:Mali; D016017:Odds Ratio; D010963:Plasmodium falciparum / Q000378:metabolism*; D011110:Polymorphism, Genetic
chemical_list: D015234:HLA-A Antigens; D000949:Histocompatibility Antigens Class II; D016753:Interleukin-10