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Association of HLA alleles with Plasmodium falciparum severity in Malian children

  1. Author:
    Lyke, K. E.
    Fernandez-Vina, 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.

  2. Author Address

    [Lyke, KE; Plowe, CV; Sztein, MB] Univ Maryland, Sch Med, Ctr Vaccine Dev, Dept Med, Baltimore, MD 21201 USA [Fernandez-Vina, MA] Univ Texas MD Anderson Canc Ctr, Lab Med, Houston, TX 77030 USA [Cao, K] Cedars Sinai Hlth Syst, HLA Lab, Comprehens Transplant Ctr, Los Angeles, CA USA [Cao, K] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA [Hollenbach, J] Childrens Hosp Oakland, Res Inst, Ctr Genet, Oakland, CA 94609 USA [Coulibaly, D; Kone, AK; Guindo, A; Doumbo, OK] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali [Burdett, LA] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA [Burdett, LA] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA [Hartzman, RJ] Georgetown Univ, CW Bill Young DoD Marrow Donor Program, Naval Med Res Inst, Kensington, MD USA [Wahl, AR; Hildebrand, WH] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA [Plowe, CV] Univ Maryland, Sch Med, Ctr Vaccine Dev, Howard Hughes Med Inst, Baltimore, MD 21201 USA;Sztein, MB (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, Dept Med, 685 W Baltimore St HSF 1,Rm 480, Baltimore, MD 21201 USA;msztein@medicine.umaryland.edu
    1. Year: 2011
    2. Date: Jun
  2. Journal: Tissue Antigens
    1. 77
    2. 6
    3. Pages: 562-571
  4. Type of Article: Article
  5. ISSN: 0001-2815
  1. 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.

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External Sources

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  2. DOI: 10.1111/j.1399-0039.2011.01661.x
  3. View record in Web of Science®
  4. WOS: 000290226600006

Library Notes

  1. Fiscal Year: FY2010-2011
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