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Title: Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA
Authors: Kouyuki Hirayasu
Jun Ohashi
Koichi Kashiwase
Hathairad Hananantachai
Izumi Naka
Atsuko Ogawa
Minoko Takanashi
Masahiro Satake
Kazunori Nakajima
Peter Parham
Hisashi Arase
Katsushi Tokunaga
Jintana Patarapotikul
Toshio Yabe
University of Tokyo
Japan Society for the Promotion of Science
Japanese Red Cross Medical Center
Osaka University
University of Tsukuba
Mahidol University
Stanford University School of Medicine
Japan Science and Technology Agency
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 1-Mar-2012
Citation: PLoS Pathogens. Vol.8, No.3 (2012)
Abstract: Cerebral malaria is a major, life-threatening complication of Plasmodium falciparum malaria, and has very high mortality rate. In murine malaria models, natural killer (NK) cell responses have been shown to play a crucial role in the pathogenesis of cerebral malaria. To investigate the role of NK cells in the developmental process of human cerebral malaria, we conducted a case-control study examining genotypes for killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) class I ligands in 477 malaria patients. We found that the combination of KIR2DL3 and its cognate HLA-C1 ligand was significantly associated with the development of cerebral malaria when compared with non-cerebral malaria (odds ratio 3.14, 95% confidence interval 1.52-6.48, P = 0.00079, corrected P = 0.02). In contrast, no other KIR-HLA pairs showed a significant association with cerebral malaria, suggesting that the NK cell repertoire shaped by the KIR2DL3-HLA-C1 interaction shows certain functional responses that facilitate development of cerebral malaria. Furthermore, the frequency of the KIR2DL3-HLA-C1 combination was found to be significantly lower in malaria high-endemic populations. These results suggest that natural selection has reduced the frequency of the KIR2DL3-HLA-C1 combination in malaria high-endemic populations because of the propensity of interaction between KIR2DL3 and C1 to favor development of cerebral malaria. Our findings provide one possible explanation for KIR-HLA co-evolution driven by a microbial pathogen, and its effect on the global distribution of malaria, KIR and HLA. © 2012 Hirayasu et al.
ISSN: 15537374
Appears in Collections:Scopus 2011-2015

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