Publication: Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA
Issued Date
2012-03-01
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ISSN
15537374
15537366
15537366
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2-s2.0-84861204784
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Mahidol University
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SCOPUS
Bibliographic Citation
PLoS Pathogens. Vol.8, No.3 (2012)
Suggested Citation
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 Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA. PLoS Pathogens. Vol.8, No.3 (2012). doi:10.1371/journal.ppat.1002565 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/13794
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Title
Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA
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.