|
|
|
|
Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA
|
|
|
|
|
|
|
|
نویسنده
|
hirayasu k. ,ohashi j. ,kashiwase k. ,hananantachai h. ,naka i. ,ogawa a. ,takanashi m. ,satake m. ,nakajima k. ,parham p. ,arase h. ,tokunaga k. ,patarapotikul j. ,yabe t.
|
|
منبع
|
plos pathogens - 2012 - دوره : 8 - شماره : 3
|
|
چکیده
|
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.
|
|
|
|
|
آدرس
|
department of human genetics,graduate school of medicine,the university of tokyo,bunkyo-ku,tokyo,japan,japan society for the promotion of science,tokyo,japan,japanese red cross tokyo blood center,koto-ku,tokyo,japan,department of immunochemistry,wpi immunology frontier research center,osaka university,suita,osaka, Japan, doctoral program in life system medical sciences,graduate school of comprehensive human sciences,university of tsukuba,tsukuba,ibaraki, Japan, japanese red cross tokyo blood center,koto-ku,tokyo, Japan, faculty of tropical medicine,mahidol university,bangkok, Thailand, doctoral program in life system medical sciences,graduate school of comprehensive human sciences,university of tsukuba,tsukuba,ibaraki, Japan, japanese red cross tokyo blood center,koto-ku,tokyo, Japan, japanese red cross tokyo blood center,koto-ku,tokyo, Japan, japanese red cross tokyo blood center,koto-ku,tokyo, Japan, japanese red cross tokyo blood center,koto-ku,tokyo, Japan, department of microbiology and immunology,school of medicine,stanford university,stanford,ca, United States, department of immunochemistry,wpi immunology frontier research center,osaka university,suita,osaka,japan,department of immunochemistry,research institute for microbial diseases,osaka university,suita,osaka,japan,core research for evolutional science and technology,japan science and technology agency,saitama, Japan, department of human genetics,graduate school of medicine,the university of tokyo,bunkyo-ku,tokyo, Japan, faculty of tropical medicine,mahidol university,bangkok, Thailand, japanese red cross tokyo blood center,koto-ku,tokyo, Japan
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|