ArticlePLoS pathogens2012
Significant association of KIR2DL3-HLA-C1 combination with cerebral malaria and implications for co-evolution of KIR and HLA.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 67 citations in OpenAlex.
- Inhibitory NK receptor expression associates with altered antimalarial function of γδ T cells.PLoS pathogens · 2026Article
- Both inhibitory and activating KIRs recognize RIFINs: a dual-edged mechanism of NK cell control in malaria.Signal transduction and targeted therapy · 2025Article
- The Role of Killer Ig-like Receptors in Diseases from A to Z.International journal of molecular sciences · 2025Review
- Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health.The journal of allergy and clinical immunology. In practice · 2022Article
- The KIR2DL2/HLA-C1C1 Gene Pairing Is Associated With an Increased Risk of SARS-CoV-2 Infection.Frontiers in immunology · 2022Article
- High-throughput Interpretation of Killer-cell Immunoglobulin-like Receptor Short-read Sequencing Data with PING.PLoS computational biology · 2021Article
- Association of Inhibitory Killer Cell Immunoglobulin-like Receptor Ligands With Higher Plasmodium falciparum Parasite Prevalence.The Journal of infectious diseases · 2021Article
- Article
- Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity.Malaria journal · 2021Article
- Variations in killer-cell immunoglobulin-like receptor and human leukocyte antigen genes and immunity to malaria.Cellular & molecular immunology · 2020Review
- Epistatic interactions between killer immunoglobulin-like receptors and human leukocyte antigen ligands are associated with ankylosing spondylitis.PLoS genetics · 2020Article
- Article
- Inhibitory killer cell immunoglobulin-like receptors strengthen CD8Science immunology · 2018Article
- HLA-C downregulation by HIV-1 adapts to host HLA genotype.PLoS pathogens · 2018Article
- Different Selected Mechanisms Attenuated the Inhibitory Interaction of KIR2DL1 with C2Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Natural killer cell education in human health and disease.Current opinion in immunology · 2018Review
- The role of KIR and HLA interactions in pregnancy complications.Immunogenetics · 2017Review
- NK Cells: Uncertain Allies against Malaria.Frontiers in immunology · 2017Review
- Reproduction, infection and killer-cell immunoglobulin-like receptor haplotype evolution.Immunogenetics · 2016Article
- Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon.World journal of hepatology · 2016Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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