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The effect of KIR and HLA polymorphisms on dengue infection and disease severity in northeastern Thais

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Abstract

Killer cell immunoglobulin-like receptors (KIRs) are cell surface receptors on natural killer (NK) cells and subsets of T cells. The interaction between KIRs and their cognate ligands (Human leukocyte antigen class I molecules, HLA class I) modulates the immune response of NK cells, in particular through clearance of virus-infected cells. Here, we investigated the effect of KIRs and HLA ligands on dengue infections and disease severity. The KIRs and HLA ligands were identified in 235 healthy controls (HC) and 253 dengue patients (DEN) using polymerase chain reaction with sequence specific primer (PCR–SSP); moreover, DEN was classified to 100 dengue fever (DF) and 153 dengue haemorrhagic fever (DHF). Risks were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) with significance set at a two-tailed P value of < 0.05. The Bonferroni correction was applied for multiple comparisons. Twelve significant associations were observed in dengue infections and disease severity; however, two outcomes survived after the Bonferroni correction. Of these, HLA-A11 was associated with an increased risk to develop dengue disease (OR 2.41, 95% CI 1.62–3.60, Pc = 0.004), while KIR3DS1+ Bw4 was a protective genotype to developing DHF (OR 0.28, 95% CI 0.16–0.48, Pc < 0.001). This study revealed an important role of KIR and HLA ligands in innate immune responses to dengue viral infections and, in particular, their effect on clinical outcomes and disease severity.

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Acknowledgements

This work was supported by Thailand Research Fund, Grant for new researcher (MRG6180172) to Suwit Chaisri. The authors thank Dr. Prida Malasit and Dr. Juthathip Mongkolsapaya for kindly sharing the dengue DNA samples and clinical data, and we thank Dr. Mayurachat Keawmanee and Dr. Wisitsak Phoksawat for helping in dengue DNA preparation. We also wish to acknowledge the support of the Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok, Thailand.

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Authors and Affiliations

  1. Chulabhorn International College of Medicine (CICM), Thammasat University, Pathum Thani, 12121, Thailand

    Suwit Chaisri

  2. The Centre for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand

    Suwit Chaisri, Amonrat Jumnainsong, Amornrat Romphruk & Chanvit Leelayuwat

  3. Department of Clinical Immunology and Transfusion Sciences, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand

    Amonrat Jumnainsong & Chanvit Leelayuwat

  4. Blood Transfusion Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Amornrat Romphruk

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  1. Suwit Chaisri
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Correspondence to Chanvit Leelayuwat.

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Ethical approval

All the samples obtained for this study have been ethically approved by ethical committees with informed consent. The control samples were by the Khon Kaen University Ethics Committee in Human Research (HE42072). The dengue infection samples were by the Human Research Ethics Committee of Thammasat University No. 1 (COA 057/59).

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Chaisri, S., Jumnainsong, A., Romphruk, A. et al. The effect of KIR and HLA polymorphisms on dengue infection and disease severity in northeastern Thais. Med Microbiol Immunol 209, 613–620 (2020). https://doi.org/10.1007/s00430-020-00685-z

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