The effect of KIR2D-HLA-C receptor-ligand interactions on clinical outcome in a HIV-1 CRF01-AE-infected Thai population

Masahiko Mori, Nuanjun Wichukchinda, Reiko Miyahara, Archawin Rojanawiwat, Panita Pathipvanich, Naho Tsuchiya, Toshiyuki Miura, Michio Yasunami, Koya Ariyoshi, Pathom Sawanpanyalert

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: Class I human leukocyte antigen (HLA) alleles interact with both cytotoxic T lymphocytes through their T-cell receptors, and natural killer cells through their killer immunoglobulin-like receptors (KIRs). Compared with the reported protective effect of KIR3DL1/S1-HLA-Bw4 interactions in HIV-infected patients, the effect of KIR2D-HLA-C combinations on HIV control remains unclear. Here, we investigate the effect of KIR2D-HLA-C combinations on HIV disease progression. Design: We performed a cross-sectional and longitudinal analysis of a Thai HIV cohort. Methods: Two hundred and nine HIV-1 CRF01-AE-infected, treatment-naive Thai patients (CD4 T-cell counts of >200/ml) and 104 exposed seronegatives were studied. The effect of KIR-HLA receptor-ligand combinations on viral transmission and survival rate was statistically analyzed. Results: We found the following results: higher frequency of patients expressing both KIR2DL3 and HLA-C1 among infected patients compared with exposed seronegative (odds ratio 4.8, P=0.004), higher viral load in patients expressing HLA-C1 with KIR2DL3 compared with those without this receptor-ligand combination (median 4.8 vs. 4.2 log copies/ml, P=0.033), higher numbers of KIR2DL3-HLA-C1 interactions was associated with a higher viral load (β=0.13, P=0.039 by linear regression model), and higher mortality rate in carriers of the KIR2DL3-HLA-C1 combination (adjusted hazard ratio 1.9, P=0.012 by Cox hazard model). Conclusion: We have identified a deleterious effect of the KIR2DL3-HLA-C1 receptor-ligand combination on HIV clinical outcomes in a Thai cohort. Further investigation into mechanisms underlying this susceptibility may aid the understanding of the role of natural killer cells in HIV disease control and pathogenesis.

Original languageEnglish
Pages (from-to)1607-1615
Number of pages9
JournalAIDS
Volume29
Issue number13
DOIs
Publication statusPublished - 2015 Aug 24
Externally publishedYes

Keywords

  • HIV-1 CRF01-AE
  • HLA-B∗46: 01
  • HLA-C1
  • KIR2DL3
  • South-east Asia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Mori, M., Wichukchinda, N., Miyahara, R., Rojanawiwat, A., Pathipvanich, P., Tsuchiya, N., Miura, T., Yasunami, M., Ariyoshi, K., & Sawanpanyalert, P. (2015). The effect of KIR2D-HLA-C receptor-ligand interactions on clinical outcome in a HIV-1 CRF01-AE-infected Thai population. AIDS, 29(13), 1607-1615. https://doi.org/10.1097/QAD.0000000000000747