title: The effect of KIR2D-HLA-C receptor-ligand interactions on clinical outcome in a HIV-1 CRF01_AE-infected Thai population.
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.
  
  
  METHODS
  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/μl) 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: aDepartment of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan bDepartment of Paediatrics, University of Oxford, Oxford, UK cThai National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi dDay Care Centre, Lampang Hospital, Lampang, Thailand eNagasaki University Global COE Program, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Mori
authors.forename: Nuanjun
authors.initials: N
authors.lastname: Wichukchinda
authors.forename: Reiko
authors.initials: R
authors.lastname: Miyahara
authors.forename: Archawin
authors.initials: A
authors.lastname: Rojanawiwat
authors.forename: Panita
authors.initials: P
authors.lastname: Pathipvanich
authors.forename: Naho
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Michio
authors.initials: M
authors.lastname: Yasunami
authors.forename: Koya
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: Pathom
authors.initials: P
authors.lastname: Sawanpanyalert
mesh_terms: D000328:Adult; D044466:Asian People; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D015236:HLA-C Antigens / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D054344:Receptors, KIR2DL3 / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D015236:HLA-C Antigens; C515078:KIR2DL3 protein, human; D054344:Receptors, KIR2DL3