The genetic predisposition of natural killer cell to BK virus-associated nephropathy in renal transplant patients

Kidney Int. 2013 Aug;84(2):359-65. doi: 10.1038/ki.2013.59. Epub 2013 Mar 13.


BK virus (BKV) infection represents a serious complication in renal transplant patients resulting in BKV-associated nephropathy and subsequent allograft loss. Natural killer cells are crucial in the antiviral immune response; however, an understanding of the role of natural killer cells in protection against BKV is limited. To elucidate whether killer-cell immunoglobulin-like receptors and their interaction between donor-/recipient-related ligands have a role in BKV infection, we performed genotyping analysis in 48 kidney transplant recipients with a history of severe BKV infection/BKV-associated nephropathy and 110 recipients with stable renal function and no BKV reactivation. Of interest, we found that telomeric gene content motif was significantly associated with severe course of BKV infection/BKV-associated nephropathy and detected significantly higher percentage of patients with BKV-associated nephropathy carrying low numbers of activating receptors compared with the control group. Detailed analysis of each single receptor revealed significantly lower frequencies of the activating receptor KIR3DS1 in patients with BKV infection/nephropathy as compared with the controls. Thus, our study supports protective effects of activating receptors in BKV infection and suggest natural killer-cell-related genetic predisposition to the development of BKV-associated nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • BK Virus / pathogenicity*
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA Antigens / genetics
  • HLA Antigens / metabolism
  • Haplotypes
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney Diseases / genetics*
  • Kidney Diseases / immunology
  • Kidney Diseases / virology
  • Kidney Transplantation / adverse effects*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / virology
  • Ligands
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polyomavirus Infections / genetics*
  • Polyomavirus Infections / immunology
  • Polyomavirus Infections / virology
  • Receptors, KIR3DS1 / genetics*
  • Receptors, KIR3DS1 / metabolism
  • Risk Factors
  • Severity of Illness Index
  • Telomere
  • Tumor Virus Infections / genetics*
  • Tumor Virus Infections / immunology
  • Tumor Virus Infections / virology


  • HLA Antigens
  • Immunosuppressive Agents
  • Ligands
  • Receptors, KIR3DS1