title: The genetic predisposition of natural killer cell to BK virus-associated nephropathy in renal transplant patients.
abstract: 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.
authors.affiliation: Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Trydzenskaya
authors.forename: Karsten
authors.initials: K
authors.lastname: Juerchott
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
authors.forename: Katja
authors.initials: K
authors.lastname: Kotsch
authors.forename: Kristina
authors.initials: K
authors.lastname: Kunert
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weist
authors.forename: Constanze
authors.initials: C
authors.lastname: Schönemann
authors.forename: Ralf
authors.initials: R
authors.lastname: Schindler
authors.forename: Peter
authors.initials: P
authors.lastname: Nickel
authors.forename: Matthias F
authors.initials: MF
authors.lastname: Melzig
authors.forename: Christian
authors.initials: C
authors.lastname: Hugo
authors.forename: Oliver
authors.initials: O
authors.lastname: Thomusch
authors.forename: Avidan U
authors.initials: AU
authors.lastname: Neumann
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Nina
authors.initials: N
authors.lastname: Babel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001739:BK Virus / Q000472:pathogenicity*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000235:genetics* / Q000276:immunology / Q000821:virology; D016030:Kidney Transplantation / Q000009:adverse effects*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008024:Ligands; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D027601:Polyomavirus Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D054349:Receptors, KIR3DS1 / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012720:Severity of Illness Index; D016615:Telomere; D014412:Tumor Virus Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology
chemical_list: D006680:HLA Antigens; D007166:Immunosuppressive Agents; D008024:Ligands; D054349:Receptors, KIR3DS1