title: Dendritic cell deficiency associated with development of BK viremia and nephropathy in renal transplant recipients.
abstract: BACKGROUND
  BK virus nephropathy (BKVN) is a significant cause of renal allograft loss. Although overall intensity of immunosuppression is the greatest risk factor, recipient immune factors likely also play a role in the pathogenesis. Dendritic cells (DC) are potent antigen-presenting cells important for the induction of anti-viral cytotoxic T-cell responses. In a previous univariate analysis, we demonstrated a peripheral blood DC (PBDC) deficiency in patients with biopsy-proven BKVN, raising the possibility that reduction in DC predisposed to BK reactivation.
  
  
  METHODS
  In this study, we refined our previous analysis by comparing random posttransplant PBDC levels between an expanded group of patients with BKVN and controls without viremia using a multivariate analysis that accounted for factors known to influence PBDC levels. Next, we compared pretransplant PBDC levels between patients stratified by the presence or absence of posttransplant viremia. Finally, we assessed the predictive value of pretransplant PBDC levels for the development of posttransplant viremia.
  
  
  RESULTS
  Analyses revealed a PBDC level deficiency not only posttransplant in patients with BKVN but also pretransplant in patients who subsequently developed posttransplant BK viremia. Furthermore, we identified a pretransplant PBDC level that is a reasonable predictor for the development of posttransplant viremia.
  
  
  CONCLUSIONS
  Our results identify PBDC deficiency as a previously unrecognized risk factor for BKV reactivation after renal transplantation. Pretransplant PBDC monitoring may prove to be a useful clinical tool in the assessment of patient vulnerability to BKVN posttransplant, which may allow more focused screening.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. kwomer1@jhmi.edu
authors.forename: Karl L
authors.initials: KL
authors.lastname: Womer
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Huang
authors.forename: Heather
authors.initials: H
authors.lastname: Herren
authors.forename: Kourosh
authors.initials: K
authors.lastname: Dibadj
authors.forename: Ruihua
authors.initials: R
authors.lastname: Peng
authors.forename: Matthew
authors.initials: M
authors.lastname: Murawski
authors.forename: Renata
authors.initials: R
authors.lastname: Shraybman
authors.forename: Pamela
authors.initials: P
authors.lastname: Patton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Clare-Salzler
authors.forename: Bruce
authors.initials: B
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology; D001739:BK Virus / Q000235:genetics; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry; D005784:Gene Amplification; D006801:Humans; D007258:Informed Consent; D007376:Interleukin-2 / Q000096:biosynthesis / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D027601:Polyomavirus Infections / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014412:Tumor Virus Infections / Q000453:epidemiology* / Q000276:immunology / Q000473:pathology; D014766:Viremia / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D007376:Interleukin-2; D008070:Lipopolysaccharides