Dendritic cell deficiency associated with development of BK viremia and nephropathy in renal transplant recipients.
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.
Womer
Karl L
KL
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. kwomer1@jhmi.edu
Huang
Yanfei
Y
Herren
Heather
H
Dibadj
Kourosh
K
Peng
Ruihua
R
Murawski
Matthew
M
Shraybman
Renata
R
Patton
Pamela
P
Clare-Salzler
Michael J
MJ
Kaplan
Bruce
B
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
D017931:DNA Primers; D004279:DNA, Viral; D007376:Interleukin-2; D008070:Lipopolysaccharides