title: Onset and progression of de novo donor-specific anti-human leukocyte antigen antibodies after BK polyomavirus and preemptive immunosuppression reduction.
abstract: BACKGROUND
  BK polyomavirus (BKPyV) viremia/nephropathy and reduction in immunosuppression following viremia may increase the risk of alloimmune activation and allograft rejection. This study investigates the impact of BKPyV viremia on de novo donor anti-human leukocyte antigen (HLA)-specific antibodies (dnDSA).
  
  
  METHODS
  All primary renal transplants at East Carolina University from March 1999 to December 2010, with at least 1 post-transplant BKPyV viral load testing, were analyzed. Patients were negative for anti-HLA antibodies to donor antigens (tested via single antigen beads) at transplantation and at first BKPyV testing.
  
  
  RESULTS
  Nineteen of 174 patients (11%) tested positive for BKPyV viremia. Within 24 months of BKPyV viremia detection, 79% of BKPyV-viremic patients developed dnDSA. Only 20% of BKPyV viremia-persistent cases, compared to 86% of BKPyV viremia-resolved cases, developed dnDSA (P = 0.03). Poor allograft survival was evident in BKPyV viremia-persistent patients (60% failure by 2 years post BKPyV diagnosis) and in BKPyV viremia-resolved patients with dnDSA (5-year post BKPyV diagnosis allograft survival of 48%).
  
  
  CONCLUSIONS
  Post-transplant BKPyV viremia and preemptive immunosuppression reduction is associated with high rates of dnDSA. When preemptively treating BKPyV viremia, dnDSA should be monitored to prevent allograft consequences.
authors.affiliation: Terasaki Research Institute, Los Angeles, California, USA.
authors.forename: G
authors.initials: G
authors.lastname: Dieplinger
authors.affiliation: Terasaki Research Institute, Los Angeles, California, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Everly
authors.affiliation: Department of Pathology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Briley
authors.affiliation: Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Haisch
authors.affiliation: Department of Medicine, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: P
authors.initials: P
authors.lastname: Bolin
authors.affiliation: Vidant Medical Center, Greenville, North Carolina, USA.
authors.forename: A Q
authors.initials: AQ
authors.lastname: Maldonado
authors.affiliation: Eastern Nephrology Associates, Greenville, North Carolina, USA.
authors.forename: W T
authors.initials: WT
authors.lastname: Kendrick
authors.affiliation: Eastern Nephrology Associates, Greenville, North Carolina, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Kendrick
authors.affiliation: Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: C
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Terasaki Research Institute, Los Angeles, California, USA.
authors.forename: P I
authors.initials: PI
authors.lastname: Terasaki
authors.affiliation: Department of Pathology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Rebellato
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood*; D001739:BK Virus / Q000302:isolation & purification*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000097:blood / Q000276:immunology*; D014412:Tumor Virus Infections / Q000097:blood / Q000276:immunology*; D014766:Viremia
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D007166:Immunosuppressive Agents
keywords: BK; anti-human leukocyte antigen antibody; immunosuppression; polyomavirus; transplantation