title: Blood levels of donor-specific human leukocyte antigen antibodies after renal transplantation: resolution of rejection in the presence of circulating donor-specific antibody.
abstract: BACKGROUND
  Accommodation to antibody is an important mechanism in successful ABO-incompatible transplantation, but its importance in human leukocyte antigen (HLA) antibody-incompatible transplantation is less clear, as sensitive techniques facilitating daily measurement of donor-specific HLA antibodies (DSAs) have only recently been developed.
  
  
  METHODS
  We report 24 patients who had HLA antibody-incompatible kidney transplantation (21 living donors, 3 deceased), 21 of whom had pretransplant plasmapheresis. Eight had positive complement-dependent cytotoxic (CDC) crossmatch (XM) pretransplant plasmapheresis, nine had positive flow cytometric (FC) XM, and seven had DSA detectable by microbead analysis only. After transplant, DSA levels were monitored closely with microbead assays.
  
  
  RESULTS
  Rejection occurred in five of eight (62.5%) CDC-positive cases, in three of nine (33%) FC-positive cases, and in two of seven (29%) of microbead-only cases at a median of 6.5 days after transplantation. Resolution occurred at a median of 15 days after transplantation, in 8 of 10 cases when the microbead level of DSA had median fluorescence intensity (MFI) >2000 U, in 6 of 10 when the microbead MFI >4000 U. In 8 of 10 cases, the microbead MFI at the time of resolution was greater than at the onset. DSA did not always cause clinical rejection. In five cases with a posttransplant DSA peaking at MFI >2000 U on microbead assay, rejection did not occur.
  
  
  CONCLUSIONS
  These data suggest that the dominant method of successful transplantation was function of the transplant in the presence of circulating DSA, and they also define the period during which this occurred.
authors.affiliation: Transplant Unit, University Hospitals Coventry and Warwickshire, Coventry, West Midlands, UK. Robert.Higgins@uhcw.nhs.uk
authors.forename: Rob
authors.initials: R
authors.lastname: Higgins
authors.forename: Mark
authors.initials: M
authors.lastname: Hathaway
authors.forename: David
authors.initials: D
authors.lastname: Lowe
authors.forename: For
authors.initials: F
authors.lastname: Lam
authors.forename: Habib
authors.initials: H
authors.lastname: Kashi
authors.forename: Lam Chin
authors.initials: LC
authors.lastname: Tan
authors.forename: Chris
authors.initials: C
authors.lastname: Imray
authors.forename: Simon
authors.initials: S
authors.lastname: Fletcher
authors.forename: Daniel
authors.initials: D
authors.lastname: Zehnder
authors.forename: Klaus
authors.initials: K
authors.lastname: Chen
authors.forename: Nithya
authors.initials: N
authors.lastname: Krishnan
authors.forename: Rizwan
authors.initials: R
authors.lastname: Hamer
authors.forename: David
authors.initials: D
authors.lastname: Briggs
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry; D001706:Biopsy; D005434:Flow Cytometry; D006085:Graft Survival; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods; D019520:Living Donors; D008875:Middle Aged; D010956:Plasmapheresis; D011137:Polystyrenes / Q000737:chemistry; D013997:Time Factors
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D011137:Polystyrenes