title: Changes in successive measures of de novo donor-specific anti-human leukocyte antigen antibodies intensity and the development of allograft dysfunction.
abstract: BACKGROUND
  Many patients develop de novo donor-specific anti-human leukocyte antigen antibodies (dnDSA) after transplantation. Despite development of dnDSA, not all patients will immediately fail. This study analyzes dnDSA intensity and longitudinal trends as prospective clinical parameters to assess subsequent allograft function.
  
  
  METHODS
  Twenty-four patients with dnDSA onset in the first 2 years after transplantation received antibody monitoring by LABScreen single antigen beads. Estimated glomerular filtration rate (eGFR) was recorded at time of dnDSA onset and up to 24 months thereafter. The dnDSA mean fluorescence intensity (MFI) of the stable function patient group (n=8; eGFR decline ≤ 25%) was compared with the impaired function patient group (n=16; eGFR decline>25%) using first year peak MFI (pMFI), eight month MFI change (ΔMFI), and eighteen month MFI trend (MFI slope).
  
  
  RESULTS
  Both groups showed similar dnDSA characteristics (time to onset after transplantation, class I/II distribution, and initial MFI). Between groups, MFI trends were analyzed. Impaired patients showed a higher pMFI during the first year (median pMFI, 13,055 vs. 2,397; P=0.007). Longitudinal analysis revealed that ΔMFI was strongly associated with dysfunction. Both a ΔMFI increase greater than 20% as well as a stronger increase (ΔMFI>50%) were followed by graft dysfunction in almost all patients and could significantly differentiate between stable and impaired function patients (P=0.001 and P=0.04, respectively).
  
  
  CONCLUSIONS
  Our study suggests that tracking dnDSA intensity, particularly in the early period after onset, is important to estimate the impact of dnDSA on the allograft and could, therefore, determine help on how best to monitor patients with dnDSA.
authors.affiliation: 1 Terasaki Foundation Laboratory, Los Angeles, CA. 2 Department of Pathology, Brody School of Medicine at East Carolina University, Greenville, NC. 3 Department of Surgery, Brody School of Medicine at East Carolina University, Greenville, NC. 4 Department of Medicine, Brody School of Medicine at East Carolina University, Greenville, NC. 5 Eastern Nephrology Associates, Greenville, NC. 6 Address correspondence to: Matthew J. Everly, Pharm.D. Terasaki Foundation, 11570 W. Olympic Blvd., Los Angeles, CA 90064.
authors.forename: Georg
authors.initials: G
authors.lastname: Dieplinger
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Everly
authors.forename: Lorita M
authors.initials: LM
authors.lastname: Rebellato
authors.forename: Carl E
authors.initials: CE
authors.lastname: Haisch
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Briley
authors.forename: Paul
authors.initials: P
authors.lastname: Bolin
authors.forename: William T
authors.initials: WT
authors.lastname: Kendrick
authors.forename: Scott A
authors.initials: SA
authors.lastname: Kendrick
authors.forename: Claire
authors.initials: C
authors.lastname: Morgan
authors.forename: Robert C
authors.initials: RC
authors.lastname: Harland
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D006680:HLA Antigens; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies