PMID- 25629531
OWN - NLM
STAT- MEDLINE
DCOM- 20150817
LR  - 20220408
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 99
IP  - 6
DP  - 2015 Jun
TI  - Characteristics of Circulating Donor Human Leukocyte Antigen-specific 
      Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and 
      Kidney Allograft Failure.
PG  - 1156-64
LID - 10.1097/TP.0000000000000511 [doi]
AB  - BACKGROUND: Characteristics of pretransplant antibodies directed at donor human 
      leukocyte antigen (HLA) donor-specific antibodies (DSA) associated with adverse 
      outcomes in kidney transplant recipients are being elucidated but uncertainties 
      exist. METHODS: We prospectively screened pretransplant sera from 543 kidney 
      recipients using single antigen bead assays and identified 154 patients with and 
      389 without DSA. We investigated the association of DSA features to acute 
      rejection and graft failure. RESULTS: One-year acute rejection incidence was 
      higher in DSA-positive group (P < 0.001), primarily due to antibody-mediated 
      rejection (AMR, 13% vs. 1.8%, P < 0.001) and not T cell-mediated rejection (ACR, 
      5% vs.6%, P = 0.65). The sum of mean fluorescence intensity of DSA (DSA MFI-Sum) 
      of 6,000 or higher (OR, 18; 95% CI, 7.0-47; P < 0.001) and the presence of DSA 
      against both HLA class I and II (OR, 39; 95% CI, 14-106; P < 0.0001) predicted 
      1-year AMR, independent of other covariates. Calculated panel reactive antibody 
      and a positive flow cytometry cross-match result were associated with AMR by 
      bivariate analysis but neither was an independent predictor in a multivariable 
      regression analysis that included DSA-MFI-Sum or HLA DSA class. In multivariable 
      Cox proportional hazards models, the covariate-adjusted hazard ratio for graft 
      failure was 2.03 (95%CI, 1.05-3.92; P = 0.04) for DSA MFI-Sum of 6,000 or higher 
      and 2.23 (95% CI, 1.04-4.80; P = 0.04) for class I and II DSA. Prediction of 
      graft failure was not independent of AMR. CONCLUSION: Our study suggests that DSA 
      MFI-Sum and HLA class of DSA are characteristics predictive of AMR and graft 
      failure. The elevated risk of graft failure in those with the identified features 
      of DSA is attributable to increased risk of AMR.
FAU - Kannabhiran, Dinesh
AU  - Kannabhiran D
AD  - 1 Division of Nephrology and Hypertension, Department of Medicine, New York 
      Presbyterian-Weill Cornell Medical Center, New York, NY. 2 Department of 
      Transplantation, OSF Saint Francis Medical Center, Peroria, IL. 3 Department of 
      Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical 
      Center, New York, NY. 4 Department of Psychiatry and Behavioral Sciences, Stony 
      Brook University, Stony Brook, NY. 5 Department of Surgery, New York Presbyterian 
      Hospital-Weill Cornell Medical Center, New York, NY. 6 Department of Pathology, 
      New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY.
FAU - Lee, John
AU  - Lee J
FAU - Schwartz, Joseph E
AU  - Schwartz JE
FAU - Friedlander, Rex
AU  - Friedlander R
FAU - Aull, Meredith
AU  - Aull M
FAU - Muthukumar, Thangamani
AU  - Muthukumar T
FAU - Campbell, Sean
AU  - Campbell S
FAU - Epstein, David
AU  - Epstein D
FAU - Seshan, Surya V
AU  - Seshan SV
FAU - Kapur, Sandip
AU  - Kapur S
FAU - Sharma, Vijay K
AU  - Sharma VK
FAU - Suthanthiran, Manikkam
AU  - Suthanthiran M
FAU - Dadhania, Darshana
AU  - Dadhania D
LA  - eng
GR  - R37 AI051652/AI/NIAID NIH HHS/United States
GR  - UL1 RR024996/RR/NCRR NIH HHS/United States
GR  - KL2 TR000458/TR/NCATS NIH HHS/United States
GR  - UL1 TR000457/TR/NCATS NIH HHS/United States
GR  - K08 DK087824/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - Acute Disease
MH  - Adult
MH  - Aged
MH  - Allografts
MH  - Antibody Specificity
MH  - Cohort Studies
MH  - Female
MH  - Graft Rejection/*etiology/*immunology
MH  - Graft Survival/immunology
MH  - HLA Antigens/*immunology
MH  - Histocompatibility Testing
MH  - Humans
MH  - Immunoglobulin G/*blood
MH  - Isoantibodies/*blood
MH  - Kidney Transplantation/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Prospective Studies
MH  - Risk Factors
MH  - Tissue Donors
PMC - PMC4729299
MID - NIHMS750116
EDAT- 2015/01/30 06:00
MHDA- 2015/08/19 06:00
PMCR- 2016/06/01
CRDT- 2015/01/29 06:00
PHST- 2015/01/29 06:00 [entrez]
PHST- 2015/01/30 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 10.1097/TP.0000000000000511 [doi]
PST - ppublish
SO  - Transplantation. 2015 Jun;99(6):1156-64. doi: 10.1097/TP.0000000000000511.