Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure.

TitleCharacteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure.
Publication TypeJournal Article
Year of Publication2015
AuthorsKannabhiran D, Lee J, Schwartz JE, Friedlander R, Aull M, Muthukumar T, Campbell S, Epstein D, Seshan SV, Kapur S, Sharma VK, Suthanthiran M, Dadhania D
JournalTransplantation
Volume99
Issue6
Pagination1156-64
Date Published2015 Jun
ISSN1534-6080
KeywordsAcute Disease, Adult, Aged, Allografts, Antibody Specificity, Cohort Studies, Female, Graft Rejection, Graft Survival, Histocompatibility Testing, HLA Antigens, Humans, Immunoglobulin G, Isoantibodies, Kidney Transplantation, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Risk Factors, Tissue Donors
Abstract

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.

DOI10.1097/TP.0000000000000511
Alternate JournalTransplantation
PubMed ID25629531
PubMed Central IDPMC4729299
Grant ListR37 AI051652 / AI / NIAID NIH HHS / United States
UL1 RR024996 / RR / NCRR NIH HHS / United States
KL2 TR000458 / TR / NCATS NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
K08 DK087824 / DK / NIDDK NIH HHS / United States
Related Faculty: 
Surya V. Seshan, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700