Characteristics of circulating donor human leukocyte antigen-specific immunoglobulin G antibodies predictive of acute antibody-mediated rejection and kidney allograft failure

Dinesh Kannabhiran, John Lee, Joseph E. Schwartz, Rex Friedlander, Meredith Aull, Thangamani Muthukumar, Sean Campbell, David Epstein, Surya V. Seshan, Sandip Kapur, Vijay K. Sharma, Manikkam Suthanthiran, Darshana Dadhania

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1156-1164
Number of pages9
JournalTransplantation
Volume99
Issue number6
DOIs
Publication statusPublished - 1 Jan 2015
Externally publishedYes

Fingerprint

HLA Antigens
Renal Insufficiency
Allografts
Immunoglobulin G
Antibodies
Tissue Donors
Transplants
Kidney
Immunoglobulin Isotypes
Graft Rejection
Proportional Hazards Models
Uncertainty

ASJC Scopus subject areas

  • Transplantation

Cite this

Characteristics of circulating donor human leukocyte antigen-specific immunoglobulin G antibodies predictive of acute antibody-mediated rejection and kidney allograft failure. / Kannabhiran, Dinesh; Lee, John; Schwartz, Joseph E.; Friedlander, Rex; Aull, Meredith; Muthukumar, Thangamani; Campbell, Sean; Epstein, David; Seshan, Surya V.; Kapur, Sandip; Sharma, Vijay K.; Suthanthiran, Manikkam; Dadhania, Darshana.

In: Transplantation, Vol. 99, No. 6, 01.01.2015, p. 1156-1164.

Research output: Contribution to journalArticle

Kannabhiran, 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 2015, 'Characteristics of circulating donor human leukocyte antigen-specific immunoglobulin G antibodies predictive of acute antibody-mediated rejection and kidney allograft failure', Transplantation, vol. 99, no. 6, pp. 1156-1164. https://doi.org/10.1097/TP.0000000000000511
Kannabhiran, Dinesh ; Lee, John ; Schwartz, Joseph E. ; Friedlander, Rex ; Aull, Meredith ; Muthukumar, Thangamani ; Campbell, Sean ; Epstein, David ; Seshan, Surya V. ; Kapur, Sandip ; Sharma, Vijay K. ; Suthanthiran, Manikkam ; Dadhania, Darshana. / Characteristics of circulating donor human leukocyte antigen-specific immunoglobulin G antibodies predictive of acute antibody-mediated rejection and kidney allograft failure. In: Transplantation. 2015 ; Vol. 99, No. 6. pp. 1156-1164.
@article{197aed2a406244fa8cf67646e3dd9a1a,
title = "Characteristics of circulating donor human leukocyte antigen-specific immunoglobulin G antibodies predictive of acute antibody-mediated rejection and kidney allograft failure",
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.",
author = "Dinesh Kannabhiran and John Lee and Schwartz, {Joseph E.} and Rex Friedlander and Meredith Aull and Thangamani Muthukumar and Sean Campbell and David Epstein and Seshan, {Surya V.} and Sandip Kapur and Sharma, {Vijay K.} and Manikkam Suthanthiran and Darshana Dadhania",
year = "2015",
month = "1",
day = "1",
doi = "10.1097/TP.0000000000000511",
language = "English",
volume = "99",
pages = "1156--1164",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Characteristics of circulating donor human leukocyte antigen-specific immunoglobulin G antibodies predictive of acute antibody-mediated rejection and kidney allograft failure

AU - Kannabhiran, Dinesh

AU - Lee, John

AU - Schwartz, Joseph E.

AU - Friedlander, Rex

AU - Aull, Meredith

AU - Muthukumar, Thangamani

AU - Campbell, Sean

AU - Epstein, David

AU - Seshan, Surya V.

AU - Kapur, Sandip

AU - Sharma, Vijay K.

AU - Suthanthiran, Manikkam

AU - Dadhania, Darshana

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84930542023&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930542023&partnerID=8YFLogxK

U2 - 10.1097/TP.0000000000000511

DO - 10.1097/TP.0000000000000511

M3 - Article

VL - 99

SP - 1156

EP - 1164

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 6

ER -