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J Heart Lung Transplant. 2017 May;36(5):540-545. doi: 10.1016/j.healun.2016.10.016. Epub 2016 Nov 17.

Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation.

Author information

1
Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York, New York.
2
Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, New York.
3
Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York.
4
Department of Medicine, Division of Cardiology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: donna.mancini@mountsinai.org.

Abstract

BACKGROUND:

Donor-specific anti-HLA antibodies (DSA) are common after heart transplantation and are associated with rejection, cardiac allograft vasculopathy, and mortality. A noninvasive diagnostic test for pathologic antibody-mediated rejection (pAMR) does not exist.

METHODS:

From January 1, 2010, through August 31, 2013, 221 consecutive adult patients underwent heart transplantation and were followed through October 1, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included association of DSA (stratified by major histocompatibility complex class and de novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of cardiac allograft vasculopathy.

RESULTS:

During the study period, 69 patients (31.2%) had DSA (24% had de novo DSA), and there were 74 episodes of pAMR in 38 patients. Sensitivity of DSA at any mean fluorescence intensity to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (odds ratio = 5.37; 95% confidence interval [CI], 1.34-21.47; p = 0.018), adjusting for age, sex, and timing of AMR. Circulating class II DSA after transplantation increased risk of future pAMR (hazard ratio = 2.97; 95% CI, 1.31-6.73; p = 0.009). Patients who developed de novo class II DSA had 151% increased risk of graft loss (contingent on 30-day survival) compared with patients who did not have DSA (95% CI, 1.11-5.69; p = 0.027).

CONCLUSIONS:

DSA were inadequate to diagnose pAMR. Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss.

KEYWORDS:

antibody mediated rejection; cardiac allograft vasculopathy; donor specific antibodies; heart transplant; mortality

PMID:
27916323
PMCID:
PMC5654313
DOI:
10.1016/j.healun.2016.10.016
[Indexed for MEDLINE]
Free PMC Article

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