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. 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

Kevin J Clerkin  1 , Maryjane A Farr  1 , Susan W Restaino  1 , Emmanuel Zorn  2 , Farhana Latif  1 , Elena R Vasilescu  3 , Charles C Marboe  3 , Paolo C Colombo  1 , Donna M Mancini  4
Affiliations

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

Kevin J Clerkin et al. J Heart Lung Transplant. 2017 May.

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.

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Figures

Figure 1
Figure 1
A. Receiver operator characteristic curve for donor specific antibodies detecting AMR B. Receiver operator characteristic curve for class II donor specific antibodies detecting AMR
Figure 2
Figure 2
A. Freedom from initial episode of AMR for based on DSA status B. Freedom from initial episode of AMR based on DSA class
Figure 3
Figure 3
Freedom from initial episode of AMR following detection of DSA
Figure 4
Figure 4
A. Freedom from graft loss depending on de-novo DSA status. B. Freedom from graft loss based on de-novo DSA status and MHC class
Figure 5
Figure 5
Freedom from CAV stratified by AMR and DSA status
See this image and copyright information in PMC

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