Racial differences in the development of de-novo donor-specific antibodies and treated antibody-mediated rejection after heart transplantation

Robert Townsend Cole; Jonathan Gandhi; Robert A Bray; Howard M Gebel; Michael Yin; Nikolaz Shekiladze; An Young; Aubrey Grant; Ian Mahoney; S Raja Laskar; Divya Gupta; Kunal Bhatt; Wendy Book; Andrew Smith; Duc Nguyen; J David Vega; Alanna A Morris

doi:10.1016/j.healun.2017.11.003

Racial differences in the development of de-novo donor-specific antibodies and treated antibody-mediated rejection after heart transplantation

J Heart Lung Transplant. 2018 Apr;37(4):503-512. doi: 10.1016/j.healun.2017.11.003. Epub 2017 Nov 4.

Authors

Robert Townsend Cole¹, Jonathan Gandhi², Robert A Bray³, Howard M Gebel³, Michael Yin², Nikolaz Shekiladze⁴, An Young², Aubrey Grant², Ian Mahoney², S Raja Laskar⁵, Divya Gupta⁵, Kunal Bhatt⁵, Wendy Book⁵, Andrew Smith⁵, Duc Nguyen⁵, J David Vega⁵, Alanna A Morris⁵

Affiliations

¹ Center for Heart Failure Therapy and Transplantation, Emory University, Atlanta, Georgia, USA. Electronic address: rtcole@emory.edu.
² Department of Medicine, Emory University, Atlanta, Georgia, USA.
³ Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
⁴ Department of Medicine, Memorial Health, Savannah, Georgia, USA.
⁵ Center for Heart Failure Therapy and Transplantation, Emory University, Atlanta, Georgia, USA.

PMID: 29198929
DOI: 10.1016/j.healun.2017.11.003

Abstract

Background: Despite improvements in outcomes after heart transplantation, black recipients have worse survival compared with non-black recipients. The source of such disparate outcomes remains largely unknown. We hypothesize that a propensity to generate de-novo donor-specific antibodies (dnDSA) and subsequent antibody-mediated rejection (AMR) may account for racial differences in sub-optimal outcomes after heart transplant. In this study we aimed to determine the role of dnDSA and AMR in racial disparities in post-transplant outcomes.

Methods: This study was a single-center, retrospective analysis of 137 heart transplant recipients (81% male, 48% black) discharged from Emory University Hospital. Patients were classified as black vs non-black for the purpose of our analysis. Kaplan-Meier and Cox regression analyses were used to evaluate the association between race and selected outcomes. The primary outcome was the development of dnDSA. Secondary outcomes included treated AMR and a composite of all-cause graft dysfunction or death.

Results: After 3.7 years of follow-up, 39 (28.5%) patients developed dnDSA and 19 (13.8%) were treated for AMR. In multivariable models, black race was associated with a higher risk of developing dnDSA (hazard ratio [HR] 3.65, 95% confidence interval [CI] 1.54 to 8.65, p = 0.003) and a higher risk of treated AMR (HR 4.86, 95% CI 1.26 to 18.72, p = 0.021) compared with non-black race. Black race was also associated with a higher risk of all-cause graft dysfunction or death in univariate analyses (HR 2.10, 95% CI 1.02 to 4.30, p = 0.044). However, in a multivariable model incorporating dnDSA, black race was no longer a significant risk factor. Only dnDSA development was significantly associated with all-cause graft dysfunction or death (HR 4.85, 95% CI 1.89 to 12.44, p = 0.001).

Conclusion: Black transplant recipients are at higher risk for the development of dnDSA and treated AMR, which may account for racial disparities in outcomes after heart transplantation.

Keywords: antibody mediated rejection; donor specific antibodies; heart transplantation; transplant disparity; transplant outcomes.

MeSH terms

Adult
Black or African American / statistics & numerical data*
Female
Graft Rejection / blood*
Graft Rejection / ethnology*
Graft Rejection / mortality
Health Status Disparities
Heart Transplantation / adverse effects*
Humans
Isoantibodies / blood*
Male
Middle Aged
Proportional Hazards Models
Retrospective Studies

Substances

Isoantibodies