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Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation.
J Heart Lung Transplant. 2017 May; 36(5):540-545.JH

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27916323

Citation

Clerkin, Kevin J., et al. "Donor-specific anti-HLA Antibodies With Antibody-mediated Rejection and Long-term Outcomes Following Heart Transplantation." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 36, no. 5, 2017, pp. 540-545.
Clerkin KJ, Farr MA, Restaino SW, et al. Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation. J Heart Lung Transplant. 2017;36(5):540-545.
Clerkin, K. J., Farr, M. A., Restaino, S. W., Zorn, E., Latif, F., Vasilescu, E. R., Marboe, C. C., Colombo, P. C., & Mancini, D. M. (2017). Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 36(5), 540-545. https://doi.org/10.1016/j.healun.2016.10.016
Clerkin KJ, et al. Donor-specific anti-HLA Antibodies With Antibody-mediated Rejection and Long-term Outcomes Following Heart Transplantation. J Heart Lung Transplant. 2017;36(5):540-545. PubMed PMID: 27916323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation. AU - Clerkin,Kevin J, AU - Farr,Maryjane A, AU - Restaino,Susan W, AU - Zorn,Emmanuel, AU - Latif,Farhana, AU - Vasilescu,Elena R, AU - Marboe,Charles C, AU - Colombo,Paolo C, AU - Mancini,Donna M, Y1 - 2016/11/17/ PY - 2016/07/25/received PY - 2016/10/15/revised PY - 2016/10/22/accepted PY - 2016/12/6/pubmed PY - 2018/3/7/medline PY - 2016/12/6/entrez KW - antibody mediated rejection KW - cardiac allograft vasculopathy KW - donor specific antibodies KW - heart transplant KW - mortality SP - 540 EP - 545 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J. Heart Lung Transplant. VL - 36 IS - 5 N2 - 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. SN - 1557-3117 UR - https://www.unboundmedicine.com/medline/citation/27916323/Donor_specific_anti_HLA_antibodies_with_antibody_mediated_rejection_and_long_term_outcomes_following_heart_transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(16)30403-X DB - PRIME DP - Unbound Medicine ER -