3. Noninvasive diagnosis of heart rejection as a predictor of long-term transplant survival

Authors

  • G.Sh. Mirzakhmetova «University Medical Center» Corporate Fund, Astana, Kazakhstan, Корпоративный фонд «UniversityMedicalCenter» Астана, Казахстан, «University Medical Center» корпоративтік қоры, Астана, Қазақстан https://orcid.org/0000-0001-8325-1267
  • S.P. Novikova «University Medical Center» Corporate Fund, Astana, Kazakhstan, Корпоративный фонд «UniversityMedicalCenter» Астана, Казахстан, «University Medical Center» корпоративтік қоры, Астана, Қазақстан https://orcid.org/0000-0001-8161-7712
  • Y.S. Yakhimovich «University Medical Center» Corporate Fund, Astana, Kazakhstan, Корпоративный фонд «UniversityMedicalCenter» Астана, Казахстан, «University Medical Center» корпоративтік қоры, Астана, Қазақстан https://orcid.org/0009-0003-5313-0378
  • M.F. Bayanova «University Medical Center» Corporate Fund, Astana, Kazakhstan, Корпоративный фонд «UniversityMedicalCenter» Астана, Казахстан, «University Medical Center» корпоративтік қоры, Астана, Қазақстан https://orcid.org/0000-0002-6167-5357
  • Sh. Kh. Altynova «University Medical Center» Corporate Fund, Astana, Kazakhstan, Корпоративный фонд «UniversityMedicalCenter» Астана, Казахстан, «University Medical Center» корпоративтік қоры, Астана, Қазақстан https://orcid.org/0009-0000-5592-0400
  • Y.V. Pya «University Medical Center» Corporate Fund, Astana, Kazakhstan, Корпоративный фонд «UniversityMedicalCenter» Астана, Казахстан, «University Medical Center» корпоративтік қоры, Астана, Қазақстан https://orcid.org/0000-0001-7249-0510

DOI:

https://doi.org/10.35805/BSK2024I003

Downloads

Abstract

Background. Currently, in Kazakhstan, the issue of chronic heart failure is becoming increasingly relevant, with high mortality from the terminal stage of chronic heart failure, especially in patients with III-IV functional class. Heart transplantation represents the "gold" standard of surgical treatment for terminal chronic heart failure, but endomyocardial biopsy, used for monitoring the transplanted heart, is an invasive and inconvenient procedure. Aim of this study is to generate data which can aid in more precise antibody-mediated rejection diagnosis, assisting in distinguishing between antibody-mediated rejectionand acute cellular rejection and helping us determine the appropriate treatment strategy Materials and

Methods. This article explores the potential of safe and accurate monitoring of acute transplant rejection using circulating donor-derived cell-free DNA(dd-cfDNA). The study included 40 patients who underwent heart transplantation.

Results. It was found that 60% of them had a repeat operation, while 40% had a primary one. Various cardiomyopathies, predominantly dilated and ischemic, were the cause of terminal chronic heart failure. The donor-derived cell-free DNA method demonstrates potential in differentiating T-cell-mediated and antibody-mediated rejection, with different patterns donor-derived cell-free DNA elevation. These differences have high clinical significance for diagnosis and treatment tactics.

Conclusion. Despite the prospects of using donor-derived cell-free DNA, further research is needed to establish threshold values and confirm its effectiveness in clinical practice.

Keywords

Chronic heart failure, Heart Transplantation, Endomyocardial Biopsy, donor-derived cell-free DNA

References

  1. Løgstrup BB, Nemec P, Schoenrath F, et al. Heart failure etiology and risk of right heart failure in adult left ventricular assist device support: the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). Scand Cardiovasc J. Oct 2020;54(5):306-314. doi:10.1080/140 17431.2020.1781239
  2. Khush KK, Cherikh WS, Chambers DC, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-sixth adult heart transplantation report - 2019; focus theme: Donor and recipient size match. J Heart Lung Transplant. Oct 2019;38(10):1056-1066. doi:10.1016/j.healun.2019.08.004
  3. Mengel M, Sis B, Kim D, et al. The molecular phenotype of heart transplant biopsies: relationship to histopathological and clinical variables. Am J Transplant. Sep 2010;10(9):2105-15. doi:10.1111/ j.1600-6143.2010.03182.x
  4. Poitier B, Chocron R, Peronino C, et al. Bioprosthetic Total Artificial Heart in Autoregulated Mode Is Biologically Hemocompatible: Insights for Multimers of von Willebrand Factor. Arterioscler Thromb Vasc Biol. Apr 2022;42(4):470-480. doi:10.1161/ATVBAHA.121.316833
  5. Saraiva F, Matos V, Gonçalves L, Antunes M, Providência LA. Complications of endomyocardial biopsy in heart transplant patients: a retrospective study of 2117 consecutive procedures. Transplant Proc. Jun 2011;43(5):1908-12. doi:10.1016/j.transproceed.2011.03.010
  6. Böhmer J, Wasslavik C, Andersson D, et al. Absolute Quantification of Donor-Derived Cell-Free DNA in Pediatric and Adult Patients After Heart Transplantation: A Prospective Study. Transpl Int. 2023;36:11260. doi:10.3389/ti.2023.11260
  7. Martuszewski A, Paluszkiewicz P, Król M, Banasik M, Kepinska M. Donor-Derived Cell-Free DNA in Kidney Transplantation as a Potential Rejection Biomarker: A Systematic Literature Review. J Clin Med. Jan 07 2021;10(2)doi:10.3390/jcm10020193
  8. Zubair H, Azim S, Maluf DG, Mas VR, Martins PN. Contribution of Proteomics in Transplantation: Identification of Injury and Rejection Markers. Transplantation. Oct 01 2023;107(10):2143-2154. doi:10.1097/TP.0000000000004542
  9. Cravedi P, Heeger PS. Immunologic monitoring in transplantation revisited. Curr Opin Organ Transplant. Feb 2012;17(1):26-32. doi:10.1097/ MOT.0b013e32834ee402
  10. Knecht KR, MacLeod SL, Hobbs CA, Li M, Morrow WR. Gene expression profiling in pediatric heart transplant rejection. Int J Cardiol. Oct 12 2013;168(5):5052-3. doi:10.1016/j.ijcard.2013.07.211
  11. Nishikawa T, Sekiguchi M, Ishibashi-Ueda H. More than 50 Years after Konno's Development of the Endomyocardial Biopsy. Int Heart J. Dec 12 2017;58(6):840-846. doi:10.1536/ihj.16-316
  12. Heitzer E, Auinger L, Speicher MR. Cell-Free DNA and Apoptosis: How Dead Cells Inform About the Living. Trends Mol Med. May 2020;26(5):519-528. doi:10.1016/j.molmed.2020.01.012
  13. Lo YMD, Han DSC, Jiang P, Chiu manuscript. Y.Y: Data collection, drafting, revising results section. B.M: Data collection, medical diagnoses, surgical pathologic evaluations. A.S: Study conception and design, overall responsibility of the study, data analysis and interpretation. All authors have approved the final version of the article.
  14. Clerkin KJ, Restaino SW, Zorn E, Vasilescu ER, Marboe CC, Mancini DM. The effect of timing and graft dysfunction on survival and cardiac allograft vasculopathy in antibody-mediated rejection. J Heart Lung Transplant. Sep 2016;35(9):1059-66. doi:10.1016/j.healun.2016.04.007
  15. Sharma D, Subramaniam G, Sharma N, Sharma P. Insight into Noninvasive Radiological Modalities to Detect Heart Transplant Rejection. Indian J Radiol Imaging. Oct 2021;31(4):946955. doi:10.1055/s-0041-1741098
  16. Sherwood K, Weimer ET. Characteristics, properties, and potential applications of circulating cell-free dna in clinical diagnostics: a focus on transplantation. J Immunol Methods. Dec 2018;463:27-38. doi:10.1016/j.jim.2018.09.011
  17. Hidestrand M, Tomita-Mitchell A, Hidestrand PM, et al. Highly sensitive noninvasive cardiac transplant rejection monitoring using targeted quantification of donor-specific cellfree deoxyribonucleic acid. J Am Coll Cardiol. Apr 01 2014;63(12):12241226. doi:10.1016/j.jacc.2013.09.029
  18. Baumann AK, Beck J, Kirchner T, et al. Elevated fractional donor-derived cell-free DNA during subclinical graft injury after liver transplantation. Liver Transpl. Dec 2022;28(12):19111919. doi:10.1002/lt.26479
  19. Qian X, Shah P, Agbor-Enoh S. Noninvasive biomarkers in heart transplant: 2020–2021 year in review. Current Opinion in Organ Transplantation. 2022;27(1):7-14
  20. Sorbini M, Togliatto GM, Simonato E, et al. HLA-DRB1 mismatch-based identification of donor-derived cell free DNA (dd-cfDNA) as a marker of rejection in heart transplant recipients: A single-institution pilot study. J Heart Lung Transplant. Aug 2021;40(8):794-804. doi:10.1016/j.healun.2021.05.001
  21. De Vlaminck I, Valantine HA, Snyder TM, et al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci Transl Med. Jun 18 2014;6(241):241ra77. doi:10.1126/scitranslmed.3007803

Published

2024-05-21

Issue

No. 1 (2024)

Section

Статьи