Biomarcadores y genes implicados en el rechazo de trasplante.
Palabras clave:
Trasplante, biomarcadores, hematología.Resumen
El trasplante de órganos es una opción de última línea para tratar la pérdida de función orgánica, pero el rechazo sigue siendo una complicación importante. Los biomarcadores no invasivos son esenciales para la detección temprana del rechazo, facilitando un mejor monitoreo y tratamiento del injerto trasplantado. Las pruebas moleculares y tecnologías no invasivas, como los miRNA y la nanotecnología, son clave tanto en el diagnóstico temprano como en el tratamiento del rechazo agudo de órgano. En este artículo se revisarán biomarcadores asociados al rechazo de órganos.
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1. Sarkar RS, Philip J, Yadav P. Transfusion medicine and solid organ transplant - Update and review of some current issues. Med J Armed Forces India. 2013; 69(2):162-7. DOI:10.1016/j.mjafi.2012.11.012
2. Beimler J, Zeier M. ABO-incompatible transplantation--a safe way to perform renal transplantation? Nephrol Dial Transplant. 2007; 22(1):25-7. DOI: 10.1093/ndt/gfl557.
3. Cooper JE. Evaluation and Treatment of Acute Rejection in Kidney Allografts. Clin J Am Soc Nephrol. 2020; 15(3):430-8. DOI: 10.2215/CJN.11991019.
4. Ortiz MA, Álvarez CM, Arrunátegui AM, Arias YR, Villegas A. Immunological follow-up of patients with renal transplants: A proposal for clinical practice in Colombia. Biomedica. 2020; 40(3):479-86. DOI: 10.7705/biomedica.5092.
5. Khachatoorian Y, Khachadourian V, Chang E, Sernas ER, Reed EF, Deng M, et al. Noninvasive biomarkers for prediction and diagnosis of heart transplantation rejection. Transplant Rev (Orlando). 2021; 35(1):100590. DOI: 10.1016/j.trre.2020.100590.
6. Duong Van Huyen JP, Tible M, Gay A, Guillemain R, Aubert O, Varnous S, et al. MicroRNAs as non-invasive biomarkers of heart transplant rejection. Eur Heart J. 2014; 35(45):3194-202. DOI: 10.1093/eurheartj/ehu346.
7. González-Molina M, Ruiz-Esteban P, Caballero A, Burgos D, Cabello M, Leon M, et al. Immune response and histology of humoral rejection in kidney transplantation. Nefrologia. 2016; 36(4):354-67. DOI: 10.1016/j.nefro.2016.03.023.
8. Cascalho M, Platt JL. Basic mechanisms of humoral rejection. Pediatr Transplant. 2005; 9(1):9-16. DOI: 10.1111/j.1399-3046.2004.00231.x.
9. Takemoto SK, Zeevi A, Feng S, et al. A national conference to assess antibody mediated rejection in solid organ transplantation. Am J Transplant. 2004; 4:1033-41.
10. Zhou Q, Li T, Wang K, Zhang Q, Geng Z, Deng S, et al. Current status of xenotransplantation research and the strategies for preventing xenograft rejection. Front Immunol. 2022;13:928173. DOI: 10.3389/fimmu.2022.928173.
11. Matter-Reissmann UB, Forte P, Schneider MK, Filgueira L, Groscurth P, Seebach JD. Xenogeneic human NK cytotoxicity against porcine endothelial cells is perforin/granzyme b dependent and not inhibited by bcl-2 overexpression. Xenotransplantation. 2002; 9(5):325–37. DOI: 10.1034/j.1399-3089.2002.01074.x.
12. Wang HT, Maeda A, Sakai R, Lo PC, Takakura C, Jiaravuthisan P, et al. Human CD31 on porcine cells suppress xenogeneic neutrophil-mediated cytotoxicity via the inhibition of NETosis. Xenotransplantation;2018, 25(5):e12396. DOI: 10.1111/xen.12396.
13. Ho J, Okoli GN, Rabbani R, Lam OLT, Reddy VK, Askin N, et al. Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis. Am J Transplant. 2022;22(3):772-85. DOI: 10.1111/ajt.16907.
14. Lin CC, Ezzelarab M, Shapiro R, Ekser B, Long C, Hara H, et al. Recipient tissue factor expression is associated with consumptive coagulopathy in pig-toprimate kidney xenotransplantation. Am J Transplant. 2010; 10(7):1556–68. DOI: 10.1111/j.1600-6143.2010.03147.x.
15. Iancu Loga LI, Dican L, Chiorean AD, Chelaru VF, Elec FI, Catana CS, et al. Association between Human Leukocyte Antigen and End-Stage Renal Disease in Patients from Transylvania, Romania. Int J Mol Sci. 2023; 24(17):13383. DOI: 10.3390/ijms241713383.
16. Little AM, Parham P. Polymorphism and evolution of HLA class I and II genes and molecules. Rev Immunogenet. 1999;1(1):105-23.
17. Argani H. Anti-HLA Antibody: The Role of Epitopes in Organ Transplantation. Exp Clin Transplant. 2019; 17(Suppl 1):38-42. DOI: 10.6002/ect.MESOT2018.L41.
18. Adebiyi OO, Gralla J, Klem P, Freed B, Davis S, Wiseman AC, et al. Clinical Significance of Pretransplant Donor-Specific Antibodies in the Setting of Negative Cell-Based Flow Cytometry Crossmatching in Kidney Transplant Recipients. Am J Transplant. 2016; 16(12):3458-67. DOI: 10.1111/ajt.13848.
19. Kwon H, Kim YH, Choi JY, Shin S, Jung JH, Park SK, et al. Impact of pretransplant donor-specific antibodies on kidney allograft recipients with negative flow cytometry cross-matches. Clin Transplant. 2018; 32(6):e13266. DOI: 10.1111/ctr.13266.
20. Ho J, Okoli GN, Rabbani R, Lam OLT, Reddy VK, Askin N, et al. Effectiveness of T cell-mediated rejection therapy: A systematic review and meta-analysis. Am J Transplant. 2022; 22(3):772-85. DOI: 10.1111/ajt.16907.
21. Hart A, Singh D, Brown SJ, Wang JH, Kasiske BL. Incidence, risk factors, treatment, and consequences of antibody-mediated kidney transplant rejection: A systematic review. Clin Transplant. 2021; 35(7):e14320. DOI: 10.1111/ctr.14320.
22. Charlton M, Levitsky J, Aqel B, OʼGrady J, Hemibach J, Rinella M, F et al. International Liver Transplantation Society Consensus Statement on Immunosuppression in Liver Transplant Recipients. Transplantation. 2018; 102(5):727-43. DOI: 10.1097/TP.0000000000002147.
23. Zhang C, Chen JZ, Dong K, Jian YY, Huang KY, Su RL, Tan XL, et al. Computational identification of novel potential genetic pathogenesis and otherwise biomarkers in acute liver allograft rejection. Heliyon. 2024; 10(15):e33359. DOI: 10.1016/j.heliyon.2024.e33359.
24. Bush N, Akshintala VS. Interpretation of serum pancreatic enzymes in pancreatic and nonpancreatic conditions. Curr Opin Gastroenterol. 2023; 39(5):403-10. DOI: 10.1097/MOG.0000000000000961.
25. Torabi J, Melvin J, Rechnitzer A, Rocca JP, Ajaimy M, Lirano-Ward L, et al. High terminal creatinine donors should not preclude simultaneous kidney and pancreas transplantation. Am J Surg. 2021; 221(4):677-80. DOI: 10.1016/j.amjsurg.2020.09.031.
26. Natarajan K, Li H, Mariuzza RA, Margulies DH. MHC class I molecules, structure and function. Rev Immunogenet. 1999; 1(1):32-46.
27. Wake CT. Molecular biology of the HLA class I and class II genes. Mol Biol Med. 1986; 3(1):1-11.
28. Khachatoorian Y, Khachadourian V, Chang E, Sernas ER, Reed EF, Deng M, et al. Noninvasive biomarkers for prediction and diagnosis of heart transplantation rejection. Transplant Rev (Orlando). 2021; 35(1):100590. DOI: 10.1016/j.trre.2020.100590.
29. Kobashigawa J, Crespo-Leiro MG, Ensminger SM, Reichenspurner H, Angelini A, Berry G, et al; Consensus Conference Participants. Report from a consensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2011; 30(3):252-69. DOI: 10.1016/j.healun.2010.11.003.
30. Rossano JW, Morales DL, Zafar F, Denfield SW, Kim JJ, Jefferies JL, et al. Impact of antibodies against human leukocyte antigens on long-term outcome in pediatric heart transplant patients: an analysis of the United Network for Organ Sharing database. J Thorac Cardiovasc Surg. 2010; 140(3):694-9, 699.e1-2. DOI: 10.1016/j.jtcvs.2010.04.009.
31. Gligorijević V, Malod-Dognin N, Pržulj N. Integrative methods for analyzing big data in precision medicine. Proteomics. 2016; 16(5):741-58. DOI: 10.1002/pmic.201500396.
32. Lim JH, Chung BH, Lee SH, Jung HY, Choi JY, Cho JH, et al. Omics-based biomarkers for diagnosis and prediction of kidney allograft rejection. Korean J Intern Med. 2022; 37(3):520-33. DOI: 10.3904/kjim.2021.518.
33. Everly MJ, Rebellato LM, Haisch CE, Ozawa M, Parker K, Briley KP, et al. Incidence and impact of de novo donor-specific alloantibody in primary renal allografts. Transplantation. 2013; 95(3):410-7. DOI: 10.1097/TP.0b013e31827d62e3.
34. Loupy A, Jordan SC. Transplantation: Donor-specific HLA antibodies and renal allograft failure. Nat Rev Nephrol. 2013;9(3):130-1. DOI: 10.1038/nrneph.2013.18.
35. Duong Van Huyen JP, Tible M, Gay A, Guillemain R, Aubert O, Varnous S, et al. MicroRNAs as non-invasive biomarkers of heart transplant rejection. Eur Heart J. 2014; 35(45):3194-202. DOI: 10.1093/eurheartj/ehu346.
36. Oetting WS, Schladt DP, Dorr CR, Wu B, Guan W, Remmel RP, et al; DeKAF Genomics and GEN03 Investigators. Analysis of 75 Candidate SNPs Associated With Acute Rejection in Kidney Transplant Recipients: Validation of rs2910164 in MicroRNA MIR146A. Transplantation. 2019; 103(8):1591-602. DOI: 10.1097/TP.0000000000002659.
37. Suthanthiran M, Schwartz JE, Ding R, Abecassis M, Dadhania D, Samstein B, et al; Clinical Trials in Organ Transplantation 04 (CTOT-04) Study Investigators. Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med. 2013; 369(1):20-31. DOI: 10.1056/NEJMoa1215555.
38. Christakoudi S, Runglall M, Mobillo P, Tsui TL, Duff C, Domingo-Vila C, et al. Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples. EBioMedicine. 2019; 41:571-583. DOI: 10.1016/j.ebiom.2019.01.060.
39. Anglicheau D, Sharma VK, Ding R, Hummel A, Snopkowski C, Dadhania D, et al. MicroRNA expression profiles predictive of human renal allograft status. Proc Natl Acad Sci U S A. 2009; 106(13):5330-5. DOI: 10.1073/pnas.0813121106.
40. Sugi MD, Joshi G, Maddu KK, Dahiya N, Menias CO. Imaging of Renal Transplant Complications throughout the Life of the Allograft: Comprehensive Multimodality Review. Radiographics. 2019; 39(5):1327-55. DOI: 10.1148/rg.2019190096.
41. Köhnke R, Kentrup D, Schütte-Nütgen K, Schäfers M, Schnöckel U, Hoerr V, et al. Update on imaging-based diagnosis of acute renal allograft rejection. Am J Nucl Med Mol Imaging. 2019; 9(2):110-26.
42. Hirai T, Mayer AT, Nobashi TW, Lin PY, Xiao Z, Udagawa T, et al. Imaging alloreactive T cells provides early warning of organ transplant rejection. JCI Insight. 2021; 6(13):e145360. DOI: 10.1172/jci.insight.145360.
43. Daly KP, Dearling JL, Seto T, Dunning P, Fahey F, Packard AB,et al. Use of [18F]FDG Positron Emission Tomography to Monitor the Development of Cardiac Allograft Rejection. Transplantation. 2015; 99(9):e132-9. DOI: 10.1097/TP.0000000000000618.
44. Chen Y, Pei P, Yang Y, et al. Diagnóstico temprano no invasivo del rechazo de aloinjertos mediante un nanosensor de bioimagen nir-ii sensible a la proteasa de granzima b. Angew Chem. Int. Ed. Engl. 2023; 62(23). DOI: 10.1002/anie.202301696
45. Ma X., Mao M., He J., et al. Imágenes moleculares basadas en nanoprobetas para la estratificación tumoral. Chem. Soc. Rev. 2023; 52(18):6447–6496. DOI: 10.1039/d3cs00063j.
46. Ding M, Gao T, Song Y, Yi L, Li W, Deng C, et al. Nanoparticle-based T cell immunoimaging and immunomodulatory for diagnosing and treating transplant rejection. Heliyon. 2024 Jan 9; 10(2):e24203. DOI: 10.1016/j.heliyon.2024.e24203.
47. Szumilas K, Wilk A, Wiśniewski P, Gimpel A, Dziedziejko V, Kipp M, et al. Current Status Regarding Immunosuppressive Treatment in Patients after Renal Transplantation. Int J Mol Sci. 2023; 24(12):10301. DOI: 10.3390/ijms241210301.
48. Ballona R. Inhibidores de calcineurina: una alternativa en el tratamiento inmunosupresor. Dermatol. Peru. 2003; 13(2):121-3.
49. Forns X, Navasa M. Liver transplant immunosuppression during the covid-19 pandemic. Gastroenterol Hepatol. 2020; 43(8):457-63.
50. Zaza G, Tomei P, Granata S, Boschiero L, Lupo A. Monoclonal antibody therapy and renal transplantation: focus on adverse effects. Toxins (Basel). 2014; 6(3):869-91. DOI: 10.3390/toxins6030869.
51. Sandal S, Bae S, McAdams-DeMarco M, Massie AB, Lentine KL, Cantarovich M, et al. Induction immunosuppression agents as risk factors for incident cardiovascular events and mortality after kidney transplantation. Am J Transplant. 2019; 19(4):1150-9. DOI: 10.1111/ajt.15148.
52. Nishihori T, Al-Kadhimi Z, Hamadani M, Kharfan-Dabaja MA. Antithymocyte globulin in allogeneic hematopoietic cell transplantation: benefits and limitations. Immunotherapy. 2016; 8(4):435-47. DOI: 10.2217/imt.15.128.
53. Taylor AL, Watson CJE, Bradley JA. Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeuticefficacy. Crit Rev Oncol Hematol. 2005; 56:23-46. DOI: 10.1016/j.critrevonc.2005.03.012.
54. Badri PS, Parikh A, Coakley EP, Ding B, Awni WM, Dutta S, et al. Pharmacokinetics of tacrolimus and cyclosporine in liver transplant recipients receiving 3 direct-acting antivirals as treatment for hepatitis c infection. Ther Drug Monit. 2016; 38:640-5. DOI: 10.1097/FTD.0000000000000315.
55. Altobelli C, Anastasio P, Cerrone A, Signoriello E, Lus G, Pluvio C, Perna AF, Capasso G, Simeoni M, Capolongo G. Therapeutic Plasmapheresis: A Revision of Literature. Kidney Blood Press Res. 2023; 48(1):66-78. DOI: 10.1159/000528556.
56. Rodriguez-Ramirez S, Al Jurdi A, Konvalinka A, Riella LV. Antibody-mediated rejection: prevention, monitoring and treatment dilemmas. Curr Opin Organ Transplant. 2022; 27(5):405-14. DOI: 10.1097/MOT.0000000000001011
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Derechos de autor 2025 Maria Clara Vargas-Zuluaga, María Alejandra Escobar-Salamanca, Lina María Martínez-Sánchez
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