Aspectos técnicos y clínicos de la prueba cruzada de histocompatibilidad en el trasplante de órganos sólidos

Ana María Arrunátegui, Daniel S. Ramón, Luz Marina Viola, Linda G. Olsen, Andrés Jaramillo, .

Palabras clave: trasplante de órganos, antígenos HLA, histocompatibilidad, pruebas inmunológicas de citotoxicidad, citometría de flujo

Resumen

La presencia de anticuerpos dirigidos contra los antígenos leucocitarios humanos (Human Leukocyte Antigens, HLA) que se expresan en las células del donante, es uno de los factores de riesgo más importantes asociados con las complicaciones clínicas después del trasplante. La prueba cruzada es una de las pruebas de histocompatibilidad más eficaces para la detección de anticuerpos específicos contra el donante en los receptores de injertos. En los primeros métodos de la prueba cruzada, se utilizaba la citotoxicidad dependiente del complemento, que es útil para detectar dichos anticuerpos responsables del rechazo hiperagudo del injerto, pero carece de la sensibilidad adecuada. Por ello, se desarrollaron métodos de pruebas cruzadas más sensibles, entre ellas, la prueba cruzada por citometría de flujo que hoy se considera el método preferido.
En este artículo se revisa la evolución de la prueba cruzada y los factores más importantes que deben tenerse en cuenta al realizarla y al interpretar los resultados de esta prueba fundamental para la supervivencia a largo plazo del injerto.

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Referencias bibliográficas

Lefaucheur C, Viglietti D, Mangiola M, Loupy A, Zeevi A. From humoral theory to performant risk stratification in kidney transplantation. J Immunol Res. 2017;2017:5201098. https://doi.org/10.1155/2017/5201098

Mehra NK, Baranwal AK. Clinical and immunological relevance of antibodies in solid organ transplantation. Int J Immunogenet. 2016;43:351-68. https://doi.org/10.1111/iji.12294

Valenzuela NM, Reed EF. Antibody-mediated rejection across solid organ transplants: Manifestations, mechanisms, and therapies. J Clin Invest. 2017;127:2492-504.

https://doi.org/10.1172/JCI90597

Loupy A, Lefaucheur C. Antibody-mediated rejection of solid-organ allografts. N Engl J Med. 2018;379:1150-60. https://doi.org/10.1056/NEJMra1802677

Loupy A, Hill GS, Jordan SC. The impact of donor-specific anti-HLA antibodies on late kidney allograft failure. Nat Rev Nephrol. 2012;8:348-57. https://doi.org/10.1038/nrneph.2012.81

Bray RA. Lymphocyte crossmatching by flow cytometry. Methods Mol Biol. 2013;1034:285-96. https://doi.org/10.1007/978-1-62703-493-7_14

Bray RA, Tarsitani C, Gebel HM, Lee JH. Clinical cytometry and progress in HLA antibody detection. Methods Cell Biol. 2011;103:285-310. https://doi.org/10.1016/B978-0-12-385493-3.00012-7

Downing J. The lymphocyte crossmatch by flow cytometry for kidney transplantation. Methods Mol Biol. 2012;882:379-90. https://doi.org/10.1007/978-1-61779-842-9_22

Graff RJ, Buchanan PM, Dzebisashvili N, Schnitzler MA, Tuttle-Newhall J, Xiao H, et al. The clinical importance of flow cytometry crossmatch in the context of CDC crossmatch results. Transplant Proc. 2010;42:3471-4. https://doi.org/10.1016/j.transproceed.2010.06.025

Jaramillo A, Ramon DS. The crossmatch assay in solid organ transplantation. In: Werner J, editor. Introduction to Flow Cytometry. Hauppauge, NY, USA: Nova Science Publishers, Inc., 2019. p. 237-73.

Jaramillo A, Ramón DS, Stoll ST. Technical aspects of crossmatching in transplantation. Clin Lab Med. 2018;38:579-93. https://doi.org/10.1016/j.cll.2018.07.002

Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969;280:735-9. https://doi.org/10.1056/NEJM196904032801401

Stiller CR, Sinclair NR, Abrahams S, Ulan RA, Fung M, Wallace AC. Lymphocyte-dependent antibody and renal graft rejection. Lancet. 1975;1:953-4. https://doi.org/10.1016/S0140-6736(75)92010-3

Takasugi M, Sengar DP, Terasaki PI. Microassays in transplantation immunology. Am J Med Technol. 1971;37:470-2.

Tanaka N, Takasugi M, Terasaki PI. Presensitization to transplants detected by cellular immunity tests. Transplantation. 1971;12:514-8. https://doi.org/10.1097/00007890-197112000-00017

Terasaki PI, McClelland JD. Microdroplet assay of human serum cytotoxins. Nature. 1964;204:998-1000. https://doi.org/10.1038/204998b0

Amos DB, Cohen I, Klein WJ Jr. Mechanisms of immunologic enhancement. Transplant Proc. 1970;2:68-75.

Fuller TC, Fuller AA, Golden M, Rodey GE. HLA alloantibodies and the mechanism of the antiglobulin-augmented lymphocytotoxicity procedure. Hum Immunol. 1997;56:94-105. https://doi.org/10.1016/S0198-8859(97)00174-2

Kerman RH, Kimball PM, van Buren CT, Lewis RM, DeVera V, Baghdahsarian V, et al. Improved renal allograft survival for AHG and DTE/AHG crossmatch-negative recipients. Transplant Proc. 1991;23:400-2.

Johnson AH, Rossen RD, Butler WT. Detection of alloantibodies using a sensitive antiglobulin microcytotoxicity test: Identification of low levels of pre-formed antibodies in accelerated allograft rejection. Tissue Antigens. 1972;2:215-26. https://doi.org/10.1111/j.1399-0039.1972.tb00138.x

Kerman RH, Kimball PM, van Buren CT, Lewis RM, DeVera V, Baghdahsarian V, et al. AHG and DTE/AHG procedure identification of crossmatch-appropriate donor-recipient pairings that result in improved graft survival. Transplantation. 1991;51:316-20. https://doi.org/10.1097/00007890-199102000-00008

Kerman RH. The role of crossmatching in organ transplantation. Arch Pathol Lab Med. 1991;115:255-9.

Soltis RD, Hasz D, Morris MJ, Wilson ID. The effect of heat inactivation of serum on aggregation of immunoglobulins. Immunology. 1979;36:37-45.

Delgado JC, Eckels DD. Positive B-cell only flow cytometric crossmatch: Implications for renal transplantation. Exp Mol Pathol. 2008;85:59-63. https://doi.org/10.1016/j.yexmp.2008.03.009

Duquesnoy RJ, Marrari M. Multilaboratory evaluation of serum analysis for HLA antibody and crossmatch reactivity by lymphocytotoxicity methods. Arch Pathol Lab Med. 2003;127:149-56. https://doi.org/10.5858/2003-127-149-MEOSAF

Cross DE, Whittier FC, Weaver P, Foxworth J. A comparison of the antiglobulin versus extended incubation time crossmatch: Results in 223 renal transplants. Transplant Proc. 1977;9:1803-6.

Garovoy MR, Rheinschmidt MA, Bigos M, Perkins H, Colombe B, Feduska N, et al. Flow cytometry analysis: A high technology cross-match technique facilitating transplantation. Transplant Proc. 1983;15:1939-44.

Bray RA. Flow cytometry in the transplant laboratory. Ann N Y Acad Sci. 1993;677:138-51. https://doi.org/10.1111/j.1749-6632.1993.tb38772.x

Bray RA. Flow cytometry crossmatching for solid organ transplantation. Methods Cell Biol. 1994;41:103-19. https://doi.org/10.1016/S0091-679X(08)61712-4

Bray RA, Lebeck LK, Gebel HM. The flow cytometric crossmatch. Dual-color analysis of T cell and B cell reactivities. Transplantation. 1989;48:834-40.

Cresswell P. Regulation of HLA class I and class II antigen expression. Br Med Bull. 1987;43:66-80. https://doi.org/10.1046/j.1365-2567.1997.00258.x

Kao KJ, Riley WJ. Genetic predetermination of quantitative expression of HLA antigens in platelets and mononuclear leukocytes. Hum Immunol. 1993;38:243-50. https://doi.org/10.1016/0198-8859(93)90551-B

Vandiedonck C, Taylor MS, Lockstone HE, Plant K, Taylor JM, Durrant C, et al. Pervasive haplotypic variation in the spliceo-transcriptome of the human major histocompatibility complex. Genome Res. 2011;21:1042-54. https://doi.org/10.1101/gr.116681.110

Good DJ, Zhang A, Kemesky J, Stopczynski N. Previously believed to be nonsensicl crossmatch results, explained by anti-HLA-C antibodies. Hum Immunol. 2017;78:S75. https://doi.org/10.1016/j.humimm.2017.06.090

Inlow J, Steller P, Eltayeb A, Rearick A, Kott M, Adams P, et al. Case study: Positive T-cell flow crossmatch (TFXM)/negative B-cell flow crossmatch (BFXM) can be mediated by a class I antibody. Hum Immunol. 2011;72:S154. https://doi.org/10.1016/j.humimm.2011.07.245

Lucas DP, Vega RM, Jackson AM. Variable expression of HLA-C impacts T versus B cell crossmatch outcomes. Hum Immunol. 2016;77:S2. https://doi.org/10.1016/j.humimm.2016.07.014

Badders JL, Jones JA, Jeresano ME, Schillinger KP, Jackson AM. Variable HLA expression on deceased donor lymphocytes: Not all crossmatches are created equal. Hum Immunol. 2015;76:795-800. https://doi.org/10.1016/j.humimm.2015.09.029

Basham TY, Merigan TC. Recombinant interferon-gamma increases HLA-DR synthesis and expression. J Immunol. 1983;130:1492-4.

Kuipers HF, Biesta PJ, Groothuis TA, Neefjes JJ, Mommaas AM, van den Elsen PJ. Statins affect cell-surface expression of major histocompatibility complex class II molecules by disrupting cholesterol-containing microdomains. Hum Immunol. 2005;66:653-65. https://doi.org/10.1016/j.humimm.2005.04.004

Le Morvan C, Cogne M, Troutaud D, Charmes JP, Sauvage P, Drouet M. Modification of HLA expression on peripheral lymphocytes and monocytes during aging. Mech Ageing Dev. 1998;105:209-20. https://doi.org/10.1016/S0047-6374(98)00096-7

Viallard JF, Bloch-Michel C, Neau-Cransac M, Taupin JL, Garrigue S, Miossec V, et al. HLA-DR expression on lymphocyte subsets as a marker of disease activity in patients with systemic lupus erythematosus. Clin Exp Immunol. 2001;125:485-91. https://doi.org/10.1046/j.1365-2249.2001.01623.x

Liwski R, Adams G, Peladeau G, Heinstein K. The impact of lymphocyte purity on flow cytometry crossmatch (FCXM) assay. It’s not purely theoretical. Hum Immunol. 2016;77:S110-S111. https://doi.org/10.1016/j.humimm.2016.07.164

Liwski RS, Greenshields AL, Conrad DM, Murphey C, Bray RA, Neumann J, et al. Rapid optimized flow cytometric crossmatch (FCXM) assays: The Halifax and Halifaster protocols. Hum Immunol. 2018;79:28-38. https://doi.org/10.1016/j.humimm.2017.10.020

Barrios K, Lunz J, Labuda B, Magas D, Freedom D, Szewczyk K, et al. Optimized flow cytometry crossmatch with increased sensitivity and specificity. Am J Transplant. 2016;16:S609.

Lobo PI, Spencer CE, Isaacs RB, McCullough C. Hyperacute renal allograft rejection from anti-HLA class 1 antibody to B cells--antibody detection by two color FCXM was possible only after using pronase-digested donor lymphocytes. Transpl Int. 1997;10:69-73. https://doi.org/10.1007/BF02044346

Lobo PI, Spencer CE, Stevenson WC, McCullough C, Pruett TL. The use of pronasedigested human leukocytes to improve specificity of the flow cytometric crossmatch. Transpl Int. 1995;8:472-80. https://doi.org/10.1111/j.1432-2277.1995.tb01558.x

Lobo PI, Winfield JB, Craig A, Westervelt FB Jr. Utility of protease-digested human peripheral blood lymphocytes for the detection of lymphocyte-reactive alloantibodies by indirect immunofluorescence. Transplantation. 1977;23:16-21. https://doi.org/10.1097/00007890-197701000-00003

Vaidya S, Cooper TY, Avandsalehi J, Barnes T, Brooks K, Hymel P, et al. Improved flow cytometric detection of HLA alloantibodies using pronase: Potential implications in renal transplantation. Transplantation. 2001;71:422-8. https://doi.org/10.1097/00007890-200102150-00015

Vaidya S, Cooper TY, Stewart D, Gugliuzza K, Daller J, Bray RA. Pronase improves detection of HLA antibodies in flow crossmatches. Transplant Proc. 2001;33:473-4. https://doi.org/10.1016/S0041-1345(00)02098-4

Hetrick SJ, Schillinger KP, Zachary AA, Jackson AM. Impact of pronase on flow cytometric crossmatch outcome. Hum Immunol. 2011;72:330-6. https://doi.org/10.1016/j.humimm.2011.01.005

Park H, Lim YM, Han BY, Hyun J, Song EY, Park MH. Frequent false-positive reactions in pronase-treated T-cell flow cytometric cross-match tests. Transplant Proc. 2012;44:87-90.

https://doi.org/10.1016/j.transproceed.2011.12.048

Hardt M, Baron T, Groschup MH. A comparative study of immunohistochemical methods for detecting abnormal prion protein with monoclonal and polyclonal antibodies. J Comp Pathol. 2000;122:43-53. https://doi.org/10.1053/jcpa.1999.0343

Lipman NS, Jackson LR, Trudel LJ, Weis-García F. Monoclonal versus polyclonal antibodies: Distinguishing characteristics, applications, and information resources. ILAR J. 2005;46:258-68. https://doi.org/10.1093/ilar.46.3.258

Kerman RH, van Buren CT, Lewis RM, DeVera V, Baghdahsarian V, Gerolami K, et al. Improved graft survival for flow cytometry and antihuman globulin crossmatch-negative retransplant recipients. Transplantation. 1990;49:52-6. https://doi.org/10.1097/00007890-199001000-00011

Bray RA, Nolen JD, Larsen C, Pearson T, Newell KA, Kokko K, et al. Transplanting the highly sensitized patient: The Emory algorithm. Am J Transplant. 2006;6:2307-15. https://doi.org/10.1111/j.1600-6143.2006.01521.x

Zangwill SD, Ellis TM, Zlotocha J, Jaquiss RD, Tweddell JS, Mussatto KA, et al. The virtual crossmatch--a screening tool for sensitized pediatric heart transplant recipients. Pediatr Transplant. 2006;10:38-41. https://doi.org/10.1111/j.1399-3046.2005.00394.x

Amico P, Hirt-Minkowski P, Honger G, Gurke L, Mihatsch MJ, Steiger J, et al. Risk stratification by the virtual crossmatch: A prospective study in 233 renal transplantations. Transpl Int. 2011;24:560-9. https://doi.org/10.1111/j.1432-2277.2011.01235.x

Amico P, Honger G, Steiger J, Schaub S. Utility of the virtual crossmatch in solid organ transplantation. Curr Opin Organ Transplant. 2009;14:656-61. https://doi.org/10.1097/MOT.0b013e328331c169

Bielmann D, Honger G, Lutz D, Mihatsch MJ, Steiger J, Schaub S. Pretransplant risk assessment in renal allograft recipients using virtual crossmatching. Am J Transplant. 2007;7:626-32. https://doi.org/10.1111/j.1600-6143.2007.01667.x

Bingaman AW, Murphey CL, Palma-Vargas J, Wright F. A virtual crossmatch protocol significantly increases access of highly sensitized patients to deceased donor kidney transplantation. Transplantation. 2008;86:1864-8. https://doi.org/10.1097/TP.0b013e318191404c

Claas FHJ, Heidt S. Virtual crossmatching for deceased donor transplantation becomes reality. Kidney Int. 2020;97:657-9. https://doi.org/10.1016/j.kint.2020.01.024

Jaramillo A, Reddy KS, Heilman RL. Using the virtual crossmatch to allow for safer and more efficient kidney transplantation of highly sensitized patients. Transplantation. 2020;104:1121-2. https://doi.org/10.1097/TP.0000000000002925

Johnson CP, Schiller JJ, Zhu YR, Hariharan S, Roza AM, Cronin DC, et al. Renal transplantation with final allocation based on the virtual crossmatch. Am J Transplant. 2016;16:1503-15. https://doi.org/10.1111/ajt.13606

Morris GP, Phelan DL, Jendrisak MD, Mohanakumar T. Virtual crossmatch by identification of donor-specific anti-human leukocyte antigen antibodies by solid-phase immunoassay: A 30-month analysis in living donor kidney transplantation. Hum Immunol. 2010;71:268-73. https://doi.org/10.1016/j.humimm.2010.01.003

Rohan VS, Pilch N, Moussa O, Nadig SN, Dubay D, Baliga PK, et al. Virtual crossmatching in kidney transplantation: The wait is over. J Am Coll Surg. 2020;230:373-9. https://doi.org/10.1016/j.jamcollsurg.2019.12.031

Roll GR, Webber AB, Gae DH, Laszik Z, Tavakol M, Mayen L, et al. A virtual crossmatchbased strategy facilitates sharing of deceased donor kidneys for highly sensitized recipients. Transplantation. 2020;104:1239-45. https://doi.org/10.1097/TP.0000000000002924

Cómo citar
1.
Arrunátegui AM, Ramón DS, Viola LM, Olsen LG, Jaramillo A. Aspectos técnicos y clínicos de la prueba cruzada de histocompatibilidad en el trasplante de órganos sólidos. biomedica [Internet]. 1 de junio de 2022 [citado 26 de junio de 2022];42(2):391-13. Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/6255

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2022-06-01
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