Beatriz Díaz Molina Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco RECHAZO AGUDO Viejos problemas con nue...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Declaración de potenciales conflictos de ...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión act...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión act...
REGISTRO ESPAÑOL DE TRASPLANTE CARDÍACO 1984-2008 Causas de Exitus . Área del Corazón Unidad de Insuficiencia Cardiaca Ava...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
ADULT HEART TRANSPLANT RECIPIENTS:  Cause of Death from Leading Causes by Era  (Deaths: January 1992 - June 2008) ISHLT 20...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión act...
PERCENTAGE OF ADULT HEART TRANSPLANT RECIPIENTS  EXPERIENCING REJECTION BETWEEN TRANSPLANT DISCHARGE AND 1-YEAR FOLLOW-UP ...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
2 episodios de rechazo 4 episodios de rechazo 63 pacientes  0.5-18.4 años posttx Área del Corazón Unidad de Insuficiencia ...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco 11 pacientes (55%) tuvieron 21 episodios ...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión act...
<ul><li>Anticuerpos anti HLA </li></ul><ul><li>Anticuerpos anti no HLA </li></ul><ul><ul><li>Autoanticuerpos: IgM no HLA, ...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
p=   0.007 Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión act...
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Am J Cardiol 2009
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco <ul><li>El rechazo agudo  postrasplante c...
Beatriz Díaz Molina Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco MUCHAS GRACIAS
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Dra. Beatriz Díaz Molina: Rechazo agudo

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Trasplante cardiaco: viejos problemas con nuevos enfoques. Rechazo agudo

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  • Because of a modification in the data collection, the analysis is limited to follow-ups occurring on or after July 2004. Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Survival rates were compared using the log-rank test statistic.
  • Because of a modification in the data collection, the analysis is limited to follow-ups occurring on or after July 2004. Comparisons were made using the chi-square statistic. No adjustments were made for multiple comparisons.
  • FIGURE 2. Immunohistochemical study of biopsies from patients with heart transplantation. (A) Positive stain in a biopsy obtained between 15 and 20 days after implantation of the graft from a patient who did not experience rejection. MICA can be observed in the capillary endothelium and lumen. (B) Longitudinal preparation from case A. MICA stain can be observed in capillary lumen. (C) Negative MICA stain in a biopsy obtained between 15 and 20 days after implantation of the graft from a patient who experienced a severe rejection episode during the first year postHTX. (D) Diffuse and moderate cytosolic stain in cardiomyocytes during the rejection but not endothelial and lumen capillary stain. (E) Negative control stained with a preimmune rabbit serum at the same dilution and (F) Positive staining using the s8p polyclonal antibody in gut epithelium.
  • FIGURE 2. Immunohistochemical study of biopsies from patients with heart transplantation. (A) Positive stain in a biopsy obtained between 15 and 20 days after implantation of the graft from a patient who did not experience rejection. MICA can be observed in the capillary endothelium and lumen. (B) Longitudinal preparation from case A. MICA stain can be observed in capillary lumen. (C) Negative MICA stain in a biopsy obtained between 15 and 20 days after implantation of the graft from a patient who experienced a severe rejection episode during the first year postHTX. (D) Diffuse and moderate cytosolic stain in cardiomyocytes during the rejection but not endothelial and lumen capillary stain. (E) Negative control stained with a preimmune rabbit serum at the same dilution and (F) Positive staining using the s8p polyclonal antibody in gut epithelium.
  • Biological Sciences Professor Chien Ho says the new technique should reduce the number of biopsy procedures and greatly improve the quality of life for cardiac transplant patients. These transplanted rat hearts show very early rejection (A), moderate rejection (B), and no rejection (C). Individual dark spots are single micrometer-sized paramagnetic iron oxide (MPIO) particle labeled macrophages. The image was taken with magnetic resonance microscopy. LV= left ventricle; RV= right ventricle. Image Courtesy of Dr. Chien Ho New Contrast Agents Track Organ Rejection: September 25, 2006 Organ transplants give patients a new lease on life. However, preventing their immune systems from rejecting the organ sometimes presents a challenge. Physicians must strike a balance between suppressing the immune system so that it does not reject the organ and maintaining enough activity to ward off infections. Tracking how well the body accepts the new organ is critical to this process. The current &amp;quot;gold standard&amp;quot; for monitoring organ rejection is tissue biopsy, an invasive procedure in which a physician removes a small sample from the transplanted organ for testing. Biopsy has two drawbacks: patient discomfort, as the physician must perform the procedure multiple times, and poor selectivity since the biopsy removes tissue from only a limited number of sites, missing rejection starting elsewhere in the organ. Tracking Immune Cells To overcome these limitations, researchers at Carnegie Mellon University are developing a new method to monitor organ rejection using magnetic resonance imaging (MRI). They inject polymer-coated nanometer- and micrometer-sized iron oxide particles into the blood where macrophages – immune cells that scavenge the body for foreign substances – ingest the particles and carry them to rejection sites in the transplanted organ. Because the highly magnetic iron particles can be clearly identified by MRI, researchers then use MRI to track the macrophages. &amp;quot;This technique may provide a way to optimize the administration of immunosuppressant drugs,&amp;quot; says Dr. Chien Ho, alumni professor of biological sciences at Carnegie Mellon University. &amp;quot;If we can detect acute rejection at an early stage, we can prevent irreversible tissue damage and the on-set of chronic rejection, which destroys the transplanted organ.&amp;quot; Larger is Better In a recent experiment, Dr. Ho&apos;s research group transplanted a living heart from one rat into the abdomen of another rat. Researchers injected the iron oxide particles into the host rat, and then performed MRI scans at regular intervals over the next several days as the rat&apos;s body rejected the transplanted heart. Previously, the researchers had studied mainly nanometer-sized particles, but in this experiment they also studied the effects of larger, micrometer-sized particles. They found that the larger iron particles allowed individual macrophages to be visualized by MRI. The researchers also observed, for the first time, that the rejection process starts in the pericardium, the membrane surrounding the heart, and spreads inward to the endocardium, the inner lining of the heart. Dr. Ho notes that the research has wider implications for tracking individual cells. &amp;quot;Tracking cell migration is not only very important in cell and developmental biology, but also in clinical medicine. This method is potentially useful for studying developing stem cells, the migration of cancer cells, inflammatory processes, and gene expression.&amp;quot; Potential for Clinical Use Echocardiography is used in heart transplantation as a screening tool for rejection, followed by tissue biopsy if actual rejection is suspected. But echocardiography lacks specificity. &amp;quot;All you can see by echocardiography is that the graft is not functioning well and that’s a subtle finding,&amp;quot; says Dr. Pedro del Nido, chair of the Department of Cardiac Surgery at Children&apos;s Hospital Boston. &amp;quot;A number of other factors could explain the dysfunction.&amp;quot; The new iron oxide contrast agents may help solve this problem by allowing physicians to visualize actual rejection. &amp;quot;In essence,&amp;quot; says Dr. del Nido, &amp;quot;this would give us a noninvasive biopsy. As a clinical tool, this has tremendous potential.&amp;quot; The new contrast agents could also allow investigators to follow the biology of transplantation over time. Currently, says Dr. del Nido, biopsies provide only &amp;quot;spot checks.&amp;quot; &amp;quot;There’s a huge sampling problem. For example, we have never been able to look at foci where there is rejection and see how it evolves.&amp;quot; Challenges to Overcome Although iron-based MRI contrast agents have great potential, Dr. del Nido cautions that there are concerns about the build-up of iron in patients receiving multiple MRI studies using the specialized imaging agents. &amp;quot;The iron becomes part of the iron pool in the body, like taking an iron pill,&amp;quot; says Dr. del Nido. &amp;quot;In adults this is less of an issue, but the question is, in children, will this be the case?&amp;quot; Monitoring rejection in other organs, such as kidneys, livers, and lungs may also be possible. But using the contrast agents in the liver and lungs will be an imaging challenge. Iron found in the liver, the body&apos;s largest iron storage site, can drown out the contrast agent&apos;s signal. To use the agents in transplanted lungs, researchers must overcome imaging artifacts created by the organ&apos;s many air sacs. Despite the technical hurdles researchers face, &amp;quot;it is becoming clear that the type of MRI experiment Dr. Ho&apos;s group has pioneered in rodents, will become clinically feasible,&amp;quot; says Dr. Alan Koretsky, chief of the Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, and director of the NIH Nuclear Magnetic Resonance Research Facility/Mouse Imaging Facility. Koretsky notes that an iron particle contrast agent is being marketed in Europe to measure macrophage accumulation in atherosclerotic plaque, the waxy fat build-up found in blood vessels. &amp;quot;It will be an exciting time to test whether this new ability of MRI to detect macrophage accumulation can translate into useful clinical information. I suspect it will become an important addition to the wide range of parameters that MRI can measure.&amp;quot; This research is supported by the National Institute of Biomedical Imaging and Bioengineering. Reference Wu YL, Ye Q, Foley LM, Hitchens TK, Sato K, Williams JB, Ho C. In situ labeling of immune cells with iron oxide particles: An approach to detect organ rejection by cellular MRI, Proceedings of the National Academy of Sciences 103: 1852-1857, 2006.
  • Dra. Beatriz Díaz Molina: Rechazo agudo

    1. 1. Beatriz Díaz Molina Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco RECHAZO AGUDO Viejos problemas con nuevos enfoques
    2. 2. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Declaración de potenciales conflictos de intereses Rechazo agudo: Viejos problemas con nuevos enfoques Relativas a esta presentación no existen relaciones que pudieran ser percibidas como potenciales conflictos de intereses.
    3. 3. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión actual Papel de los anticuerpos no-HLA Diagnóstico del rechazo agudo
    4. 4. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión actual Papel de los anticuerpos no-HLA Diagnóstico del rechazo agudo
    5. 5. REGISTRO ESPAÑOL DE TRASPLANTE CARDÍACO 1984-2008 Causas de Exitus . Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Rev Esp Cardiol. 2008;61:1178-90.
    6. 6. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    7. 7. ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death from Leading Causes by Era (Deaths: January 1992 - June 2008) ISHLT 2009 J Heart Lung Transplant 2009;28: 989-1049 CAUSE OF DEATH DATE OF DEATH 0-30 Days (N = 3,531) 31 Days – 1 Year (N = 3,513) >1 Year – 3 Years (N = 2,716) >3 Years – 5 Years (N = 2,356) >5 Years – 10 Years (N = 5,335) >10 Years (N = 3,677) ACUTE REJECTION 1992-1997 135 (7.4%) 267 (14.6%) 123 (8.9%) 42 (4.0%) 21 (1.3%) 3 (1.5%) 1998-6/2008 92 (5.4%) 160 (9.5%) 151 (11.3%) 62 (4.7%) 67 (1.8%) 30 (0.9%) CARDIAC ALLOGRAFT VASCULOPATHY 1992-1997 39 (2.1%) 100 (5.5%) 224 (16.3%) 222 (21.3%) 314 (19.2%) 47 (24.2%) 1998-6/2008 23 (1.3%) 63 (3.7%) 159 (11.9%) 147 (11.2%) 453 (12.2%) 473 (13.6%) GRAFT FAILURE 1992-1997 798 (44.0%) 383 (21.0%) 326 (23.7%) 186 (17.8%) 299 (18.3%) 33 (17.0%) 1998-6/2008 654 (38.1%) 243 (14.4%) 310 (23.2%) 287 (21.9%) 666 (18.0%) 576 (16.5%) MALIGNANCY, OTHER 1992-1997 4 (0.2%) 49 (2.7%) 158 (11.5%) 202 (19.3%) 303 (18.5%) 26 (13.4%) 1998-6/2008 0 (0.0%) 29 (1.7%) 143 (10.7%) 238 (18.1%) 696 (18.8%) 664 (19.1%)
    8. 8. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    9. 9. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión actual Papel de los anticuerpos no-HLA Diagnóstico del rechazo agudo
    10. 10. PERCENTAGE OF ADULT HEART TRANSPLANT RECIPIENTS EXPERIENCING REJECTION BETWEEN TRANSPLANT DISCHARGE AND 1-YEAR FOLLOW-UP Stratified by Type of Induction (Follow-ups: July 1, 2004 - June 30, 2008) ISHLT No induction: N=3,133 Polyclonal: 1,304 IL2R-antagonist: N=1,866 OKT3: N=161 Overall: no induct vs. poly (p<0.0001); no induct vs. IL2 (p<0.0001), no induct vs. OKT3 (p=0.048), poly vs. IL2 (p=0.038) 18-44: no induct vs. poly (p=0.009); no induct vs. IL2 (p=0.001) 45-62: no induct vs. poly (p=0.024); no induct vs. IL2 (p<0.0001) 63+: no induct vs. poly (p=0.015); no induct vs. IL2 (p<0.0001); no induct vs. OKT3 (p=0.002) F: no induct vs. poly (p=0.001); no induct vs. IL2 (p<0.0001) M: no induct vs. poly (p=0.011); no induct vs. IL2 (p<0.0001); poly vs. IL2 (p=0.021) Analysis is limited to patients who were alive at the time of the follow-up Treated rejection = Recipient was reported to (1) have at least one acute rejection episode that was treated with an anti-rejection agent; or (2) have been hospitalized for rejection. No rejection = Recipient had (i) no acute rejection episodes and (ii) was reported either as not hospitalized for rejection or did not receive anti-rejection agents. 2009 J Heart Lung Transplant 2009;28: 989-1049 Overall 18-44 45-62 63+ Female Male
    11. 11. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    12. 12. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    13. 13. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    14. 14. 2 episodios de rechazo 4 episodios de rechazo 63 pacientes 0.5-18.4 años posttx Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    15. 15. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco 11 pacientes (55%) tuvieron 21 episodios de rechazo 5 en la conversión de ISP a ICN Mayor rechazo en pacientes sin inducción
    16. 16. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    17. 17. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión actual Papel de los anticuerpos no-HLA Diagnóstico del rechazo agudo
    18. 18. <ul><li>Anticuerpos anti HLA </li></ul><ul><li>Anticuerpos anti no HLA </li></ul><ul><ul><li>Autoanticuerpos: IgM no HLA, Vimentina y anticuerpos anticorazón. </li></ul></ul><ul><ul><li>Anticuerpos anti cadena A del CMH clase I (MICA). </li></ul></ul><ul><ul><li>Anticuerpos anti cadena B del CMH clase I (MICB). </li></ul></ul><ul><ul><li>Anticuerpos anti antigenos endoteliales inespecíficos. </li></ul></ul>Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    19. 19. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    20. 20. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    21. 21. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    22. 22. p= 0.007 Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    23. 23. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Magnitud del problema Inmunosupresión actual Papel de los anticuerpos no-HLA Diagnóstico del rechazo agudo
    24. 24. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    25. 25. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    26. 26. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    27. 27. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco Am J Cardiol 2009
    28. 28. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco
    29. 29. Área del Corazón Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco <ul><li>El rechazo agudo postrasplante cardiaco es la causa de muerte de aproximadamente 10% de los pacientes en los tres primeros años. </li></ul><ul><li>Según el registro de la ISHLT el porcentaje de pacientes que fallecen del primer al tercer año ha aumentado. </li></ul><ul><li>Las pautas de inmunosupresión libres de anticalcineurínicos tienen una incidencia de rechazo mayor que las estrategias de minimización sumadas a ISP. </li></ul><ul><li>Los anticuerpos no HLA con más implicación en el rechazo agudo son los anticuerpos antiMICA. </li></ul><ul><li>El empleo de biopsia endomiocárdica en la rutina del seguimiento podría ser sustituida por biomarcadores y técnicas de imagen. </li></ul>En resumen…
    30. 30. Beatriz Díaz Molina Unidad de Insuficiencia Cardiaca Avanzada y Trasplante Cardiaco MUCHAS GRACIAS

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