medigraphic.com
Boletín Médico del Hospital Infantil de México

2010, Número 6

<< Anterior Siguiente >>

Bol Med Hosp Infant Mex 2010; 67 (6)


Anticuerpos anti-HLA y rechazo agudo del injerto renal en los niños

Galeas RA, Gomezchico-Velasco R, Valverde S, Ramón-García G, Velásquez-Jones L, Romero-Navarro B, Hernández AM, Vargas A, De Leo C, Medeiros M

Idioma: Español
Referencias bibliográficas: 38
Paginas: 492-502
Archivo PDF: 429.73 Kb.


RESUMEN

Introducción. A pesar de que las nuevas terapias inmunosupresoras han mejorado notablemente la evolución clínica de los trasplantes renales, los rechazos agudo y crónico siguen limitando la sobrevida a largo plazo del injerto. En base a lo anterior, el objetivo de este estudio fue determinar la presencia de anticuerpos séricos contra antígenos de histocompatibilidad (HLA) clase I y clase II en niños con rechazo agudo del injerto renal.
Métodos. Se realizó un estudio clínico prospectivo en pacientes con trasplante renal que presentaron rechazo agudo del injerto. Se les tomó muestra de suero al momento de la biopsia renal, misma que fue utilizada para la detección de anticuerpos contra antígenos HLA de clase I y II por ensayo basado en equipo fluoroanalizador (Luminex) y microperlas cubiertas con antígenos clase I y clase II de One Lambda.
Resultados. De 21 pacientes estudiados, 17 pacientes (81%), fueron diagnosticados con rechazo celular y cuatro (19%) con rechazo agudo mediado por anticuerpos. El tiempo post-trasplante promedio de presentación del rechazo humoral agudo fue de 18.7 meses y para el rechazo celular de 36.7 meses.
Once pacientes (52.3%) presentaron anticuerpos específicos contra el donador. Los anticuerpos contra antígenos HLA clase I donador específicos se encontraron en seis pacientes, siendo más frecuente el rechazo agudo mediado por anticuerpos (humoral), donde todos los pacientes tuvieron anti HLA clase I con Chi cuadrada (P =0.004). En cuanto a los anticuerpos inespecíficos, el 95.2% de los pacientes desarrollaron este tipo de anticuerpos.
Conclusiones. El 95% de los niños con rechazo del injerto renal presentan anticuerpos anti HLA, específicos y/o no específicos contra el donador. Los anticuerpos anti HLA donador específicos clase I se presentan con mayor frecuencia en el rechazo humoral.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Bumgardner G. Evidence for multiple allograft rejection mechanisms within the same experimental system. Curr Opin Organ Transplant 2005;10:20-27.

  2. Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med 1994;331:365-376.

  3. Gloor J, Cosio F, Lager DJ, Stegall MD. The spectrum of antibody-mediated renal allograft injury: implications for treatment. Am J Transplant 2008;8:1367-1373.

  4. Heeger PS, Fairchild RL. Taking aim at a moving target: the complexity of immune-mediated organ rejection. Curr Opin Organ Transplant 2005;10:3-8.

  5. Obata F, Yoshida K, Ohkubo M, Ikeda Y, Taoka Y, Takeuchi Y, et al. Contribution of CD4+ and CD8+ T cells and interferon-gamma to the progress of chronic rejection of kidney allografts: the Th1 response mediates both acute and chronic rejection. Transpl Immunol 2005;14:21-25.

  6. Zhu L, Lee PC, Everly MJ, Terasaki PI. Detailed examination of HLA antibody development on renal allograft failure and function. Clin Transpl 2008:171-187.

  7. Mauiyyedi S, Crespo M, Collins AB, Schneeberger EE, Pascual MA, Saidman SL, et al. Acute humoral rejection in kidney transplantation: II. Morphology, immunopathology, and pathologic classification. J Am Soc Nephrol 2002;13:779-787.

  8. Watschinger B, Pascual M. Capillary C4d deposition as a marker of humoral immunity in renal allograft rejection. J Am Soc Nephrol 2002;13:2420-2423.

  9. Böhmig GA, Exner M, Habicht A, Schillinger M, Lang U, Kletzmayr J, et al. Capillary C4d deposition in kidney allografts: a specific marker of alloantibody-dependent graft injury. J Am Soc Nephrol 2002;13:1091-1099.

  10. Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008;8:753-760.

  11. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987;34:571-590.

  12. Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol 2007;22:1839-1848.

  13. Schwartz GJ, Haycock GB, Spitzer A. Plasma creatinine and urea concentration in children: normal values for age and sex. J Pediatr 1976;88:828-830.

  14. Ulibarri B, Martinez–Duncker C, Camarrillo C, Guadarrama EO, García P, Munoz AR, et al. Comparison of 99m Tc DTPA vs five methods to estimate glomerular filtration rate in children with renal transplantation. Pediatric Oncall 2009;6:67-70.

  15. Everly MJ, Terasaki PI. Monitoring and treating posttransplant human leukocyte antigen antibodies. Hum Immunol 2009;70:655-659.

  16. Gebel HM, Moussa O, Eckels DD, Bray RA. Donor-reactive HLA antibodies in renal allograft recipients: considerations, complications, and conundrums. Hum Immunol 2009;70:610-617.

  17. Cantú G, Sales F, Reyes A, Rodríguez-Ortega G, Medeiros M. En Hospitales de México: criterios de asignación de riñón de pacientes fallecidos. Persona Bioética 2009;13:20-34.

  18. Michaels PJ, Fishbein MC, Colvin RB. Humoral rejection of human organ transplants. Springer Semin Immunopathol 2003;25:119-140.

  19. Zhang Q, Liang LW, Gjertson DW, Lassman C, Wilkinson AH, Kendrick E, et al. Development of posttransplant antidonor HLA antibodies is associated with acute humoral rejection and early graft dysfunction. Transplantation 2005;79:591-598.

  20. Lee PC, Zhu L, Terasaki PI, Everly MJ. HLA-specific antibodies developed in the first year posttransplant are predictive of chronic rejection and renal graft loss. Transplantation 2009;88:568-574.

  21. Billen EV, Christiaans MH, Lee J, van den Berg-Loonen EM. Donor-directed HLA antibodies before and after transplantectomy detected by the luminex single antigen assay. Transplantation 2009;87:563-569.

  22. Stastny P, Lavingia B, Fixler DE, Yancy CW, Ring WS. Antibodies against donor human leukocyte antigens and the outcome of cardiac allografts in adults and children. Transplantation 2007;84:738-45.

  23. Hourmant M, Cesbron-Gautier A, Terasaki PI, Mizutani K, Moreau K, Meurette A, et al. Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation. J Am Soc Nephrol 2005;16:2804-2812.

  24. Morales-Buenrostro LE, Rodríguez-Romo R, de Leo-Cervantes C, López M, Pérez-Garrido J, Uribe-Uribe N, et al. HLA and MICA antibodies: further evidence of their impact on graft loss two years after their detection. Clin Transpl 2006:207-218.

  25. Morales-Buenrostro LE, Rodríguez-Romo R, de Leo-Cervantes C, López M, Pérez-Garrido J, Uribe-Uribe N, et al. Evidence on the role of HLA and MICA antibodies in renal graft loss. Gac Med Mex 2008;144:315-322.

  26. Halloran PF, Wadgymar A, Ritchie S, Falk J, Solez K, Srinivasa NS. The significance of the anti-class I antibody response. I. Clinical and pathologic features of anti-class I-mediated rejection. Transplantation 1990;49:85-91.

  27. Crespo M, Pascual M, Tolkoff-Rubin N, Mauiyyedi S, Collins AB, Fitzpatrick D, et al. Acute humoral rejection in renal allograft recipients. I. Incidence, serology and clinical characteristics. Transplantation 2001;71:652-658.

  28. Burns JM, Cornell LD, Perry DK, Pollinger HS, Gloor JM, Kremers WK, et al. Alloantibody levels and acute humoral rejection early after positive crossmatch kidney transplantation. Am J Transplant 2008;8:2684-2694.

  29. Magil AB, Tinckam KJ. Focal peritubular capillary C4d deposition in acute rejection. Nephrol Dial Transplant 2006;21:1382-1388.

  30. Poduval RD, Kadambi PV, Josephson MA, Cohn RA, Harland RC, Javaid B, et al. Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection. Transplantation 2005;79:228-235.

  31. Sis B, Halloran PF. Endothelial transcripts uncover a previously unknown phenotype: C4d-negative antibody-mediated rejection. Curr Opin Organ Transpl 2010;15:42-48.

  32. Sis B, Jhangri GS, Bunnag S, Allanach K, Kaplan B, Halloran PF. Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining. Am J Transplant 2009;9:2312-2323.

  33. Lehrich RW, Rocha PN, Reinsmoen N, Greenberg A, Butterly DW, Howell DN, et al. Intravenous immunoglobulin and plasmapheresis in acute humoral rejection: experience in renal allograft transplantation. Hum Immunol 2005;66:350-358.

  34. Jordan SC, Vo AA, Toyoda M, Tyan D, Nast CC. Post-transplant therapy with high-dose intravenous gammaglobulin: applications to treatment of antibody-mediated rejection. Pediatr Transplant 2005;9:155-161.

  35. Pescovitz MD. The use of rituximab, anti-CD20 monoclonal antibody, in pediatric transplantation. Pediatr Transplant 2004;8:9-21.

  36. Basta M, Dalakas MC. High-dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments. J Clin Invest 1994;94:1729-1735.

  37. Lutz HU, Stammler P, Jelezarova E, Nater M, Späth PJ. High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn-IgG complexes. Blood 1996;88:184-193.

  38. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009;9(Suppl 3):S1-S155.




2020     |     www.medigraphic.com