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Journal of Transplantation
Volume 2012 (2012), Article ID 193724, 9 pages
http://dx.doi.org/10.1155/2012/193724
Review Article

Antibody-Mediated Rejection in Kidney Transplantation: A Review

1Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA
2Division of Transplantation, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213-2582, USA

Received 22 October 2011; Accepted 9 January 2012

Academic Editor: Enver Akalin

Copyright © 2012 Chethan Puttarajappa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Patel and P. I. Terasaki, “Significance of the positive crossmatch test in kidney transplantation,” New England Journal of Medicine, vol. 280, no. 14, pp. 735–739, 1969. View at Scopus
  2. P. Terasaki and K. Mizutani, “Antibody mediated rejection: update 2006,” Clinical Journal of the American Society of Nephrology, vol. 1, no. 3, pp. 400–403, 2006. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Mauiyyedi and R. B. Colvin, “Humoral rejection in kidney transplantation: new concepts in diagnosis and treatment,” Current Opinion in Nephrology and Hypertension, vol. 11, no. 6, pp. 609–618, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. R. B. Colvin and R. N. Smith, “Antibody-mediated organ-allograft rejection,” Nature Reviews Immunology, vol. 5, no. 10, pp. 807–817, 2005. View at Publisher · View at Google Scholar · View at Scopus
  5. K. Trpkov, P. Campbell, F. Pazderka, S. Cockfield, K. Solez, and P. F. Halloran, “Pathologic features of acute renal allograft rejection associated with donor-specific antibody: analysis using the Banff grading schema,” Transplantation, vol. 61, no. 11, pp. 1586–1592, 1996. View at Publisher · View at Google Scholar · View at Scopus
  6. H. Regele, G. A. Böhmig, A. Habicht et al., “Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: a contribution of humoral immunity to chronic allograft rejection,” Journal of the American Society of Nephrology, vol. 13, no. 9, pp. 2371–2380, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. J. Fotheringham, C. A. Angel, and W. McKane, “Transplant glomerulopathy: morphology, associations and mechanism,” Nephron—Clinical Practice, vol. 113, no. 1, pp. c1–c7, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. F. G. Cosio, J. M. Gloor, S. Sethi, and M. D. Stegall, “Transplant glomerulopathy: morphology, associations and mechanismsm,” American Journal of Transplantation, vol. 8, pp. 292–296, 2008.
  9. P. Stastny, Y. Zou, Y. Fan, Z. Qin, and B. Lavingia, “The emerging issue of MICA antibodies: antibodies to MICA and other antigens of endothelial cells,” Contributions to Nephrology, vol. 162, pp. 99–106, 2009. View at Publisher · View at Google Scholar
  10. Y. Zou, P. Stastny, C. Süsal, B. Döhler, and G. Opelz, “Antibodies against MICA antigens and kidney-transplant rejection,” New England Journal of Medicine, vol. 357, no. 13, pp. 1293–1300, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. V. Carter, B. K. Shenton, B. Jaques et al., “Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation,” Transplantation Proceedings, vol. 37, no. 2, pp. 654–657, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Kekomäki, L. Kyllönen, K. Salmela, S. Koskimies, and R. Kekomäki, “Platelet-specific alloantigens in cadaveric renal transplantation. A prospective study. Effect of HPA-5b mismatch in acute vascular rejection of renal allografts,” Tissue Antigens, vol. 57, no. 2, pp. 154–157, 2001. View at Publisher · View at Google Scholar · View at Scopus
  13. K. Tinckam, D. Rush, I. Hutchinson et al., “The relative importance of cytokine gene polymorphisms in the development of early and late acute rejection and six-month renal allograft pathology,” Transplantation, vol. 79, no. 7, pp. 836–841, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. R. Abdi, T. T. Bich Huong, A. Sahagun-Ruiz et al., “Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation,” Journal of the American Society of Nephrology, vol. 13, no. 3, pp. 754–758, 2002. View at Scopus
  15. D. Dragun, D. N. Müller, J. H. Bräsen et al., “Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection,” New England Journal of Medicine, vol. 352, no. 6, pp. 558–569, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. G. Hönger, H. Hopfer, M. -L. Arnold, B. M. Spriewald, S. Schaub, and P. Amico, “Pretransplant IgG subclasses of donor-specific human leukocyte antigen antibodies and development of antibody-mediated rejection,” Transplantation, vol. 92, no. 1, pp. 41–47, 2011. View at Publisher · View at Google Scholar
  17. C. Y. Lee, S. Lotfi-Emran, M. Erdinc et al., “The involvement of fcr mechanisms in antibody-mediated rejection,” Transplantation, vol. 84, no. 10, pp. 1324–1334, 2007. View at Publisher · View at Google Scholar · View at Scopus
  18. C. N. Morrell, K. Murata, A. M. Swaim et al., “In vivo platelet-endothelial cell interactions in response to major histocompatibility complex alloantibody,” Circulation Research, vol. 102, no. 7, pp. 777–785, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Yamakuchi, N. C. Kirkiles-Smith, M. Ferlito et al., “Antibody to human leukocyte antigen triggers endothelial exocytosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 4, pp. 1301–1306, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. K. Solez, R. B. Colvin, L. C. Racusen et al., “Banff 07 classification of renal allograft pathology: updates and future directions,” American Journal of Transplantation, vol. 8, no. 4, pp. 753–760, 2008. View at Publisher · View at Google Scholar · View at Scopus
  21. H. E. Feucht, “Complement C4d in graft capillaries - The missing link in the recognition of humoral alloreactivity,” American Journal of Transplantation, vol. 3, no. 6, pp. 646–652, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. R. B. Colvin, “Antibody-mediated renal allograft rejection: diagnosis and pathogenesis,” Journal of the American Society of Nephrology, vol. 18, no. 4, pp. 1046–1056, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. C. A. Seemayer, A. Gaspert, V. Nickeleit, and M. J. Mihatsch, “C4d staining of renal allograft biopsies: a comparative analysis of different staining techniques,” Nephrology Dialysis Transplantation, vol. 22, no. 2, pp. 568–576, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. H. E. Feucht, E. Felber, M. J. Gokel et al., “Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection,” Clinical and Experimental Immunology, vol. 86, no. 3, pp. 464–470, 1991. View at Scopus
  25. A. B. Collins, E. E. Schneeberger, M. A. Pascual et al., “Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries,” Journal of the American Society of Nephrology, vol. 10, no. 10, pp. 2208–2214, 1999. View at Scopus
  26. M. Crespo, M. Pascual, N. Tolkoff-Rubin et al., “Acute humoral rejection in renal allograft recipients: I. Incidence, serology and clinical characteristics,” Transplantation, vol. 71, no. 5, pp. 652–658, 2001. View at Scopus
  27. S. Mauiyyedi, P. Della Pelle, S. Saidman et al., “Chronic humoral rejection: identification of antibody-mediated chronic renal allograft rejection by C4d deposits in peritubular capillaries,” Journal of the American Society of Nephrology, vol. 12, no. 3, pp. 574–582, 2001. View at Scopus
  28. H. Regele, G. A. Böhmig, A. Habicht et al., “Capillary deposition of complement split product C4d in renal allografts is associated with basement membrane injury in peritubular and glomerular capillaries: a contribution of humoral immunity to chronic allograft rejection,” Journal of the American Society of Nephrology, vol. 13, no. 9, pp. 2371–2380, 2002. View at Publisher · View at Google Scholar · View at Scopus
  29. B. Sis, P. M. Campbell, T. Mueller et al., “Transplant glomerulopathy, late antibody-mediated rejection and the ABCD tetrad in kidney allograft biopsies for cause,” American Journal of Transplantation, vol. 7, no. 7, pp. 1743–1752, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. E. Akalin, R. Dinavahi, S. Dikman et al., “Transplant glomerulopathy may occur in the absence of donor-specific antibody and C4d staining,” Clinical Journal of the American Society of Nephrology, vol. 2, no. 6, pp. 1261–1267, 2007. View at Publisher · View at Google Scholar · View at Scopus
  31. Z. Al Aly, P. Yalamanchili, C. Cortese, L. Salinas-Madrigal, and B. Bastani, “C4d peritubular capillary staining in chronic allograft nephropathy and transplant glomerulopathy: an uncommon finding,” Transplant International, vol. 18, no. 7, pp. 800–805, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. A. Loupy, G. S. Hill, C. Suberbielle et al., “Significance of C4d Banff scores in early protocol biopsies of kidney transplant recipients with preformed donor-specific antibodies (DSA),” American Journal of Transplantation, vol. 11, no. 1, pp. 56–65, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. B. Sis, G. S. Jhangri, S. Bunnag, K. Allanach, B. Kaplan, and P. F. Halloran, “Endothelial gene expression in kidney transplants with alloantibody indicates Antibody-mediated damage despite lack of C4d staining,” American Journal of Transplantation, vol. 9, no. 10, pp. 2312–2323, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Pei, J. H. Lee, N. J. Shih, M. Chen, and P. I. Terasaki, “Single human leukocyte antigen flow cytometry beads for accurate identification of human leukocyte antigen antibody specificities,” Transplantation, vol. 75, no. 1, pp. 43–49, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. N. El-Awar, J. Lee, and P. I. Terasaki, “HLA antibody identification with single antigen beads compared to conventional methods,” Human Immunology, vol. 66, no. 9, pp. 989–997, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. H. M. Gebel and R. A. Bray, “The evolution and clinical impact of human leukocyte antigen technology,” Current Opinion in Nephrology and Hypertension, vol. 19, no. 6, pp. 598–602, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. R. A. Bray and H. M. Gebel, “Strategies for human leukocyte antigen antibody detection,” Current Opinion in Organ Transplantation, vol. 14, no. 4, pp. 392–397, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. J. M. Yabu, J. P. Higgins, G. Chen, F. Sequeira, S. Busque, and D. B. Tyan, “C1q-fixing human leukocyte antigen antibodies are specific for predicting transplant glomerulopathy and late graft failure after kidney transplantation,” Transplantation, vol. 91, no. 3, pp. 342–347, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. O. Bocrie, A. A. Hussein Aly, F. Guignier et al., “Distribution of donor-specific antibodies in the cortex and the medulla of renal transplants with chronic allograft nephropathy,” Transplant Immunology, vol. 17, no. 3, pp. 227–229, 2007. View at Publisher · View at Google Scholar · View at Scopus
  40. M. D. Kazatchkine and S. V. Kaveri, “Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin,” New England Journal of Medicine, vol. 345, no. 10, pp. 747–755, 2001. View at Publisher · View at Google Scholar · View at Scopus
  41. F. Nimmerjahn and J. V. Ravetch, “The antiinflammatory activity of IgG: the intravenous IgG paradox,” Journal of Experimental Medicine, vol. 204, no. 1, pp. 11–15, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. R. M. Anthony and J. V. Ravetch, “A novel role for the IgG Fc glycan: the anti-inflammatory activity of sialylated IgG Fcs,” Journal of Clinical Immunology, vol. 30, no. 1, supplement 1, pp. S9–S14, 2010. View at Publisher · View at Google Scholar · View at Scopus
  43. S. C. Jordan, A. Vo, S. Bunnapradist et al., “Intravenous immune globulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients,” Transplantation, vol. 76, no. 4, pp. 631–636, 2003. View at Publisher · View at Google Scholar · View at Scopus
  44. P. P. W. Luke, V. P. Scantlebury, M. L. Jordan et al., “IVIG rescue therapy in renal transplantation,” Transplantation Proceedings, vol. 33, no. 1-2, pp. 1093–1094, 2001. View at Publisher · View at Google Scholar · View at Scopus
  45. M. H. Levine and P. L. Abt, “Treatmentoptions and strategies for antibody mediated rejection after renal transplantation,” Seminars in Immunology. In press.
  46. R. A. Montgomery, A. A. Zachary, L. C. Racusen et al., “Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients,” Transplantation, vol. 70, no. 6, pp. 887–895, 2000. View at Scopus
  47. P. N. Rocha, D. W. Butterly, A. Greenberg et al., “Beneficial effect of plasmapheresis and intravenous immunoglobulin on renal allograft survival of patients with acute humoral rejection,” Transplantation, vol. 75, no. 9, pp. 1490–1495, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. C. Okafor, D. M. Ward, M. H. Mokrzycki, R. Weinstein, P. Clark, and R. A. Balogun, “Introduction and overview of therapeutic apheresis,” Journal of Clinical Apheresis, vol. 25, no. 5, pp. 240–249, 2010. View at Publisher · View at Google Scholar
  49. G. A. Böhmig, M. Wahrmann, H. Regele et al., “Immunoadsorption in severe C4d-positive acute kidney allograft rejection: a randomized controlled trial,” American Journal of Transplantation, vol. 7, no. 1, pp. 117–121, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. Y. T. Becker, B. N. Becker, J. D. Pirsch, and H. W. Sollinger, “Rituximab as treatment for refractory kidney transplant rejection,” American Journal of Transplantation, vol. 4, no. 6, pp. 996–1001, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Faguer, N. Kamar, C. Guilbeaud-Frugier et al., “Rituximab therapy for acute humoral rejection after kidney transplantation,” Transplantation, vol. 83, no. 9, pp. 1277–1280, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. Z. Kaposztas, H. Podder, S. Mauiyyedi et al., “Impact of rituximab therapy for treatment of acute humoral rejection,” Clinical Transplantation, vol. 23, no. 1, pp. 63–73, 2009. View at Publisher · View at Google Scholar · View at Scopus
  53. C. Lefaucheur, D. Nochy, J. Andrade et al., “Comparison of combination plasmapheresis/IVIg/Anti-CD20 versus high-dose ivig in the treatment of antibody-mediated rejection,” American Journal of Transplantation, vol. 9, no. 5, pp. 1099–1107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. RITUXAN_ (RITUXIMAB): highlights of prescription information, Genentech, Inc., 1DNA way, South San Francisco, Calif, USA.
  55. B. Sadaka, R. R. Alloway, and E. S. Woodle, “Clinical and investigational use of proteasome inhibitors for transplant rejection,” Expert Opinion on Investigational Drugs, vol. 20, no. 11, pp. 1535–1542, 2011. View at Publisher · View at Google Scholar
  56. M. J. Everly, J. J. Everly, B. Susskind et al., “Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection,” Transplantation, vol. 86, no. 12, pp. 1754–1761, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. H. L. Trivedi, P. I. Terasaki, A. Feroz et al., “Abrogation of Anti-HLA antibodies via proteasome inhibition,” Transplantation, vol. 87, no. 10, pp. 1555–1561, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. R. C. Walsh, J. J. Everly, P. Brailey et al., “Proteasome inhibitor-based primary therapy for antibody-mediated renal allograft rejection,” Transplantation, vol. 89, no. 3, pp. 277–284, 2010. View at Publisher · View at Google Scholar · View at Scopus
  59. B. E. Lonze, N. N. Dagher, C. E. Simpkins et al., “The fate of anti-HLA antibody among renal transplantation recipients treated with bortezomib,” Clinical Transplants, pp. 377–384, 2009. View at Scopus
  60. W. Manitpisitkul, N. Wilson, M. Cooper et al., “Rescue therapy for early antibody mediated rejection with a proteasome inhibitor: a case report,” Clinical Transplants, pp. 461–463, 2009. View at Scopus
  61. D. K. Perry, J. M. Burns, H. S. Pollinger et al., “Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production,” American Journal of Transplantation, vol. 9, no. 1, pp. 201–209, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Wahrmann, M. Haidinger, G. F. Körmöczi et al., “Effect of the proteasome inhibitor bortezomib on humoral immunity in two presensitized renal transplant candidates,” Transplantation, vol. 89, no. 11, pp. 1385–1390, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. M. J. Everly, “An update on antibody reduction and rejection reversal following bortezomib use: a report of 52 cases across 10 centers,” Clinical transplants, pp. 353–362, 2010.
  64. R. Sberro-Soussan, J. Zuber, C. Suberbielle-Boissel et al., “Bortezomib as the sole post-renal transplantation desensitization agent does not decrease donor-specific anti-HLA antibodies,” American Journal of Transplantation, vol. 10, no. 3, pp. 681–686, 2010. View at Publisher · View at Google Scholar · View at Scopus
  65. J. E. Locke, C. M. Magro, A. L. Singer et al., “The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection,” American Journal of Transplantation, vol. 9, no. 1, pp. 231–235, 2009. View at Publisher · View at Google Scholar · View at Scopus
  66. M. D. Stegall, T. Diwan, S. Raghavaiah, et al., “Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients,” American Journal of Transplantation, vol. 11, no. 11, pp. 2405–2413, 2011. View at Publisher · View at Google Scholar
  67. B. Kaplan, A. Gangemi, J. Thielke, J. Oberholzer, H. Sankary, and E. Benedetti, “Successful rescue of refractory, severe antibody mediated rejection with splenectomy,” Transplantation, vol. 83, no. 1, pp. 99–100, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. J. E. Locke, A. A. Zachary, M. Haas et al., “The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection,” American Journal of Transplantation, vol. 7, no. 4, pp. 842–846, 2007. View at Publisher · View at Google Scholar · View at Scopus
  69. V. Nickeleit, M. Zeiler, F. Gudat, G. Thiel, and M. J. Mihatsch, “Detection of the complement degradation product C4d in renal allografts: diagnostic and therapeutic implications,” Journal of the American Society of Nephrology, vol. 13, no. 1, pp. 242–251, 2002. View at Scopus
  70. S. R. Lederer, B. Kluth-Pepper, H. Schneeberger, E. Albert, W. Land, and H. E. Feucht, “Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts,” Kidney International, vol. 59, no. 1, pp. 334–341, 2001. View at Publisher · View at Google Scholar · View at Scopus
  71. R. D. Poduval, P. V. Kadambi, M. A. Josephson et al., “Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection,” Transplantation, vol. 79, no. 2, pp. 228–235, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. M. Haas, “The significance of C4d staining with minimal histologic abnormalities,” Current Opinion in Organ Transplantation, vol. 15, no. 1, pp. 21–27, 2010. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Haas, M. H. Rahman, L. C. Racusen et al., “C4d and C3d staining in biopsies of ABO- and HLA-Incompatible renal allografts: correlation with histologic findings,” American Journal of Transplantation, vol. 6, no. 8, pp. 1829–1840, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. K. Setoguchi, H. Ishida, H. Shimmura et al., “Analysis of renal transplant protocol biopsies in ABO-incompatible kidney transplantation,” American Journal of Transplantation, vol. 8, no. 1, pp. 86–94, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Dickenmann, J. Steiger, B. Descœudres, M. Mihatsch, and V. Nickeleit, “The fate of C4d positive kidney allografts lacking histological signs of acute rejection,” Clinical Nephrology, vol. 65, no. 3, pp. 173–179, 2006. View at Scopus
  76. R. L. Kedainis, M. J. Koch, D. C. Brennan, and H. Liapis, “Focal C4d+ in renal allografts is associated with the presence of donor-specific antibodies and decreased allograft survival,” American Journal of Transplantation, vol. 9, no. 4, pp. 812–819, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. R. A. Montgomery, B. E. Lonze, K. E. King et al., “Desensitization in HLA-incompatible kidney recipients and survival,” New England Journal of Medicine, vol. 365, no. 4, pp. 318–326, 2011. View at Publisher · View at Google Scholar
  78. F. L. Delmonico, P. E. Morrissey, G. S. Lipkowitz et al., “Donor kidney exchanges,” American Journal of Transplantation, vol. 4, no. 10, pp. 1628–1634, 2004. View at Publisher · View at Google Scholar · View at Scopus