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Clinical and Developmental Immunology
Volume 2013, Article ID 678180, 8 pages
http://dx.doi.org/10.1155/2013/678180
Review Article

The Importance of C4d in Biopsies of Kidney Transplant Recipients

1Discipline of General Pathology, Nephropathology Service, Federal University of Triângulo Mineiro, Frei Paulino, 30, 38025-180 Uberaba, Brazil
2Discipline of Immunology, Federal University of Triângulo Mineiro, Frei Paulino, 30, 38025-180 Uberaba, Brazil
3Discipline of Cell Biology, Federal University of Triângulo Mineiro, Frei Paulino, 30, 38025-180 Uberaba, Brazil

Received 31 January 2013; Revised 15 May 2013; Accepted 23 June 2013

Academic Editor: Aron Chakera

Copyright © 2013 Rosana Rosa Miranda Corrêa 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. B. J. Nankivell and S. I. Alexander, “Rejection of the kidney allograft,” The New England Journal of Medicine, vol. 363, no. 15, pp. 1451–1462, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. M. Mengel, B. Sis, M. Haas et al., “Banff 2011 meeting report: new concepts in antibody-mediated rejection,” The American Journal of Transplantation, vol. 12, no. 3, pp. 563–570, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. G. Einecke, B. Sis, J. Reeve et al., “Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure,” The American Journal of Transplantation, vol. 9, no. 11, pp. 2520–2531, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. R. S. Gaston, J. M. Cecka, B. L. Kasiske et al., “Evidence for antibody-mediated injury as a major determinant of late kidney allograft failure,” Transplantation, vol. 90, no. 1, pp. 68–74, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. V. López-Jiménez, L. Fuentes, T. Jiménez et al., “Transplant glomerulopathy: clinical course and factors relating to graft survival,” Transplantation Proceedings, vol. 44, no. 9, pp. 2599–2600, 2012. View at Publisher · View at Google Scholar
  6. J. G. Lucas, J. P. Co, U. T. Nwaogwugwu, I. Dosani, and K. K. Sureshkumar, “Antibody-mediated rejection in kidney transplantation: an update,” Expert Opinion on Pharmacotherapy, vol. 12, no. 4, pp. 579–592, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. C. Puttarajappa, R. Shapiro, and H. P. Tan, “Antibody-mediated rejection in kidney transplantation: a review,” Journal of Transplantation, vol. 2012, Article ID 193724, 9 pages, 2012. View at Publisher · View at Google Scholar
  8. D. Cohen, R. B. Colvin, M. R. Daha et al., “Pros and cons for C4d as a biomarker,” Kidney International, vol. 81, no. 7, pp. 628–639, 2012. View at Publisher · View at Google Scholar · View at Scopus
  9. L. C. Racusen, R. B. Colvin, K. Solez et al., “Antibody-mediated rejection criteria—an addition to the Banff '97 classification of renal allograft rejection,” The American Journal of Transplantation, vol. 3, no. 6, pp. 708–714, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. 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,” The American Journal of Transplantation, vol. 9, no. 10, pp. 2312–2323, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. B. Sis and P. F. Halloran, “Endothelial transcripts uncover a previously unknown phenotype: C4d-negative antibody-mediated rejection,” Current Opinion in Organ Transplantation, vol. 15, no. 1, pp. 42–48, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. 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 Google Scholar · View at Scopus
  13. S. K. Takemoto, A. Zeevi, S. Feng et al., “National conference to assess antibody-mediated rejection in solid organ transplantation,” The American Journal of Transplantation, vol. 4, no. 7, pp. 1033–1041, 2004. View at Publisher · View at Google Scholar · View at Scopus
  14. 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
  15. D. Noone, J. Al-Matrafi, K. Tinckam et al., “Antibody mediated rejection associated with complement factor h-related protein 3/1 deficiency successfully treated with eculizumab,” The American Journal of Transplantation, vol. 12, no. 9, pp. 2546–2553, 2012. View at Publisher · View at Google Scholar
  16. 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, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. J. A. N. Klein and A. Sato, “The HLA system: first of two parts,” The New England Journal of Medicine, vol. 343, no. 10, pp. 702–709, 2000. View at Publisher · View at Google Scholar · View at Scopus
  18. 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
  19. 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,” The American Journal of Transplantation, vol. 9, no. 1, pp. 231–235, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. M. D. Stegall, M. F. Chedid, and L. D. Cornell, “The role of complement in antibody-mediated rejection in kidney transplantation,” Nature Reviews Nephrology, vol. 8, no. 11, pp. 670–678, 2012. View at Google Scholar
  21. K. Keven, S. Sengul, Z. K. Celebi et al., “Kidney transplantation in immunologically high-risk patients,” Transplantation Proceedings, vol. 45, no. 3, pp. 919–922, 2013. View at Publisher · View at Google Scholar
  22. A. Bosch, S. Llorente, J. A. Diaz et al., “Low median fluorescence intensity could be a nonsafety concept of immunologic risk evaluation in patients with shared molecular eplets in kidney transplantation,” Human Immunology, vol. 73, no. 5, pp. 522–525, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. P. D. de Menezes Neves, J. R. Machado, M. A. dos Reis, A. C. Faleiros, S. A. de Lima Pereira, and D. B. Rodrigues, “Distinct expression of interleukin 17, tumor necrosis factor α, transforming growth factor β, and forkhead box P3 in acute rejection after kidney transplantation,” Annals of Diagnostic Pathology, vol. 17, no. 1, pp. 75–79, 2013. View at Publisher · View at Google Scholar
  24. S. V. Petersen, S. Thiel, L. Jensen, R. Steffensen, and J. C. Jensenius, “An assay for the mannan-binding lectin pathway of complement activation,” Journal of Immunological Methods, vol. 257, no. 1-2, pp. 107–116, 2001. View at Publisher · View at Google Scholar · View at Scopus
  25. S. Thiel, T. Vorup-Jensen, C. M. Stover et al., “A second serine protease associated with mannan-binding lectin that activates complement,” Nature, vol. 386, no. 6624, pp. 506–510, 1997. View at Publisher · View at Google Scholar · View at Scopus
  26. L. G. Hidalgo, J. Sellares, B. Sis, M. Mengel, J. Chang, and P. F. Halloran, “Interpreting NK cell transcripts versus T cell transcripts in renal transplant biopsies,” The American Journal of Transplantation, vol. 12, no. 5, pp. 1180–1191, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. J. M. Gloor, S. Sethi, M. D. Stegall et al., “Transplant glomerulopathy: subclinical incidence and association with alloantibody,” The American Journal of Transplantation, vol. 7, no. 9, pp. 2124–2132, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. 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
  29. J. Sellarés, D. G. de Freitas, M. Mengel et al., “Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence,” The American Journal of Transplantation, vol. 12, no. 2, pp. 388–399, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. L. C. Racusen, K. Solez, R. B. Colvin et al., “The Banff 97 working classification of renal allograft pathology,” Kidney International, vol. 55, no. 2, pp. 713–723, 1999. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Vongwiwatanaa, S. Gourishankara, P. M. Campbella, K. Solez, and P. F. Hallorana, “Peritubular capillary changes and C4d deposits are associated with transplant glomerulopathy but not IgA nephropathy,” The American Journal of Transplantation, vol. 4, no. 1, pp. 124–129, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. J. M. Gloor, F. G. Cosio, D. J. Rea et al., “Histologic findings one year after positive crossmatch or ABO blood group incompatible living donor kidney transplantation,” The American Journal of Transplantation, vol. 6, no. 8, pp. 1841–1847, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. F. G. Cosio, J. P. Grande, H. Wadei, T. S. Larson, M. D. Griffin, and M. D. Stegall, “Predicting subsequent decline in kidney allograft function from early surveillance biopsies,” The American Journal of Transplantation, vol. 5, no. 10, pp. 2464–2472, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Habib and M. Broyer, “Clinical significance of allograft glomerulopathy,” Kidney International, Supplement, vol. 43, pp. S95–S98, 1993. View at Google Scholar · View at Scopus
  35. R. Habib, A. Zurowska, N. Hinglais et al., “A specific glomerular lesion of the graft: allograft glomerulopathy,” Kidney International, Supplement, vol. 42, pp. S104–S111, 1993. View at Google Scholar · View at Scopus
  36. J. Gough, A. Yilmaz, D. Miskulin et al., “Peritubular capillary basement membrane reduplication in allografts and native kidney disease,” Transplantation, vol. 71, no. 10, pp. 1390–1393, 2001. View at Google Scholar · View at Scopus
  37. M. D. Wavamunno, P. J. O'Connell, M. Vitalone et al., “Transplant glomerulopathy: ultrastructural abnormalities occur early in longitudinal analysis of protocol biopsies,” The American Journal of Transplantation, vol. 7, no. 12, pp. 2757–2768, 2007. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Haas and J. Mirocha, “Early ultrastructural changes in renal allografts: correlation with antibody-mediated rejection and transplant glomerulopathy,” The American Journal of Transplantation, vol. 11, no. 10, pp. 2123–2131, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. P. Lipták, E. Kemény, Z. Morvay et al., “Peritubular capillary damage in acute humoral rejection: an ultrastructural study on human renal allografts,” The American Journal of Transplantation, vol. 5, no. 12, pp. 2870–2876, 2005. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Haas, “C4d-negative antibody-mediated rejection in renal allografts: evidence for its existence and effect on graft survival,” Clinical Nephrology, vol. 75, no. 4, pp. 271–278, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. H. E. Feucht, “Complement C4d in graft capillaries—the missing link in the recognition of humoral alloreactivity,” The American Journal of Transplantation, vol. 3, no. 6, pp. 646–652, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Husain and B. Sis, “Advances in the understanding of transplant glomerulopathy,” The American Journal of Kidney Diseases, 2013. View at Publisher · View at Google Scholar
  43. F. G. Cosio, J. M. Gloor, S. Sethi, and M. D. Stegall, “Transplant glomerulopathy,” The American Journal of Transplantation, vol. 8, no. 3, pp. 492–496, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. G. Canaud, V. Audard, T. Kofman, P. Lang, C. Legendre, and P. Grimbert, “Recurrence from primary and secondary glomerulopathy after renal transplant,” Transplant International, vol. 25, no. 8, pp. 812–824, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. 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
  46. P. Hirt-Minkowski, S. Schaub, M. Mayr et al., “Haemolytic uraemic syndrome caused by factor H mutation: is single kidney transplantation under intensive plasmatherapy an option,” Nephrology Dialysis Transplantation, vol. 24, no. 11, pp. 3548–3551, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. D. K. de Vries, A. F. Schaapherder, and M. E. Reinders, “Mesenchymal stromal cells in renal ischemia/reperfusion injury,” Frontiers in Immunology, vol. 3, article 162, 2012. View at Google Scholar
  48. V. Roberts, B. Lu, S. Rajakumar, P. J. Cowan, and K. M. Dwyer, “The CD39-adenosinergic axis in the pathogenesis of renal ischemia-reperfusion injury,” Purinergic Signalling, vol. 9, no. 2, pp. 135–143, 2013. View at Publisher · View at Google Scholar
  49. J. T. Powell, D. S. Tsapepas, S. T. Martin, M. A. Hardy, and L. E. Ratner, “Managing renal transplant ischemia reperfusion injury: novel therapies in the pipeline,” Clinical Transplantation, 2013. View at Publisher · View at Google Scholar
  50. C. A. Farrar, E. Asgari, W. J. Schwaeble, and S. H. Sacks, “Which pathways trigger the role of complement in ischaemia/reperfusion injury?” Frontiers in Immunology, vol. 3, article 341, 2012. View at Google Scholar
  51. M. J. Walport, “Advances in immunology: complement (first of two parts),” The New England Journal of Medicine, vol. 344, no. 14, pp. 1058–1066, 2001. View at Publisher · View at Google Scholar · View at Scopus
  52. M. J. Walport, “Advances in immunology: complement (second of two parts),” The New England Journal of Medicine, vol. 344, no. 15, pp. 1140–1144, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. W. E. Paul, Fundamental Immunology, Wolters Kluwer/Lippincott Williams & Wilkins, 2008.
  54. P. F. Zipfel and C. Skerka, “Complement regulators and inhibitory proteins,” Nature Reviews Immunology, vol. 9, no. 10, pp. 729–740, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. C. A. Ogden and K. B. Elkon, “Role of complement and other innate immune mechanisms in the removal of apoptotic cells,” Current Directions in Autoimmunity, vol. 9, pp. 120–142, 2006. View at Google Scholar · View at Scopus
  56. D. Ricklin, G. Hajishengallis, K. Yang, and J. D. Lambris, “Complement: a key system for immune surveillance and homeostasis,” Nature Immunology, vol. 11, no. 9, pp. 785–797, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. C. W. Strey, M. Markiewski, D. Mastellos et al., “The proinflammatory mediators C3a and C5a are essential for liver regeneration,” Journal of Experimental Medicine, vol. 198, no. 6, pp. 913–923, 2003. View at Publisher · View at Google Scholar · View at Scopus
  58. P. Mukherjee, S. Thomas, and G. M. Pasinetti, “Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo,” Journal of Neuroinflammation, vol. 5, article 5, 2008. View at Publisher · View at Google Scholar · View at Scopus
  59. M. K. Pangburn and H. J. Muller-Eberhard, “The alternative pathway of complement,” Springer Seminars in Immunopathology, vol. 7, no. 2-3, pp. 163–192, 1984. View at Google Scholar · View at Scopus
  60. Z. Fishelson, M. K. Pangburn, and H. J. Muller-Eberhard, “Characterization of the initial C3 convertase of the alternative pathway of human complement,” Journal of Immunology, vol. 132, no. 3, pp. 1430–1434, 1984. View at Google Scholar · View at Scopus
  61. I. Ohsawa, H. Ohi, M. Endo, T. Fujita, M. Matsushita, and T. Fujita, “Evidence of lectin complement pathway activation in poststreptococcal glomerulonephritis,” Kidney International, vol. 56, no. 3, pp. 1158–1159, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Takahashi, Y. Endo, T. Fujita, and M. Matsushita, “A truncated form of mannose-binding lectin-associated serine protease (MASP)-2 expressed by alternative polyadenylation is a component of the lectin complement pathway,” International Immunology, vol. 11, no. 5, pp. 859–863, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. C. D. Collard, A. Vakeva, M. A. Morrissey et al., “Complement activation after oxidative stress: role of the lectin complement pathway,” The American Journal of Pathology, vol. 156, no. 5, pp. 1549–1556, 2000. View at Google Scholar · View at Scopus
  64. M. Matsushita, Y. Endo, N. Hamasaki, and T. Fujita, “Activation of the lectin complement pathway by ficolins,” International Immunopharmacology, vol. 1, no. 3, pp. 359–363, 2001. View at Publisher · View at Google Scholar · View at Scopus
  65. T. Fujita, M. Matsushita, and Y. Endo, “The lectin-complement pathway—its role in innate immunity and evolution,” Immunological Reviews, vol. 198, pp. 185–202, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. L. Marnell, C. Mold, and T. W. Du Clos, “C-reactive protein: ligands, receptors and role in inflammation,” Clinical Immunology, vol. 117, no. 2, pp. 104–111, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. J. E. Volanakis, “Human C-reactive protein: expression, structure, and function,” Molecular Immunology, vol. 38, no. 2-3, pp. 189–197, 2001. View at Publisher · View at Google Scholar · View at Scopus
  68. T. C. Farries and J. P. Atkinson, “Evolution of the complement system,” Immunology Today, vol. 12, no. 9, pp. 295–300, 1991. View at Google Scholar · View at Scopus
  69. C. Gaboriaud, N. M. Thielens, L. A. Gregory, V. Rossi, J. C. Fontecilla-Camps, and G. J. Arlaud, “Structure and activation of the C1 complex of complement: unraveling the puzzle,” Trends in Immunology, vol. 25, no. 7, pp. 368–373, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. U. Amara, D. Rittirsch, M. Flierl et al., “Interaction between the coagulation and complement system,” Advances in Experimental Medicine and Biology, vol. 632, pp. 71–79, 2008. View at Google Scholar · View at Scopus
  71. M. Huber-Lang, J. V. Sarma, F. S. Zetoune et al., “Generation of C5a in the absence of C3: a new complement activation pathway,” Nature Medicine, vol. 12, no. 6, pp. 682–687, 2006. View at Publisher · View at Google Scholar · View at Scopus
  72. A. P. Sjöberg, L. A. Trouw, and A. M. Blom, “Complement activation and inhibition: a delicate balance,” Trends in Immunology, vol. 30, no. 2, pp. 83–90, 2009. View at Publisher · View at Google Scholar · View at Scopus
  73. F. Forneris, J. Wu, and P. Gros, “The modular serine proteases of the complement cascade,” Current Opinion in Structural Biology, vol. 22, no. 3, pp. 333–341, 2012. View at Publisher · View at Google Scholar
  74. M. W. Ollert, J. V. Kadlec, K. David, E. C. Petrella, R. Bredehorst, and C. Vogel, “Antibody-mediated complement activation on nucleated cells: a quantitative analysis of the individual reaction steps,” Journal of Immunology, vol. 153, no. 5, pp. 2213–2221, 1994. View at Google Scholar · View at Scopus
  75. K. Murata and W. M. Baldwin III, “Mechanisms of complement activation, C4d deposition, and their contribution to the pathogenesis of antibody-mediated rejection,” Transplantation Reviews, vol. 23, no. 3, pp. 139–150, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. S. C. Nilsson, R. B. Sim, S. M. Lea, V. Fremeaux-Bacchi, and A. M. Blom, “Complement factor I in health and disease,” Molecular Immunology, vol. 48, no. 14, pp. 1611–1620, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Takeda, Y. Otsuka, K. Horike et al., “Significance of C4d deposition in antibody-mediated rejection,” Clinical Transplantation, vol. 26, supplement 24, pp. 43–48, 2012. View at Publisher · View at Google Scholar
  78. G. A. Böhmig, G. Bartel, and M. Wahrmann, “Antibodies, isotypes and complement in allograft rejection,” Current Opinion in Organ Transplantation, vol. 13, no. 4, pp. 411–418, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. V. Nickeleit and M. J. Mihatsch, “Kidney transplants, antibodies and rejection: is C4d a magic marker?” Nephrology Dialysis Transplantation, vol. 18, no. 11, pp. 2232–2239, 2003. View at Publisher · View at Google Scholar · View at Scopus
  80. 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
  81. A. M. Herzenberg, J. S. Gill, O. Djurdjev, and A. B. Magil, “C4d deposition in acute rejection: an independent long-term prognostic factor,” Journal of the American Society of Nephrology, vol. 13, no. 1, pp. 234–241, 2002. View at Google Scholar · View at Scopus
  82. H. E. Feucht, H. Schneeberger, G. Hillebrand et al., “Capillary deposition of C4d complement fragment and early renal graft loss,” Kidney International, vol. 43, no. 6, pp. 1333–1338, 1993. View at Google Scholar · View at Scopus
  83. E. Morelon, J. Kanitakis, and P. Petruzzo, “Immunological issues in clinical composite tissue allotransplantation: where do we stand today?” Transplantation, vol. 93, no. 9, pp. 855–859, 2012. View at Publisher · View at Google Scholar
  84. S. Mauiyyedi, P. D. 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 Google Scholar · View at Scopus
  85. 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
  86. 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
  87. M. Miura, Y. Ogawa, K. C. Kubota et al., “Donor-specific antibody in chronic rejection is associated with glomerulopathy, thickening of peritubular capillary basement membrane, but not C4d deposition,” Clinical Transplantation, vol. 21, no. 18, pp. 8–12, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. 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,” The American Journal of Transplantation, vol. 7, no. 7, pp. 1743–1752, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. 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),” The American Journal of Transplantation, vol. 11, no. 1, pp. 56–65, 2011. View at Publisher · View at Google Scholar · View at Scopus
  90. 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
  91. 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
  92. S. M. Meehan, J. Kremer, F. N. Ali et al., “Thrombotic microangiopathy and peritubular capillary C4d expression in renal allograft biopsies,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 2, pp. 395–403, 2011. View at Publisher · View at Google Scholar · View at Scopus
  93. R. P. Rother, S. A. Rollins, C. F. Mojcik, R. A. Brodsky, and L. Bell, “Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria,” Nature Biotechnology, vol. 25, no. 11, pp. 1256–1264, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. M. D. Stegall, T. Diwan, S. Raghavaiah et al., “Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients,” The American Journal of Transplantation, vol. 11, no. 11, pp. 2405–2413, 2011. View at Publisher · View at Google Scholar · View at Scopus