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Advances in diagnosing and managing antibody-mediated rejection

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Abstract

Antibody-mediated rejection (AMR) is a unique, significant, and often severe form of allograft rejection that is not amenable to treatment with standard immunosuppressive medications. Significant advances have occurred in our ability to predict patients at risk for, and to diagnose, AMR. These advances include the development of newer anti-human leukocyte antigen (HLA)-antibody detection techniques and assays for non-HLA antibodies associated with AMR. The pathophysiology of AMR suggests a prime role for antibodies, B cells and plasma cells, but other effector molecules, especially the complement system, point to potential targets that could modify the AMR process. An emerging and potentially larger problem is the development of chronic AMR (CAMR) resulting from de novo donor-specific anti-HLA antibodies (DSA) that emerge more than 100 days posttransplantation. Therapeutic options include: (1) High-dose intravenously administered immunoglobulin (IVIG), which has many potential benefits. (2) The use of IVIG + rituximab (anti-CD20, anti-B cell). (3) The combination of plasmapheresis (PP) + low-dose IVIG with or without rituximab. Data support the efficacy of all of the above approaches. Newer approaches to treating AMR include using the proteosome inhibitor (bortezomib), which induces apoptosis in plasma cells, and eculizumab (anti-C5, anticomplement monoclonal antibody).

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References

  1. Evans RW, Manninen DL, Garrison LP Jr, Hart LG, Blagg CR, Gutman RA, Hull AR, Lowrie EG (1985) The quality of life of patients with end-stage renal disease. N Engl J Med 312:553–559

    Article  PubMed  CAS  Google Scholar 

  2. Port FK, Wolfe RA, Mauger EA, Berling DP, Jiang K (1993) Comparison of survival probabilities for dialysis patients vs cadaveric renal transplant recipients. JAMA 270:1339–1343

    Article  PubMed  CAS  Google Scholar 

  3. Russell JD, Beecroft ML, Ludwin D, Churchill DN (1992) The quality of life in renal transplantation–a prospective study. Transplantation 54:656–660

    Article  PubMed  CAS  Google Scholar 

  4. Organ Procurement Transplantation Network/Scientific Registry of Transplant Recipients: OPTN. (2009); http://www.optn.org/data/

  5. United Network for Organ Sharing Data Base as of 5/30/2008. http://www.unos.org

  6. Jordan SC, Tyan D, Stablein D, McIntosh M, Rose S, Vo A, Toyoda M, Davis C, Shapiro R, Adey D, Milliner D, Graff R, Steiner R, Ciancio G, Sahney S, Light J (2004) Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: report of the NIH IG02 trial. J Am Soc Nephrol 15:3256–3262

    Article  PubMed  Google Scholar 

  7. Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC (2008) Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med 359:242–251

    Article  PubMed  CAS  Google Scholar 

  8. Montgomery RA, Locke JE, King KE, Segev DL, Warren DS, Kraus ES, Cooper M, Simpkins CE, Singer AL, Stewart ZA, Melancon JK, Ratner L, Zachary AA, Haas M (2009) ABO incompatible renal transplantation: a paradigm ready for broad implementation. Transplantation 87:1246–1255

    Article  PubMed  Google Scholar 

  9. Gloor JM, DeGoey SR, Pineda AA, Moore SB, Prieto M, Nyberg SL, Larson TS, Griffin MD, Textor SC, Velosa JA, Schwab TR, Fix LA, Stegall MD (2003) Overcoming a positive crossmatch in living-donor kidney transplantation. Am J Transplant 3:1017–1023

    Article  PubMed  Google Scholar 

  10. Montgomery RA, Cooper M, Kraus E, Rabb H, Samaniego M, Simpkins CE, Sonnenday CJ, Ugarte RM, Warren DS, Zachary AA (2003) Renal transplantation at the Johns Hopkins Comprehensive Transplant Center. Clin Transpl: 199–213

  11. Jordan SC, Pescovitz MD (2006) Presensitization: the problem and its management. Clin J Am Soc Nephrol 1:421–432

    Article  PubMed  CAS  Google Scholar 

  12. Glotz D, Antoine C, Julia P, Pegaz-Fiornet B, Duboust A, Boudjeltia S, Fraoui R, Combes M, Bariety J (2004) Intravenous immunoglobulins and transplantation for patients with anti-HLA antibodies. Transpl Int 17:1–8

    Article  PubMed  CAS  Google Scholar 

  13. Schweitzer EJ, Wilson JS, Fernandez-Vina M, Fox M, Gutierrez M, Wiland A, Hunter J, Farney A, Philosophe B, Colonna J, Jarrell BE, Bartlett ST (2000) A high panel-reactive antibody rescue protocol for cross-match-positive live donor kidney transplants. Transplantation 70:1531–1536

    Article  PubMed  CAS  Google Scholar 

  14. Jordan SC, Vo AA, Tyan D, Nast CC, Toyoda M (2005) Current approaches to treatment of antibody-mediated rejection. Pediatr Transplant 9:408–415

    Article  PubMed  CAS  Google Scholar 

  15. Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M, Halloran PF, Baldwin W, Banfi G, Collins AB, Cosio F, David DS, Drachenberg C, Einecke G, Fogo AB, Gibson IW, Glotz D, Iskandar SS, Kraus E, Lerut E, Mannon RB, Mihatsch M, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Roberts I, Seron D, Smith RN, Valente M (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 8:753–760

    Article  PubMed  CAS  Google Scholar 

  16. Everly MJ, Everly JJ, Arend LJ, Brailey P, Susskind B, Govil A, Rike A, Roy-Chaudhury P, Mogilishetty G, Alloway RR, Tevar A, Woodle ES (2009) Reducing de novo donor-specific antibody levels during acute rejection diminishes renal allograft loss. Am J Transplant 9:1063–1071

    Article  PubMed  CAS  Google Scholar 

  17. Singh N, Pirsch J, Samaniego M (2009) Antibody-mediated rejection: treatment alternatives and outcomes. Transplant Rev (Orlando) 23:34–46

    Google Scholar 

  18. Lefaucheur C, Suberbielle-Boissel C, Hill GS, Nochy D, Andrade J, Antoine C, Gautreau C, Charron D, Glotz D (2008) Clinical relevance of preformed HLA donor-specific antibodies in kidney transplantation. Am J Transplant 8:324–331

    Article  PubMed  CAS  Google Scholar 

  19. Reinsmoen NL, Lai CH, Vo A, Cao K, Ong G, Naim M, Wang Q, Jordan SC (2008) Acceptable donor-specific antibody levels allowing for successful deceased and living donor kidney transplantation after desensitization therapy. Transplantation 86:820–825

    Article  PubMed  CAS  Google Scholar 

  20. Bray RA, Nickerson PW, Kerman RH, Gebel HM (2004) Evolution of HLA antibody detection: technology emulating biology. Immunol Res 29:41–54

    Article  PubMed  CAS  Google Scholar 

  21. Scornik JC, Clapp W, Patton PR, Van der Werf WJ, Hemming AW, Reed AI, Howard RJ (2001) Outcome of kidney transplants in patients known to be flow cytometry crossmatch positive. Transplantation 71:1098–1102

    Article  PubMed  CAS  Google Scholar 

  22. Wen R, Wu V, Dmitrienko S, Yu A, Balshaw R, Keown PA (2006) Biomarkers in transplantation: Prospective, blinded measurement of predictive value for the flow cytometry crossmatch after negative antiglobulin crossmatch in kidney transplantation. Kidney Int 70:1474–1481

    Article  PubMed  CAS  Google Scholar 

  23. Vasilescu ER, Ho EK, Colovai AI, Vlad G, Foca-Rodi A, Markowitz GS, D'Agati V, Hardy MA, Ratner LE, Suciu-Foca N (2006) Alloantibodies and the outcome of cadaver kidney allografts. Hum Immunol 67:597–604

    Article  PubMed  CAS  Google Scholar 

  24. Zachary AA, Montgomery RA, Leffell MS (2005) Factors associated with and predictive of persistence of donor-specific antibody after treatment with plasmapheresis and intravenous immunoglobulin. Hum Immunol 66:364–370

    Article  PubMed  CAS  Google Scholar 

  25. Fredrich R, Toyoda M, Czer LS, Galfayan K, Galera O, Trento A, Freimark D, Young S, Jordan SC (1999) The clinical significance of antibodies to human vascular endothelial cells after cardiac transplantation. Transplantation 67:385–391

    Article  PubMed  CAS  Google Scholar 

  26. Toyoda M, Petrosian A, Jordan SC (1999) Immunological characterization of anti-endothelial cell antibodies induced by cytomegalovirus infection. Transplantation 68:1311–1318

    Article  PubMed  CAS  Google Scholar 

  27. Dragun D, Hegner B (2009) Non-HLA antibodies post-transplantation: clinical relevance and treatment in solid organ transplantation. Contrib Nephrol 162:129–139

    Article  PubMed  Google Scholar 

  28. Breimer ME, Rydberg L, Jackson AM, Lucas DP, Zachary AA, Melancon JK, Von Visger J, Pelletier R, Saidman SL, Williams WW Jr, Holgersson J, Tyden G, Klintmalm GK, Coultrup S, Sumitran-Holgersson S, Grufman P (2009) Multicenter evaluation of a novel endothelial cell crossmatch test in kidney transplantation. Transplantation 87:549–556

    Article  PubMed  CAS  Google Scholar 

  29. Grandtnerova B, Mackova N, Hovoricova B, Jahnova E (2008) Hyperacute rejection of living related kidney grafts caused by endothelial cell-specific antibodies: case reports. Transplant Proc 40:2422–2424

    Article  PubMed  CAS  Google Scholar 

  30. Stastny P, Zou Y, Fan Y, Qin Z, Lavingia B (2009) The emerging issue of MICA antibodies: antibodies to MICA and other antigens of endothelial cells. Contrib Nephrol 162:99–106

    Article  PubMed  Google Scholar 

  31. Zou Y, Stastny P, Susal C, Dohler B, Opelz G (2007) Antibodies against MICA antigens and kidney-transplant rejection. N Engl J Med 357:1293–1300

    Article  PubMed  CAS  Google Scholar 

  32. Jordan SC, Toyoda M, Vo AA (2009) Intravenous immunoglobulin a natural regulator of immunity and inflammation. Transplantation 88:1–6

    Article  PubMed  CAS  Google Scholar 

  33. Nimmerjahn F, Ravetch JV (2008) Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 26:513–533

    Article  PubMed  CAS  Google Scholar 

  34. Tha-In T, Bayry J, Metselaar HJ, Kaveri SV, Kwekkeboom J (2008) Modulation of the cellular immune system by intravenous immunoglobulin. Trends Immunol 29:608–615

    Article  PubMed  CAS  Google Scholar 

  35. Clynes R (2007) Protective mechanisms of IVIG. Curr Opin Immunol 19:646–651

    Article  PubMed  CAS  Google Scholar 

  36. Kaveri SV, Lacroix-Desmazes S, Bayry J (2008) The antiinflammatory IgG. N Engl J Med 359:307–309

    Article  PubMed  CAS  Google Scholar 

  37. Arumugam TV, Tang SC, Lathia JD, Cheng A, Mughal MR, Chigurupati S, Magnus T, Chan SL, Jo DG, Ouyang X, Fairlie DP, Granger DN, Vortmeyer A, Basta M, Mattson MP (2007) Intravenous immunoglobulin (IVIG) protects the brain against experimental stroke by preventing complement-mediated neuronal cell death. Proc Natl Acad Sci USA 104:14104–14109

    Article  PubMed  CAS  Google Scholar 

  38. Arumugam TV, Selvaraj PK, Woodruff TM, Mattson MP (2008) Targeting ischemic brain injury with intravenous immunoglobulin. Expert Opin Ther Targets 12:19–29

    Article  PubMed  CAS  Google Scholar 

  39. Basta M, Van Goor F, Luccioli S, Billings EM, Vortmeyer AO, Baranyi L, Szebeni J, Alving CR, Carroll MC, Berkower I, Stojilkovic SS, Metcalfe DD (2003) F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins. Nat Med 9:431–438

    Article  PubMed  CAS  Google Scholar 

  40. Arumugam TV, Woodruff TM, Lathia JD, Selvaraj PK, Mattson MP, Taylor SM (2009) Neuroprotection in stroke by complement inhibition and immunoglobulin therapy. Neuroscience 158:1074–1089

    Article  PubMed  CAS  Google Scholar 

  41. Basta M (2008) Ambivalent effect of immunoglobulins on the complement system: activation versus inhibition. Mol Immunol 45:4073–4079

    Article  PubMed  CAS  Google Scholar 

  42. Thurman JM (2007) Triggers of inflammation after renal ischemia/reperfusion. Clin Immunol 123:7–13

    Article  PubMed  CAS  Google Scholar 

  43. Sameulsson A, Towers TL, Ravetch JV (2001) Anti-inflamatory activity of IVIG mediated through the inhibitory Fc receptor. Science 29:484–6

    Article  Google Scholar 

  44. Kaneko Y, Nimmerjahn F, Madaio MP, Ravetch JV (2006) Pathology and protection in nephrotoxic nephritis is determined by selective engagement of specific Fc receptors. J Exp Med 203:789–797

    Article  PubMed  CAS  Google Scholar 

  45. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV (2008) Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320:373–376

    Article  PubMed  CAS  Google Scholar 

  46. Kaneko Y, Nimmerjahn F, Ravetch JV (2006) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313:670–673

    Article  PubMed  CAS  Google Scholar 

  47. Anthony RM, Wermeling F, Karlsson MC, Ravetch JV (2008) Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci USA 105:19571–19578

    Article  PubMed  Google Scholar 

  48. Jordan SC, Quartel AW, Czer LS, Admon D, Chen G, Fishbein MC, Schwieger J, Steiner RW, Davis C, Tyan DB (1998) Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action. Transplantation 66:800–805

    Article  PubMed  CAS  Google Scholar 

  49. Casadei DH, del CRM, Opelz G, Golberg JC, Argento JA, Greco G, Guardia OE, Haas E, Raimondi EH (2001) A randomized and prospective study comparing treatment with high-dose intravenous immunoglobulin with monoclonal antibodies for rescue of kidney grafts with steroid-resistant rejection. Transplantation 71:53–58

    Article  PubMed  CAS  Google Scholar 

  50. Luke PP, Scantlebury VP, Jordan ML, Vivas CA, Hakala TR, Jain A, Somani A, Fedorek S, Randhawa P, Shapiro R (2001) Reversal of steroid- and anti-lymphocyte antibody-resistant rejection using intravenous immunoglobulin (IVIG) in renal transplant recipients. Transplantation 72:419–422

    Article  PubMed  CAS  Google Scholar 

  51. Lefaucheur C, Nochy D, Andrade J, Verine J, Gautreau C, Charron D, Hill GS, Glotz D, Suberbielle-Boissel C (2009) Comparison of combination Plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection. Am J Transplant 9:1099–1107

    Article  PubMed  CAS  Google Scholar 

  52. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445

    PubMed  CAS  Google Scholar 

  53. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM, Shaw T (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med 350:2572–2581

    Article  PubMed  CAS  Google Scholar 

  54. Salama AD, Pusey CD (2006) Drug insight: rituximab in renal disease and transplantation. Nat Clin Pract Nephrol 2:221–230

    Article  PubMed  CAS  Google Scholar 

  55. Edwards JC, Cambridge G (2006) B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 6:394–403

    Article  PubMed  CAS  Google Scholar 

  56. Stasi R, Cooper N, Del Poeta G, Stipa E, Laura Evangelista M, Abruzzese E, Amadori S (2008) Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 112:1147–1150

    Article  PubMed  CAS  Google Scholar 

  57. Liossis SN, Sfikakis PP (2008) Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T cells. Clin Immunol 127:280–285

    Article  PubMed  CAS  Google Scholar 

  58. Genberg H, Hansson A, Wernerson A, Wennberg L, Tyden G (2007) Pharmacodynamics of rituximab in kidney transplantation. Transplantation 84:S33–36

    Article  PubMed  CAS  Google Scholar 

  59. Ramos EJ, Pollinger HS, Stegall MD, Gloor JM, Dogan A, Grande JP (2007) The effect of desensitization protocols on human splenic B-cell populations in vivo. Am J Transplant 7:402–407

    Article  PubMed  CAS  Google Scholar 

  60. Anolik JH, Barnard J, Owen T, Zheng B, Kemshetti S, Looney RJ, Sanz I (2007) Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis Rheum 56:3044–3056

    Article  PubMed  CAS  Google Scholar 

  61. Levesque MC, St Clair EW (2008) B cell-directed therapies for autoimmune disease and correlates of disease response and relapse. J Allergy Clin Immunol 121:13–21, quiz 22–23

    Article  PubMed  CAS  Google Scholar 

  62. Sarwal M, Chua MS, Kambham N, Hsieh SC, Satterwhite T, Masek M, Salvatierra O Jr (2003) Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N Engl J Med 349:125–138

    Article  PubMed  CAS  Google Scholar 

  63. Zarkhin V, Li L, Kambham N, Sigdel T, Salvatierra O, Sarwal MM (2008) A randomized, prospective trial of rituximab for acute rejection in pediatric renal transplantation. Am J Transplant 8:2607–2617

    Article  PubMed  CAS  Google Scholar 

  64. Steinmetz OM, Lange-Husken F, Turner JE, Vernauer A, Helmchen U, Stahl RA, Thaiss F, Panzer U (2007) Rituximab removes intrarenal B cell clusters in patients with renal vascular allograft rejection. Transplantation 84:842–850

    Article  PubMed  CAS  Google Scholar 

  65. Becker YT, Becker BN, Pirsch JD, Sollinger HW (2004) Rituximab as treatment for refractory kidney transplant rejection. Am J Transplant 4:996–1001

    Article  PubMed  CAS  Google Scholar 

  66. Kaposztas Z, Podder H, Mauiyyedi S, Illoh O, Kerman R, Reyes M, Pollard V, Kahan BD (2009) Impact of rituximab therapy for treatment of acute humoral rejection. Clin Transplant 23:63–73

    Article  PubMed  CAS  Google Scholar 

  67. Faguer S, Kamar N, Guilbeaud-Frugier C, Fort M, Modesto A, Mari A, Ribes D, Cointault O, Lavayssiere L, Guitard J, Durand D, Rostaing L (2007) Rituximab therapy for acute humoral rejection after kidney transplantation. Transplantation 83:1277–1280

    Article  PubMed  CAS  Google Scholar 

  68. Celik A, Saglam F, Cavdar C, Sifil A, Atila K, Sarioglu S, Bora S, Gulay H, Camsari T (2008) Successful therapy with rituximab of refractory acute humoral renal transplant rejection: a case report. Transplant Proc 40:302–304

    Article  PubMed  CAS  Google Scholar 

  69. Mulley WR, Hudson FJ, Tait BD, Skene AM, Dowling JP, Kerr PG, Kanellis J (2009) A single low-fixed dose of rituximab to salvage renal transplants from refractory antibody-mediated rejection. Transplantation 87:286–289

    Article  PubMed  CAS  Google Scholar 

  70. Moscoso-Solorzano GT, Baltar JM, Seco M, Lopez-Larrea C, Mastroianni-Kirsztajn G, Ortega F (2007) Single dose of Rituximab plus plasmapheresis in an HIV patient with acute humoral kidney transplant rejection: a case report. Transplant Proc 39:3460–3462

    Article  PubMed  CAS  Google Scholar 

  71. Wade E, Goral S, Kearns J, Pierce E, Trofe J, Bloom R, Kamoun M (2006) Experience with antibody-mediated rejection in kidney allograft recipients. Clin Transpl:439–446

  72. Yang YW, Lin WC, Wu MS, Lee PH, Tsai MK (2008) Early diagnosis and successful treatment of acute antibody-mediated rejection of a renal transplant. Exp Clin Transplant 6:211–214

    PubMed  Google Scholar 

  73. Vo A, Cao K, Lai C-H, Reinsmoen N, Toyoda M, Ge S, Peng A, Villicana R, Jordan SC (2009) Characteristics of patients who develop antibody-mediated rejection (AMR) post-transplant after desensitization with IVIG + rituximab: analysis of risk factors and outcomes. Am J Transplantation 9:334 (Abstract #494)

    Google Scholar 

  74. Liu C, Noorchashm H, Sutter JA, Naji M, Prak EL, Boyer J, Green T, Rickels MR, Tomaszewski JE, Koeberlein B, Wang Z, Paessler ME, Velidedeoglu E, Rostami SY, Yu M, Barker CF, Naji A (2007) B lymphocyte-directed immunotherapy promotes long-term islet allograft survival in nonhuman primates. Nat Med 13:1295–1298

    Article  PubMed  CAS  Google Scholar 

  75. Kessler L, Parissiadis A, Bayle F, Moreau F, Pinget M, Froelich N, Cazenave JP, Berney T, Benhamou PY, Hanau D (2009) Evidence for humoral rejection of a pancreatic islet graft and rescue with rituximab and IV immunoglobulin therapy. Am J Transplant 9:1961–1966

    Article  PubMed  CAS  Google Scholar 

  76. Billing H, Rieger S, Ovens J, Susal C, Melk A, Waldherr R, Opelz G, Tonshoff B (2008) Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients. Transplantation 86:1214–1221

    Article  PubMed  CAS  Google Scholar 

  77. Fehr T, Rusi B, Fischer A, Hopfer H, Wuthrich RP, Gaspert A (2009) Rituximab and intravenous immunoglobulin treatment of chronic antibody-mediated kidney allograft rejection. Transplantation 87:1837–1841

    Article  PubMed  CAS  Google Scholar 

  78. Curran MP, McKeage K (2009) Bortezomib: a review of its use in patients with multiple myeloma. Drugs 69:859–888

    Article  PubMed  CAS  Google Scholar 

  79. Trivedi HL, Terasaki PI, Feroz A, Everly MJ, Vanikar AV, Shankar V, Trivedi VB, Kaneku H, Idica AK, Modi PR, Khemchandani SI, Dave SD (2009) Abrogation of anti-HLA antibodies via proteasome inhibition. Transplantation 87:1555–1561

    Article  PubMed  CAS  Google Scholar 

  80. Everly MJ, Everly JJ, Susskind B, Brailey P, Arend LJ, Alloway RR, Roy-Chaudhury P, Govil A, Mogilishetty G, Rike AH, Cardi M, Wadih G, Tevar A, Woodle ES (2008) Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection. Transplantation 86:1754–1761

    Article  PubMed  CAS  Google Scholar 

  81. Parker C (2009) Eculizumab for paroxysmal nocturnal haemoglobinuria. Lancet 373:759–767

    Article  PubMed  CAS  Google Scholar 

  82. Williams JM, Holzknecht ZE, Plummer TB, Lin SS, Brunn GJ, Platt JL (2004) Acute vascular rejection and accommodation: divergent outcomes of the humoral response to organ transplantation. Transplantation 78:1471–1478

    Article  PubMed  Google Scholar 

  83. Stegall M, Diwan T, Burns J, Dean P (2009) Prevention of acute humoral rejection with C5 inhibition. Am J Transplantation 9:241 (Abstract #174)

    Google Scholar 

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Acknowledgements

This work was supported by The Rebecca Sakai Memorial Fund and The Joyce Jillson Fund for Transplant Research. We also express our gratitude to the entire staff of the Transplant Immunotherapy Program, HLA Laboratory, and Transplant Immunology Laboratory at Cedars-Sinai Medical Center for their hard work and dedication.

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Authors and Affiliations

  1. The Transplant Immunotherapy Program, Comprehensive Transplant Center, Los Angeles, CA, 90048, USA

    Stanley C. Jordan, Alice Peng, Rafael Villicana, Joseph Kahwaji & Ashley A. Vo

  2. HLA & Immunogenetics Laboratory, Los Angeles, CA, 90048, USA

    Nancy Reinsmoen, Chih-Hung Lai & Kai Cao

  3. Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Mieko Toyoda

  4. David Geffen School of Medicine at UCLA, Division of Nephrology & Transplant Immunology, Kidney Transplant Program, Cedars-Sinai Medical Center, 8635 W. 3rd St. Suite 590 W, Los Angeles, CA, 90048, USA

    Stanley C. Jordan

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  1. Stanley C. Jordan
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Additional information

Answers

1. d

2. b

3. b

4. b

5. b

6. a

Questions:

Questions:

(Answers appear following the reference list)

  1. 1.

    Which of the following is NOT a characteristic of antibody-mediated rejection (AMR)?

  2. a.

    C4d deposition

  3. b.

    Thrombotic microangiopathy

  4. c.

    DSA detection

  5. d.

    T-cell infiltrates

  6. e.

    Rapid onset of allograft dysfunction

  7. 2.

    The most up to date way for detecting DSA is the use of CDC assays.

    1. a.

      True

    2. b.

      False

  8. 3.

    When dealing with suspected AMR in a highly-HLA sensitized patient, the most important aspect is to wait for biopsy results before initiation of antirejection therapy for AMR.

    1. a.

      True

    2. b.

      False

  9. 4.

    Which of the following would NOT be considered a primary therapy for treatment of AMR?

    1. a.

      Plasmapheresis + low-dose IVIG

    2. b.

      Thymoglobulin

    3. c.

      Rituximab

    4. d.

      High-dose IVIG

    5. e.

      High-dose IVIG + rituximab

  10. 5.

    Chronic allograft nephropathy (CAN) is not mediated by immunologic mechanisms.

    1. a.

      True

    2. b.

      False

  11. 6.

    Newer approaches to preventing and treating AMR include bortezomib and anticomplement therapies.

    1. a.

      True

    2. b.

      False

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Jordan, S.C., Reinsmoen, N., Peng, A. et al. Advances in diagnosing and managing antibody-mediated rejection. Pediatr Nephrol 25, 2035–2048 (2010). https://doi.org/10.1007/s00467-009-1386-4

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