Reconsidering the detection of tolerance to individualize immunosuppression minimization and to improve long-term kidney graft outcomes

Transplant International

Volumn 28, Issue 8, 2015, Pages 938-959

  Baron, Daniel ^a,b,c   Giral, Magali ^a,b,c   Brouard, Sophie ^a,b,c  

^a Centre National de la Recherche Scientifique   (France)

^b NANTES UNIVERSITY HOSPITAL   (France)

^c UNIVERSITÉ DE NANTES   (France)

Author keywords

biomarker; immunosuppression; kidney allograft; tolerance; transplantation

Indexed keywords

ALEMTUZUMAB; AZATHIOPRINE; BASILIXIMAB; CALCINEURIN INHIBITOR; CORTICOSTEROID; CYCLOSPORIN; DACLIZUMAB; IMMUNOSUPPRESSIVE AGENT; MYCOPHENOLATE MOFETIL; MYCOPHENOLIC ACID; RAPAMYCIN; TACROLIMUS; THYMOCYTE ANTIBODY; BIOLOGICAL MARKER;

B LYMPHOCYTE ACTIVATION; CLINICAL FEATURE; COMPLEMENT ACTIVATION; COST BENEFIT ANALYSIS; DRUG EFFECT; GRAFT RECIPIENT; GRAFT SURVIVAL; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOSUPPRESSIVE TREATMENT; KIDNEY ALLOGRAFT; KIDNEY ALLOGRAFT REJECTION; LYMPHOCYTE SUBPOPULATION; MORTALITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; TREATMENT OUTCOME; TREATMENT PLANNING; ADVERSE EFFECTS; B LYMPHOCYTE; BLOOD; DRUG ADMINISTRATION; GRAFT REJECTION; IMMUNOLOGY; KIDNEY TRANSPLANTATION; METABOLISM; PERSONALIZED MEDICINE; PROCEDURES; TRANSPLANTATION TOLERANCE;

B-LYMPHOCYTE SUBSETS; BIOMARKERS; DRUG ADMINISTRATION SCHEDULE; GRAFT REJECTION; HUMANS; IMMUNOSUPPRESSION; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; PRECISION MEDICINE; TRANSPLANTATION TOLERANCE;

EID: 84947018044     PISSN: 09340874     EISSN: 14322277     Source Type: Journal    
DOI: 10.1111/tri.12578     Document Type: Review

References (251)

1. St Clair EW, Turka LA, Saxon A, et al,. New reagents on the horizon for immune tolerance. Annu Rev Med 2007; 58: 329.
2. Martinez-Llordella M, Lozano JJ, Puig-Pey I, et al,. Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients. J Clin Invest 2008; 118: 2845.
3. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al,. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999; 341: 1725.
4. Pascual M, Theruvath T, Kawai T, Tolkoff-Rubin N, Cosimi AB,. Strategies to improve long-term outcomes after renal transplantation. N Engl J Med 2002; 346: 580.
5. Dantal J, Hourmant M, Cantarovich D, et al,. Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens. Lancet 1998; 351: 623.
6. Opelz G,. Influence of treatment with cyclosporine, azathioprine and steroids on chronic allograft failure. The Collaborative Transplant Study. Kidney Int Suppl 1995; 52: S89.
7. Vincenti F, Kirk AD,. What's next in the pipeline. Am J Transplant 2008; 8: 1972.
8. Hardinger KL, Brennan DC,. Novel immunosuppressive agents in kidney transplantation. World J Transplant 2013; 3: 68.
9. Hariharan S, McBride MA, Cherikh WS, Tolleris CB, Bresnahan BA, Johnson CP,. Post-transplant renal function in the first year predicts long-term kidney transplant survival. Kidney Int 2002; 62: 311.
10. Hariharan S, Stablein DE,. Improvements in long-term renal transplant graft survival. Am J Transplant 2005; 5: 630.
11. Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR,. The natural history of chronic allograft nephropathy. N Engl J Med 2003; 349: 2326.
12. Earnshaw SR, Graham CN, Irish WD, Sato R, Schnitzler MA,. Lifetime cost-effectiveness of calcineurin inhibitor withdrawal after de novo renal transplantation. J Am Soc Nephrol 2008; 19: 1807.
13. Fishman JA, Rubin RH,. Infection in organ-transplant recipients. N Engl J Med 1998; 338: 1741.
14. Fishman JA,. Infection in solid-organ transplant recipients. N Engl J Med 2007; 357: 2601.
15. Morelon E, Stern M, Kreis H,. Interstitial pneumonitis associated with sirolimus therapy in renal-transplant recipients. N Engl J Med 2000; 343: 225.
16. Morelon E, Stern M, Israel-Biet D, et al,. Characteristics of sirolimus-associated interstitial pneumonitis in renal transplant patients. Transplantation 2001; 72: 787.
17. Rabot N, Buchler M, Foucher Y, et al,. CNI withdrawal for post-transplant lymphoproliferative disorders in kidney transplant is an independent risk factor for graft failure and mortality. Transpl Int 2014; 27: 956.
18. Soulillou JP, Giral M,. Controlling the incidence of infection and malignancy by modifying immunosuppression. Transplantation 2001; 72: S89.
19. London NJ, Farmery SM, Will EJ, Davison AM, Lodge JP,. Risk of neoplasia in renal transplant patients. Lancet 1995; 346: 403.
20. Halloran PF,. Immunosuppressive drugs for kidney transplantation. N Engl J Med 2004; 351: 2715.
21. Halloran PF, Bromberg J, Kaplan B, Vincenti F,. Tolerance versus immunosuppression: a perspective. Am J Transplant 2008; 8: 1365.
22. Miller LW,. Cardiovascular toxicities of immunosuppressive agents. Am J Transplant 2002; 2: 807.
23. Rama I, Grinyo JM,. Malignancy after renal transplantation: the role of immunosuppression. Nat Rev Nephrol 2010; 6: 511.
24. Casey MJ, Meier-Kriesche HU,. Calcineurin inhibitors in kidney transplantation: friend or foe? Curr Opin Nephrol Hypertens 2011; 20: 610.
25. Ojo AO, Held PJ, Port FK, et al,. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003; 349: 931.
26. Grinyo JM, Gil-Vernet S, Cruzado JM, et al,. Calcineurin inhibitor-free immunosuppression based on antithymocyte globulin and mycophenolate mofetil in cadaveric kidney transplantation: results after 5 years. Transpl Int 2003; 16: 820.
27. Stegall MD, Everson GT, Schroter G, et al,. Prednisone withdrawal late after adult liver transplantation reduces diabetes, hypertension, and hypercholesterolemia without causing graft loss. Hepatology 1997; 25: 173.
28. Wimmer CD, Rentsch M, Crispin A, et al,. The janus face of immunosuppression-de novo malignancy after renal transplantation: the experience of the Transplantation Center Munich. Kidney Int 2007; 71: 1271.
29. Hardinger KL, Koch MJ, Brennan DC,. Current and future immunosuppressive strategies in renal transplantation. Pharmacotherapy 2004; 24: 1159.
30. Augustine JJ, Hricik DE,. Minimization of immunosuppression in kidney transplantation. Curr Opin Nephrol Hypertens 2007; 16: 535.
31. Lechler RI, Garden OA, Turka LA,. The complementary roles of deletion and regulation in transplantation tolerance. Nat Rev Immunol 2003; 3: 147.
32. Schroeder RA, Marroquin CE, Kuo PC,. Tolerance and the "Holy Grail" of transplantation. J Surg Res 2003; 111: 109.
33. Yang H,. Maintenance immunosuppression regimens: conversion, minimization, withdrawal, and avoidance. Am J Kidney Dis 2006; 47: S37.
34. Londono MC, Lopez MC, Sanchez-Fueyo A,. Minimization of immunosuppression in adult liver transplantation: new strategies and tools. Curr Opin Organ Transplant 2010; 15: 685.
35. Shapiro R, Young JB, Milford EL, Trotter JF, Bustami RT, Leichtman AB,. Immunosuppression: evolution in practice and trends, 1993-2003. Am J Transplant 2005; 5: 874.
36. Vanrenterghem Y, van Hooff JP, Squifflet JP, et al,. Minimization of immunosuppressive therapy after renal transplantation: results of a randomized controlled trial. Am J Transplant 2005; 5: 87.
37. Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B,. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004; 4: 378.
38. Kirk AD, Guasch A, Xu H, et al,. Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors. Am J Transplant 2014; 14: 1142.
39. Karam VH, Gasquet I, Delvart V, et al,. Quality of life in adult survivors beyond 10 years after liver, kidney, and heart transplantation. Transplantation 2003; 76: 1699.
40. Hirsch HH, Knowles W, Dickenmann M, et al,. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med 2002; 347: 488.
41. Cortesini R, Suciu-Foca N,. The concept of "partial" clinical tolerance. Transpl Immunol 2004; 13: 101.
42. Kirk AD,. Less is more: maintenance minimization as a step toward tolerance. Am J Transplant 2003; 3: 643.
43. Ekberg H, Bernasconi C, Tedesco-Silva H, et al,. Calcineurin inhibitor minimization in the Symphony study: observational results 3 years after transplantation. Am J Transplant 2009; 9: 1876.
44. Sayegh MH,. Looking into the crystal ball: kidney transplantation in 2025. Nat Clin Pract Nephrol 2009; 5: 117.
45. Calne R, Friend P, Moffatt S, et al,. Prope tolerance, perioperative campath 1H, and low-dose cyclosporin monotherapy in renal allograft recipients. Lancet 1998; 351: 1701.
46. Calne RY,. Prope tolerance- The future of organ transplantation from the laboratory to the clinic. Int Immunopharmacol 2005; 5: 163.
47. Monaco AP,. The beginning of clinical tolerance in solid organ allografts. Exp Clin Transplant 2004; 2: 153.
48. Vincenti F,. Immunosuppression minimization: current and future trends in transplant immunosuppression. J Am Soc Nephrol 2003; 14: 1940.
49. Vincenti F,. Is complete avoidance of calcineurin inhibitors or steroids now possible? Importance of patient selection and choice of regimen. Transplant Proc 2001; 33: 11S.
50. Danovitch GM,. Immunosuppressive medications for renal transplantation: a multiple choice question. Kidney Int 2001; 59: 388.
51. Gaber AO, First MR, Tesi RJ, et al,. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation 1998; 66: 29.
52. Vincenti F,. The role of newer monoclonal antibodies in renal transplantation. Transplant Proc 2001; 33: 1000.
53. Vincenti F,. What's in the pipeline? New immunosuppressive drugs in transplantation. Am J Transplant 2002; 2: 898.
54. Lunsford KE, Barbas AS, Brennan TV,. Recent advances in immunosuppressive therapy for prevention of renal allograft rejection. Curr Opin Organ Transplant 2011; 16: 390.
55. Pilat N, Schwarz C, Wekerle T,. Modulating T-cell costimulation as new immunosuppressive concept in organ transplantation. Curr Opin Organ Transplant 2012; 17: 368.
56. Page AJ, Ford ML, Kirk AD,. Memory T-cell-specific therapeutics in organ transplantation. Curr Opin Organ Transplant 2009; 14: 643.
57. Wood KJ, Bushell A, Hester J,. Regulatory immune cells in transplantation. Nat Rev Immunol 2012; 12: 417.
58. Marks SD,. New immunosuppressants in pediatric solid organ transplantation. Curr Opin Organ Transplant 2012; 17: 503.
59. Webber A, Hirose R, Vincenti F,. Novel strategies in immunosuppression: issues in perspective. Transplantation 2011; 91: 1057.
60. Billingham RE, Brent L, Medawar PB,. Actively acquired tolerance of foreign cells. Nature 1953; 172: 603.
61. Ashton-Chess J, Brouard S, Soulillou JP,. Is clinical tolerance realistic in the next decade? Transpl Int 2006; 19: 539.
62. Fehr T, Sykes M,. Tolerance induction in clinical transplantation. Transpl Immunol 2004; 13: 117.
63. Girlanda R, Kirk AD,. Frontiers in nephrology: immune tolerance to allografts in humans. J Am Soc Nephrol 2007; 18: 2242.
64. Page EK, Dar WA, Knechtle SJ,. Tolerogenic therapies in transplantation. Front Immunol 2012; 3: 198.
65. Cosimi AB, Burton RC, Colvin RB, et al,. Treatment of acute renal allograft rejection with OKT3 monoclonal antibody. Transplantation 1981; 32: 535.
66. Poirier N, Azimzadeh AM, Zhang T, et al,. Inducing CTLA-4-dependent immune regulation by selective CD28 blockade promotes regulatory T cells in organ transplantation. Sci Transl Med 2010; 2: 17ra10.
67. Vincenti F, Nashan B, Light S,. Daclizumab: outcome of phase III trials and mechanism of action. Double Therapy and the Triple Therapy Study Groups. Transplant Proc 1998; 30: 2155.
68. Vincenti F, Larsen C, Durrbach A, et al,. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005; 353: 770.
69. Kawai T, Cosimi AB, Spitzer TR, et al,. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2008; 358: 353.
70. Scandling JD, Busque S, Jbakhsh-Jones S, et al,. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med 2008; 358: 362.
71. Sharabi Y, Sachs DH,. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen. J Exp Med 1989; 169: 493.
72. Burlingham WJ, Grailer AP, Fechner JH Jr, et al,. Microchimerism linked to cytotoxic T lymphocyte functional unresponsiveness (clonal anergy) in a tolerant renal transplant recipient. Transplantation 1995; 59: 1147.
73. Kingsley CI, Nadig SN, Wood KJ,. Transplantation tolerance: lessons from experimental rodent models. Transpl Int 2007; 20: 828.
74. Monk NJ, Hargreaves RE, Simpson E, Dyson JP, Jurcevic S,. Transplant tolerance: models, concepts and facts. J Mol Med (Berl) 2006; 84: 295.
75. Hamawy MM, Knechtle SJ,. Strategies for tolerance induction in nonhuman primates. Curr Opin Immunol 1998; 10: 513.
76. Kawai T, Cosimi AB, Sachs DH,. Preclinical and clinical studies on the induction of renal allograft tolerance through transient mixed chimerism. Curr Opin Organ Transplant 2011; 16: 366.
77. Eason JD, Cohen AJ, Nair S, Alcantera T, Loss GE,. Tolerance: is it worth the risk? Transplantation 2005; 79: 1157.
78. Salama AD, Remuzzi G, Harmon WE, Sayegh MH,. Challenges to achieving clinical transplantation tolerance. J Clin Invest 2001; 108: 943.
79. Kirk AD,. Ethics in the quest for transplant tolerance. Transplantation 2004; 77: 947.
80. Ojo A, Wolfe RA, Agodoa LY, et al,. Prognosis after primary renal transplant failure and the beneficial effects of repeat transplantation: multivariate analyses from the United States Renal Data System. Transplantation 1998; 66: 1651.
81. Auchincloss H Jr,. In search of the elusive Holy Grail: the mechanisms and prospects for achieving clinical transplantation tolerance. Am J Transplant 2001; 1: 6.
82. Millan MT, Shizuru JA, Hoffmann P, et al,. Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation. Transplantation 2002; 73: 1386.
83. Budde K, Matz M, Durr M, Glander P,. Biomarkers of over-immunosuppression. Clin Pharmacol Ther 2011; 90: 316.
84. Sayegh MH, Remuzzi G,. Clinical update: immunosuppression minimisation. Lancet 2007; 369: 1676.
85. Ashton-Chess J, Giral M, Soulillou JP, Brouard S,. Can immune monitoring help to minimize immunosuppression in kidney transplantation? Transpl Int 2009; 22: 110.
86. Tredger JM, Brown NW, Dhawan A,. Immunosuppression in pediatric solid organ transplantation: opportunities, risks, and management. Pediatr Transplant 2006; 10: 879.
87. Abboudi H, Macphee IA,. Individualized immunosuppression in transplant patients: potential role of pharmacogenetics. Pharmgenomics Pers Med 2012; 5: 63.
88. Matthews JB, Ramos E, Bluestone JA,. Clinical trials of transplant tolerance: slow but steady progress. Am J Transplant 2003; 3: 794.
89. Cobbold SP, Li XC,. Translating Tolerogenic Therapies to the Clinic-Where Do We Stand and What are the Barriers? Front Immunol 2012; 3: 317.
90. Issa F, Wood KJ,. Translating tolerogenic therapies to the clinic-where do we stand? Front Immunol 2012; 3: 254.
91. Adams AB, Williams MA, Jones TR, et al,. Heterologous immunity provides a potent barrier to transplantation tolerance. J Clin Invest 2003; 111: 1887.
92. Heeger PS,. Frontiers in nephrology: tolerance. J Am Soc Nephrol 2007; 18: 2240.
93. Salisbury EM, Game DS, Lechler RI,. Transplantation tolerance. Pediatr Nephrol 2014; 29: 2263.
94. Sanchez-Fueyo A, Strom TB,. Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs. Gastroenterology 2011; 140: 51.
95. Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S,. Induced immune tolerance for kidney transplantation. N Engl J Med 2011; 365: 1359.
96. Chandrasekharan D, Issa F, Wood KJ,. Achieving operational tolerance in transplantation: how can lessons from the clinic inform research directions? Transpl Int 2013; 26: 576.
97. Najafian N, Albin MJ, Newell KA,. How can we measure immunologic tolerance in humans? J Am Soc Nephrol 2006; 17: 2652.
98. Newell KA, Larsen CP,. Tolerance assays: measuring the unknown. Transplantation 2006; 81: 1503.
99. Turka LA, Lechler RI,. Towards the identification of biomarkers of transplantation tolerance. Nat Rev Immunol 2009; 9: 521.
100. Lachenbruch PA, Rosenberg AS, Bonvini E, Cavaille-Coll MW, Colvin RB,. Biomarkers and surrogate endpoints in renal transplantation: present status and considerations for clinical trial design. Am J Transplant 2004; 4: 451.
101. Sis B, Mengel M, Haas M, et al,. Banff '09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant 2010; 10: 464.
102. Bellomo R, Kellum JA, Ronco C,. Defining acute renal failure: physiological principles. Intensive Care Med 2004; 30: 33.
103. Londono MC, Danger R, Giral M, Soulillou JP, Sanchez-Fueyo A, Brouard S,. A need for biomarkers of operational tolerance in liver and kidney transplantation. Am J Transplant 2012; 12: 1370.
104. Heidt S, Wood KJ,. Biomarkers of operational tolerance in solid organ transplantation. Expert Opin Med Diagn 2012; 6: 281.
105. Naesens M, Sarwal MM,. Molecular diagnostics in transplantation. Nat Rev Nephrol 2010; 6: 614.
106. Roedder S, Vitalone M, Khatri P, Sarwal MM,. Biomarkers in solid organ transplantation: establishing personalized transplantation medicine. Genome Med 2011; 3: 37.
107. Sawitzki B, Pascher A, Babel N, Reinke P, Volk HD,. Can we use biomarkers and functional assays to implement personalized therapies in transplantation? Transplantation 2009; 87: 1595.
108. Nickerson P,. Post-transplant monitoring of renal allografts: are we there yet? Curr Opin Immunol 2009; 21: 563.
109. Townamchai N, Safa K, Chandraker A,. Immunologic monitoring in kidney transplant recipients. Kidney Res Clin Pract 2013; 32: 52.
110. Brouard S, Shton-Chess J, Soulillou JP,. Surrogate markers for the prediction of long-term outcome in transplantation: Nantes Actualite Transplantation (NAT) 2007 meeting report. Hum Immunol 2008; 69: 2.
111. Chowdhury P, Hernandez-Fuentes MP,. Non-invasive biomarkers to guide management following renal transplantation: the need for a multiplatform approach. Curr Opin Organ Transplant 2013; 18: 1.
112. Orlando G, Hematti P, Stratta RJ, et al,. Clinical operational tolerance after renal transplantation: current status and future challenges. Ann Surg 2010; 252: 915.
113. Ashton-Chess J, Giral M, Brouard S, Soulillou JP,. Spontaneous operational tolerance after immunosuppressive drug withdrawal in clinical renal allotransplantation. Transplantation 2007; 84: 1215.
114. Newell KA,. Clinical transplantation tolerance. Semin Immunopathol 2011; 33: 91.
115. Dugast E, Chesneau M, Soulillou JP, Brouard S,. Biomarkers and possible mechanisms of operational tolerance in kidney transplant patients. Immunol Rev 2014; 258: 208.
116. Sawitzki B, Reinke P, Pascher A, Volk HD,. State of the art on the research for biomarkers allowing individual, tailor-made minimization of immunosuppression. Curr Opin Organ Transplant 2010; 15: 691.
117. Aiba Y, Yamazaki T, Okada T, et al,. BANK negatively regulates Akt activation and subsequent B cell responses. Immunity 2006; 24: 259.
118. Brouard S, Pallier A, Renaudin K, et al,. The natural history of clinical operational tolerance after kidney transplantation through twenty-seven cases. Am J Transplant 2012; 12: 3296.
119. Roussey-Kesler G, Giral M, Moreau A, et al,. Clinical operational tolerance after kidney transplantation. Am J Transplant 2006; 6: 736.
120. Soulillou JP, Giral M, Brouard S,. Operational tolerance in kidney transplantation-improved terminology may enable more precise investigation. Transplantation 2013; 96: e36.
121. Zoller KM, Cho SI, Cohen JJ, Harrington JT,. Cessation of immunosuppressive therapy after successful transplantation: a national survey. Kidney Int 1980; 18: 110.
122. Starzl TE, Murase N, Demetris AJ, et al,. Lessons of organ-induced tolerance learned from historical clinical experience. Transplantation 2004; 77: 926.
123. Weil R III, Starzl TE, Porter KA, Kershaw M, Schroter GP, Koep LJ,. Renal isotransplantation without immunosuppression. Ann Surg 1980; 192: 108.
124. Maltzman JS, Koretzky GA,. Azathioprine: old drug, new actions. J Clin Invest 2003; 111: 1122.
125. Murray JE, Merrill JP, Harrison JH, Wilson RE, Dammin GJ,. Prolonged survival of human-kidney homografts by immunosuppressive drug therapy. N Engl J Med 1963; 268: 1315.
126. Bererhi L, Pallet N, Zuber J, et al,. Clinical and immunological features of very long-term survivors with a single renal transplant. Transpl Int 2012; 25: 545.
127. Braun WE, Protiva DA, Schold JD,. Decreased total CD19(+) B lymphocytes and the occurrence of monoclonal proteins are frequent in ultra-long (30 to 44-year) renal transplant recipients: implications for allograft and patient survival. Transplant Proc 2013; 45: 1466.
128. Moreso F, Torres IB, Martinez-Gallo M, et al,. Gene expression signature of tolerance and lymphocyte subsets in stable renal transplants: results of a cross-sectional study. Transpl Immunol 2014; 31: 11.
129. Calne RY, Wood AJ,. Cyclosporin in cadaveric renal transplantation: 3-year follow-up of a European multicentre trial. Lancet 1985; 2: 549.
130. El-Zoghby ZM, Stegall MD, Lager DJ, et al,. Identifying specific causes of kidney allograft loss. Am J Transplant 2009; 9: 527.
131. Gourishankar S, Leduc R, Connett J, et al,. Pathological and clinical characterization of the 'troubled transplant': data from the DeKAF study. Am J Transplant 2010; 10: 324.
132. Matas AJ,. Chronic progressive calcineurin nephrotoxicity: an overstated concept. Am J Transplant 2011; 11: 687.
133. Pinto JR, Rellano Torres EM, Franco A, et al,. Sirolimus monotherapy as maintenance immunosuppression: a multicenter experience. Transpl Int 2010; 23: 307.
134. Snanoudj R, Royal V, Elie C, et al,. Specificity of histological markers of long-term CNI nephrotoxicity in kidney-transplant recipients under low-dose cyclosporine therapy. Am J Transplant 2011; 11: 2635.
135. Starzl TE, Marchioro TL, Waddell WR,. The reversal of rejection in human renal homografts with subsequent development of homograft tolerance. Surg Gynecol Obstet 1963; 117: 385.
136. Starzl TE, Zinkernagel RM,. Transplantation tolerance from a historical perspective. Nat Rev Immunol 2001; 1: 233.
137. Starzl TE,. The saga of liver replacement, with particular reference to the reciprocal influence of liver and kidney transplantation (1955-1967). J Am Coll Surg 2002; 195: 587.
138. Christensen LL, Grunnet N, Rudiger N, Moller B, Birkeland SA,. Indications of immunological tolerance in kidney transplantation. Tissue Antigens 1998; 51: 637.
139. Fischer T, Schobel H, Barenbrock M,. Specific immune tolerance during pregnancy after renal transplantation. Eur J Obstet Gynecol Reprod Biol 1996; 70: 217.
140. Haynes LD, Jankowska-Gan E, Sheka A, et al,. Donor-specific indirect pathway analysis reveals a B-cell-independent signature which reflects outcomes in kidney transplant recipients. Am J Transplant 2012; 12: 640.
141. Uehling DT, Hussey JL, Weinstein AB, Wank R, Bach FH,. Cessation of immunosuppression after renal transplantation. Surgery 1976; 79: 278.
142. Ballet C, Roussey-Kesler G, Aubin JT, et al,. Humoral and cellular responses to influenza vaccination in human recipients naturally tolerant to a kidney allograft. Am J Transplant 2006; 6: 2796.
143. VanBuskirk AM, Burlingham WJ, Jankowska-Gan E, et al,. Human allograft acceptance is associated with immune regulation. J Clin Invest 2000; 106: 145.
144. Baeten D, Louis S, Braud C, et al,. Phenotypically and functionally distinct CD8+ lymphocyte populations in long-term drug-free tolerance and chronic rejection in human kidney graft recipients. J Am Soc Nephrol 2006; 17: 294.
145. Becker LE, de Oliveira BF, Conrad H, et al,. Cellular infiltrates and NFkappaB subunit c-Rel signaling in kidney allografts of patients with clinical operational tolerance. Transplantation 2012; 94: 729.
146. Braud C, Baeten D, Giral M, et al,. Immunosuppressive drug-free operational immune tolerance in human kidney transplant recipients: Part I. Blood gene expression statistical analysis. J Cell Biochem 2008; 103: 1681.
147. Braudeau C, Racape M, Giral M, et al,. Variation in numbers of CD4+ CD25 high FOXP3+ T cells with normal immuno-regulatory properties in long-term graft outcome. Transpl Int 2007; 20: 845.
148. Braudeau C, Shton-Chess J, Giral M, et al,. Contrasted blood and intragraft toll-like receptor 4 mRNA profiles in operational tolerance versus chronic rejection in kidney transplant recipients. Transplantation 2008; 86: 130.
149. Brouard S, Dupont A, Giral M, et al,. Operationally tolerant and minimally immunosuppressed kidney recipients display strongly altered blood T-cell clonal regulation. Am J Transplant 2005; 5: 330.
150. Brouard S, Le BA, Dufay A, et al,. Identification of a gene expression profile associated with operational tolerance among a selected group of stable kidney transplant patients. Transpl Int 2011; 24: 536.
151. Danger R, Thervet E, Grisoni ML, et al,. PARVG gene polymorphism and operational renal allograft tolerance. Transplant Proc 2012; 44: 2845.
152. Danger R, Pallier A, Giral M, et al,. Upregulation of miR-142-3p in peripheral blood mononuclear cells of operationally tolerant patients with a renal transplant. J Am Soc Nephrol 2012; 23: 597.
153. Louis S, Braudeau C, Giral M, et al,. Contrasting CD25hiCD4+T cells/FOXP3 patterns in chronic rejection and operational drug-free tolerance. Transplantation 2006; 81: 398.
154. Lozano JJ, Pallier A, Martinez-Llordella M, et al,. Comparison of transcriptional and blood cell-phenotypic markers between operationally tolerant liver and kidney recipients. Am J Transplant 2011; 11: 1916.
155. Moraes-Vieira PM, Silva HM, Takenaka MC, et al,. Differential monocyte STAT6 activation and CD4(+)CD25(+)Foxp3(+) T cells in kidney operational tolerance transplanted individuals. Hum Immunol 2010; 71: 442.
156. Moraes-Vieira PM, Takenaka MC, Silva HM, et al,. GATA3 and a dominant regulatory gene expression profile discriminate operational tolerance in human transplantation. Clin Immunol 2012; 142: 117.
157. Newell KA, Asare A, Kirk AD, et al,. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest 2010; 120: 1836.
158. Pallier A, Hillion S, Danger R, et al,. Patients with drug-free long-term graft function display increased numbers of peripheral B cells with a memory and inhibitory phenotype. Kidney Int 2010; 78: 503.
159. Sagoo P, Perucha E, Sawitzki B, et al,. Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans. J Clin Invest 2010; 120: 1848.
160. Najafian N, Salama AD, Fedoseyeva EV, Benichou G, Sayegh MH,. Enzyme-linked immunosorbent spot assay analysis of peripheral blood lymphocyte reactivity to donor HLA-DR peptides: potential novel assay for prediction of outcomes for renal transplant recipients. J Am Soc Nephrol 2002; 13: 252.
161. Poggio ED, Clemente M, Hricik DE, Heeger PS,. Panel of reactive T cells as a measurement of primed cellular alloimmunity in kidney transplant candidates. J Am Soc Nephrol 2006; 17: 564.
162. Perkins D, Verma M, Park KJ,. Advances of genomic science and systems biology in renal transplantation: a review. Semin Immunopathol 2011; 33: 211.
163. Hoffmann SC, Pearl JP, Blair PJ, Kirk AD,. Immune profiling: molecular monitoring in renal transplantation. Front Biosci 2003; 8: e444.
164. Sigdel TK, Gao X, Sarwal MM,. Protein and peptide biomarkers in organ transplantation. Biomark Med 2012; 6: 259.
165. Braza F, Soulillou JP, Brouard S,. Reconsidering the bio-detection of tolerance in renal transplantation. Chimerism 2013; 4: 15.
166. Danger R, Racape M, Soulillou JP, Brouard S,. What can we learn from the transcriptional characterization of spontaneously tolerant transplant recipients? Curr Opin Organ Transplant 2010; 15: 435.
167. Braza F, Soulillou JP, Brouard S,. Gene expression signature in transplantation tolerance. Clin Chim Acta 2012; 413: 1414.
168. Hernandez-Fuentes MP, Lechler RI,. A 'biomarker signature' for tolerance in transplantation. Nat Rev Nephrol 2010; 6: 606.
169. Demetris AJ, Lunz JG III, Randhawa P, Wu T, Nalesnik M, Thomson AW,. Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology perspective. Transpl Int 2009; 22: 120.
170. Hilton R, Hernandez-Fuentes M,. Biomarkers of tolerance: hope or hype? Trends Transplant 2010; 4: 68.
171. Ilie M, Hofman V, Long-Mira E, et al,. "Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS ONE 2014; 9: e111597.
172. Villeda SA, Plambeck KE, Middeldorp J, et al,. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med 2014; 20: 659.
173. Ashton-Chess J, Dugast E, Colvin RB, et al,. Regulatory, effector, and cytotoxic T cell profiles in long-term kidney transplant patients. J Am Soc Nephrol 2009; 20: 1113.
174. Mas VR, Mas LA, Archer KJ, et al,. Evaluation of gene panel mRNAs in urine samples of kidney transplant recipients as a non-invasive tool of graft function. Mol Med 2007; 13: 315.
175. Muthukumar T, Dadhania D, Ding R, et al,. Messenger RNA for FOXP3 in the urine of renal-allograft recipients. N Engl J Med 2005; 353: 2342.
176. Perucha E, Rebollo-Mesa I, Sagoo P, Hernandez-Fuentes MP,. Biomarkers of tolerance: searching for the hidden phenotype. Kidney Int Suppl 2011; 2011: 40.
177. Brouard S, Mansfield E, Braud C, et al,. Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Proc Natl Acad Sci USA 2007; 104: 15448.
178. Newell KA, Phippard D, Turka LA,. Regulatory cells and cell signatures in clinical transplantation tolerance. Curr Opin Immunol 2011; 23: 655.
179. Baron D, Ramstein G, Chesneau M, et al,. A common gene signature across multiple studies identifies biomarkers and functional regulation in tolerance to renal allograft. Kidney Int 2015 Jan 28. doi: 10.1038/ki.2014.395. [Epub ahead of print].
180. Chesneau M, Pallier A, Braza F, et al,. Unique B cell differentiation profile in tolerant kidney transplant patients. Am J Transplant 2014; 14: 144.
181. Bouaziz JD, Yanaba K, Tedder TF,. Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev 2008; 224: 201.
182. Girndt M, Sester M, Sester U, Kaul H, Kohler H,. Molecular aspects of T- and B-cell function in uremia. Kidney Int Suppl 2001; 78: S206.
183. Pahl MV, Gollapudi S, Sepassi L, Gollapudi P, Elahimehr R, Vaziri ND,. Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression. Nephrol Dial Transplant 2010; 25: 205.
184. Smogorzewski M, Massry SG,. Defects in B-cell function and metabolism in uremia: role of parathyroid hormone. Kidney Int Suppl 2001; 78: S186.
185. Porcheray F, Wong W, Saidman SL, et al,. B-cell immunity in the context of T-cell tolerance after combined kidney and bone marrow transplantation in humans. Am J Transplant 2009; 9: 2126.
186. Heidt S, Hester J, Shankar S, Friend PJ, Wood KJ,. B cell repopulation after alemtuzumab induction-transient increase in transitional B cells and long-term dominance of naive B cells. Am J Transplant 2012; 12: 1784.
187. Redfield RR III, Rodriguez E, Parsons R, et al,. Essential role for B cells in transplantation tolerance. Curr Opin Immunol 2011; 23: 685.
188. Jindal RM, Joseph JT, Morris MC, Santella RN, Baines LS,. Noncompliance after kidney transplantation: a systematic review. Transplant Proc 2003; 35: 2868.
189. Silva HM, Takenaka MC, Moraes-Vieira PM, et al,. Preserving the B-cell compartment favors operational tolerance in human renal transplantation. Mol Med 2012; 18: 733.
190. Coelho V, Saitovitch D, Kalil J, Silva HM,. Rethinking the multiple roles of B cells in organ transplantation. Curr Opin Organ Transplant 2013; 18: 13.
191. Clatworthy MR, Watson CJ, Plotnek G, et al,. B-cell-depleting induction therapy and acute cellular rejection. N Engl J Med 2009; 360: 2683.
192. Le Texier L, Thebault P, Lavault A, et al,. Long-term allograft tolerance is characterized by the accumulation of B cells exhibiting an inhibited profile. Am J Transplant 2011; 11: 429.
193. Ashoor IF, Najafian N,. Rejection and regulation: a tight balance. Curr Opin Organ Transplant 2012; 17: 1.
194. Mauri C, Blair PA,. Regulatory B cells in autoimmunity: developments and controversies. Nat Rev Rheumatol 2010; 6: 636.
195. Adams AB, Newell KA,. B cells in clinical transplantation tolerance. Semin Immunol 2012; 24: 92.
196. Chesneau M, Michel L, Degauque N, Brouard S,. Regulatory B cells and tolerance in transplantation: from animal models to human. Front Immunol 2013; 4: 497.
197. Stolp J, Turka LA, Wood KJ,. B cells with immune-regulating function in transplantation. Nat Rev Nephrol 2014; 10: 389.
198. Zarkhin V, Chalasani G, Sarwal MM,. The yin and yang of B cells in graft rejection and tolerance. Transplant Rev (Orlando) 2010; 24: 67.
199. Mizoguchi A, Bhan AK,. A case for regulatory B cells. J Immunol 2006; 176: 705.
200. Lampropoulou V, Calderon-Gomez E, Roch T, et al,. Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll-like receptors in immunity. Immunol Rev 2010; 233: 146.
201. Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF,. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 2008; 28: 639.
202. Yanaba K, Bouaziz JD, Matsushita T, Tsubata T, Tedder TF,. The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals. J Immunol 2009; 182: 7459.
203. Hagn M, Jahrsdorfer B,. Why do human B cells secrete granzyme B? Insights into a novel B-cell differentiation pathway. Oncoimmunology 2012; 1: 1368.
204. Chesneau M, Michel L, Chenouard A, et al,. Tolerant kidney transplant patients display B cells with a CD5+CD27+CD138+ phenotype that express Granzyme B and show regulatory properties. J Am Soc Nephrol 2015 Feb 2. pii: JASN.2014040404. [Epub ahead of print].
205. Perez-Andres M, Paiva B, Nieto WG, et al,. Human peripheral blood B-cell compartments: a crossroad in B-cell traffic. Cytometry B Clin Cytom 2010; 78 (Suppl 1): S47.
206. Nouel A, Segalen I, Jamin C, et al,. B cells display an abnormal distribution and an impaired suppressive function in patients with chronic antibody-mediated rejection. Kidney Int 2014; 85: 590.
207. Cherukuri A, Rothstein DM, Clark B, et al,. Immunologic human renal allograft injury associates with an altered IL-10/TNF-alpha expression ratio in regulatory B cells. J Am Soc Nephrol 2014; 25: 1575.
208. hi memory Tregs in clinical kidney transplantation tolerance. J Am Soc Nephrol 2015 Jan 2. pii: ASN.2014050480. [Epub ahead of print].
209. Parker A, Bowles K, Bradley JA, et al,. Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients-BCSH and BTS Guidelines. Br J Haematol 2010; 149: 693.
210. Wahl SM, Rosenstreich DL,. Role of B lymphocytes in cell-mediated immunity. I. Requirement for T cells or T-cell products for antigen-induced B-cell activation. J Exp Med 1976; 144: 1175.
211. Brouard S, Giral M, Soulillou JP, Shton-Chess J,. Elaboration of gene expression-based clinical decision aids for kidney transplantation: where do we stand? Transplantation 2011; 91: 691.
212. Mazariegos GV,. Immunosuppression withdrawal after liver transplantation: what are the next steps? Transplantation 2011; 91: 697.
213. Orlando G, Soker S, Wood K,. Operational tolerance after liver transplantation. J Hepatol 2009; 50: 1247.
214. Benseler V, McCaughan GW, Schlitt HJ, Bishop GA, Bowen DG, Bertolino P,. The liver: a special case in transplantation tolerance. Semin Liver Dis 2007; 27: 194.
215. Crispe IN, Giannandrea M, Klein I, John B, Sampson B, Wuensch S,. Cellular and molecular mechanisms of liver tolerance. Immunol Rev 2006; 213: 101.
216. Steger U, Denecke C, Sawitzki B, Karim M, Jones ND, Wood KJ,. Exhaustive differentiation of alloreactive CD8+ T cells: critical for determination of graft acceptance or rejection. Transplantation 2008; 85: 1339.
217. Demetris AJ, Ruppert K, Dvorchik I, et al,. Real-time monitoring of acute liver-allograft rejection using the Banff schema. Transplantation 2002; 74: 1290.
218. Wiesner RH, Demetris AJ, Belle SH, et al,. Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. Hepatology 1998; 28: 638.
219. Mazariegos GV, Reyes J, Marino IR, et al,. Weaning of immunosuppression in liver transplant recipients. Transplantation 1997; 63: 243.
220. Ramos HC, Reyes J, Bu-Elmagd K, et al,. Weaning of immunosuppression in long-term liver transplant recipients. Transplantation 1995; 59: 212.
221. Demetris AJ, Murase N, Nakamura K, et al,. Immunopathology of antibodies as effectors of orthotopic liver allograft rejection. Semin Liver Dis 1992; 12: 51.
222. Demetris A, Adams D, Bellamy C, et al,. Update of the International Banff Schema for Liver Allograft Rejection: working recommendations for the histopathologic staging and reporting of chronic rejection. An International Panel. Hepatology 2000; 31: 792.
223. Sanchez-Fueyo A,. Hot-topic debate on tolerance: immunosuppression withdrawal. Liver Transpl 2011; 17 (Suppl 3): S69.
224. Viklicky O, Krystufkova E, Brabcova I, et al,. B-cell-related biomarkers of tolerance are up-regulated in rejection-free kidney transplant recipients. Transplantation 2013; 95: 148.
225. Salinas-Carmona MC, Perez LI, Galan K, Vazquez AV,. Immunosuppressive drugs have different effect on B lymphocyte subsets and IgM antibody production in immunized BALB/c mice. Autoimmunity 2009; 42: 537.
226. Kwun J, Bulut P, Kim E, et al,. The role of B cells in solid organ transplantation. Semin Immunol 2012; 24: 96.
227. Poppe D, Tiede I, Fritz G, et al,. Azathioprine suppresses ezrin-radixin-moesin-dependent T cell-APC conjugation through inhibition of Vav guanosine exchange activity on Rac proteins. J Immunol 2006; 176: 640.
228. Taylor AL, Watson CJ, Bradley JA,. Immunosuppressive agents in solid organ transplantation: mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol 2005; 56: 23.
229. Tiede I, Fritz G, Strand S, et al,. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 2003; 111: 1133.
230. Elion GB,. The George Hitchings and Gertrude Elion Lecture. The pharmacology of azathioprine. Ann N Y Acad Sci 1993; 685: 400.
231. Poirier N, Blancho G, Vanhove B,. Alternatives to calcineurin inhibition in renal transplantation: belatacept, the first co-stimulation blocker. Immunotherapy 2010; 2: 625.
232. Poirier N, Blancho G, Vanhove B,. A more selective costimulatory blockade of the CD28-B7 pathway. Transpl Int 2011; 24: 2.
233. Pilat N, Wekerle T,. Belatacept and Tregs: friends or foes? Immunotherapy 2012; 4: 351.
234. Abramowicz D, Del Carmen RM, Vitko S, et al,. Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen: results of a five-year, prospective, randomized study. J Am Soc Nephrol 2005; 16: 2234.
235. Ekberg H, Tedesco-Silva H, Demirbas A, et al,. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007; 357: 2562.
236. Pallardo LM, Oppenheimer F, Guirado L, et al,. Calcineurin inhibitor reduction based on maintenance immunosuppression with mycophenolate mofetil in renal transplant patients: POP study. Transplant Proc 2007; 39: 2187.
237. Vivek K, Mustafa MM, Rodriguez E, et al,. Strategies for B-lymphocyte repertoire remodeling in transplantation tolerance. Immunol Res 2011; 51: 1.
238. Newell KA, Chong AS,. Making a B-line for transplantation tolerance. Am J Transplant 2011; 11: 420.
239. Bluestone JA, Thomson AW, Shevach EM, Weiner HL,. What does the future hold for cell-based tolerogenic therapy? Nat Rev Immunol 2007; 7: 650.
240. Liu C, Noorchashm H, Sutter JA, et al,. B lymphocyte-directed immunotherapy promotes long-term islet allograft survival in nonhuman primates. Nat Med 2007; 13: 1295.
241. Kopchaliiska D, Zachary AA, Montgomery RA, Leffell MS,. Reconstitution of peripheral allospecific CD19+ B-cell subsets after B-lymphocyte depletion therapy in renal transplant patients. Transplantation 2009; 87: 1394.
242. Kelishadi SS, Azimzadeh AM, Zhang T, et al,. Preemptive CD20+ B cell depletion attenuates cardiac allograft vasculopathy in cyclosporine-treated monkeys. J Clin Invest 2010; 120: 1275.
243. Alwayn IP, Xu Y, Basker M, et al,. Effects of specific anti-B and/or anti-plasma cell immunotherapy on antibody production in baboons: depletion of CD20- and CD22-positive B cells does not result in significantly decreased production of anti-alphaGal antibody. Xenotransplantation 2001; 8: 157.
244. Kozlowski T, Andreoni K,. Limitations of rituximab/IVIg desensitization protocol in kidney transplantation; is this better than a tincture of time? Ann Transplant 2011; 16: 19.
245. Munoz AS, Rioveros AA, Cabanayan-Casasola CB, Danguilan RA, Ona ET,. Rituximab in highly sensitized kidney transplant recipients. Transplant Proc 2008; 40: 2218.
246. Ramos EJ, Pollinger HS, Stegall MD, Gloor JM, Dogan A, Grande JP,. The effect of desensitization protocols on human splenic B-cell populations in vivo. Am J Transplant 2007; 7: 402.
247. Parsons RF, Vivek K, Rostami SY, et al,. Acquisition of humoral transplantation tolerance upon de novo emergence of B lymphocytes. J Immunol 2011; 186: 614.
248. Parsons RF, Redfield RR III, Rodriguez E, et al,. Primary B cell repertoire remodeling to achieve humoral transplantation tolerance. Semin Immunol 2012; 24: 109.
249. Fan X, Ang A, Pollock-Barziv SM, et al,. Donor-specific B-cell tolerance after ABO-incompatible infant heart transplantation. Nat Med 2004; 10: 1227.
250. Zarkhin V, Li L, Sarwal MM,. BAFF may modulate the rate of B-cell repopulation after rituximab therapy for acute renal transplant rejection. Transplantation 2009; 88: 1229.
251. Parsons RF, Vivek K, Redfield RR, et al,. B-cell tolerance in transplantation: is repertoire remodeling the answer? Expert Rev Clin Immunol 2009; 5: 703.