Abstract
Background: The 20th century represents a breakthrough in the transplantation era, since the first kidney transplantation between identical twins was performed. This was the first case of tolerance, since the recipient did not need immunosuppression. However, as transplantation became possible, an immunosuppression-free status became the ultimate goal, since the first tolerance case was a clear exception from the hard reality nowadays represented by rejection.
Methods: A plethora of studies was described over the past decades to understand the molecular mechanisms responsible for rejection. This review focuses on the most relevant studies found in the literature where renal tolerance cases are claimed. Contrasting, and at the same time, encouraging outcomes are herein discussed and a glimpse on the main renal biomarkers analyzed in this field is provided.
Results: The activation of the immune system has been shown to play a central role in organ failure, but also it seems to induce a tolerance status when an allograft is performed, despite tolerance is still rare to register. Although there are still overwhelming challenges to overcome and various immune pathways remain arcane; the immunosuppression minimization might be more attainable than previously believed.
Conclusion:. Multiple biomarkers and tolerance mechanisms suspected to be involved in renal transplantation have been investigated to understand their real role, with still no clear answers on the topic. Thus, the actual knowledge provided necessarily leads to more in-depth investigations, although many questions in the past have been answered, there are still many issues on renal tolerance that need to be addressed.
Keywords: Clinical operational tolerance, immune system, immunosuppression minimization, kidney transplantation, rejection, renal biomarker.
[1]
Saran R, Robinson B, Abbott KC, et al. US renal data system 2017 annual data report: Epidemiology of kidney disease in the United States. Am J Kidney Dis 2018; 71(3): A7.
[2]
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(8): 580-90.
[3]
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(12): 1699-704.
[4]
Berlanda M, Di Cocco P, Mazzotta C, et al. Clinical operational tolerance after kidney transplantation: A short literature review. Transplant Proc 2008; 40(6): 1847-51.
[5]
Nankivell BJ, Borrows RJ, Fung CL, et al. Calcineurin inhibitor nephrotoxicity: Longitudinal assessment by protocol histology. Transplantation 2004; 78(4): 557-65.
[6]
Dharnidharka VR, Stablein DM, Harmon WE. Post-transplant infections now exceed acute rejection as cause for hospitalization: A report of the NAPRTCS. Am J Transplant 2004; 4(3): 384-9.
[7]
Sayegh MH, Remuzzi G. Clinical update: Immunosuppression minimisation. Lancet 2007; 369(9574): 1676-8.
[8]
Ashton-Chess J, Giral M, Brouard S, Soulillou JP. Spontaneous operational tolerance after immunosuppressive drug withdrawal in clinical renal allotransplantation. Transplantation 2007; 84(10): 1215-9.
[9]
Di Cocco P, Bonanni L, D’Angelo M, et al. Clinical operational tolerance after solid organ transplantation. Transplant Proc 2009; 41(4): 1278-82.
[10]
Orlando G, Hematti P, Stratta RJ, et al. Clinical operational tolerance after renal transplantation: Current status and future challenges. Ann Surg 2010; 252(6): 915-28.
[11]
Massart A, Pallier A, Pascual J, et al. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients. Nephrol Dial Transplant 2016; 31(6): 1002-13.
[12]
Lerut J, Bonaccorsi-Riani E, Finet P, Gianello P. Minimization of steroids in liver transplantation. Transpl Int 2009; 22(1): 2-19.
[13]
Manzia TM, Angelico R, Baiocchi L, et al. The Tor Vergata weaning of immunosuppression protocols in stable hepatitis C virus liver transplant patients: The 10-year follow-up. Transpl Int 2013; 26(3): 259-66.
[14]
Manzia TM, Angelico R, Ciano P, et al. Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients. World J Gastroenterol 2014; 20(34): 12217-25.
[15]
Orlando G, Soker S, Wood K. Operational tolerance after liver transplantation. J Hepatol 2009; 50(6): 1247-57.
[16]
Pons JA, Revilla-Nuin B, Baroja-Mazo A, et al. FoxP3 in peripheral blood is associated with operational tolerance in liver transplant patients during immunosuppression withdrawal. Transplantation 2008; 86(10): 1370-8.
[17]
Pons Minano JA. Operational tolerance in liver transplantation is more frequent than expected and increases with time after the intervention. Gastroenterol Hepatol 2013; 36(9): 551-4.
[18]
Christensen LL, Grunnet N, Rudiger N, Moller B, Birkeland SA. Indications of immunological tolerance in kidney transplantation. Tissue Antigens 1998; 51(6): 637-44.
[19]
Owens MLMG, Goodnight J, et al. Discontinuance of immunosuppression in renal transplant patients. Arch Surg 1975; 110: 1450-1.
[20]
Uehling DT, Hussey JL, Weinstein AB, Wank R, Bach FH. Cessation of immunosuppression after renal transplantation. Surgery 1976; 79(3): 278-82.
[21]
Meier D, Rumbo M, Gondolesi GE. Current status of allograft tolerance in intestinal transplantation. Int Rev Immunol 2014; 33(3): 245-60.
[22]
Comerci GD Jr, Williams TM, Kellie S. Immune tolerance after total lymphoid irradiation for heart transplantation: Immunosuppressant-free survival for 8 years. J Heart Lung Transplant 2009; 28(7): 743-5.
[23]
Svendsen UG, Aggestrup S, Heilmann C, et al. Transplantation of a lobe of lung from mother to child following previous transplantation with maternal bone marrow. Eur Respir J 1995; 8(2): 334-7.
[24]
Demetris AJ, Lunz JG 3rd, Randhawa P, et al. Monitoring of human liver and kidney allograft tolerance: A tissue/histopathology perspective. Transpl Int 2009; 22(1): 120-41.
[25]
Danger R, Chesneau M, Paul C, et al. A composite score associated with spontaneous operational tolerance in kidney transplant recipients. Kidney Int 2017; 91(6): 1473-81.
[26]
Clatworthy MR. B-cell regulation and its application to transplantation. Transpl Int 2014; 27(2): 117-28.
[27]
Kirk AD, Turgeon NA, Iwakoshi NN. B cells and transplantation tolerance. Nat Rev Nephrol 2010; 6(10): 584-93.
[28]
Lu J, Zhang X. Immunological characteristics of renal transplant tolerance in humans. Mol Immunol 2016; 77: 71-8.
[29]
Chesneau M, Michel L, Dugast E, et al. Tolerant kidney transplant patients produce b cells with regulatory properties. J Am Soc Nephrol 2015; 26(10): 2588-98.
[30]
Newell KA, Adams AB, Turka LA. Biomarkers of operational tolerance following kidney transplantation - The immune tolerance network studies of spontaneously tolerant kidney transplant recipients. Hum Immunol 2018; 79(5): 380-7.
[31]
Chesneau M, Pallier A, Braza F, et al. Unique B cell differentiation profile in tolerant kidney transplant patients. Am J Transplant 2014; 14(1): 144-55.
[32]
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(6): 1848-61.
[33]
Chenouard A, Chesneau M, Bui Nguyen L, et al. Renal operational tolerance is associated with a defect of blood tfh cells that exhibit impaired b cell help. Am J Transplant 2017; 17(6): 1490-501.
[34]
Reichardt P, Dornbach B, Rong S, et al. Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse. Blood 2007; 110(5): 1519-29.
[35]
Cherukuri A, Salama AD, Carter CR, et al. Reduced human transitional B cell T1/T2 ratio is associated with subsequent deterioration in renal allograft function. Kidney Int 2017; 91(1): 183-95.
[36]
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(3): 590-9.
[37]
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(39): 15448-53.
[38]
Akoglu B, Lafferton B, Kalb S, et al. Rejection quantity in kidney transplant recipients is associated with increasing intracellular interleukin-2 in CD8+ T-cells. Transpl Immunol 2014; 31(1): 17-21.
[39]
Braudeau C, Racape M, Giral M, et al. Variation in numbers of CD4+CD25highFOXP3+ T cells with normal immuno-regulatory properties in long-term graft outcome. Transpl Int 2007; 20(10): 845-55.
[40]
Braza F, Dugast E, Panov I, et al. Central role of CD45RA- Foxp3hi memory regulatory T cells in clinical kidney trans-plantation tolerance. J Am Soc Nephrol 2015; 26(8): 1795-805.
[41]
Velasquez SY, Arias LF, Garcia LF, Alvarez CM. T cell receptor beta chain (TCR-Vbeta) repertoire of circulating CD4(+) CD25(-), CD4(+) CD25(low) and CD4(+) CD25(high) T cells in patients with long-term renal allograft survival. Transpl Int 2010; 23(1): 54-63.
[42]
Schaier M, Seissler N, Schmitt E, et al. DR(high+)CD45RA(-)-Tregs potentially affect the suppressive activity of the total Treg pool in renal transplant patients. PLoS One 2012; 7(3): e34208.
[43]
Hoffmann U, Neudorfl C, Daemen K, et al. NK cells of kidney transplant recipients display an activated phenotype that is influenced by immunosuppression and pathological staging. PLoS One 2015; 10(7): e0132484.
[44]
Trojan K, Zhu L, Aly M, et al. Association of peripheral NK cell counts with Helios(+) IFN-gamma(-) Tregs in patients with good long-term renal allograft function. Clin Exp Immunol 2017; 188(3): 467-79.
[45]
Mirzakhani M, Shahbazi M, Oliaei F, Mohammadnia-Afrouzi M. Immunological biomarkers of tolerance in human kidney transplantation: An updated literature review. J Cell Physiol 2018; 234(5): 5762-74.
[46]
Scandling JD, Busque S, Dejbakhsh-Jones S, et al. Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant 2012; 12(5): 1133-45.
[47]
Hidalgo LG, Sis B, Sellares J, et al. NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibody-mediated rejection. Am J Transplant 2010; 10(8): 1812-22.
[48]
Brouard S, Puig-Pey I, Lozano JJ, et al. Comparative transcriptional and phenotypic peripheral blood analysis of kidney recipients under cyclosporin A or sirolimus monotherapy. Am J Transplant 2010; 10(12): 2604-14.
[49]
Galante NZ, Ozaki KS, Cenedeze MA, et al. Frequency of Valpha24+Vbeta11+ NKT cells in peripheral blood of human kidney transplantation recipients. Int Immunopharmacol 2005; 5(1): 53-8.
[50]
Neudoerfl C, Mueller BJ, Blume C, et al. The peripheral NK cell repertoire after kidney transplantation is modulated by different immunosuppressive drugs. Front Immunol 2013; 4: 46.
[51]
Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 2013; 496(7446): 445-55.
[52]
Bergler T, Jung B, Bourier F, et al. Infiltration of macrophages correlates with severity of allograft rejection and outcome in human kidney transplantation. PLoS One 2016; 11(6): e0156900.
[53]
Toki D, Zhang W, Hor KL, et al. The role of macrophages in the development of human renal allograft fibrosis in the first year after transplantation. Am J Transplant 2014; 14(9): 2126-36.
[54]
Ikezumi Y, Suzuki T, Yamada T, et al. Alternatively activated macrophages in the pathogenesis of chronic kidney allograft injury. Pediatr Nephrol 2015; 30(6): 1007-17.
[55]
Hutchinson JA, Riquelme P, Sawitzki B, et al. Cutting edge: Immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients. J Immunol 2011; 187(5): 2072-8.
[56]
Pontrelli P, Cariello M, Rascio F, et al. Thrombin may modulate dendritic cell activation in kidney transplant recipients with delayed graft function. Nephrol Dial Transplant 2015; 30(9): 1480-7.
[57]
Womer KL, Huang Y, Herren H, et al. Dendritic cell deficiency associated with development of BK viremia and nephropathy in renal transplant recipients. Transplantation 2010; 89(1): 115-23.
[58]
Woltman AM, de Fijter JW, Zuidwijk K, et al. Quantification of dendritic cell subsets in human renal tissue under normal and pathological conditions. Kidney Int 2007; 71(10): 1001-8.
[59]
Ma L, Liu Y, Wu J, et al. Changes in dendritic cells and dendritic cell subpopulations in peripheral blood of recipients during acute rejection after kidney transplantation. Chin Med J 2014; 127(8): 1469-73.
[60]
Chessa F, Mathow D, Wang S, et al. The renal microenvironment modifies dendritic cell phenotype. Kidney Int 2016; 89(1): 82-94.
[61]
Ezzelarab MB, Zahorchak AF, Lu L, et al. Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates. Am J Transplant 2013; 13(8): 1989-2005.
[62]
Stallone G, Pontrelli P, Infante B, et al. Rapamycin induces ILT3(high)ILT4(high) dendritic cells promoting a new immunoregulatory pathway. Kidney Int 2014; 85(4): 888-97.
[63]
Boros P, Ochando JC, Chen SH, Bromberg JS. Myeloid-derived suppressor cells: Natural regulators for transplant tolerance. Hum Immunol 2010; 71(11): 1061-6.
[64]
Safarzadeh E, Orangi M, Mohammadi H, Babaie F, Baradaran B. Myeloid-derived suppressor cells: Important contributors to tumor progression and metastasis. J Cell Physiol 2018; 233(4): 3024-36.
[65]
Yazdani Y, Mohammadnia-Afrouzi M, Yousefi M, et al. Myeloid-derived suppressor cells in B cell malignancies. Tumour Biol 2015; 36(10): 7339-53.
[66]
Hock BD, Mackenzie KA, Cross NB, et al. Renal transplant recipients have elevated frequencies of circulating myeloid-derived suppressor cells. Nephrol Dial Transplant 2012; 27(1): 402-10.
[67]
Luan Y, Mosheir E, Menon MC, et al. Monocytic myeloid-derived suppressor cells accumulate in renal transplant patients and mediate CD4(+) Foxp3(+) Treg expansion. Am J Transplant 2013; 13(12): 3123-31.
[68]
Meng F, Chen S, Guo X, et al. Clinical significance of myeloid-derived suppressor cells in human renal transplantation with acute T cell-mediated rejection. Inflammation 2014; 37(5): 1799-805.
[69]
Rekers NV, Bajema IM, Mallat MJ, et al. Beneficial immune effects of myeloid-related proteins in kidney transplant rejection. Am J Transplant 2016; 16(5): 1441-55.
[70]
Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 2001; 69(3): 89-95.
[71]
Londono MC, Danger R, Giral M, et al. A need for biomarkers of operational tolerance in liver and kidney transplantation. Am J Transplant 2012; 12(6): 1370-7.
[72]
Massart A, Ghisdal L, Abramowicz M, Abramowicz D. Operational tolerance in kidney transplantation and associated biomarkers. Clin Exp Immunol 2017; 189(2): 138-57.
[73]
Sarwal MM. Fingerprints of transplant tolerance suggest opportunities for immunosuppression minimization. Clin Biochem 2016; 49(4-5): 404-10.
[74]
Baron D, Ramstein G, Chesneau M, et al. A common gene signature across multiple studies relate biomarkers and functional regulation in tolerance to renal allograft. Kidney Int 2015; 87(5): 984-95.
[75]
Crowley LE, Mekki M, Chand S. Biomarkers and pharmacogenomics in kidney transplantation. Mol Diagn Ther 2018; 22(5): 537-50.
[76]
Nissaisorakarn V, Lee JR, Lubetzky M, Suthanthiran M. Urine biomarkers informative of human kidney allograft rejection and tolerance. Hum Immunol 2018; 79(5): 343-55.
[77]
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(6): 1836-47.
[78]
Roedder S, Li L, Alonso MN, et al. A Three-gene assay for monitoring immune quiescence in kidney transplantation. J Am Soc Nephrol 2015; 26(8): 2042-53.
[79]
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(4): 597-606.
[80]
Fehr T, Sykes M. Tolerance induction in clinical transplantation. Transpl Immunol 2004; 13(2): 117-30.
[81]
Roussey-Kesler G, Giral M, Moreau A, et al. Clinical operational tolerance after kidney transplantation. Am J Transplant 2006; 6(4): 736-46.
[82]
VanBuskirk AM, Burlingham WJ, Jankowska-Gan E, et al. Human allograft acceptance is associated with immune regulation. J Clin Invest 2000; 106(1): 145-55.
[83]
Xu Q, Lee J, Jankowska-Gan E, et al. Human CD4+CD25low adaptive T regulatory cells suppress delayed-type hypersensitivity during transplant tolerance. J Immunol 2007; 178(6): 3983-95.
[84]
Fischer T, Schobel H, Barenbrock M. Specific immune tolerance during pregnancy after renal transplantation. Eur J Obstet Gynecol Reprod Biol 1996; 70(2): 217-9.
[85]
Trowsdale J, Betz AG. Mother’s little helpers: Mechanisms of maternal-fetal tolerance. Nat Immunol 2006; 7(3): 241-6.
[86]
Dutta P, Burlingham WJ. Tolerance to noninherited maternal antigens in mice and humans. Curr Opin Organ Transplant 2009; 14(4): 439-47.
[87]
Zoller KM, Cho SI, Cohen JJ, Harrington JT. Cessation of immunosuppressive therapy after successful transplantation: A national survey. Kidney Int 1980; 18(1): 110-4.
[88]
Miller J, Mathew JM, Esquenazi V. Toward tolerance to human organ transplants: A few additional corollaries and questions. Transplantation 2004; 77(6): 940-2.
[89]
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(11): 2796-801.
[90]
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(3): 398-407.
[91]
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(12): 3296-307.
[92]
Devuyst O, Knoers NV, Remuzzi G, Schaefer F. Rare inherited kidney diseases: Challenges, opportunities, and perspectives. Lancet 2014; 383(9931): 1844-59.
[93]
Zuber J, Sykes M. Mechanisms of mixed chimerism-based transplant tolerance. Trends Immunol 2017; 38(11): 829-43.
[94]
Starzl TE, Murase N, Abu-Elmagd K, et al. Tolerogenic immunosuppression for organ transplantation. Lancet 2003; 361(9368): 1502-10.
[95]
Pearl JP, Parris J, Hale DA, et al. Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. Am J Transplant 2005; 5(3): 465-74.
[96]
Trzonkowski P, Zilvetti M, Friend P, Wood KJ. Recipient memory-like lymphocytes remain unresponsive to graft antigens after CAMPATH-1H induction with reduced maintenance immunosuppression. Transplantation 2006; 82(10): 1342-51.
[97]
Butcher JA, Hariharan S, Adams MB, et al. Renal transplantation for end-stage renal disease following bone marrow transplantation: A report of six cases, with and without immunosuppression. Clin Transpl 1999; 13(4): 330-5.
[98]
Delis S, Ciancio G, Burke GW, Garcia-Morales R, Miller J. Donor bone marrow transplantation: Chimerism and tolerance. Transpl Immunol 2004; 13(2): 105-15.
[99]
Sayegh MH, Fine NA, Smith JL, et al. Immunologic tolerance to renal allografts after bone marrow transplants from the same donors. Ann Intern Med 1991; 114(11): 954-5.
[100]
Helg C, Chapuis B, Bolle JF, et al. Renal transplantation without immunosuppression in a host with tolerance induced by allogeneic bone marrow transplantation. Transplantation 1994; 58(12): 1420-2.
[101]
Jacobsen N, Taaning E, Ladefoged J, Kristensen JK, Pedersen FK. Tolerance to an HLA-B,DR disparate kidney allograft after bone-marrow transplantation from same donor. Lancet 1994; 343(8900): 800.
[102]
Sellers MT, Deierhoi MH, Curtis JJ, et al. Tolerance in renal transplantation after allogeneic bone marrow transplantation-6-year follow-up. Transplantation 2001; 71(11): 1681-3.
[103]
Sorof JM, Koerper MA, Portale AA, et al. Renal transplantation without chronic immunosuppression after T cell-depleted, HLA-mismatched bone marrow transplantation. Transplantation 1995; 59(11): 1633-5.
[104]
Buhler LH, Spitzer TR, Sykes M, et al. Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease. Transplantation 2002; 74(10): 1405-9.
[105]
Fudaba Y, Spitzer TR, Shaffer J, et al. Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: In vivo and in vitro analyses. Am J Transplant 2006; 6(9): 2121-33.
[106]
Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: The induction of allograft tolerance through mixed lymphohematopoietic chimerism. Transplantation 1999; 68(4): 480-4.
[107]
Trivedi HL, Mishra VV, Vanikar AV, et al. Embryonic stem cell derived and adult hematopoietic stem cell transplantation for tolerance induction in a renal allograft recipient: A case report. Transplant Proc 2006; 38(9): 3103-8.
[108]
Kawai T, Sachs DH, Sykes M, Cosimi AB. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2013; 368(19): 1850-2.
[109]
Burlingham WJ, Jankowska-Gan E, VanBuskirk A, et al. Loss of tolerance to a maternal kidney transplant is selective for HLA class II: Evidence from trans-vivo DTH and alloantibody analysis. Hum Immunol 2000; 61(12): 1395-402.
[110]
Scandling JD, Busque S, Dejbakhsh-Jones S, et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med 2008; 358(4): 362-8.
[111]
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(9): 1386-91.
[112]
Scandling JD, Busque S, Shizuru JA, et al. Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation. Am J Transplant 2015; 15(3): 695-704.
[113]
Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S. Induced immune tolerance for kidney transplantation. N Engl J Med 2011; 365(14): 1359-60.
[114]
Leventhal JR, Mathew JM, Ildstad S, et al. HLA identical non-chimeric and HLA disparate chimeric renal transplant tolerance. Clin Transpl 2013; 145-56.
[115]
Leventhal JR, Mathew JM, Salomon DR, et al. Nonchimeric HLA-Identical renal transplant tolerance: Regulatory immunophenotypic/ genomic biomarkers. Am J Transplant 2016; 16(1): 221-34.
[116]
Leventhal JR, Mathew JM, Salomon DR, et al. Genomic biomarkers correlate with HLA-identical renal transplant tolerance. J Am Soc Nephrol 2013; 24(9): 1376-85.
[117]
Leventhal JR, Miller J, Mathew JM, et al. Updated follow-up of a tolerance protocol in HLA-identical renal transplant pairs given donor hematopoietic stem cells. Hum Immunol 2018; 79(5): 277-82.
[118]
Leventhal J, Abecassis M, Miller J, et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci Transl Med 2012; 4(124): 124ra28.
[119]
Leventhal JR, Ildstad ST. Tolerance induction in HLA disparate living donor kidney transplantation by facilitating cell-enriched donor stem cell Infusion: The importance of durable chimerism. Hum Immunol 2018; 79(5): 272-6.
[120]
Colson YL, Christopher K, Glickman J, et al. Absence of clinical GVHD and the in vivo induction of regulatory T cells after transplantation of facilitating cells. Blood 2004; 104(12): 3829-35.
[121]
Huang Y, Bozulic LD, Miller T, et al. CD8α + plasmacytoid precursor DCs induce antigen-specific regulatory T cells that enhance HSC engraftment in vivo. Blood 2011; 117(8): 2494-505.
[122]
Kaufman CL, Colson YL, Wren SM, et al. Phenotypic characterization of a novel bone marrow-derived cell that facilitates engraftment of allogeneic bone marrow stem cells. Blood 1994; 84(8): 2436-46.
[123]
Leventhal JR, Elliott MJ, Yolcu ES, et al. Immune reconstitution/immunocompetence in recipients of kidney plus hematopoietic stem/facilitating cell transplants. Transplantation 2015; 99(2): 288-98.
[124]
Hutchinson JA, Brem-Exner BG, Riquelme P, et al. A cell-based approach to the minimization of immunosuppression in renal transplantation. Transpl Int 2008; 21(8): 742-54.
[125]
Hutchinson JA, Riquelme P, Brem-Exner BG, et al. Transplant acceptance-inducing cells as an immune-conditioning therapy in renal transplantation. Transpl Int 2008; 21(8): 728-41.
[126]
Starzl TE, Demetris AJ, Murase N, et al. Cell migration, chimerism, and graft acceptance. Lancet 1992; 339(8809): 1579-82.
[127]
Edgar L, Altamimi A, Garcia Sanchez M, et al. Utility of extracellular matrix powders in tissue engineering. Organogenesis 2018; 2018: 1-15.
[128]
Nagao RJ, Xu J, Luo P, et al. Decellularized human kidney cortex hydrogels enhance kidney microvascular endothelial cell maturation and quiescence. Tissue Eng Part A 2016; 22(19-20): 1140-50.
[129]
Orlando G, Danger R, Okut H, et al. Molecular pathways underlying adaptive repair of the injured kidney: Novel donation after cardiac death and acute kidney injury platforms. Ann Surg 2018.
[http://dx.doi.org/10.1097/SLA.0000000000002946]
[http://dx.doi.org/10.1097/SLA.0000000000002946]
[130]
Crop M, Baan C, Weimar W, Hoogduijn M. Potential of mesenchymal stem cells as immune therapy in solid-organ transplantation. Transpl Int 2009; 22(4): 365-76.
[131]
Dahlke MH, Hoogduijn M, Eggenhofer E, et al. Toward MSC in solid organ transplantation: 2008 position paper of the MISOT study group. Transplantation 2009; 88(5): 614-9.
[132]
Muthukumar T, Ding R, Dadhania D, et al. Serine proteinase inhibitor-9, an endogenous blocker of granzyme B/perforin lytic pathway, is hyperexpressed during acute rejection of renal allografts. Transplantation 2003; 75(9): 1565-70.
[133]
Tatapudi RR, Muthukumar T, Dadhania D, et al. Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine. Kidney Int 2004; 65(6): 2390-7.
[134]
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(22): 2342-51.
[135]
Afaneh C, Muthukumar T, Lubetzky M, et al. Urinary cell levels of mRNA for OX40, OX40L, PD-1, PD-L1, or PD-L2 and acute rejection of human renal allografts. Transplantation 2010; 90(12): 1381-7.
[136]
Suthanthiran M, Schwartz JE, Ding R, et al. Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med 2013; 369(1): 20-31.
[137]
Suhre K, Schwartz JE, Sharma VK, et al. Urine metabolite profiles predictive of human kidney allograft status. J Am Soc Nephrol 2016; 27(2): 626-36.
[138]
Reese PP, Hall IE, Weng FL, et al. Associations between deceased-donor urine injury biomarkers and kidney transplant outcomes. J Am Soc Nephrol 2016; 27(5): 1534-43.
[139]
Nguyen MT, Fryml E, Sahakian SK, et al. Pretransplant recipient circulating CD4+CD127lo/- tumor necrosis factor receptor 2+ Regulatory T cells: A surrogate of regulatory t cell-suppressive function and predictor of delayed and slow graft function after kidney transplantation. Transplantation 2016; 100(2): 314-24.
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Related Books
Drug Addiction Mechanisms in the Brain
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Biotechnology and Drug Development for Targeting Human Diseases
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Enzymatic Targets for Drug Discovery Against Alzheimer's Disease
Medicinal Plants, Phytomedicines and Traditional Herbal Remedies for Drug Discovery and Development against COVID-19
Advanced Pharmacy
Plant-derived Hepatoprotective Drugs
Brain Tumor Targeting Drug Delivery Systems: Advanced Nanoscience for Theranostics Applications
Article Metrics
54
2