Current Transplantation Reports

, Volume 6, Issue 1, pp 60–68 | Cite as

High-Dimensional Renal Profiling: Towards a Better Understanding of Renal Transplant Immune Suppression

  • Cyd M. Castro-Rojas
  • Rita R. Alloway
  • E. Steve Woodle
  • David A. HildemanEmail author
Immunology (R Fairchild, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Immunology


Purpose of Review

The goal of this review is to discuss new approaches to avoid calcineurin inhibitor (CNI)/corticosteroids (CCS) toxicities with a focus on new biologics and new methods to understand transplant rejection at the single-cell level.

Recent Findings

Recently developed biologics hold significant promise as the next wave of therapeutics designed to promote CNI/CCS-free long-term allograft acceptance. Indeed, belatacept, soluble CTLA4-Ig, is largely devoid of CNI-like toxicities, although it is accompanied by an increased frequency of acute rejection. Besides belatacept, other biologics hold promise as CNI-free immune suppressive approaches. Finally, powerful new single-cell approaches can enable characterization of cellular populations that drive rejection within the rejecting allograft.


We propose that the incorporated single-cell profiling into studies investigating new biologics in transplantation could be tailored to each patient, correlated with potential biomarkers in the blood and urine, and provide a platform where therapeutic targets can be rationally defined, mechanistically based, and exploited.


Kidney allograft rejection Calcineurin inhibitor Immunosuppression Toxicity Belatacept mTOR inhibitor High-dimension profiling Single-cell RNA sequencing 


Compliance with Ethical Standards

Conflict of Interest

David Hildeman reports grants from University of Cincinnati Center for Clinical & Translational Science & Training. David. A. Hildeman, Cyd Castro-Rojas, Rita R. Alloway, and E. Steve Woodle declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Prabhakaran D, Anand S, Watkins D, Gaziano T, Wu Y, Mbanya JC et al. Cardiovascular, respiratory, and related disorders: key messages from Disease Control Priorities, 3rd edition. Lancet. 2018;391(10126):1224–36.
  2. 2.
    Bindroo S, Challa HJ. Renal failure. Treasure Island: StatPearls; 2018.Google Scholar
  3. 3.
    Fouli GE, Gnudi L. The future: experimental therapies for renal disease in diabetes. Nephron. 2018:1–5.
  4. 4.
    Swaminathan S, Mor V, Mehrotra R, Trivedi A. Medicare’s payment strategy for end-stage renal disease now embraces bundled payment and pay-for-performance to cut costs. Health Aff (Millwood). 2012;31(9):2051–8. Scholar
  5. 5.
    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(23):1725–30. Scholar
  6. 6.
    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(3):378–83.CrossRefPubMedGoogle Scholar
  7. 7.
    Grgic I, Chandraker A. Significance of biologics in renal transplantation: past, present, and future. Curr Opin Organ Transplant. 2018;23(1):51–62. Scholar
  8. 8.
    Azzi JR, Sayegh MH, Mallat SG. Calcineurin inhibitors: 40 years later, can’t live without. J Immunol. 2013;191(12):5785–91. Scholar
  9. 9.
    Gaston RS. Our evolving understanding of late kidney allograft failure. Curr Opin Organ Transplant. 2011;16(6):594–9. Scholar
  10. 10.
    Tutschka PJ, Beschorner WE, Hess AD, Santos GW. Cyclosporin-A to prevent graft-versus-host disease: a pilot study in 22 patients receiving allogeneic marrow transplants. Blood. 1983;61(2):318–25.PubMedGoogle Scholar
  11. 11.
    Bowman LJ, Brennan DC. The role of tacrolimus in renal transplantation. Expert Opin Pharmacother. 2008;9(4):635–43.
  12. 12.
    Naesens M, Kuypers DR, Sarwal M. Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol. 2009;4(2):481–508. Scholar
  13. 13.
    Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12(2):388–99. Scholar
  14. 14.
    Guerra G, Srinivas TR, Meier-Kriesche HU. Calcineurin inhibitor-free immunosuppression in kidney transplantation. Transpl Int. 2007;20(10):813–27. Scholar
  15. 15.
    Leas BF, Uhl S, Sawinski DL, Trofe-Clark J, Tuteja S, Kaczmarek JL, et al. Calcineurin inhibitors for renal transplant. Rockville: AHRQ Comparative Effectiveness Reviews; 2016.Google Scholar
  16. 16.
    Ekberg H, Tedesco-Silva H, Demirbas A, Vitko S, Nashan B, Gurkan A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med. 2007;357(25):2562–75. Scholar
  17. 17.
    Srinivas TR, Meier-Kriesche HU. Minimizing immunosuppression, an alternative approach to reducing side effects: objectives and interim result. Clin J Am Soc Nephrol. 2008;3(Suppl 2):S101–16. Scholar
  18. 18.
    Thierry A, Le Meur Y, Ecotiere L, Abou-Ayache R, Etienne I, Laurent C, et al. Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study. Transpl Int. 2016;29(1):23–33. Scholar
  19. 19.
    Salvadori M, Bertoni E. Is it time to give up with calcineurin inhibitors in kidney transplantation? World J Transplant. 2013;3(2):7–25. Scholar
  20. 20.
    Diekmann F, Campistol JM. Practical considerations for the use of mTOR inhibitors. Transplant Res. 2015;4(Suppl 1):5–17. Scholar
  21. 21.
    Grimbert P, Thaunat O. mTOR inhibitors and risk of chronic antibody-mediated rejection after kidney transplantation: where are we now? Transpl Int. 2017;30(7):647–57. Scholar
  22. 22.
    Croze LE, Tetaz R, Roustit M, Malvezzi P, Janbon B, Jouve T, et al. Conversion to mammalian target of rapamycin inhibitors increases risk of de novo donor-specific antibodies. Transpl Int. 2014;27(8):775–83. Scholar
  23. 23.
    Murakami N, Riella LV, Funakoshi T. Risk of metabolic complications in kidney transplantation after conversion to mTOR inhibitor: a systematic review and meta-analysis. Am J Transplant. 2014;14(10):2317–27. Scholar
  24. 24.
    Andrassy J, Hoffmann VS, Rentsch M, Stangl M, Habicht A, Meiser B, et al. Is cytomegalovirus prophylaxis dispensable in patients receiving an mTOR inhibitor-based immunosuppression? A systematic review and meta-analysis. Transplantation. 2012;94(12):1208–17. Scholar
  25. 25.
    Havenith SH, Yong SL, van Donselaar-van der Pant KA, van Lier RA, ten Berge IJ, Bemelman FJ. Everolimus-treated renal transplant recipients have a more robust CMV-specific CD8+ T-cell response compared with cyclosporine- or mycophenolate-treated patients. Transplantation. 2013;95(1):184–91. Scholar
  26. 26.
    Mulay AV, Hussain N, Fergusson D, Knoll GA. Calcineurin inhibitor withdrawal from sirolimus-based therapy in kidney transplantation: a systematic review of randomized trials. Am J Transplant. 2005;5(7):1748–56. Scholar
  27. 27.
    Kamar N, Rostaing L, Cassuto E, Villemain F, Moal MC, Ladriere M, et al. A multicenter, randomized trial of increased mycophenolic acid dose using enteric-coated mycophenolate sodium with reduced tacrolimus exposure in maintenance kidney transplant recipients. Clin Nephrol. 2012;77(2):126–36. Scholar
  28. 28.
    Abramowicz D, Manas D, Lao M, Vanrenterghem Y, Del Castillo D, Wijngaard P, et al. Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen in stable kidney transplant recipients: a randomized, controlled study. Transplantation. 2002;74(12):1725–34. Scholar
  29. 29.
    Schold JD, Andreoni KA, Chandraker AK, Gaston RS, Locke JE, Mathur AK, et al. Expanding clarity or confusion? Volatility of the 5-tier ratings assessing quality of transplant centers in the United States. Am J Transplant. 2018;18(6):1494–501. Scholar
  30. 30.
    Ippoliti G, D'Armini AM, Lucioni M, Marjieh M, Vigano M. Introduction to the use of belatacept: a fusion protein for the prevention of posttransplant kidney rejection. Biologics. 2012;6:355–62. Scholar
  31. 31.
    Martin ST, Tichy EM, Gabardi S. Belatacept: a novel biologic for maintenance immunosuppression after renal transplantation. Pharmacotherapy. 2011;31(4):394–407. Scholar
  32. 32.
    • Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, et al. Belatacept and long-term outcomes in kidney transplantation. N Engl J Med. 2016;374(4):333–43. This study provides long-term outcomes data of kidney transplant recipients treated with belatacept for immunosuppression. The authors show significant increased renal function in belatacept-treated patients when compared to CNI-treated patients. CrossRefPubMedGoogle Scholar
  33. 33.
    Vincenti F. Are calcineurin inhibitors-free regimens ready for prime time? Kidney Int. 2012;82(10):1054–60. Scholar
  34. 34.
    Vincenti F, Charpentier B, Vanrenterghem Y, Rostaing L, Bresnahan B, Darji P, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2010;10(3):535–46. Scholar
  35. 35.
    Mou D, Espinosa J, Lo DJ, Kirk AD. CD28 negative T cells: is their loss our gain? Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2014;14(11):2460–6. Scholar
  36. 36.
    Xu H, Perez SD, Cheeseman J, Mehta AK, Kirk AD. The allo- and viral-specific immunosuppressive effect of belatacept, but not tacrolimus, attenuates with progressive T cell maturation. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2014;14(2):319–32. Scholar
  37. 37.
    Trzonkowski P, Zilvetti M, Chapman S, Wieckiewicz J, Sutherland A, Friend P, et al. Homeostatic repopulation by CD28-CD8+ T cells in alemtuzumab-depleted kidney transplant recipients treated with reduced immunosuppression. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2008;8(2):338–47. Scholar
  38. 38.
    Mathews DV, Wakwe WC, Kim SC, Lowe MC, Breeden C, Roberts ME, et al. Belatacept-resistant rejection is associated with CD28(+) memory CD8 T cells. Am J Transplant. 2017;17(9):2285–99. Scholar
  39. 39.
    Lo DJ, Weaver TA, Stempora L, Mehta AK, Ford ML, Larsen CP, et al. Selective targeting of human alloresponsive CD8+ effector memory T cells based on CD2 expression. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2011;11(1):22–33. Scholar
  40. 40.
    Weaver TA, Charafeddine AH, Agarwal A, Turner AP, Russell M, Leopardi FV, et al. Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates. Nat Med. 2009;15(7):746–9. Scholar
  41. 41.
    • Ferguson R, Grinyo J, Vincenti F, Kaufman DB, Woodle ES, Marder BA, et al. Immunosuppression with belatacept-based, corticosteroid-avoiding regimens in de novo kidney transplant recipients. Am J Transplant. 2011;11(1):66–76. This pilot study describes CNI/CCS-free belatacept-based regimen provided effective immunosuppression with better renal function in kidney transplant recipients compared to CNI-based regimens. CrossRefPubMedGoogle Scholar
  42. 42.
    Woodle EKD, Shields A, Leone J, Wiseman A, Matas A, West-Thielke P, et al. The BEST trial: a prospective randomized multicenter trial of belatacept-based CNI- and corticosteroid-free immunosuppression. [Abstract]. In press 2018.Google Scholar
  43. 43.
    Myrvang H. Transplantation: alemtuzumab induction is safe for renal transplant recipients. Nat Rev Nephrol. 2011;7(7):362. Scholar
  44. 44.
    Mourad G, Garrigue V, Squifflet JP, Besse T, Berthoux F, Alamartine E, et al. Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression. Transplantation. 2001;72(6):1050–5.CrossRefPubMedGoogle Scholar
  45. 45.
    Tian JH, Wang X, Yang KH, Liu AP, Luo XF, Zhang J. Induction with and without antithymocyte globulin combined with cyclosporine/tacrolimus-based immunosuppression in renal transplantation: a meta-analysis of randomized controlled trials. Transplant Proc. 2009;41(9):3671–6. Scholar
  46. 46.
    Hanaway MJ, Woodle ES, Mulgaonkar S, Peddi VR, Kaufman DB, First MR, et al. Alemtuzumab induction in renal transplantation. N Engl J Med. 2011;364(20):1909–19. Scholar
  47. 47.
    Lo DJ, Anderson DJ, Weaver TA, Leopardi F, Song M, Farris AB, et al. Belatacept and sirolimus prolong nonhuman primate renal allograft survival without a requirement for memory T cell depletion. Am J Transplant. 2013;13(2):320–8. Scholar
  48. 48.
    Lowe MC, Badell IR, Turner AP, Thompson PW, Leopardi FV, Strobert EA, et al. Belatacept and sirolimus prolong nonhuman primate islet allograft survival: adverse consequences of concomitant alefacept therapy. Am J Transplant. 2013;13(2):312–9. Scholar
  49. 49.
    Kothary N, Diak IL, Brinker A, Bezabeh S, Avigan M, Dal PG. Progressive multifocal leukoencephalopathy associated with efalizumab use in psoriasis patients. J Am Acad Dermatol. 2011;65(3):546–51. Scholar
  50. 50.
    Vincenti F, Mendez R, Pescovitz M, Rajagopalan PR, Wilkinson AH, Butt K, et al. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant. 2007;7(7):1770–7. Scholar
  51. 51.
    Salomon B, Bluestone JA. Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol. 2001;19:225–52. Scholar
  52. 52.
    Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006;355(10):1018–28. Scholar
  53. 53.
    Stebbings R, Findlay L, Edwards C, Eastwood D, Bird C, North D, et al. “Cytokine storm” in the phase I trial of monoclonal antibody TGN1412: better understanding the causes to improve preclinical testing of immunotherapeutics. J Immunol. 2007;179(5):3325–31.CrossRefPubMedGoogle Scholar
  54. 54.
    Ville S, Poirier N, Branchereau J, Charpy V, Pengam S, Nerriere-Daguin V, et al. Anti-CD28 antibody and belatacept exert differential effects on mechanisms of renal allograft rejection. J Am Soc Nephrol. 2016;27(12):3577–88. Scholar
  55. 55.
    Poirier N, Blancho G, Hiance M, Mary C, Van Assche T, Lempoels J, et al. First-in-human study in healthy subjects with FR104, a pegylated monoclonal antibody fragment antagonist of CD28. J Immunol. 2016;197(12):4593–602. Scholar
  56. 56.
    Watkins BK, Tkachev V, Furlan SN, Hunt DJ, Betz K, Yu A, et al. CD28 blockade controls T cell activation to prevent graft-versus-host disease in primates. J Clin Invest. 2018;128(9):3991–4007. Scholar
  57. 57.
    Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev. 2009;229(1):152–72. Scholar
  58. 58.
    Grewal IS, Flavell RA. The role of CD40 ligand in costimulation and T-cell activation. Immunol Rev. 1996;153:85–106.CrossRefPubMedGoogle Scholar
  59. 59.
    Sidiropoulos PI, Boumpas DT. Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients. Lupus. 2004;13(5):391–7. Scholar
  60. 60.
    Okimura K, Maeta K, Kobayashi N, Goto M, Kano N, Ishihara T, et al. Characterization of ASKP1240, a fully human antibody targeting human CD40 with potent immunosuppressive effects. Am J Transplant. 2014;14(6):1290–9. Scholar
  61. 61.
    Imai A, Suzuki T, Sugitani A, Itoh T, Ueki S, Aoyagi T, et al. A novel fully human anti-CD40 monoclonal antibody, 4D11, for kidney transplantation in cynomolgus monkeys. Transplantation. 2007;84(8):1020–8. Scholar
  62. 62.
    Badell IR, Thompson PW, Turner AP, Russell MC, Avila JG, Cano JA, et al. Nondepleting anti-CD40-based therapy prolongs allograft survival in nonhuman primates. Am J Transplant. 2012;12(1):126–35. Scholar
  63. 63.
    Mohiuddin MM, Singh AK, Corcoran PC, Thomas ML 3rd, Clark T, Lewis BG, et al. Chimeric 2C10R4 anti-CD40 antibody therapy is critical for long-term survival of GTKO.hCD46.hTBM pig-to-primate cardiac xenograft. Nat Commun. 2016;7:11138. Scholar
  64. 64.
    Adams AB, Shirasugi N, Jones TR, Durham MM, Strobert EA, Cowan S, et al. Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival. J Immunol. 2005;174(1):542–50.CrossRefPubMedGoogle Scholar
  65. 65.
    Ristov J, Espie P, Ulrich P, Sickert D, Flandre T, Dimitrova M, et al. Characterization of the in vitro and in vivo properties of CFZ533, a blocking and non-depleting anti-CD40 monoclonal antibody. Am J Transplant. 2018;18:2895–904. Scholar
  66. 66.
    Cordoba F, Wieczorek G, Audet M, Roth L, Schneider MA, Kunkler A, et al. A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion. Am J Transplant. 2015;15(11):2825–36. Scholar
  67. 67.
    Boumpas DT, Furie R, Manzi S, Illei GG, Wallace DJ, Balow JE, et al. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum. 2003;48(3):719–27. Scholar
  68. 68.
    Kanmaz T, Fechner JJ Jr, Torrealba J, Kim HT, Dong Y, Oberley TD, et al. Monotherapy with the novel human anti-CD154 monoclonal antibody ABI793 in rhesus monkey renal transplantation model. Transplantation. 2004;77(6):914–20.CrossRefPubMedGoogle Scholar
  69. 69.
    Ulrich P, Flandre T, Espie P, Sickert D, Rubic-Schneider T, Shaw DA, et al. Non-clinical safety assessment of CFZ533, a Fc-silent anti-CD40 antibody, in cynomolgus monkeys. Toxicol Sci. 2018.
  70. 70.
    Cardin RD, Brooks JW, Sarawar SR, Doherty PC. Progressive loss of CD8+ T cell-mediated control of a gamma-herpesvirus in the absence of CD4+ T cells. J Exp Med. 1996;184(3):863–71.CrossRefPubMedGoogle Scholar
  71. 71.
    Van Aelst LN, Summer G, Li S, Gupta SK, Heggermont W, De Vusser K, et al. RNA profiling in human and murine transplanted hearts: identification and validation of therapeutic targets for acute cardiac and renal allograft rejection. Am J Transplant. 2016;16(1):99–110. Scholar
  72. 72.
    Halloran PF, Pereira AB, Chang J, Matas A, Picton M, De Freitas D, et al. Microarray diagnosis of antibody-mediated rejection in kidney transplant biopsies: an international prospective study (INTERCOM). Am J Transplant. 2013;13(11):2865–74. Scholar
  73. 73.
    Flechner SM, Kurian SM, Head SR, Sharp SM, Whisenant TC, Zhang J, et al. Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes. Am J Transplant. 2004;4(9):1475–89. Scholar
  74. 74.
    Sigdel TK, Nguyen M, Dobi D, Hsieh SC, Liberto JM, Vincenti F, et al. Targeted transcriptional profiling of kidney transplant biopsies. Kidney Int Rep. 2018;3(3):722–31. Scholar
  75. 75.
    Saint-Mezard P, Berthier CC, Zhang H, Hertig A, Kaiser S, Schumacher M, et al. Analysis of independent microarray datasets of renal biopsies identifies a robust transcript signature of acute allograft rejection. Transpl Int. 2009;22(3):293–302. Scholar
  76. 76.
    Halloran PF, Venner JM, Madill-Thomsen KS, Einecke G, Parkes MD, Hidalgo LG, et al. Review: the transcripts associated with organ allograft rejection. Am J Transplant. 2018;18(4):785–95. Scholar
  77. 77.
    Halloran PF, Reeve JP, Pereira AB, Hidalgo LG, Famulski KS. Antibody-mediated rejection, T cell-mediated rejection, and the injury-repair response: new insights from the Genome Canada studies of kidney transplant biopsies. Kidney Int. 2014;85(2):258–64. Scholar
  78. 78.
    • Halloran PF, Venner JM, Famulski KS. Comprehensive analysis of transcript changes associated with allograft rejection: combining universal and selective features. Am J Transplant. 2017;17(7):1754–69. This study provides insight into mechanisms and classification of mRNAs associated with renal allograft rejection. CrossRefPubMedGoogle Scholar
  79. 79.
    Malone AF, Wu H, Humphreys BD. Bringing renal biopsy interpretation into the molecular age with single-cell RNA sequencing. Semin Nephrol. 2018;38(1):31–9. Scholar
  80. 80.
    Potter SS. Single-cell RNA sequencing for the study of development, physiology and disease. Nat Rev Nephrol. 2018;14(8):479–92. Scholar
  81. 81.
    • Wu H, Malone AF, Donnelly EL, Kirita Y, Uchimura K, Ramakrishnan SM, et al. Single-cell transcriptomics of a human kidney allograft biopsy specimen defines a diverse inflammatory response. J Am Soc Nephrol. 2018;29(8):2069–80. This study highlights the feasibility of performing scRNA-seq analysis of a single human kidney allograft biopsy. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    • Adam M, Potter AS, Potter SS. Psychrophilic proteases dramatically reduce single-cell RNA-seq artifacts: a molecular atlas of kidney development. Development. 2017;144(19):3625–32. This study describes a cold protease method of single-cell dissociation that can reduce gene expression artefacts allowing for more precise gene expression datasets. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Cyd M. Castro-Rojas
    • 1
  • Rita R. Alloway
    • 2
  • E. Steve Woodle
    • 3
  • David A. Hildeman
    • 1
    • 4
    Email author
  1. 1.Division of ImmunobiologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA
  2. 2.Division of Nephrology, Department of Internal MedicineUniversity of Cincinnati College of MedicineCincinnatiUSA
  3. 3.Division of Transplantation, Department of SurgeryUniversity of Cincinnati College of MedicineCincinnatiUSA
  4. 4.Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiUSA

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