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Immunologic Response of the Child to Short- and Long-Term Immunosuppression

  • Deborah M. Consolini
Reference work entry
Part of the Organ and Tissue Transplantation book series (OTT)

Abstract

Solid organ transplantation has become a proven and accepted therapy in pediatric patients with organ failure that is not only lifesaving but also greatly contributes to a better quality of life in organ recipients. This development was possible because of a remarkable expansion in the available repertoire of immunosuppressive medications. Over the past 30 years, however, despite considerable improvement in short-term outcomes, long-term allograft survival has only minimally improved. Chronic allograft dysfunction is the leading cause of allograft loss in pediatric organ transplant recipients. In addition, the consequences of the long-term use of immunosuppressive medications can be severe and include increased susceptibility to infection, drug toxicities, and the development of comorbid conditions such as chronic kidney disease, cardiovascular disease, and cancer. This chapter will review current immunosuppressive strategies used in solid organ transplantation with a particular focus on the immunologic response of pediatric patients to both short- and long-term immunosuppression strategies. Further research will hopefully provide us with newer strategies that promote immunologic tolerance of the transplanted organ without the severe side effects and with improved long-term allograft survival.

Keywords

Immunosuppression Corticosteroids Calcineurin inhibitor Antiproliferatives mTOR inhibitor Antibody therapies Acute cellular rejection Antibody mediated rejection Chronic allograft dysfunction Nephrotoxicity Posttransplant lymphoproliferative disorder Nonadherence Tolerance 

Abbreviations

ACR

acute cellular rejection

AMR

Antibody-mediated rejection

APC

Antigen-presenting cell

ATG

Anti-thymocyte globulin

AV

Allograft vasculopathy

CAD

Chronic allograft dysfunction

CKD

Chronic kidney disease

CMV

Cytomegalovirus

CNI

Calcineurin inhibitor

DSA

Donor-specific antibodies

EBV

Epstein-Barr virus

ESKD

End-stage kidney disease

FKBP12

FK506-binding protein12

HAT

Hepatic artery thrombosis

IL-2

Interleukin-2

IVIG

Intravenous immune globulin

MMF

Mycophenolate mofetil

6-MP

6-mercaptopurine

MRI

Magnetic resonance imaging

mTOR

Mammalian targets of rapamycin

NFAT

Nuclear factor of activated T-cells

NF-κB

Nuclear factor kappa-light-chain-enhancer of activated B cells

NODAT

New onset diabetes after transplantation

PPH

Plasmapheresis

PRES

Posterior reversible encephalopathy syndrome

PTLD

Posttransplant lymphoproliferative disease

SOT

Solid organ transplantation

TPMT

Thiopurine S-methyltransferase

References

  1. Bamgbola O (2016) Metabolic consequences of modern immunosuppressive agents in solid organ transplantation. Ther Adv Endocrinol Metab 7:110–127CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bamoulid J, Staeck O, Halleck F et al (2015) The need for minimization strategies: current problems of immunosuppression. Transpl Int 28:891–900CrossRefPubMedGoogle Scholar
  3. Barnett A, Asgari E, Chowdhury P et al (2013) The use of eculizumab in renal transplantation. Clin Transpl 27:E216–E229CrossRefGoogle Scholar
  4. Benden C, Dipchand A, Danziger-Isakov L et al (2008) Pediatric transplanation: ten years on. Pediatr Transplant 13:272–277CrossRefGoogle Scholar
  5. Coelho T, Tredger M, Dhawan A (2012) Current status of immunosuppressive agents for solid organ transplantation in children. Pediatr Transplant 16:106–122CrossRefPubMedGoogle Scholar
  6. Dalla Pozza R, Urschel S, Bechtold S et al (2008) Subclinical atherosclerosis after heart and heart-lung transplantation in childhood. Pediatr Transplant 12:577–581CrossRefPubMedGoogle Scholar
  7. Dharnidharka V, Lamb K, Zheng J et al (2015a) Lack of significant improvements in long-term allograft survival in pediatric solid organ transplantation: a US national registry analysis. Pediatr Transplant 19: 477–483CrossRefPubMedGoogle Scholar
  8. Dharnidharka V, Lamb K, Zheng J et al (2015b) Across all solid organs, adolescent age recipients have worse transplant organ survival than younger children: a US national registry analysis. Pediatr Transplant 19: 471–476CrossRefPubMedGoogle Scholar
  9. Djamali A, Kaufman D, Ellis T et al (2014) Diagnosis and management of antibody-mediated rejection: current status and novel approaches. Am J Transplant 14: 255–271CrossRefPubMedPubMedCentralGoogle Scholar
  10. Eisen H, Tuzcu E, Dorent R et al (2003) Everolimus for the prevention of allograft vasculopathy in cardiac-transplant recipients. N Engl J Med 349:847–858CrossRefPubMedGoogle Scholar
  11. Enderby C, Keller C (2015) An overview of immunosuppression in solid organ transplantation. Am J Manag Care 21:S12–S23PubMedGoogle Scholar
  12. Feng S, Ekong U, Lobritto S et al (2012) Complete immunosuppression withdrawal and subsequent allograft function among pediatric recipients of parental living donor liver transplants. JAMA 307:283–293CrossRefPubMedGoogle Scholar
  13. Grimbert P, Thaunat O (2017) mTOR inhibitors and risk of chronic antibody-mediated rejection after kidney transplantation: where are we now? Transpl Int 30:647–657CrossRefPubMedGoogle Scholar
  14. Heidt S, Wood K (2012) Biomarkers of operational tolerance in solid organ transplantation. Expert Opin Med Diagn 6:281–293CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kim J, Marks S (2014) Long-term outcomes of children after solid organ transplantation. Clinics (Sao Paulo) 69:28–38CrossRefGoogle Scholar
  16. Krmar R, Balzano R, Jogestrand T et al (2008) Prospective analysis of carotid arterial wall structure in pediatric renal transplants with ambulatory normotension and in treated hypertensive recipients. Pediatr Transplant 12:412–419CrossRefPubMedGoogle Scholar
  17. Lodhi S, Lamb K, Meier-Kriesche H (2011) Solid organ allograft survival improvement in the United States: the long-term does not mirror the dramatic short-term success. Am J Transplant 11:1226–1235CrossRefPubMedGoogle Scholar
  18. Manuel O, Kralidis G, Mueller N et al (2013) Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 13:2402–2410CrossRefPubMedGoogle Scholar
  19. Martin-Gandul C, Mueller N, Pascual M et al (2015) The impact of infection on chronic allograft dysfunction and allograft survival after solid organ transplantation. Am J Transplant 15:3024–3040CrossRefPubMedGoogle Scholar
  20. Miettinen J, Peräsaari J, Lauronen J et al (2012) Donor-specific HLA antibodies and graft function in children after renal transplantation. Pediatr Nephrol 27:1011–1019CrossRefPubMedGoogle Scholar
  21. Mynarek M, Schober T, Behrends U et al (2013) Posttransplant lymphoproliferative disease after pediatric solid organ transplantation. Clin Dev Immunol 2013: 1–14CrossRefGoogle Scholar
  22. Ruebner R, Reese P, Dinburg M et al (2013) End-stage kidney disease after pediatric nonrenal solid organ transplantation. Pediatrics 132:1319–1326CrossRefGoogle Scholar
  23. Van Sandwijk M, Bemelman F, ten Berge I (2013) Immunosuppressive drugs after solid organ transplantation. Neth J Med 71:281–289PubMedGoogle Scholar
  24. Vincenti F, Rostaing L, Grinyo J et al (2016) Belatacept and long-term outcomes in kidney transplantation. N Engl J Med 374:333–343CrossRefPubMedGoogle Scholar
  25. Waiser J, Duerr M, Schonemann C et al (2016) Rituximab in combination with Bortezomib, plasmapheresis, and high-dose IVIG to treat antibody-mediated renal allograft rejection. Transplant Direct 2:e91CrossRefPubMedPubMedCentralGoogle Scholar
  26. Webster A, Ruster L, McGee R et al (2010) Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst Rev 20:CD003897Google Scholar
  27. Wiebe C, Gibson I, Blydt-Hansen T et al (2012) Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 12:1157CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Nemours/Alfred I. duPont Hospital for ChildrenWilmingtonUSA

Section editors and affiliations

  • Deborah M Consolini
    • 1
  1. 1.Nemours/Alfred I. duPont Hospital for ChildrenWilmingtonUSA

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