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Sirolimus in renal transplant recipients with tuberous sclerosis complex: clinical effectiveness and implications for innate immunity.

Abstract
Tuberous sclerosis complex (TSC) is caused by constitutively activated mammalian target of rapamycin (mTOR) resulting in nonmalignant tumours of several organs and consequently renal failure. Recent reports suggest a possible beneficial role of the mTOR-inhibitor (mTOR-I) sirolimus for TSC; however, safety and efficiency of sirolimus in TSC patients after renal transplantation, both as primary immunosuppressant as well as anti-proliferative agent, are still undefined. Moreover, it is currently unknown whether the TSC mutation affects the primary immune response in these patients. In this article, we report on three TSC patients after renal transplantation who have been converted from a calcineurin-inhibitor (CNI)-based immunosuppression to sirolimus. During 2 years of follow-up, renal allograft function was stable or even improved, and no significant sirolimus-associated side-effects were noted. Beneficial effects of sirolimus against TSC were detected in the skin, along with improved spirometric measurements and an arrest of astrocytoma progression. We show that the inflammatory immune response was significantly altered in TSC patients as compared with controls and sirolimus potently affected both inflammatory cytokine production and vascular endothelial growth factor levels in these patients. Larger studies are warranted to further examine the relationship between clinical parameters and the molecular response to mTOR-inhibition in TSC patients after renal transplantation.
AuthorsMichael Haidinger, Manfred Hecking, Thomas Weichhart, Marko Poglitsch, Wolfgang Enkner, Karin Vonbank, Daniela Prayer, Alexandra Geusau, Rainer Oberbauer, Gerhard J Zlabinger, Afschin Soleiman, Walter H Hörl, Marcus D Säemann
JournalTransplant international : official journal of the European Society for Organ Transplantation (Transpl Int) Vol. 23 Issue 8 Pg. 777-85 (Aug 2010) ISSN: 1432-2277 [Electronic] Switzerland
PMID20070623 (Publication Type: Case Reports, Journal Article)
Chemical References
  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Intracellular Signaling Peptides and Proteins
  • MTOR protein, human
  • Protein Serine-Threonine Kinases
  • TOR Serine-Threonine Kinases
  • Sirolimus
Topics
  • Adult
  • Calcineurin Inhibitors
  • Female
  • Graft Rejection (complications, drug therapy, immunology)
  • Humans
  • Immune System (drug effects, immunology)
  • Immunosuppressive Agents (administration & dosage, adverse effects)
  • Intracellular Signaling Peptides and Proteins (antagonists & inhibitors)
  • Kidney Transplantation
  • Lymphangioleiomyomatosis (complications, immunology)
  • Male
  • Protein Serine-Threonine Kinases (antagonists & inhibitors)
  • Sirolimus (administration & dosage, adverse effects)
  • TOR Serine-Threonine Kinases
  • Treatment Outcome
  • Tuberous Sclerosis (complications, immunology)

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