HLA-mismatched renal transplantation without maintenance immunosuppression

N Engl J Med. 2008 Jan 24;358(4):353-61. doi: 10.1056/NEJMoa071074.

Abstract

Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biopsy
  • Bone Marrow Transplantation*
  • Combined Modality Therapy
  • Female
  • Graft Rejection / immunology
  • Granzymes / genetics
  • Granzymes / metabolism
  • Hepatocyte Nuclear Factor 3-alpha / genetics
  • Hepatocyte Nuclear Factor 3-alpha / metabolism
  • Histocompatibility Testing
  • Humans
  • Immunosuppression
  • Kidney / anatomy & histology
  • Kidney / ultrastructure
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • RNA, Messenger / isolation & purification
  • RNA, Messenger / metabolism
  • T-Lymphocytes / immunology
  • Transplantation Chimera / immunology*
  • Transplantation Conditioning
  • Transplantation Immunology
  • Transplantation Tolerance / immunology*
  • Transplantation, Homologous / immunology

Substances

  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • RNA, Messenger
  • Granzymes