Genomic biomarkers correlate with HLA-identical renal transplant tolerance

J Am Soc Nephrol. 2013 Sep;24(9):1376-85. doi: 10.1681/ASN.2013010068. Epub 2013 Jun 20.


The ability to achieve immunologic tolerance after transplantation is a therapeutic goal. Here, we report interim results from an ongoing trial of tolerance in HLA-identical sibling renal transplantation. The immunosuppressive regimen included alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, and complete drug withdrawal by 24 months post-transplantation. Recipients were considered tolerant if they had normal biopsies and renal function after an additional 12 months without immunosuppression. Of the 20 recipients enrolled, 10 had at least 36 months of follow-up after transplantation. Five of these 10 recipients had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence, and 3 had subclinical rejection in protocol biopsies (nontolerant). Microchimerism disappeared after 1 year, and CD4(+)CD25(high)CD127(-)FOXP3(+) regulatory T cells and CD19(+)IgD/M(+)CD27(-) B cells were increased through 5 years post-transplantation in both tolerant and nontolerant recipients. Immune/inflammatory gene expression pathways in the peripheral blood and urine, however, were differentially downregulated between tolerant and nontolerant recipients. In summary, interim results from this trial of tolerance in HLA-identical renal transplantation suggest that predictive genomic biomarkers, but not immunoregulatory phenotyping, may be able to discriminate tolerant from nontolerant patients.

Publication types

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

MeSH terms

  • Adult
  • Biomarkers
  • Biopsy
  • Chimerism
  • DNA / genetics*
  • Female
  • Follow-Up Studies
  • Genome / genetics*
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • HLA Antigens / genetics*
  • HLA Antigens / immunology*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immune Tolerance / immunology*
  • Immunosuppressive Agents / therapeutic use
  • Kidney / pathology
  • Kidney Transplantation / immunology*
  • Kidney Transplantation / pathology
  • Male
  • Middle Aged
  • Retrospective Studies


  • Biomarkers
  • HLA Antigens
  • Immunosuppressive Agents
  • DNA