Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers

Area of Science:

• Transplantation immunology
• Regenerative medicine

Background:

• Operational tolerance is a key goal in transplantation.
• Previous studies showed early promise for a nonchimeric protocol in HLA-identical living donor renal transplants.

Purpose of the Study:

• To update results of a nonchimeric operational tolerance protocol.
• To investigate the association of Treg immunophenotypes and gene expression profiles with operational tolerance.

Main Methods:

• Recipients received alemtuzumab, tacrolimus/MPA with early sirolimus conversion, and donor hematopoietic CD34(+) stem cells.
• Immunosuppression was withdrawn by 24 months, with follow-up biopsies at 12 months and 5 years post-transplant.
• Circulating Tregs and gene expression signatures from whole blood and biopsy samples were analyzed.

Main Results:

• Four of five initially tolerant recipients remained rejection-free at 5 years post-transplant.
• New subjects showed time-dependent increases in regulatory T cells (Tregs) in tolerant individuals.
• Gene expression signatures in blood and biopsies were highly associated with operational tolerance at 1 year post-transplant.

Conclusions:

• The nonchimeric operational tolerance protocol demonstrates sustained tolerance in a subset of patients.
• Increases in Tregs and specific gene expression profiles are associated with operational tolerance.
• This approach offers insights into achieving long-term transplant tolerance.