Genomic biomarkers correlate with HLA-identical renal transplant tolerance

Joseph R. Leventhal, James M. Mathew, Daniel R. Salomon, Sunil M. Kurian, Manikkam Suthanthiran, Anat Tambur, John Friedewald, Lorenzo Gallon, Jane Charette, Josh Levitsky, Yashpal Kanwar, Michael Abecassis, Joshua Miller

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Abstract

The ability to achieve immunologic tolerance after transplantation is a therapeutic goal. Here, we report interim results from an ongoing trial of tolerance in HLAidentical 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 Five of these 10 recipients had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence, and 3 had subclinical rejection in protocol biopsies (nontolerant).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+CD25highCD1272FOXP3+ regulatory T cells and CD19+IgD/M+CD272 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.

Original languageEnglish
Pages (from-to)1376-1385
Number of pages10
JournalJournal of the American Society of Nephrology
Volume24
Issue number9
DOIs
Publication statusPublished - 1 Sep 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Nephrology

Cite this

Leventhal, J. R., Mathew, J. M., Salomon, D. R., Kurian, S. M., Suthanthiran, M., Tambur, A., Friedewald, J., Gallon, L., Charette, J., Levitsky, J., Kanwar, Y., Abecassis, M., & Miller, J. (2013). Genomic biomarkers correlate with HLA-identical renal transplant tolerance. Journal of the American Society of Nephrology, 24(9), 1376-1385. https://doi.org/10.1681/ASN.2013010068