Journal
KIDNEY INTERNATIONAL
Volume 91, Issue 6, Pages 1473-1481Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.kint.2016.12.020
Keywords
biomarker; gene expression; graft survival; operational tolerance; renal transplantation
Categories
Funding
- National Research Agency [ANR-11-LABX-0016-01]
- LABEX TRANSPLANTEX [ANR-11-LABX0070_TRANSPLANTEX]
- INSERM
- French Government
- European Commission's Seventh Framework Program [305147]
- FP7 VISICORT [602470]
- Fondation Jean Valade
- National Institute of Allergy And Infectious Diseases of the National Institutes of Health [UM1AI109565]
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New challenges in renal transplantation include using biological information to devise a useful clinical test for discerning high- and low-risk patients for individual therapy and ascertaining the best combination and appropriate dosages of drugs. Based on a 20-gene signature from a microarray meta-analysis performed on 46 operationally tolerant patients and 266 renal transplant recipients with stable function, we applied the sparse Bolasso methodology to identify a minimal and robust combination of six genes and two demographic parameters associated with operational tolerance. This composite score of operational tolerance discriminated operationally tolerant patients with an area under the curve of 0.97 (95% confidence interval 0.94-1.00). The score was not influenced by immunosuppressive treatment, center of origin, donor type, or post-transplant lymphoproliferative disorder history of the patients. This composite score of operational tolerance was significantly associated with both de novo anti-HLA antibodies and tolerance loss. It was validated by quantitative polymerase chain reaction using independent samples and demonstrated specificity toward a model of tolerance induction. Thus, our score would allow clinicians to improve follow-up of patients, paving the way for individual therapy.
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