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
transplanted 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.