A composite score associated with spontaneous operational tolerance in kidney transplant recipients

Richard Danger 1, 2 Mélanie Chesneau 1, 2 Chloé Paul 1, 2 Pierrick Guérif 1, 2 Maxim Durand 1, 2 Kenneth Newell 3 Sai Kanaparthi 4 Laurence Turka 5 Jean-Paul Soulillou 1, 2 Rémi Houlgatte 6 Magali Giral 1, 2, 7, 8 Gérard Ramstein 9, 10 Sophie Brouard 1, 2, 7, *
* Corresponding author
1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 ITUN - Institut de transplantation urologie-néphrologie
3 Department of Surgery [Atlanta, Georgia, USA]
4 Immune Tolerance Network
5 BioMEMS Resource Center - Department of Surgery [Boston, MA, USA]
6 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
7 CIC biothérapies CBT 0503 [Nantes]
8 Faculté de Médecine - Université de Nantes
9 LS2N - Laboratoire des Sciences du Numérique de Nantes
10 DUKe - Data User Knowledge
LS2N - Laboratoire des Sciences du Numérique de Nantes
Abstract : 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.
Keywords : operational tolerance biomarker renal transplantation gene expression graft survival
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Richard Danger, Mélanie Chesneau, Chloé Paul, Pierrick Guérif, Maxim Durand, et al.. A composite score associated with spontaneous operational tolerance in kidney transplant recipients. Kidney International, Nature Publishing Group, 2017, 91 (6), pp.1473-1481. ⟨10.1016/j.kint.2016.12.020⟩. ⟨inserm-02156039⟩

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