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Presenter: Lionel, Badet, Lyon, France
Authors: Palmina Petruzzo, Emmanuel Morelon, Cristophe Malcus, Olivier Thaunat, Lionel Badet, Aram Gazarian, Maria Brunet, Sylvie Testelin, Bernard Devauchelle, Jean Kanitakis, Celine Dagot, Jean Michel Dubernard, Annaick Pallier, Jean-Paul Soulillou, Sophie Brouard
Palmina Petruzzo1, Emmanuel Morelon1, Cristophe Malcus1, Olivier Thaunat1, Lionel Badet1, Aram Gazarian1, Maria Brunet1, Sylvie Testelin2, Bernard Devauchelle2, Jean Kanitakis1, Celine Dagot1, Jean Michel Dubernard1, Annaick Pallier3, Jean-Paul Soulillou3, Sophie Brouard3.
1Dept of Transplantation Hospices Civils de Lyon, Lyon, France; 2Dept of Maxillofacial Surgery University Hospital of Amiens, Amiens, France; 3Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
Despite a high incidence of acute rejection, composite tissue allotransplantations (CTAs) display low incidence of chronic rejection.
Aim of this study was to search for the signature of tolerance in CTAs testing biomarkers previously identified in operational tolerant kidney transplant recipients (TOL-DF).
Five bilateral hand transplantations and one face transplantation (Tx) were studied. They showed no evidence of chronic rejection in the follow-up period, ranging from 1 to 10 years. The immunosuppressive regimen included tacrolimus, mycophenolate mofetil and steroid, except for the face Tx, where tacrolimus was replaced by sirolimus. Tolerance footprint was assessed by quantitative PCR with a set of 20 genes selectively chosen among the 49 genes previously described in TOL-DF and by TcLandscape spectrapying assay. Peripheral blood B-cells, regulatory and effector T lymphocytes were analyzed by FACS.
One year after Tx a hand Tx presented a genomic footprint of tolerance, combined with a Gaussian-like pattern of T-cell repertoire and an increased percentage of peripheral blood B-cells (32%), evoking an operationally tolerant state. Another hand Tx and the face Tx had a genomic footprint of rejection and a skewed pattern of T-cell repertoire. A high mean percentage of CD4+DR+, CD8+DR+, CD8highCD28- was also found in the face transplantation. Therefore, these two patients displayed a rejection profile. The 3 remaining patients had a biomarker profile evoking a stable state on immunosuppressive treatment. No significant difference in the percentages of peripheral blood CD4+CD25hiCD127- Treg was detected among the patients.
This preliminary study suggests that 1/6 CTA patients display an operationally tolerant state. The similarity of biomarker profiles between CTAs and kidney Tx supports the hypothesis that the biomarkers developed in renal Tx can be also used in CTA.
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