Epitope Load Is Predictive of De Novo Donor Specific Antibodies Occurrence in Renal Transplant Recipients After Conversion from Cyclosporine to Everolimus.
1Necker Hospital, Paris, France
2Saint-Louis Hospital, Paris, France
3Rangueil Hospital, Toulouse, France
4Pasteur Hospital, Nice, France
5CHRU, Strasbourg, France
6Tenon Hospital, Paris, France.
Meeting: 2016 American Transplant Congress
Abstract number: 279
Keywords: Alloantibodies, HLA antigens, HLA matching, Kidney transplantation
Session Information
Session Name: Concurrent Session: Antibody Mediated Rejection in Kidney Transplantation: De Novo DSA
Session Type: Concurrent Session
Date: Monday, June 13, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 5:06pm-5:18pm
Location: Ballroom B
Introduction
The degree of HLA compatibility between donor and recipient is an important risk factor of developing de novo DSA, but misjudged by the number of HLA antigenic incompatibilities. The HLAMatchmaker software compares the HLA molecules of the recipient and the donor, as a succession of eplets corresponding to amino acid residues accessible to antibodies. The epitope load is the number of incompatible eplets, i.e. expressed by the donor but not by the recipient.
Methods
86 patients were switched at three months post-renal transplantation from cyclosporine to everolimus in the randomized CERTITEM study. The most likely allelic typing was estimated from the generic typing using the HAPLOSTAT database. The epitope load was calculated by the HLAMatchmaker software.
Results
During the 2-years follow-up, 6 patients (7%) developed class I and 26 patients (30%) developed class II DSA (20 DQ, 2 DR and 4 DQ+DR). The corresponding epitope load was significantly higher in patients who developed class I DSA (22.7±7.1 vs 14.5±6.1 class I eplets, p=0.008), class II DSA (36.0±12.7 vs 20.0±16.9 class II eplets, p<0.0001) and DQ DSA: 14.3 ± 4.8 vs 7.4±6.6 DQ eplets (p <0.0001). In patients with more than 13 incompatible DQ eplets, frequency of de novo DSA was 50% versus 2.5% (RR=20, p <0.0001). In the subgroup of DQ7-negative patients who received a DQ7-positive graft (n=22), the number of incompatible DQ7 eplets was significantly higher in patients who developed DQ7 DSA:12.6±3.5 vs 6.7±3.3, p=0.002. In those patients with a DQ7 DSA, some incompatible eplets were expressed by donor DQ7 with a significantly higher frequency (66ER, 67VT, 70RT, 74EL, 77T, 37YA, 52PL3; p <0.05) than in patients who did not.
Conclusion
A high epitope load appears as a risk factor of developing DSA after conversion to everolimus. Regarding DQ DSA, which are the most frequent, a cut-off of 13 incompatible eplets clearly allows discriminating patients who will develop DSA or not. Moreover, some eplets expressed by mismatched antigens appear to be more immunogenic than others. This epitope load should be assessed before considering minimization of immunosuppression.
CITATION INFORMATION: Snanoudj R, Suberbielle C, Kamar N, Cassuto E, Caillard S, Taupin J.-L, Anglicheau D, Legendre C, Hertig A, Rondeau E. Epitope Load Is Predictive of De Novo Donor Specific Antibodies Occurrence in Renal Transplant Recipients After Conversion from Cyclosporine to Everolimus. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Snanoudj R, Suberbielle C, Kamar N, Cassuto E, Caillard S, Taupin J-L, Anglicheau D, Legendre C, Hertig A, Rondeau E. Epitope Load Is Predictive of De Novo Donor Specific Antibodies Occurrence in Renal Transplant Recipients After Conversion from Cyclosporine to Everolimus. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/epitope-load-is-predictive-of-de-novo-donor-specific-antibodies-occurrence-in-renal-transplant-recipients-after-conversion-from-cyclosporine-to-everolimus/. Accessed May 21, 2025.« Back to 2016 American Transplant Congress