TY - JOUR
T1 - Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression
AU - Snanoudj, Renaud
AU - Kamar, Nassim
AU - Cassuto, Elisabeth
AU - Caillard, Sophie
AU - Metzger, Marie
AU - Merville, Pierre
AU - Thierry, Antoine
AU - Jollet, Isabelle
AU - Grimbert, Philippe
AU - Anglicheau, Dany
AU - Hazzan, Marc
AU - Choukroun, Gabriel
AU - Hurault De Ligny, Bruno
AU - Janbon, Bénedicte
AU - Vuiblet, Vincent
AU - Devys, Anne
AU - Le Meur, Yann
AU - Delahousse, Michel
AU - Morelon, Emmanuel
AU - Bailly, Elodie
AU - Girerd, Sophie
AU - Amokrane, Kahina
AU - Legendre, Christophe
AU - Hertig, Alexandre
AU - Rondeau, Eric
AU - Taupin, Jean Luc
N1 - Publisher Copyright:
© 2019 International Society of Nephrology
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Human leukocyte antigen (HLA)mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or (“epitope load”)would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%)developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.
AB - Human leukocyte antigen (HLA)mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or (“epitope load”)would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%)developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.
KW - HLA mismatching
KW - acute rejection
KW - antibody-mediated rejection
KW - epitopes
KW - immunosuppression minimization
KW - kidney transplantation
UR - http://www.scopus.com/inward/record.url?scp=85063760025&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2018.12.029
DO - 10.1016/j.kint.2018.12.029
M3 - Article
C2 - 30955869
AN - SCOPUS:85063760025
SN - 0085-2538
VL - 95
SP - 1471
EP - 1485
JO - Kidney International
JF - Kidney International
IS - 6
ER -