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Pretransplant HLA Antibodies Are Associated with Reduced Graft Survival After Clinical Islet Transplantation
Author(s) -
Campbell P. M.,
Salam A.,
Ryan E. A.,
Senior P.,
Paty B. W.,
Bigam D.,
McCready T.,
Halpin A.,
Imes S.,
Al Saif F.,
Lakey J. R. T.,
Shapiro A. M. J.
Publication year - 2007
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2007.01777.x
Subject(s) - medicine , immunosuppression , islet , immunology , antibody , transplantation , human leukocyte antigen , panel reactive antibody , population , tacrolimus , antigen , diabetes mellitus , endocrinology , environmental health
Despite significant improvements in islet transplantation, long‐term graft function is still not optimal. It is likely that both immune and nonimmune factors are involved in the deterioration of islet function over time. Historically, the pretransplant T‐cell crossmatch and antibody screening were done by anti‐human globulin—complement‐dependent cytotoxicity (AHG‐CDC). Class II antibodies were not evaluated. In 2003, we introduced solid‐phase antibody screening using flow‐based beads and flow crossmatching. We were interested to know whether pretransplant human leukocyte antigen (HLA) antibodies or a positive flow crossmatch impacted islet function post‐transplant. A total of 152 islet transplants was performed in 81 patients. Islet function was determined by a positive C‐peptide. Results were analyzed by procedure. Class I and class II panel reactive antibody (PRA) > 15% and donor‐specific antibodies (DSA) were associated with a reduced C‐peptide survival (p < 0.0001 and p < 0.0001, respectively). A positive T‐ and or B‐cell crossmatch alone was not. Pretransplant HLA antibodies detectable by flow beads are associated with reduced graft survival. This suggests that the sirolimus and low‐dose tacrolimus‐based immunosuppression may not control the alloimmune response in this presensitized population and individuals with a PRA > 15% may require more aggressive inductive and maintenance immunosuppression, or represent a group that may not benefit from islet transplantation.