Effect of amino acid mismatch in the UNOS 2007 dataset.
1. The study began with the 2007 UNOS dataset of 270,690 kidney transplant, from which were selected post-1995 first transplants with Caucasian donor/patients and available ABDR typing data, yielding 87,616 cases. These were split into cadaver donor (n=46,927) and living donor (n=40,689) populations. 2. Cases with broad antigens such as A9, A10, B12 and B17 were eliminated, as were cases that had failed within 30 days. That left 28,264 cadaver donor and 26,211 living donor cases. 3. We looked at every theoretical mismatch between donors and patients in the living donor population. Overall, 405 single, 21,269 double, and 391,325 triple position/amino acid mismatches were included in the analysis. Two tallies for each mismatch were generated: "function" and "fail" based on patient's associated graft survival. 4. We generated a list of "fail" single, double, and triple position/amino acid mismatches and computed 10-year survival curves for each of the mismatches, comparing them with the average 10-year survival curve using the log-rank test. Based on the log-rank statistics, a ranking of the bad mismatches was established. 5. We looked at the long-term graft survival of additive single, double, and triple "fail" mismatches in cadaver donor transplants. 6. Survival curves of transplants with position/ amino acid mismatches were generated and compared with the survival curves of the traditional standards: 0 ABDR mismatch; 1 A, 1 B and 1 DR mismatch; and full 6 ABDR mismatches. 7. The greatest effect was seen in first transplants with a male recipient, but that were not Caucasian-to-Caucasian. Up to 125 double mismatches resulted in a 10-year survival 29% lower than 0 ABDR mismatches. 8. In first transplants that were not Caucasian-to-Caucasian 1154 out of 1177 (98%) pos/aa mismatches (single, double, or triple) had lower 10-year survival than cases with one mismatch, each, in A, B and DR. Looking at re-grafts, we see that 498 out of 499 with single, double and triple mismatches had lower 10-year survival than that of cases with one mismatch, each, in A, B and DR. 9. Overall, position/amino acid mismatches had consistently lower 10-year survival than 1 A, 1 B, 1 DR mismatches. We believe our selection of "fail" pos/aa mismatches provide a good starting point for establishing a list of mismatches to be looked for and avoided in future transplants in order to give them a better chance of survival.
Sasaki
Nori
N
One Lambda, Inc., Canoga Park, CA, USA.
Idica
Adam
A
Hall
Bob
B
Terasaki
Paul
P
D000595:Amino Acid Sequence; D016208:Databases, Factual / Q000706:statistics & numerical data*; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006648:Histocompatibility / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality*; D019520:Living Donors / Q000706:statistics & numerical data; D016019:Survival Analysis; D044465:White People / Q000706:statistics & numerical data
D006680:HLA Antigens