title: Using the mimetic epitope concept to find a possible way to widen the graft-survival difference between matched and mismatched renal transplants.
abstract: 1. Immunological responses cause antibodies to be produced, and transplant patients often produce HLA antibodies against their donors' HLA. But in many cases, more antibodies are produced than just those against mismatched HLA. Many patients with zero mismatched transplants also produce antibodies, and some of these grafts fail. This study used graft survival analysis that contemplated the primary epitopes against the donors' alleles and the corresponding mimetic epitopes, less those shared with the patients' alleles. 2. A table of primary epitopes and corresponding mimetic epitopes was built in a previous study. For each case studied, here, a subset of the table was selected for all of the donor's HLA alleles. The subset was reduced by eliminating all primary and mimetic epitopes shared by the patient's own HLA alleles. The remaining mimetic and primary epitopes-the maximum pool of epitopes (MaxPEpi)-produced epitope frequency (Efr) for each allele. Using a zero-HLA-AB-mismatch subset (n = 16) of the Greenville and Holland kidney transplant data set (n = 451), the Efr for each allele in the MaxPEpi of each case was tallied and compared with the corresponding observed antibody specificities. The average frequencies were 2,869 and 1,975, respectively, and the t-test was significant at the p-value of less than 0.00001, indicating that the higher the frequency, the more likely that the corresponding allele appears as a part of the specificity. 3. The trends were used to perform survival analysis on zero-mismatch kidney transplant cases in the 2007 UNOS data file. Different variables of MaxPEpi parameters and cutoff points were tried with half of the deceased-donor cases in the file, survival rates for those below and above each cutoff point were compared by the log-rank test. The average Efr with a cutoff of 3,700 yielded the best 10-year graft survival in this subgroup of the 2007 UNOS cases. The results were supported and verified by analyzing the second half of the deceased-donor cases and the living-donor cases in the 2007 UNOS data set. 4. With the 2007 file living-donor cases, 10-year graft survival rate was 86.2% for cases below the cutoff, and 85.4% for those above, and the difference was significant at a p-value less than 0.01. A larger difference was observed for 2007 living-donor cases, excluding identical sibling transplants, but the difference was not statistically significant due to the low number of cases. 5. The same trends were found for 10-year survivals with cases in the 2008 data, but were not statistically significant. With living donors, the rates below and above the cutoff were 85.7% and 85.2%, respectively, and with deceased donors, 72.7% and 72.1%, respectively, p < 0.125. As with the 2007 data, cases in the 2008 file with living donors--excluding identical sibling transplants--had survival rates of 91.7% and 79.0%, respectively, but the 12.7% difference was not statistically significant because of the low number of cases.
authors.affiliation: One Lambda Inc, Canoga Park, CA, USA.
authors.forename: Nori
authors.initials: N
authors.lastname: Sasaki
authors.forename: Adam
authors.initials: A
authors.lastname: Idica
authors.forename: Bob
authors.initials: B
authors.lastname: Hall
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000906:Antibodies / Q000097:blood*; D000918:Antibody Specificity; D000939:Epitopes; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D018448:Models, Immunological; D018716:Molecular Mimicry; D009426:Netherlands; D012042:Registries; D013997:Time Factors; D023001:Transplantation Tolerance; D016896:Treatment Outcome; D014481:United States
chemical_list: D000906:Antibodies; D000939:Epitopes; D006680:HLA Antigens