EVIDENCE FOR RENAL TRANSPLANT TOLERANCE TO NON-INHERITED MATERNAL ANTIGENS (NIMA) IN 1 HLA-HAPLOTYPE MATCHED SIBLINGS: A MULTICENTER STUDY

Abstract

324 Background: A form of tolerance may occur in fetal and early postnatal life that results in decreased adult immune responses to the noninherited maternal antigens (NIMA). To identify HLA-specific NIMA effects in renal transplantation (RTX), we analyzed the effects of NIMA vs. noninherited paternal antigens (NIPA) HLA-mismatches on allograft survival and incidence of rejection episodes in living donor RTX between single HLA-haplotype-matched siblings. Methods: In sibling living donor RTX for whom at least one parental tissue type was known, we identified siblings mismatched for NIMA and NIPA HLA antigens. Data for graft survival and rejection episodes were compared by the log rank test. Results: In the Seattle group (n = 84), a sibling kidney mismatched for a NIMA HLA-haplotype was significantly (p < .03) less likely to undergo immunologic graft loss than a kidney mismatched for NIPA. These results were validated in analysis of sibling RTX (n = 114) at four other transplant centers: University of WI - Madison, University of Leiden, Washington Univ - St. Louis, and University of Rotterdam (p< .02). The 10-yr. graft survival was 30% greater in NIMA-mismatched vs. NIPA-mismatched sibling donor kidneys both pre- and post-1986 (p< .005, p = .08, respectively). Overall the risk ratio of graft loss in NIPA vs. NIMA-mismatched siblings was 2.7 (n=198; p <.003). Paradoxically, there was significantly (p < .04) greater incidence of early rejection onset in NIMA-mismatched grafts; this tendency toward earlier first rejection episode was abrogated by donor-specific transfusions (p = .32; NS). Conclusion: A powerful beneficial effect of NIMA HLA mismatches is seen in sibling RTX, where the matched HLA haplotype is ofpaternal origin, but NOT in NIMA-mismatched RTX from mothers, where the matched HLA haplotype is of maternal origin. Our results suggest a possible way to exploit neonatally-acquired tolerance in clinical transplant patients, using appropriate HLA matching as well as NIMA mismatching.