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The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors
Abstract
BACKGROUND: During pregnancy and nursing, a baby's developing immune system is intimately exposed to the mother's antigens. To determine whether this exposure is of clinical benefit to patients who later receive an allograft as an adult, we analyzed the outcome of primary renal transplantations from sibling donors. METHODS: We retrospectively studied graft survival and rejection episodes in 205 patients who had received renal transplants at nine centers between 1966 and 1996 from sibling donors bearing maternal or paternal HLA antigens not inherited by the recipient. The sibling donors were categorized by analysis of family HLA-typing data. RESULTS: In the multicenter analysis, graft survival was higher at 5 years and at 10 years after transplantation in recipients of kidneys from siblings expressing maternal HLA antigens not inherited by the recipient than in recipients of kidneys from siblings expressing paternal HLA antigens not inherited by the recipient (86 percent vs. 67 percent at 5 years and 77 percent vs. 49 percent at 10 years, P=0.006 for both). Paradoxically, there was a higher incidence of early rejection in the former group, suggesting that fetal and neonatal exposure to maternal antigens results in immunologic priming. Pretransplantation transfusions of donor blood reduced the incidence of acute rejection while preserving the beneficial effect of tolerance to noninherited maternal antigens on graft survival. Since 1986, new immunosuppressive drugs have lessened the short-term, but not the long-term, survival advantage of grafts expressing maternal HLA antigens not inherited by the recipient. CONCLUSIONS: In the transplantation of a kidney from a sibling donor who is mismatched with the recipient for one HLA haplotype, graft survival is higher when the donor has maternal HLA antigens not inherited by the recipient than when the donor has paternal HLA antigens not inherited by the recipient.
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Citations
Cited by
Evolution of the immune system in humans from infancy to old age
Simon, A. K., Hollander, G. A., & McMichael, A. (2015) · Proceedings of the Royal Society B: Biological Sciences · doi:10.1098/rspb.2014.3085 · Cited by 1,796
Maternal Alloantigens Promote the Development of Tolerogenic Fetal Regulatory T Cells in Utero
Mold, J. E., Michaëlsson, J., Burt, T. D., Muench, M. O., Beckerman, K. P., Busch, M. P., Lee, T.-H., Nixon, D. F., & McCune, J. M. (2008) · Science · doi:10.1126/science.1164511 · Cited by 836
Fetal and Adult Hematopoietic Stem Cells Give Rise to Distinct T Cell Lineages in Humans
Mold, J. E., Venkatasubrahmanyam, S., Burt, T. D., Michaëlsson, J., Rivera, J. M., Galkina, S. A., Weinberg, K., Stoddart, C. A., & McCune, J. M. (2010) · Science · doi:10.1126/science.1196509 · Cited by 444
Extracellular vesicles in allograft rejection and tolerance
Benichou, G., Wang, M., Ahrens, K., & Madsen, J. C. (2020) · Cellular Immunology · doi:10.1016/j.cellimm.2020.104063 · Cited by 67
Metadata
- Authors
- Burlingham, W. J., Grailer, A. P., Heisey, D. M., Claas, F. H. J., Norman, D., Mohanakumar, T., Brennan, D. C., de Fijter, H., van Gelder, T., Pirsch, J. D., Sollinger, H. W., & Bean, M. A.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1998-12-03
- Volume
- 339
- Issue
- 23
- Pages
- 1657-1664
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2073696038
- Cited by
- 276
- References
- 0
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors. https://app.cochat.ai/papers/10.1056/nejm199812033392302
- The paper
- Burlingham, W. J., Grailer, A. P., Heisey, D. M., Claas, F. H. J., Norman, D., Mohanakumar, T., Brennan, D. C., de Fijter, H., van Gelder, T., Pirsch, J. D., Sollinger, H. W., & Bean, M. A. (1998). The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors. New England Journal of Medicine. https://doi.org/10.1056/nejm199812033392302
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