FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 339:1657-1664 December 3, 1998 Number 23 Next

	Full Text PDF Editorial by Sanfilippo, F. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

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 5 years and 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 comparisons). 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.

Source Information

From the Department of Surgery, University of Wisconsin, Madison (W.J.B., A.P.G., D.M.H., J.D.P., H.W.S.); the Departments of Immunohematology (F.H.J.C.) and Nephrology (H.F.), Leiden University Medical Center, Leiden, the Netherlands; the Laboratory of Immunogenetics and Transplantation, Oregon Health Sciences University, Portland (D.N.); the Departments of Pathology and Medicine, Washington University, St. Louis (T.M., D.C.B.); Dijkzigt University Hospital, Rotterdam, the Netherlands (T.G.); and Dendreon Corporation, Mountainview, Calif. (M.A.B.).

Address reprint requests to Dr. Burlingham at the Department of Surgery, University of Wisconsin Medical School, H4/748 Clinical Science Center, 600 Highland Ave., Madison, WI 53792.

Full Text of this Article

Related Letters:

The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors
Opelz G., Burlingham W. J., Heisey D. M., Bean M. A.
Extract | Full Text  
N Engl J Med 1999; 340:1369-1370, Apr 29, 1999. Correspondence

This article has been cited by other articles:

• Janes, S., Dhaliwal, P., Wood, K. (2009). Tolerance in renal transplantation: is mixed chimerism the missing link?. Nephrol Dial Transplant 24: 1726-1729 [Full Text]  
• Aalten, J., Bemelman, F. J., van den Berg-Loonen, E. M., Claas, F. H., Christiaans, M. H., de Fijter, J. W., Hepkema, B. G., Hene, R. J., van der Heide, J. J. H., van Hooff, J. P., Lardy, N. M., Lems, S. P., Otten, H. G., Weimar, W., Allebes, W. A., Hoitsma, A. J. (2009). Pre-kidney-transplant blood transfusions do not improve transplantation outcome: a Dutch national study. Nephrol Dial Transplant 0: gfp233v1-gfp233 [Abstract] [Full Text]  
• Burlingham, W. J. (2009). A Lesson in Tolerance -- Maternal Instruction to Fetal Cells. NEJM 360: 1355-1357 [Full Text]  
• Aoyama, K., Koyama, M., Matsuoka, K.-i., Hashimoto, D., Ichinohe, T., Harada, M., Akashi, K., Tanimoto, M., Teshima, T. (2009). Improved outcome of allogeneic bone marrow transplantation due to breastfeeding-induced tolerance to maternal antigens. Blood 113: 1829-1833 [Abstract] [Full Text]  
• Mold, J. E., Michaelsson, J., Burt, T. D., Muench, M. O., Beckerman, K. P., Busch, M. P., Lee, T.-H., Nixon, D. F., McCune, J. M. (2008). Maternal Alloantigens Promote the Development of Tolerogenic Fetal Regulatory T Cells in Utero. Science 322: 1562-1565 [Abstract] [Full Text]  
• Feitsma, A L, van der Helm-van Mil, A H M, Huizinga, T W J, de Vries, R R P, Toes, R E M (2008). Protection against rheumatoid arthritis by HLA: nature and nurture. Ann Rheum Dis 67: iii61-iii63 [Abstract] [Full Text]  
• Opiela, S. J., Levy, R. B., Adkins, B. (2008). Murine neonates develop vigorous in vivo cytotoxic and Th1/Th2 responses upon exposure to low doses of NIMA-like alloantigens. Blood 112: 1530-1538 [Abstract] [Full Text]  
• Maurel, M.-C., Kanellopoulos-Langevin, C. (2008). Heredity--Venturing Beyond Genetics. Biol. Reprod. 79: 2-8 [Abstract] [Full Text]  
• Griffith, B. P., Haddad, M., Poston, R. S. (2008). Immunobiology of Heart and Heart-Lung Transplantation. Card Surg Adult 3: 1513-1538 [Full Text]  
• Feitsma, A. L., Worthington, J., van der Helm-van Mil, A. H. M., Plant, D., Thomson, W., Ursum, J., van Schaardenburg, D., van der Horst-Bruinsma, I. E., van Rood, J. J., Huizinga, T. W. J., Toes, R. E. M., de Vries, R. R. P. (2007). Protective effect of noninherited maternal HLA-DR antigens on rheumatoid arthritis development. Proc. Natl. Acad. Sci. USA 104: 19966-19970 [Abstract] [Full Text]  
• Molitor-Dart, M. L., Andrassy, J., Kwun, J., Kayaoglu, H. A., Roenneburg, D. A., Haynes, L. D., Torrealba, J. R., Bobadilla, J. L., Sollinger, H. W., Knechtle, S. J., Burlingham, W. J. (2007). Developmental Exposure to Noninherited Maternal Antigens Induces CD4+ T Regulatory Cells: Relevance to Mechanism of Heart Allograft Tolerance. J. Immunol. 179: 6749-6761 [Abstract] [Full Text]  
• van Rood, J. J. (2006). You will never forget your mother!. Blood 107: 7-8 [Full Text]  
• Matsuoka, K.-i., Ichinohe, T., Hashimoto, D., Asakura, S., Tanimoto, M., Teshima, T. (2006). Fetal tolerance to maternal antigens improves the outcome of allogeneic bone marrow transplantation by a CD4+CD25+ T-cell-dependent mechanism. Blood 107: 404-409 [Abstract] [Full Text]  
• Kaplan, J., Land, S. (2005). Influence of Maternal-Fetal Histocompatibility and MHC Zygosity on Maternal Microchimerism. J. Immunol. 174: 7123-7128 [Abstract] [Full Text]  
• Vernochet, C., Caucheteux, S. M., Gendron, M.-C., Wantyghem, J., Kanellopoulos-Langevin, C. (2005). Affinity-Dependent Alterations of Mouse B Cell Development by Noninherited Maternal Antigen. Biol. Reprod. 72: 460-469 [Abstract] [Full Text]  
• Spitzer, T. R. (2005). Haploidentical Stem Cell Transplantation: The Always Present but Overlooked Donor. ASH Education Book 2005: 390-395 [Abstract] [Full Text]  
• Ichinohe, T., Uchiyama, T., Shimazaki, C., Matsuo, K., Tamaki, S., Hino, M., Watanabe, A., Hamaguchi, M., Adachi, S., Gondo, H., Uoshima, N., Yoshihara, T., Hatanaka, K., Fujii, H., Kawa, K., Kawanishi, K., Oka, K., Kimura, H., Itoh, M., Inukai, T., Maruya, E., Saji, H., Kodera, Y., for the Japanese Collaborative Study Group for NIM, (2004). Feasibility of HLA-haploidentical hematopoietic stem cell transplantation between noninherited maternal antigen (NIMA)-mismatched family members linked with long-term fetomaternal microchimerism. Blood 104: 3821-3828 [Abstract] [Full Text]  
• Adams, K. M., Nelson, J. L. (2004). Microchimerism: An Investigative Frontier in Autoimmunity and Transplantation. JAMA 291: 1127-1131 [Abstract] [Full Text]  
• Andrassy, J., Kusaka, S., Jankowska-Gan, E., Torrealba, J. R., Haynes, L. D., Marthaler, B. R., Tam, R. C., Illigens, B. M.-W., Anosova, N., Benichou, G., Burlingham, W. J. (2003). Tolerance to Noninherited Maternal MHC Antigens in Mice. J. Immunol. 171: 5554-5561 [Abstract] [Full Text]  
• Griffith, B. P., Poston, R. S. (2003). Immunobiology of Heart and Heart-Lung Transplantation. Card Surg Adult 2: 1403-1426 [Full Text]  
• Harney, S., Newton, J., Milicic, A., Brown, M. A., Wordsworth, B. P. (2003). Non-inherited maternal HLA alleles are associated with rheumatoid arthritis. Rheumatology (Oxford) 42: 171-174 [Abstract] [Full Text]  
• van Rood, J. J., Loberiza, F. R. Jr, Zhang, M.-J., Oudshoorn, M., Claas, F., Cairo, M. S., Champlin, R. E., Gale, R. P., Ringden, O., Hows, J. M., Horowitz, M. H. (2002). Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling. Blood 99: 1572-1577 [Abstract] [Full Text]  
• Lo, Y.M. D., Lau, T. K., Chan, L. Y.S., Leung, T. N., Chang, A. M.Z. (2000). Quantitative Analysis of the Bidirectional Fetomaternal Transfer of Nucleated Cells and Plasma DNA. Clin. Chem. 46: 1301-1309 [Abstract] [Full Text]  
• Kusaka, S., Grailer, A. P., Fechner, J. H. Jr., Jankowska-Gan, E., Oberley, T., Sollinger, H. W., Burlingham, W. J. (2000). Clonotype Analysis of Human Alloreactive T Cells: A Novel Approach to Studying Peripheral Tolerance in a Transplant Recipient. J. Immunol. 164: 2240-2247 [Abstract] [Full Text]  
• Gore, S.M., Hutchinson, S.J., Brettle, R.P. (1999). Study requirements for investigating HLA-associated progression of HIV disease, and review. QJM 92: 609-617 [Full Text]  
• Opelz, G., Burlingham, W. J., Heisey, D. M., Bean, M. A. (1999). The Effect of Tolerance to Noninherited Maternal HLA Antigens on the Survival of Renal Transplants from Sibling Donors. NEJM 340: 1369-1370 [Full Text]  
• Sanfilippo, F. (1998). Transplantation Tolerance-- The Search Continues. NEJM 339: 1700-1702 [Full Text]