HLA matching promotes the growth and development of new healthy blood cells (called engraftment) and reduces the risk of a post-transplant complication called graft-versus-host (GVHD) disease. It is interesting to note that NK cells recognize and respond differentially to even a single amino acid substitution in the HLA-C molecule (28) and such changes alter the protection of target cells from lysis by NK cells (29). Freytes CO, Beatty PG. 0000009336 00000 n In addition to the clinical observations, the laboratory evidence for a relationship between HLA-C and the immune response has also strengthened in the last few years.
HLA-C disparity between patients and unrelated donors matched for HLA-A, -B, and -DRB1 alleles: impact of serological vs. DNA typing for HLA-A and -B loci: Biol Blood Marrow Transplant 1999; 5(2): 77. 0000087957 00000 n Proc Natl Acad Sci USA 1993; 90(24): 12000.
22. 0000009258 00000 n 0000009818 00000 n These haplotypes contained HLA-A, -B, -C, and -DRB1 alleles as defined by high resolution DNA typing. 0000018722 00000 n Sasazuki T, Juji T, Morishima Y, et al. Although these findings are noteworthy, their conclusions may not be directly applied to the United States population, which is much more ethnoracially mixed and remarkably more diverse with regards to the HLA alleles. Zelterman's statistic was used to test for global LD between HLA loci. The probability of HLA-C matching for specific HLA-B allele was estimated from contingency table generated from the HLA-B and -C haplotypes. Blood 1997; 89(5): 1818. Moretta A, Sivori S, Vitale M, et al. Analysis of 462 transplantations From unrelated donors facilitated by the National Marrow Donor Program. Anasetti C, Etzioni R, Petersdorf EW, Martin PJ, Hansen JA. Recent clinical reports suggest that a donor-recipient mismatch at the HLA-C locus may be associated with GVHD (38), marrow graft rejection (19, 38), and renal transplant rejection (39). Biassoni R, Falco M, Cambiaggi A, et al. A locally developed computer program was used to analyze the hybridization pattern of each sample and then to assign alleles.
0000006542 00000 n 17. Please try after some time. 126 0 obj <> endobj 0000009180 00000 n
0000024441 00000 n All rights reserved. The values are presented as a dot plot in Figure 1, and the distribution is presented in Table 4. 31. The probability of HLA-C matching was calculated from the allelic association with HLA-B locus because the LD was strongest between these two loci. Transplantation 1988; 45(4): 714. N Engl J Med 1990; 323(26): 1818.
For the majority of patients lacking a sibling donor, an extended family search for an human leukocyte antigen (HLA)-identical donor is also unsuccessful (2). Probability of finding HLA-matched unrelated marrow donors. 35.
Additionally, if the donor and recipients share one of the more promiscuous HLA-B alleles like B*5101 or B*1501, the chances of matching at the HLA-C locus is extremely low. A correlation between HLA-C matching and donor antirecipient CTL precursor frequency in bone marrow transplantation. HLA-C is the inhibitory ligand that determines dominant resistance to lysis by NK1- and NK2-specific natural killer cells. 0000031302 00000 n 0000016268 00000 n Bone Marrow Transplant 1996; 17(3): 323. Although all three pairs demonstrated LD, it was strongest between HLA-B and HLA-C (P<0.01). 9. 0000005549 00000 n The nucleated cells from the blood samples were collected, and genomic DNA was isolated.
Immunity. for the 4 age groups was 54.0% in group 1, 64.5% in. Three dots with a probability of 1 for matching at both of the HLA-C alleles represent B*0801/B*0801, B*0801/B*4901, and B*4901/B*4901.
Further, storing cord blood from newborns in families with a known genetic disease would yield an acceptable future stem cell transplant product in nearly 40% of cases. 126 146 The study included 727 haplotypes from 849 individuals who were HLA-A, -B, -C and -DRB1 typed by high-resolution PCR-SSOP technique.
A rapid growth in the number of URD-BMT (3, 4, 9) further increases the significance of such an endeavor. Assuming that a four of six antigen HLA-A, -B, -DR match is acceptable, it is possible to find unrelated donors for patients of any race from a putative registry with fewer than 10,000 potential donors. 10. 0000007567 00000 n
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0000007994 00000 n 12.
0000025948 00000 n Novel in vitro functional studies to delineate the precise role played by HLA-C gene products in alloreaction will further enhance the under-standing of its implications for marrow and organ transplantation. Our study illustrates not only the existence of LD between HLA-B and HLA-C alleles at the genotypic level but also the presence of a marked variation in the degree of LD between various HLA-B and HLA-C alleles. Petersdorf EW, Longton GM, Anasetti C, et al.
Proc Natl Acad Sci USA 1992; 89(17): 7983. 0000087202 00000 n 0000031693 00000 n Such haplotyping would result in a very large number of possible combinations and pose a major barrier to a meaningful analysis. Data is temporarily unavailable. 0000007112 00000 n 38.
0000013924 00000 n In: Tsuzi K, Aizawa M, Sasazuki T, eds. 0000087694 00000 n 0000017492 00000 n Probability tables for common alleles are presented. DNA typing for HLA-A, -B, and -DRB1 was performed by a DNA-based PCR-SSOP technique as described previously (33-35).
Within the immediate family, the members that match for HLA-A, -B, and -DRB1 by routine testing are likely to be genotypically identical for HLA-A, -B, and -DRB1, as well as for the other untested loci within the HLA complex, because of the inheritance of a haplotype comprising the whole HLA complex from each parent and also because of a the low frequency of recombination observed within the HLA complex. In addition, the probability was greater than 90% for only the following 9 (2.77%) of 325 HLA-B combinations: B*0801/B*1402, B*0801/B*3502, B*0801/B*3801, B*1402/B*4901, B*3502/B*4901, B*3801/B*4901, B*0801/B*0801, B*0801/B*4901, and B*4901/B*4901. In addition, the accuracy of such findings may be limited because of biases arising from self-reported racial designations. Large-scale DRB and DQB1 oligonucleotide typing for the NMDP registry: progress report from year 2. 24. Heterozygotes were identified by the presence of two different hybridization score patterns.
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