A comparative study of HLA-DRBl typiig by standard serology and hybridization of non-radioactive ... more A comparative study of HLA-DRBl typiig by standard serology and hybridization of non-radioactive sequence-specific oligonucleotide probes to PCR-amplified DNA.
Twelve patients with acute leukemia and nine with aplastic anemia received marrow transplants fro... more Twelve patients with acute leukemia and nine with aplastic anemia received marrow transplants from donors other than genotypically HLA-identical siblings. All donor-recipient pairs were genotypically identical for one HLA haplotype and shared antigens of the other. Of nine transplants ...
study, there are many such families in the HLA IBD = 2 group, yielding a high expected Gm concord... more study, there are many such families in the HLA IBD = 2 group, yielding a high expected Gm concordance rate in that group. When repeating our analysis, correcting for expected Gm concordance rates, there was no significant HLA-GM interaction (p > 0.8).
We analyzed pretransplant donor anti-recipient cytotoxic and helper T lymphocyte (CTL and HTL) re... more We analyzed pretransplant donor anti-recipient cytotoxic and helper T lymphocyte (CTL and HTL) responses separately in two cohorts of unrelated marrow transplant recipients. Donors and recipients were typed for HLA-A and -B antigens by serologic methods, and for HLA-DRB1 by molecular methods. A single mismatch for a cross-reactive HLA-A or -B antigen or the -DRB1 allele was accepted in patients younger than 36 years if an HLA-A, -B, or -DRB1-matched donor could not be identified. The combination of methotrexate and cyclosporine was used for graft-vs.-host disease (GVHD) prophylaxis, and marrows were not T cell depleted. Donor anti-recipient CTL precursor frequencies showed no correlation with the severity of acute GVHD or with survival after transplantation. HTL responses were detected in the presence of HLA-class II disparity and showed weak correlations with the severity of acute GVHD (p = 0.054) and with survival after transplantation (p = 0.08). These results suggest that testing donor anti-recipient CTL responses before unmodified marrow transplantation does not predict clinically important events and is not likely to help select unrelated donors. With the current availability of molecular genetic methods for assessing HLA-class II compatibility, testing donor anti-recipient HTL responses is not likely to add information that would help select unrelated donors.
A new DR beta-chain allele is defined that is identical to the previously described DR6b molecule... more A new DR beta-chain allele is defined that is identical to the previously described DR6b molecule except for the first hyperpolymorphic region, where the new allele displays the same polymorphisms found on DR8 and DR12 genes. Two distinct epitopes have been mapped on this new allele. The polymorphism in common with DRw8 and DRw12 is recognized by mAb GS313-9D11. However, alloreactive T cell clones specific for DR6b cells (Dw9) recognize this allele, whereas Dw8-specific T cell clones do not. The mAb determinant maps to the first beta-sheet and probably involves a polymorphic residue lying outside the helix. The binding of mAb 9D11 to this region does not interfere with TCR binding. Alloreactive T cell recognition is associated with polymorphisms located predominantly on the alpha-helical portion of the molecule.
Disparity for HLA-A or HLA-B antigens increases the risk of marrow graft rejection, but the relev... more Disparity for HLA-A or HLA-B antigens increases the risk of marrow graft rejection, but the relevance of HLA-C is unknown because typing methods have not been sufficiently accurate for clinical use. We designed a matched case-control study and employed DNA sequencing methods to evaluate the role of HLA-C disparity in 21 patients who experienced graft failure (cases) following transplantation with unmanipulated marrow from either HLA-A, B serologically matched, DRB1 matched (n = 14) or single locus mismatched (n = 7) unrelated donors. For each case, two patients who successfully engrafted were selected as controls based on similarity for factors known or suspected to influence engraftment. The estimated odds ratio (OR) of graft failure for an HLA-C mismatch relative to match (univariable model) was 5.2 (95% CI, 1.4, 19; P = .01). Serologically undetectable HLA-A or HLA-B allele disparity was also associated with graft failure. The association between HLA-C disparity and graft failure...
HLA-DR4 is one of the most heterogeneous of the serologically defined HLA class II specificities.... more HLA-DR4 is one of the most heterogeneous of the serologically defined HLA class II specificities. Sequence analyses (1) of the HLA-D subtypes of DR4 indicate that the amino acid sequences of Dw4, Dw10, Dw13, Dw14, Dw15, and DKT2 are identical from residues 1 through 56 of the DR β-I molecule, with the single exception of a Y → S substitution at position 37 in DKT2 (Fig. 1). Eight T-cell clones were submitted to the Tenth Interna- tional Workshop which recognized polymorphisms of HLA-DR4, and these clustered into four groups: 1) those recognizing Dw4 (clones 6026, 6096, and 6099), 2) those recognizing Dw13 and DKT2 (clones 6001 and 6006), 3) those recognizing Dw14 (clones 6010 and 6078), and 4) a single clone (6097) recognizing Dw1O. Additionally, clone 6021 recognized cells typing as Dw4, Dw10, Dw13, and Dw14. The reactivities of these clones are illustrated in Figure 1.
ABSTRACT Evaluation of results of clinical marrow transplantation is a complex problem in which t... more ABSTRACT Evaluation of results of clinical marrow transplantation is a complex problem in which the effect of histocompatibility differences between recipient and donor is only one of several factors to be considered. Significant heterogeneity can exist within any group of patients, and variations in therapeutic procedures, especially between different transplant centers, make pooling of data difficult. Improvements in clinical management makes retrospective analysis and historical comparisons unreliable. Factors that influence the prognosis of individual patients include the age and general condition of the patient, the primary disease, leukemia remission status, previous transfusions, the pregraft conditioning, and the kind of immunosuppressive agents used postgrafting for control of GVHD.
The development of accurate and reproducible high-resolution DNA-based HLA typing methods has sig... more The development of accurate and reproducible high-resolution DNA-based HLA typing methods has significantly improved the prospects for identifying well-matched donors for patients undergoing HCT, particularly those who lack a matched relative to serve as donor. Analysis of high-resolution typing data has shown that donor-recipient compatibility for HLA alleles is an important predictor of transplant outcome. The risk of graft failure is increased by patient incompatibility for HLA alleles expressed by the donor, and by the presence of patient anti-donor alloantibody. The impact of HLA class I and class II allele disparity on transplant outcome in unrelated HCT has been demonstrated in several large studies, and it is now evident that complete donor-recipient matching for HLA-A,-B,-C,-DRB1 and -DQB1 genes can significantly reduce the incidence of GVHD and risk of mortality. Patient-donor disparity for multiple HLA class I and class II alleles is clearly related to poor outcome, in te...
The lymphocyte responses of 51 human marrow graft recipients were tested in vitro 18 to 45 days a... more The lymphocyte responses of 51 human marrow graft recipients were tested in vitro 18 to 45 days after marrow grafting by stimulation with lymphocytes from unrelated individuals or phytohemagglutinin (PHA). Fourteen of the 51 patients subsequently developed interstitial pneumonia (IP). The relative responses of the lymphocytes of patients who developed IP were significantly lower than those of individuals not developing IP (P less than 0.01 for allogeneic cells, P = 0.02 for PHA). These nonspecific in vitro tests of cell-mediated immunity are of value in identifying patients at risk of developing IP.
Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: Matching for trans... more Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: Matching for transplants from related haploidentical donors.
Proceedings of the National Academy of Sciences, 1990
Although HLA genes have been shown to be associated with certain diseases, the basis for this ass... more Although HLA genes have been shown to be associated with certain diseases, the basis for this association is unknown. Recent studies, however, have documented patterns of nucleotide sequence variation among some HLA genes associated with a particular disease. For rheumatoid arthritis, HLA genes in most patients have a shared nucleotide sequence encoding a key structural element of an HLA class II polypeptide; this sequence element is critical for the interaction of the HLA molecule with antigenic peptides and with responding T cells, suggestive of a direct role for this sequence element in disease susceptibility. We describe the serological and cellular immunologic characteristics encoded by this rheumatoid arthritis-associated sequence element. Site-directed mutagenesis of the DRB1 gene was used to define amino acids critical for antibody and T-cell recognition of this structural element, focusing on residues that distinguish the rheumatoid arthritis-associated alleles Dw4 and Dw14...
A third allele at the DRB3 locus, DRw52c, represents an intermediate sequence between DRw52a and ... more A third allele at the DRB3 locus, DRw52c, represents an intermediate sequence between DRw52a and DRw52b and may have arisen by a gene conversion-like event. The recognition of cells bearing these molecules by a number of alloreactive and antigen-specific DR-restricted T cell clones was analyzed. On the basis of a theoretical model of HLA class II structure, distinct amino acid clusters have been identified as motifs controlling TCR recognition. These are located both in the cleft and in the alpha-helical edge of the MHC class II recognition platform. Motifs shared between two alleles may restrict public T cell clones.
Two-dimensional (2D) gel electrophoresis of immunoprecipitated HLA-DR antigens from eight homozyg... more Two-dimensional (2D) gel electrophoresis of immunoprecipitated HLA-DR antigens from eight homozygous typing cells (HTC) expressing the HLA-DRw8 specificity revealed a clustering of polymorphic beta chain patterns into distinct electrophoretic variants. The variant patterns correlate with three discrete HLA-D clusters that are defined in the mixed leukocyte culture reaction (MLR) using DRw8-positive HTC. These HLA-D clusters have been provisionally designated Dw"8.1", detected primarily in Caucasoids, Dw"8.2", detected primarily in American Indians, and Dw"8.3", detected predominantly in Orientals. All three HLA-Dw"8.1" cell lines express a single DR-locus product as defined by immunoprecipitation with a DR-specific monoclonal antibody, P4.1. This DR beta chain is identical among the Dw"8.1" cell lines and different from the DR beta chains of the Dw"8.2" and Dw"8.3" cell lines. Two separate Dw"8.2" HTC express a shared DR beta chain that is slightly more basic than the 8.1 DR molecule; interestingly, one of these lines also expresses an additional DR-like beta chain not found in the other cells. Thus, the two lines defining the Dw"8.2" cluster share one distinct class II molecule, but differ in another and therefore are not biochemically HLA-identical. Cells from the Dw"8.3" cluster are likewise distinct from all other Dw8 clusters. One additional DRw8-positive HTC has been analyzed and found to be distinct from the Dw"8.1", "8.2" and "8.3" clusters by both MLR and 2D gels. Immunoprecipitates using monoclonal antibody 1B5 [anti-DR and anti-DQ(DS)] identify additional polymorphic class II variants among the cell lines tested. These data indicate that HLA-DRw8 is a public serologic specificity present on class II molecules expressed on multiple distinct haplotypes. These haplotypes differ from each other in expression of polymorphic class II molecules encoded by at least two HLA loci. They also differ in HLA-D, even though they all type as HLA-DRw8 homozygous. In Dw"8.2", variation in expressed beta chains is not reflected in variation in HLA-D, indicating that MLR, as well as serologic typing, does not detect the full degree of allelic polymorphism within HLA.
Homozygous typing cells eHTC) and responder ,ells from a pand of randoml) sdecled unrelated cauca... more Homozygous typing cells eHTC) and responder ,ells from a pand of randoml) sdecled unrelated caucasians were used in a study of the HLA. Dw6 antigen complex. Using HTC characterized by the Eighth International Histocompattbility Workshop. the Du6 sp~cifici(, was shown to be a broadly deft'ned, heIerogeneous cluster that could be subdivided. An HTC from our laboratoy, 8W146, and a second focally identified cell, EMJ. u'ere used to define one clearl5 distinguishable subcluster of Dw6. provisionally ternted "6.1." HTC 8W146 and EAfJ u~r* mutually nonreactive in mixed leukocyte culture and showed strong association ¢r = 0.85J uhen used as stimulators against the caucasian cell panel. The calculated gene frequeno" of the 8W146/EMJ determinant in this population was 0.024, In an informatite family, the 6.~ specificity could b,. shown to segregate independently of other Dw6 subgroups. DR t)lJing of 8W146 and EMJ showed both to be positive for MT-I and MT-2 but negatire for DRu "3 +6." ABBREVIATIONS cpm DNV 8thWorkshop counts per minute HTC homozygous typ'ng double normalized cells value MLC mixed leukocyte Eighth International culture Histocompatibility Workshop
Progress in hematopoietic cell transplantation has been greatly facilitated by our increasing kno... more Progress in hematopoietic cell transplantation has been greatly facilitated by our increasing knowledge of the HLA system, as well as by improved therapies for achieving sustained engraftment, preventing graftversus-host disease, and protecting the patient from infection. Disparity for HLA genes can cause graft rejection and graft-versus-host disease and decrease survival in patients receiving grafts from both related and unrelated donors. The presence of patient alloantibodies against donor antigens demonstrated by a positive crossmatch is a strong risk factor for graft rejection. The availability of matched donors for patients lacking a genotypically HLAmatched sibling has been greatly improved by the establishment of international registries of HLA-typed volunteer donors. The development of accurate and reproducible high-resolution DNA-based typing methods has significantly improved the prospects for identifying unrelated donors who are well matched with the patient for HLA. The use of these methods to optimize donor selection will improve both donor identification and the success of unrelated donor transplants.
A comparative study of HLA-DRBl typiig by standard serology and hybridization of non-radioactive ... more A comparative study of HLA-DRBl typiig by standard serology and hybridization of non-radioactive sequence-specific oligonucleotide probes to PCR-amplified DNA.
Twelve patients with acute leukemia and nine with aplastic anemia received marrow transplants fro... more Twelve patients with acute leukemia and nine with aplastic anemia received marrow transplants from donors other than genotypically HLA-identical siblings. All donor-recipient pairs were genotypically identical for one HLA haplotype and shared antigens of the other. Of nine transplants ...
study, there are many such families in the HLA IBD = 2 group, yielding a high expected Gm concord... more study, there are many such families in the HLA IBD = 2 group, yielding a high expected Gm concordance rate in that group. When repeating our analysis, correcting for expected Gm concordance rates, there was no significant HLA-GM interaction (p > 0.8).
We analyzed pretransplant donor anti-recipient cytotoxic and helper T lymphocyte (CTL and HTL) re... more We analyzed pretransplant donor anti-recipient cytotoxic and helper T lymphocyte (CTL and HTL) responses separately in two cohorts of unrelated marrow transplant recipients. Donors and recipients were typed for HLA-A and -B antigens by serologic methods, and for HLA-DRB1 by molecular methods. A single mismatch for a cross-reactive HLA-A or -B antigen or the -DRB1 allele was accepted in patients younger than 36 years if an HLA-A, -B, or -DRB1-matched donor could not be identified. The combination of methotrexate and cyclosporine was used for graft-vs.-host disease (GVHD) prophylaxis, and marrows were not T cell depleted. Donor anti-recipient CTL precursor frequencies showed no correlation with the severity of acute GVHD or with survival after transplantation. HTL responses were detected in the presence of HLA-class II disparity and showed weak correlations with the severity of acute GVHD (p = 0.054) and with survival after transplantation (p = 0.08). These results suggest that testing donor anti-recipient CTL responses before unmodified marrow transplantation does not predict clinically important events and is not likely to help select unrelated donors. With the current availability of molecular genetic methods for assessing HLA-class II compatibility, testing donor anti-recipient HTL responses is not likely to add information that would help select unrelated donors.
A new DR beta-chain allele is defined that is identical to the previously described DR6b molecule... more A new DR beta-chain allele is defined that is identical to the previously described DR6b molecule except for the first hyperpolymorphic region, where the new allele displays the same polymorphisms found on DR8 and DR12 genes. Two distinct epitopes have been mapped on this new allele. The polymorphism in common with DRw8 and DRw12 is recognized by mAb GS313-9D11. However, alloreactive T cell clones specific for DR6b cells (Dw9) recognize this allele, whereas Dw8-specific T cell clones do not. The mAb determinant maps to the first beta-sheet and probably involves a polymorphic residue lying outside the helix. The binding of mAb 9D11 to this region does not interfere with TCR binding. Alloreactive T cell recognition is associated with polymorphisms located predominantly on the alpha-helical portion of the molecule.
Disparity for HLA-A or HLA-B antigens increases the risk of marrow graft rejection, but the relev... more Disparity for HLA-A or HLA-B antigens increases the risk of marrow graft rejection, but the relevance of HLA-C is unknown because typing methods have not been sufficiently accurate for clinical use. We designed a matched case-control study and employed DNA sequencing methods to evaluate the role of HLA-C disparity in 21 patients who experienced graft failure (cases) following transplantation with unmanipulated marrow from either HLA-A, B serologically matched, DRB1 matched (n = 14) or single locus mismatched (n = 7) unrelated donors. For each case, two patients who successfully engrafted were selected as controls based on similarity for factors known or suspected to influence engraftment. The estimated odds ratio (OR) of graft failure for an HLA-C mismatch relative to match (univariable model) was 5.2 (95% CI, 1.4, 19; P = .01). Serologically undetectable HLA-A or HLA-B allele disparity was also associated with graft failure. The association between HLA-C disparity and graft failure...
HLA-DR4 is one of the most heterogeneous of the serologically defined HLA class II specificities.... more HLA-DR4 is one of the most heterogeneous of the serologically defined HLA class II specificities. Sequence analyses (1) of the HLA-D subtypes of DR4 indicate that the amino acid sequences of Dw4, Dw10, Dw13, Dw14, Dw15, and DKT2 are identical from residues 1 through 56 of the DR β-I molecule, with the single exception of a Y → S substitution at position 37 in DKT2 (Fig. 1). Eight T-cell clones were submitted to the Tenth Interna- tional Workshop which recognized polymorphisms of HLA-DR4, and these clustered into four groups: 1) those recognizing Dw4 (clones 6026, 6096, and 6099), 2) those recognizing Dw13 and DKT2 (clones 6001 and 6006), 3) those recognizing Dw14 (clones 6010 and 6078), and 4) a single clone (6097) recognizing Dw1O. Additionally, clone 6021 recognized cells typing as Dw4, Dw10, Dw13, and Dw14. The reactivities of these clones are illustrated in Figure 1.
ABSTRACT Evaluation of results of clinical marrow transplantation is a complex problem in which t... more ABSTRACT Evaluation of results of clinical marrow transplantation is a complex problem in which the effect of histocompatibility differences between recipient and donor is only one of several factors to be considered. Significant heterogeneity can exist within any group of patients, and variations in therapeutic procedures, especially between different transplant centers, make pooling of data difficult. Improvements in clinical management makes retrospective analysis and historical comparisons unreliable. Factors that influence the prognosis of individual patients include the age and general condition of the patient, the primary disease, leukemia remission status, previous transfusions, the pregraft conditioning, and the kind of immunosuppressive agents used postgrafting for control of GVHD.
The development of accurate and reproducible high-resolution DNA-based HLA typing methods has sig... more The development of accurate and reproducible high-resolution DNA-based HLA typing methods has significantly improved the prospects for identifying well-matched donors for patients undergoing HCT, particularly those who lack a matched relative to serve as donor. Analysis of high-resolution typing data has shown that donor-recipient compatibility for HLA alleles is an important predictor of transplant outcome. The risk of graft failure is increased by patient incompatibility for HLA alleles expressed by the donor, and by the presence of patient anti-donor alloantibody. The impact of HLA class I and class II allele disparity on transplant outcome in unrelated HCT has been demonstrated in several large studies, and it is now evident that complete donor-recipient matching for HLA-A,-B,-C,-DRB1 and -DQB1 genes can significantly reduce the incidence of GVHD and risk of mortality. Patient-donor disparity for multiple HLA class I and class II alleles is clearly related to poor outcome, in te...
The lymphocyte responses of 51 human marrow graft recipients were tested in vitro 18 to 45 days a... more The lymphocyte responses of 51 human marrow graft recipients were tested in vitro 18 to 45 days after marrow grafting by stimulation with lymphocytes from unrelated individuals or phytohemagglutinin (PHA). Fourteen of the 51 patients subsequently developed interstitial pneumonia (IP). The relative responses of the lymphocytes of patients who developed IP were significantly lower than those of individuals not developing IP (P less than 0.01 for allogeneic cells, P = 0.02 for PHA). These nonspecific in vitro tests of cell-mediated immunity are of value in identifying patients at risk of developing IP.
Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: Matching for trans... more Role of the mixed lymphocyte culture (MLC) reaction in marrow donor selection: Matching for transplants from related haploidentical donors.
Proceedings of the National Academy of Sciences, 1990
Although HLA genes have been shown to be associated with certain diseases, the basis for this ass... more Although HLA genes have been shown to be associated with certain diseases, the basis for this association is unknown. Recent studies, however, have documented patterns of nucleotide sequence variation among some HLA genes associated with a particular disease. For rheumatoid arthritis, HLA genes in most patients have a shared nucleotide sequence encoding a key structural element of an HLA class II polypeptide; this sequence element is critical for the interaction of the HLA molecule with antigenic peptides and with responding T cells, suggestive of a direct role for this sequence element in disease susceptibility. We describe the serological and cellular immunologic characteristics encoded by this rheumatoid arthritis-associated sequence element. Site-directed mutagenesis of the DRB1 gene was used to define amino acids critical for antibody and T-cell recognition of this structural element, focusing on residues that distinguish the rheumatoid arthritis-associated alleles Dw4 and Dw14...
A third allele at the DRB3 locus, DRw52c, represents an intermediate sequence between DRw52a and ... more A third allele at the DRB3 locus, DRw52c, represents an intermediate sequence between DRw52a and DRw52b and may have arisen by a gene conversion-like event. The recognition of cells bearing these molecules by a number of alloreactive and antigen-specific DR-restricted T cell clones was analyzed. On the basis of a theoretical model of HLA class II structure, distinct amino acid clusters have been identified as motifs controlling TCR recognition. These are located both in the cleft and in the alpha-helical edge of the MHC class II recognition platform. Motifs shared between two alleles may restrict public T cell clones.
Two-dimensional (2D) gel electrophoresis of immunoprecipitated HLA-DR antigens from eight homozyg... more Two-dimensional (2D) gel electrophoresis of immunoprecipitated HLA-DR antigens from eight homozygous typing cells (HTC) expressing the HLA-DRw8 specificity revealed a clustering of polymorphic beta chain patterns into distinct electrophoretic variants. The variant patterns correlate with three discrete HLA-D clusters that are defined in the mixed leukocyte culture reaction (MLR) using DRw8-positive HTC. These HLA-D clusters have been provisionally designated Dw"8.1", detected primarily in Caucasoids, Dw"8.2", detected primarily in American Indians, and Dw"8.3", detected predominantly in Orientals. All three HLA-Dw"8.1" cell lines express a single DR-locus product as defined by immunoprecipitation with a DR-specific monoclonal antibody, P4.1. This DR beta chain is identical among the Dw"8.1" cell lines and different from the DR beta chains of the Dw"8.2" and Dw"8.3" cell lines. Two separate Dw"8.2" HTC express a shared DR beta chain that is slightly more basic than the 8.1 DR molecule; interestingly, one of these lines also expresses an additional DR-like beta chain not found in the other cells. Thus, the two lines defining the Dw"8.2" cluster share one distinct class II molecule, but differ in another and therefore are not biochemically HLA-identical. Cells from the Dw"8.3" cluster are likewise distinct from all other Dw8 clusters. One additional DRw8-positive HTC has been analyzed and found to be distinct from the Dw"8.1", "8.2" and "8.3" clusters by both MLR and 2D gels. Immunoprecipitates using monoclonal antibody 1B5 [anti-DR and anti-DQ(DS)] identify additional polymorphic class II variants among the cell lines tested. These data indicate that HLA-DRw8 is a public serologic specificity present on class II molecules expressed on multiple distinct haplotypes. These haplotypes differ from each other in expression of polymorphic class II molecules encoded by at least two HLA loci. They also differ in HLA-D, even though they all type as HLA-DRw8 homozygous. In Dw"8.2", variation in expressed beta chains is not reflected in variation in HLA-D, indicating that MLR, as well as serologic typing, does not detect the full degree of allelic polymorphism within HLA.
Homozygous typing cells eHTC) and responder ,ells from a pand of randoml) sdecled unrelated cauca... more Homozygous typing cells eHTC) and responder ,ells from a pand of randoml) sdecled unrelated caucasians were used in a study of the HLA. Dw6 antigen complex. Using HTC characterized by the Eighth International Histocompattbility Workshop. the Du6 sp~cifici(, was shown to be a broadly deft'ned, heIerogeneous cluster that could be subdivided. An HTC from our laboratoy, 8W146, and a second focally identified cell, EMJ. u'ere used to define one clearl5 distinguishable subcluster of Dw6. provisionally ternted "6.1." HTC 8W146 and EAfJ u~r* mutually nonreactive in mixed leukocyte culture and showed strong association ¢r = 0.85J uhen used as stimulators against the caucasian cell panel. The calculated gene frequeno" of the 8W146/EMJ determinant in this population was 0.024, In an informatite family, the 6.~ specificity could b,. shown to segregate independently of other Dw6 subgroups. DR t)lJing of 8W146 and EMJ showed both to be positive for MT-I and MT-2 but negatire for DRu "3 +6." ABBREVIATIONS cpm DNV 8thWorkshop counts per minute HTC homozygous typ'ng double normalized cells value MLC mixed leukocyte Eighth International culture Histocompatibility Workshop
Progress in hematopoietic cell transplantation has been greatly facilitated by our increasing kno... more Progress in hematopoietic cell transplantation has been greatly facilitated by our increasing knowledge of the HLA system, as well as by improved therapies for achieving sustained engraftment, preventing graftversus-host disease, and protecting the patient from infection. Disparity for HLA genes can cause graft rejection and graft-versus-host disease and decrease survival in patients receiving grafts from both related and unrelated donors. The presence of patient alloantibodies against donor antigens demonstrated by a positive crossmatch is a strong risk factor for graft rejection. The availability of matched donors for patients lacking a genotypically HLAmatched sibling has been greatly improved by the establishment of international registries of HLA-typed volunteer donors. The development of accurate and reproducible high-resolution DNA-based typing methods has significantly improved the prospects for identifying unrelated donors who are well matched with the patient for HLA. The use of these methods to optimize donor selection will improve both donor identification and the success of unrelated donor transplants.
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Papers by Eric Mickelson