The HLA dictionary 2008: a summary of HLA-A, -B, -C, -DRB1/3/4/5, and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR, and -DQ antigens.

The 2008 report of the human leukocyte antigen (HLA) data dictionary presents serologic equivalents of HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, and -DQB1 alleles. The dictionary is an update of the one published in 2004. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for Factors of the HLA System, the International Cell Exchange, UCLA, the National Marrow Donor Program, recent publications, and individual laboratories. The 2008 edition includes information on 832 new alleles (685 class I and 147 class II) and updated information on 766 previously listed alleles (577 class I and 189 class II). The tables list the alleles with remarks on the serologic patterns and the equivalents. The serological equivalents are listed as expert assigned types, and the data are useful for identifying potential stem cell donors who were typed by either serology or DNA-based methods. The tables with HLA equivalents are available as a searchable form on the IMGT/HLA database Web site (http://www.ebi.ac.uk/imgt/hla/dictionary.html).

The HLA Dictionary 2004: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.

This report presents serological equivalents of HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5 and -DQB1 alleles. The dictionary is an update of that published in 2001. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for Factors of the HLA System, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP), recent publications and individual laboratories. This latest update of the dictionary is enhanced by the inclusion of results from studies performed during the 13th International Histocompatibility Workshop and from neural network analyses. A summary of the data as recommended serological equivalents is presented as expert assigned types. The tables include remarks for alleles, which are or may be expressed as antigens with serological reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated haematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. The serological DNA equivalent dictionary will also aid in typing and matching procedures for organ transplant programmes whose waiting lists of potential donors and recipients comprise mixtures of serological and DNA-based typings. The tables with HLA equivalents and a questionnaire for submission of serological reaction patterns for poorly identified allelic products will be made available through the WMDA web page (http://www.worldmarrow.org) and, in the near future, also in a searchable form on the IMGT/HLA database.

The HLA Dictionary 2004: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.

This report presents serologic equivalents of human leucocyte antigen (HLA)-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5 and -DQB1 alleles. The dictionary is an update of the one published in 2001. The data summarize equivalents obtained by the World Health Organization Nomenclature Committee for factors of the HLA System, the International Cell Exchange, the National Marrow Donor Program, recent publications and individual laboratories. This latest update of the dictionary is enhanced by the inclusion of results from studies performed during the 13th International Histocompatibility Workshop and from neural network analyses. A summary of the data as recommended serologic equivalents is presented as expert assigned types. The tables include remarks for alleles, which are or may be expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. The serological DNA equivalent dictionary will also aid in typing and matching procedures for organ transplant programs whose waiting lists of potential donors and recipients comprise of mixtures of serologic and DNA-based typings. The tables with HLA equivalents and a questionnaire for submission of serologic reaction patterns for poorly identified allelic products will be made available through the WMDA web page: www.worldmarrow.org. and in the near future also in a searchable form on the IMGT/HLA database.

The HLA Dictionary 2001: a summary of HLA-A, -B, -C, -DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.

This report presents the serologic equivalents of 123 HLA-A, 272 HLA-B and 155 HLA-DRB1 alleles. The equivalents cover over 64% of the presently identified HLA-A, -B and -DRB1 alleles. The dictionary is an update of the one published in 1999 and also includes equivalents for HLA-C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize information obtained by the WHO Nomenclature Committee for Factors of the HLA System, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP) and individual laboratories. In addition, a listing is provided of alleles which are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. The tables with HLA equivalents and a questionnaire for submission of serologic reaction patterns for poorly identified allelic products will also be available on the WMDA web page: http://www.worldmarrow.org.

The HLA dictionary 2001: a summary of HLA-A, -B, -C, -DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR, and -DQ antigens.

This report presents the serologic equivalents of 123 HLA-A, 272 HLA-B, and 155 HLA-DRB1 alleles. The equivalents cover over 64 percent of the presently identified HLA-A, -B, and -DRB1 alleles. The dictionary is an update of the one published in 1999 (Schreuder GMTh, Hurley CK, Marsh SGE, Lau M, Maiers M, Kollman C, Noreen H. The HLA dictionary 1999: a summary of HLA-A, -B, -C, -DRB1/3/4/5, -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens. Tissue Antigens 54:407, 1999) and also includes equivalents for HLA-C, DRB3, DRB4, DRB5, and DQB1 alleles. The data summarize information obtained by the WHO Nomenclature Committee for Factors of the HLA System, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP), and individual laboratories. In addition, a listing is provided of alleles which are expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programs where HLA typings from donors and from recipients on waiting lists represent mixtures of serologic and molecular typings. The tables with HLA equivalents and a questionnaire for submission of serologic reaction patterns for poorly identified allelic products will also be available on the WMDA web page: www.worldmarrow.org.

Validation of DNA-based HLA-A and HLA-B testing of volunteers for a bone marrow registry through parallel testing with serology.

A total of 42,160 individuals were typed for HLA-A and HLA-B by both serology and PCR-based typing. The HLA assignments included all of the known serological equivalents. The majority of the individuals (99.9%) were from U.S. minority population groups. The serologic typing was performed between 1993 and 1997 at the time of recruitment for the National Bone Marrow Program (NMDP) registry. The polymerase chain reaction (PCR)-based typing was carried out in two phases. In phase I, DNA typing was performed by PCR using sequence-specific oligonucleotide probes (PCR-SSOP) or PCR using sequence-specific primers (PCR-SSP) without knowledge of the serologic assignments. Discrepancies were identified between the serologic and DNA assignments in 24% of the volunteers (8% of volunteers differed for only HLA-A assignments, 13% for HLA-B, and 3% for both HLA-A and -B) and a potential explanation was assigned each discrepant serology/DNA pair. In phase II, a random sampling scheme was used to select a statistically significant number of individuals for repeat DNA typing from each of these categories. The categories included antigens missed by serology, nonexpressed (null) alleles, PCR amplification failures, misassignment of antigens and nomenclature issues. Only a single individual was found to carry a null allele. DNA-based testing correctly typed nearly 99% of the donors at HLA-A, more than 98% at HLA-B, and more than 97% at both HLA-A and -B validating this methodology for registry typing.

The HLA Dictionary 2001: a summary of HLA-A, -B, -C, -DRB1/3/4/5 and -DQB1 alleles and their association with serologically defined HLA-A, -B, -C, -DR and -DQ antigens.

This report presents the serological equivalents of 123 HLA-A, 272 HLA-B and 155 HLA-DRB1 alleles. The equivalents cover over 64% of the presently identified HLA-A, -B and -DRB1 alleles. The dictionary is an update of the one published in 1999 (<1>Schreuder et al., 1999, Tissue Antigens, 54, 409) and also includes equivalents for HLA-C, DRB3, DRB4, DRB5 and DQB1 alleles. The data summarize information obtained by the WHO Nomenclature Committee for Factors of the HLA System, the International Cell Exchange (UCLA), the National Marrow Donor Program (NMDP) and individual laboratories. In addition, a listing is provided of alleles that are expressed as antigens with serological reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. These equivalents will also serve typing and matching procedures for organ transplant programmes where HLA typings from donors and from recipients on waiting lists represent mixtures of serological and molecular typings. The tables with HLA equivalents and a questionnaire for submission of serological reaction patterns for poorly identified allelic products will also be available on the WMDA web page: www.worldmarrow.org

Three new DP alleles identified in a study of 800 unrelated bone marrow donor-recipient pairs.

HLA-DP genotyping of 800 unrelated donor-recipient pairs in phase 5 of a retrospective analysis of unrelated bone marrow transplantation, sponsored by the National Marrow Donor Program (NMDP), has identified two new DPB1 alleles (DPB1*8701 and DBP1*8801) and one new DPA1 (DPA1*0108) allele. Sequencing confirmed that all three of these new alleles represent novel combinations of previously described sequence motifs, reinforcing the notion that "gene conversion-like" events play an important role in generating HLA allelic diversity. The identification of these new alleles brings the total number of DPA1 alleles to 20 and the total number of DPB1 alleles to 94.

Four new DP alleles identified in a study of 500 unrelated bone marrow donor-recipient pairs.

HLA-DP genotyping of 500 donor recipient pairs in a retrospective analysis sponsored by the National Marrow Donor Program (NMDP) identified four new DP alleles, two DPB1 and two DPA1. DNA sequencing confirmed that DPB1*8001 and *8101, each found in a single individual, are novel combinations of previously described sequence motifs in the six variable regions of DPB1. DPA1*02014, found in two individuals, is identical to DPA1*02011 except for a novel silent substitution, a G to A transition at the third position of codon 14. DPA1*01032, found in one individual, is identical to DPB1*01031 except for a silent G to A transition at the third position of codon 20. The identification of these novel alleles brings the total number of reported DPB1 alleles to 85 and DPA1 alleles to 15.

Does re-exposure to mismatched HLA antigens decrease renal re-transplant allograft survival?

UNLABELLED: We analyzed 420 kidney retransplants at the University of Minnesota, 87 of which did and 333 which did not share HLA mismatches with the previous transplant. There was no difference in outcome. We conclude that exceptions to routine HLA matching policies do not have to be made for kidney retransplants. OBJECTIVE: To determine if the kidney graft functional survival rate for retransplants is influenced by presence of HLA mismatches in common with the previous (failed) transplant. SUMMARY BACKGROUND DATA: Kidney retransplants have a lower function rate than primary grafts. An anamnestic response to HLA antigens shared with the previous donor could be one factor responsible, but reports in the literature are conflicting. METHODS: Of 420 kidney retransplants with HLA information done at the University of Minnesota, 87 shared > or = 1 HLA antigens specifically mismatched with the previous donor (63 cadaver and 24 living donor retransplants), while 333 did not (247 cadaver, 86 living donor). Patient and graft survival rates were calculated by life-table analysis for recipients with vs. without repeat mismatches, with the significance of differences determined by the Lee-Desu statistic. RESULTS: Patient and kidney graft retransplant survival rate curves were not significantly different (p > or = 0.41) for those exposed or not exposed to the same HLA mismatches as before. At 2 years, 70% vs. 61%, respectively, of cadaver grafts and 71% vs. 78%, respectively, of living donor grafts were functioning. CONCLUSIONS: The probability of a successful outcome with a kidney retransplant is no different for patients who do than for those who do not receive an organ sharing HLA mismatches with the previous donor. Exceptions to routine HLA matching policies do not need to be made for kidney retransplants.

The role of natural antibodies in the activation of xenogenic endothelial cells.

Hyperacute rejection of organ xenografts is thought to be mediated by the reaction of naturally occurring antibodies and complement of the recipient with blood vessels in the donor organ. We have suggested previously that the pathogenesis of hyperacute rejection might involve the activation of endothelial cells in the graft. To evaluate the potential role of natural antibodies and complement in hyperacute xenograft rejection, sixteen human sera were tested for variation in the ability to activate porcine endothelial cells as manifested by the release of biosynthetically labeled heparan sulfate from the cells. It was then asked to which extent such variation might reflect differences in natural antibody titer and/or complement activity. The sera mediated release of 3.6-57% of endothelial cell-associated heparan sulfate. Heparan sulfate release correlated significantly with the titer, in the sera, of IgM antibodies that bound to cultured endothelial cells (P = 0.0008) or to a triad of glycoproteins believed to represent the major targets of natural antibodies in porcine to primate xenografts (P = 0.001); correlation was also observed with the total concentration of IgM (P = 0.0046). The release of heparan sulfate did not correlate with corresponding properties of serum IgG, with anti-swine hemagglutination or with isohemagglutination titers. Heparan sulfate release correlated with deposition on endothelial cells of iC3b (P = 0.0095), but not with serum complement activity. Our findings indicate that in the reaction between human serum and xenogeneic endothelial cells, it is the concentration of xenoreactive IgM and not differences in complement activity that limits the ensuing pathophysiologic events.

Serology, restriction fragment length polymorphism, and sequence analysis of a unique HLA class II antigen, DR5x6.

We analyzed a new class II HLA haplotype, which we have designated DR5x6, by serology, restriction fragment length polymorphism (RFLP), and sequence analysis. As the name DR5x6 implies, the antigen is serologically closely related to both DR5 and DRw6. RFLP analysis of this haplotype suggests a close similarity with DRw11 haplotypes. The DNA sequences encoded by the second exon of its DRB1, DRB3, and DQB1 genes were also determined. Comparison of these sequences with those of alleles at these loci in other haplotypes suggests that this haplotype could have evolved from a DRw11 ancestor haplotype (DRw11-DRw52b (Dw25)-DQw7) by means of: (a) a gene conversion at the DRB1 locus involving DRw8 (Dw8.3) as the sequence donor, plus a point mutation or a gene conversion involving DR4-Dw4; and (b) a recombination event by which this haplotype would have acquired the DRw5a (Dw24) allele at the DRB3 locus.

The impact of HLA matching on graft survival and on sensitization after a failed transplant--evidence that failure of poorly matched renal transplants does not result in increased sensitization.

There are costs (both financial and ethical) to distributing kidneys by HLA-match (time, transportation, repeat crossmatch; possibly bypassing a more deserving recipient). Arguments favoring matching include better short- and long-term survival, and decreased panel-reactive antibody (PRA) if a well-matched vs. poorly matched transplant fails. We studied these phenomena in a single institution. Since 1970, 1329 patients received cadaver (CAD) transplants; for those with defined antigens (n = 1316) there was no difference in 10-year graft survival in those with a less than or equal to 1 AB match vs. those with greater than 1 AB match or those with less than or equal to 1 AB mismatch (mm) vs. greater than 1 AB mm. Similarly there was no difference in those with less than or equal to 2 BDR mm vs. greater than 2 BDR mm. In fact, those with less than ABDR mm had worse 10-year graft survival (55%) than those with greater than or equal to 3 ABDR mm (61%) (P = .001). For patients with function greater than 6 months there was no difference in long-term outcome based on HLA match or mm. These findings were similar for patients both with and without CsA immunosuppression, and for primary and retransplants. A total of 382 patients transplanted since 1980 have lost their grafts (146 died with function). All had received pretransplant transfusions. Of 236 alive after graft loss, 64 had no postgraft failure PRAs (22 out of state, 23 chose to remain on dialysis, 19 died less than 3 months after graft loss); 172 had PRAs after failure; 106 (62%) have been retransplanted. Mean peak PRA in those retransplanted was 23 +/- 31 (range 0-100) vs. 46 +/- 39 (range 0-100) in those not retransplanted (P less than .05). Patients were stratified by PRA prior to first transplant (0%, 1-20%, greater than 20%). For recipients with 0% PRA, failure of a CAD transplant (n = 58) was no more likely to result in an increase of PRA than failure of a living-related donor (LRD) transplant (n = 49) (NS). For those with an increase, mean increase was 45% +/- 34 after LRD transplant and 41% +/- 28 after CAD transplant (NS). The proportion developing PRA greater than or equal to 60% was not different after a failed LRD (7/49) or CAD (11/58) transplant (NS). Other subgroups had similar results. AZA or CsA immunosuppression did not affect development of increased PRA after a failed graft.(ABSTRACT TRUNCATED AT 400 WORDS)

HLA class I and II antigen phenotypes of North American Indians from Minnesota: implications for marrow transplants using unrelated donors.

As a result of an appeal for a bone marrow donor for a North American Indian (Native American) patient, 261 Native Americans from our community were typed for HLA-A,B,DR antigens, and 51 were typed for HLA-A,B antigens only. The HLA antigen frequencies of the Native Americans were compared with those of 12,881 white bone marrow donors and were found to differ markedly. To investigate the implications these differences in HLA antigen frequencies would have for the location of unrelated bone marrow donors, the HLA types of 12 Native American bone marrow transplant patients from our institution were used to search among 5389 HLA-A,B,DR-typed white donors in the National Marrow Donor Program file and the file of 261 HLA-A,B,DR-typed Native American donors. In the white donor file, at least two donors were found that matched at all HLA-A,B,DR antigen loci of one Native American patient (8%). Using the Native American donor file, which was less than one-twentieth the size of the white donor file, and HLA-A,B,DR-matched donor was also found for one (8%) of the patients. These results suggest that although donors for nonwhites can be identified in a file of HLA-typed white volunteers, the probability of finding a suitably matched donor for such individuals is enhanced if donors representing racial or ethnic minorities are included in unrelated donor registries.