A high degree of HLA disparity arises from limited allelic diversity: analysis of 1775 unrelated bone marrow transplant donor-recipient pairs.

The allelic diversity and associated human leukocyte antigen (HLA) disparity of 1775 bone marrow recipients and their unrelated donors, matched for six of six (1361/1775,77%), five of six (397/1775, 22%), or four of six (17/1775, 1%) HLA-A, -B, -DR antigens, were retrospectively evaluated. The comprehensive HLA analysis included the class I (A, B, C) and II (DRB1, DQA1, DQB1, DPA1, DPB1) loci. Most (>66%) of the predominantly Caucasian study population carried one or two of five to seven common alleles at each HLA locus. In spite of this limited diversity, 29% of the six of six antigen-matched transplants carried allele mismatches at HLA-A, -B, and/or -DRB1, and 92% carried at least one allele mismatch at one of the eight HLA loci tested. Of the 968 HLA-A,-B,-DRB1 allele-matched pairs, 89% carried mismatches at other HLA loci, predominantly at DP loci. The substantially greater than expected HLA allelic disparity between donor and recipient suggests extensive haplotypic diversity and underscores the importance of enhancing approaches to mitigate the deleterious effect of HLA mismatches.

HLA dictionary 2004: 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 serologic equivalents of human leukocyte 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 (WHO) Nomenclature Committee for Factors of the HLA System, the International Cell Exchange (UCLA), 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 are comprised 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 World Marrow Donor Association Web page (www.worldmarrow.org).

Positive remote crossmatch: impact on short-term and long-term outcome in cadaver renal transplantation.

BACKGROUND: A positive crossmatch with a "current" recipient serum (drawn shortly before the proposed transplant) is a contraindication to renal transplantation because of the risk of hyperacute rejection. Conflicting data have been reported concerning the significance of a positive crossmatch with "remote" sera (obtained months or years earlier) when the current crossmatch is negative. METHODS: Recipients of a first or second cadaver transplant between June 1988 and April 1994 were studied. All transplants were performed with a negative "current" crossmatch. Retrospective crossmatches using "remote" sera were performed for all sensitized recipients. RESULTS: Recipients with a positive remote crossmatch (RXM) demonstrated a higher incidence of delayed graft function and of acute rejection and graft loss occurring in the first year posttransplant than did sensitized recipients with a negative RXM or unsensitized recipients. In multivariate analysis, only recipients with both a positive RXM and delayed graft function were at significantly higher risk for graft loss. Grafts surviving the first year demonstrated similar half-lives whether the RXM was positive or negative. CONCLUSIONS: The positive RXM, possibly in conjunction with other factors leading to very early graft damage, is a significant predictor of unfavorable transplant outcome in first and second renal transplants. This effect is seen early in the transplant course, and there seems to be no impact on outcome after the first year. Newer immunosuppressive modalities may help to reduce the early negative impact.

HLA alloimmunization in patients requiring ventricular assist device support.

BACKGROUND: Ventricular assist devices (VADs) are often necessary to maintain circulation in patients with heart failure prior to cardiac transplantation. However, the use of such devices has been reported to be associated with a high incidence of development of human leukocyte antigen (HLA) antibodies, due perhaps, according to some investigators, to immune-activating properties of the VAD itself. We looked at HLA antibody formation in our patients during VAD support to determine the rate and potential causes of antibody formation. METHODS: Between 1995 and 2000, 54 patients were placed on a VAD at our institution. We reviewed clinical and blood transfusion history and HLA antibody testing of the 29 patients without HLA antibodies prior to implantation. HLA antibody testing was performed by an anti-globulin-augmented cytotoxicity method or by a commercial enzyme-linked immunoassay (ELISA) kit. RESULTS: Eight of 29 patients (28%) developed HLA antibodies. Patients who developed HLA antibodies after VAD implantation received significantly more total peri- and post-operative transfusions than did those who remained negative (99 transfusions vs 34 transfusions, p = 0.0014). Within this small study group, gender, age, etiology of heart failure, previous cardiac surgery and duration of VAD support showed no statistically significant correlation with formation of HLA antibodies. CONCLUSIONS: Our data suggest that HLA alloimmunization during VAD support may be due to extensive blood transfusion. The rate of HLA alloimmunization does not appear to be greater than that reported in other populations of multi-transfused patients. Leukoreduction of cellular components, as well as plasma, or other initiatives is needed to reduce the rate of alloimmunization and, potentially, the wait to transplantation.