Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry.

Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.

The South African bone marrow registry (SABMR) in 2004.

Because of the presence of rare HLA antigens, particularly in patients of African ancestry, the SABMR was established in 1991. Currently approximately 20% of unique HLA types in the international database is from the SABMR. The SABMR donors now total approximately 45,000. Sixty-five South African patients have received matched unrelated donor transplants, 20 (30%) with a local donor. Most donors are from Caucasian background. To increase the genetic diversity of the SABMR donor pool, the policy is now to enrol more black and mixed ancestry donors.

The use of short tandem repeat polymorphisms for monitoring chimerism following bone marrow transplantation: a short report.

Following immunohaematopoietic stem cell transplantation, it is of importance to determine whether the new blood forming system is of recipient or donor origin and such phenotypic characterisation is called chimerism analysis. This is a dynamic process, which may be complete, mixed or split between compartments and in this way, plays an increasingly important role in predicting outcome for engraftment, rejection or residual disease predicating the need for pre-emptive immunotherapy. Based on recent workshop recommendations, peripheral blood cells have been used in the short tandem repeat (STR) assay to serially characterise the haematologic course and so evaluate the usefulness of this system. Forty-six patients from a single centre were followed serially for periods ranging between 3 and 60 months. The analysis was initially performed using the Applied Biosystems Profiler Plus Kit; currently, the Promega Powerplex 16 system is used. The overlap between the two assays has allowed for continuous comparison. The initial analysis was performed at 14 days post-transplant and repeated monthly. Stored DNA from the patient and donor was used to establish the pre-transplant profile. All post-transplant analyses were performed using peripheral blood. The results obtained were expressed as a percentage of the donor profile. To illustrate the ability of this technology, three representative profiles are described. In the first, stable engraftment is confirmed at 20 months with only donor pattern present. The second is intermediate, and while the patient is clinically disease free, there exists stable mixed chimerism at about 75% of donor cells. The third patient initially engrafted but the reappearance of recipient alleles presaged a haematological relapse; the latter is an indication for salvage with donor lymphocyte infusion and here this assay will be used to show the effectiveness of the intervention. These preliminary results show this to be a useful additional tool in monitoring post-transplant engraftment. As a basis for pro-active therapy, a larger study integrating the results of haematological and cytogenetic markers is planned.