No abstract

HLA-B44 is among the most frequent class I antigens in many populations studied so far. It has been subdivided into seven allelic forms that can only be discriminated by DNA typing. Using a simple PCR/sequence-specific oligonucleotide hybridization procedure, we have analysed the frequency distribution of B44 subtypes in three European populations from Slovenia, the Netherlands, and Switzerland. B*4402 and B*4403 were by far the predominant alleles, B*4404 and 4405 were rare, while B*4406 and B*4407 were not observed. Interestingly, B*4402 and 4403 occurred with different frequencies in the three populations, with B*4402 being most frequent in the Swiss (65% vs. 57% in the Dutch, and 46.5% in the Slovenes). Of the 139 individuals studied, 60 HLA-B44 ABDR haplotypes could be determined by family studies. In the respective populations, the linkage disequilibria between B44 and other HLA antigens occurred with different frequencies. A2-B*4402 haplotypes were very frequent in the Swiss sample, mostly associated with DRB1*0101, 0401 and 1301. B*4402 was more often linked with non-A2 antigens in the Slovenes (predominantly A24, A28) than in the Swiss and the Dutch. The predominant association of B*4403 was with DR7: this haplotype was very frequent in the Swiss (82% of the B*4403 haplotypes), while lower frequencies were found in the Dutch (72%) and Slovenian (59%) populations. In the Swiss population, more than half of the B44-DR7 haplotypes were A23-B*4403-DR7 (53% of all B*4403 haplotypes). This haplotype was significantly less frequent in the Slovenian (6%) and in the Dutch (14%) populations. The second most frequent B*4403 haplotype in both the Swiss and Slovenes is the A29-B*4403-CW*1601-DR7 haplotype (17.6 and 29.4%, respectively). Concomitant with the increased frequency of B*4403 in the Slovenes, a higher diversity of non-DR7 B44 haplotypes was observed in this population (41% of all B*4403 haplotypes). HLA-B44 oligotyping analysis allowed us to detect B44-subtype incompatibilities in several AB-sero, DRB1/B3/B5-oligo matched unrelated bone marrow donor/patient combinations. The different frequency distributions of HLA-B44 haplotypes in the three populations analysed in this study argue in favour of local volunteer bone marrow donor recruitment. This might significantly improve the chance of finding a highly matched donor for patients with less frequent A-B-DRB1 haplotypes.

Studies both in spontaneously hypertensive rats and in humans have suggested that genes within or near to the HLA complex on chromosome 6p may be associated and linked to the regulation of blood pressure. The aim of this study was to determine whether HLA alleles and their combinations contribute to increased blood pressure, as well as to identify chromosome region that may contain genes involved in the pathogenesis of essential hypertension. Our results suggest that presence of HLA-DRB1*0101/2 DQB1*0501/2 DQA1*0102 allelic combination represents risk factor for development of essential hypertension in Slovenians, while the risk is decreased in individuals possessing HLA-DRB1*1601/2 DQB1*0502 DQA1*0102 or DRB3*. The linkage study indicates a possibility that at least one of the genes responsible for increased blood pressure is located near or within the HLA complex. A possible candidate is human endotelin-1 gene encoding a highly potent vasoactive peptide.

The variability in the immune response modulated by HLA alleles may be an important factor for the induction of the protective effect of HBsAg vaccines. We present here the analysis of HLA-DRB1, DQB1 and DQA1 alleles and their combinations in the group of 36 individuals with poor humoral immmune response to HBsAg vaccination. Comparison with the control group, consisted of 60 randomly choosen healthy subjects, revealed that the DRB1*1601, DQB1*0502, DQA1*0102 haplotype is overrepresented in the group of hyporesponders and may therefore be regarded as a factor influencing poor antibody responsiveness. We observed that after revaccination two of three individuals who failed to develop anti-HBs antibodies carry the same phenotype DRB1*0101,DRB1*0301;DQB1*0501,DQB1*0201;DQA1+ ++*0101,DQA1*0501, which supports the conjecture that immunogenicity of the HBsAg vaccine depends on specific combination of HLA DR and DQ molecules on antigen presenting cells.

The role of human platelet alloantigens (HPA) in clinical bone marrow allotransplantation was investigated. The leading hypothesis was that HPA alloepitopes act as minor histocompatibility antigens and aggravate graft-versus-host disease (GVHD). To exclude the effect of MHC disparity, only HLA identical donor-recipient pairs were entered into the study. The influence of HPA compatibility on overall survival, occurrence of relapses and haematopoietic recovery was also investigated. A total of 223 patients who received a graft from an HLA-identical sibling, genotyped for HPA -1, -2, -3, -4 and -5, were observed over a post-transplant period of 24 months following the protocol recommended by EBMT. The data from patients having received grafts from HPA compatible donors were compared to data from patients having received grafts that were mismatched in HPA allotypes in the GVH direction. Analysis of the incidence of acute and chronic (GVHD), overall survival, relapse incidence, haematopoietic recovery and some other clinical parameters did not reveal any significant difference between the HPA-matched and -mismatched groups of patients, regardless of their age. Our results give no evidence that HPA-1, -2, -3 and -5 alloantigens should be considered minor transplantation antigens in clinical bone marrow transplantation.