HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA-A, -B and -DRB1 in Central Europe.

Systematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA-A, -B, and -DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central-European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA-A accurately depicts the effects of genetic drift, HLA-B, and -DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection.

Low occurrence of the HLA-C*04:09N allele in a large Hungarian cohort.

The presence of null alleles may affect the outcome of stem cell transplantation. HLA-C*04:09N was defined as 'common' with a frequency of 2-5/1000 in Caucasians, and its presence is routinely tested as part of haplotypes HLA-A*02:01/A*23:01-B*44:03-DRB1*07:01-DQB1*02:01. We aimed to investigate HLA-C*04:09N in a representative Hungarian cohort. HLA-typing data of 7345 unrelated persons were analyzed. The presence of HLA-C*04:09N was excluded in 157 chromosomes with either serology typing or with an allele-specific polymerase chain reaction for HLA-C*04:09N. HLA-C*04:09N was identified in a single chromosome with HLA-A*02, B*44, C*04, DRB1*07 resulting in a HLA-C*04:09N allele frequency of 0.0068% (1/14,690). This is approximately a 10- to 40-fold lower frequency compared with the previous data. Our results emphasize the need of precise local population-specific HLA-data, allowing appropriate modifications of local HLA-typing protocols.

Serum concentration of immunoglobulin G-type antibodies against the whole Epstein-Barr nuclear antigen 1 and its aa35-58 or aa398-404 fragments in the sera of patients with systemic lupus erythematosus and multiple sclerosis.

Several studies suggest that infection by Epstein-Barr virus (EBV) might be one of the environmental factors which facilitates the development of autoimmune disorders in genetically susceptible individuals. Recent data indicate that high anti-Epstein-Barr nuclear antigen 1 (EBNA)-1 immunoglobulin (Ig)G titre is a strong risk factor for multiple sclerosis (MS) in patients both with and without the main genetic predisposing trait, human leucocyte antigen (HLA)-DRB1*15:01. Because no similar studies have been published in systemic lupus erythematosus (SLE) patients, we determined the HLA-DRB1*15:01 carrier state and the serum titres against the whole EBNA-1 and its small fragments aa35-58 and aa398-404 in 301 SLE patients, 135 MS patients and in 345 healthy controls. The carrier state of the HLA-DRB1*15:01 allele was deduced from genotyping of a tagSNP (rs3135388) by applying a Taqman-based assay. The serum concentrations of antibodies to EBNA-1 and its aa35-58 or aa398-404 fragments were determined using a commercial assay (ETI-EBNA-G) and home-made enzyme-linked immunosorbent assays, respectively. The serum concentration of anti-EBNA-1 antibodies was significantly (P < 0·001) higher both in MS and SLE patients than in controls. Similar significant differences were found both in HLA-DRB1*15:01 carriers and non-carriers. Furthermore, titres of antibodies against the aa35-58 EBNA-1 fragment were elevated both in MS and SLE patients. By contrast, the levels of aa398-404 EBNA-1 antibodies were elevated significantly only in the SLE patients. These findings indicate that high anti-EBNA-1 IgG titres are HLA-DRB1*15:01-independent risk factors not only for MS, but also for SLE, while high antibody titres against the aa398-404 fragment are characteristic for SLE.

Decrease in cold ischemic times as a result of protocol changes of urgent immunogenetic testing during cadaveric kidney transplantation in Hungary.

BACKGROUND: Based on national ethics committee permission, the procedure of urgent immunogenetics testing prior to cadaveric kidney transplantation was changed in Hungary from January 1, 2011 allowing HLA typing of the donor and prospective crossmatching using peripheral blood samples from the donor prior to the definitive declaration of brain death. The aim of the current study was to compare key indicators of transplantation primarily cold ischemic time [CIT], between time periods with outcomes. METHODS: The following indicators were systematically collected prospectively and retrospectively for each deceased heart-beating donor transplantation between January 1, 2010 and October 31, 2010 (n = 114) versus January 1, 2011 and October 31, 2011 (n = 91): CIT for the first and second kidney; laboratory turnaround times (TAT), and time for final preparation of the selected recipient. RESULTS: As a result of the new procedure, the CIT for the first kidney decreased from 16.5 ± 3.5 to 12.4 ± 3.2 hours (P < .001). Similarly, for the second kidney the parameters were a 19.8 ± 3.4 versus 16.0 ± 3.8 hours (P < .001). As a consequence of more hands-on time in the laboratory, the TAT increased from 5.6 ± 0.8 hours to 7.2 ± 1.1 hours (TAT1) followed by an additional 4.2 ± 1.0 hours (TAT2). We also compared the times necessary for preparation of immunologically suitable recipients for transplantation, namely, 9.5 ± 2.3 hours in the earlier system, increasing to 15.5 ± 4.3 hours during the new procedure. CONCLUSION: As a consequence of the procedural change, the CIT parameter decreased significantly for both kidneys, which may have contributed to improved short-term outcomes of transplantation. The time available for final preparation of selected recipients was increased allowing improvements in CIT.