Добірка наукової літератури з теми "HLA-DQB1*06"

ABSTRACT We studied multiple sclerosis (MS) patients with the HLA-DQB1*06:02 allele and compared them with MS patients who did not carry the HLA-DQB1*06:02 allele. We analyzed clinical and neurophysiological criteria for narcolepsy in six MS patients with HLA-DQB1*06:02, compared with 12 MS patients who were HLA-DQB1*06:02 non-carriers. Only two patients with HLA-DQB1*06:02 allele scored higher than 10 on the Epworth Sleepiness Scale. Polysomnography recording parameters and the multiple sleep latency test showed an absence of narcolepsy in the study group. Our study suggested no significant correlation between narcolepsy, MS and HLA-DQB1*06:02. The HLA-DQB1*06:02 allele alone was not sufficient to cause MS patients to develop narcolepsy.

Abstract Human narcolepsy is a sleep disorder characterized by excessive daytime sleepiness (EDS), cataplexy, and abnormalities of rapid eye movement (REM). Strong HLA class II association was determined where the narcoleptic individuals of diverse ethnic backgrounds share a specific HLA class II haplotype, DQA1*01:02-DQB1*06:02. It has been also reported that hypocretin in the CSF of narcoleptic patients are significantly decreased and that hypocretin producing cells are disrupted in patients’ brain. We hypothesized that hypocretin or other proteins specifically expressed in hypocretin producing cells in the hypothalamus, are presented by HLA-DQA1*01:02-DQB1*06:02, and induce activation of self-reactive T cells. To analyze the peptide-binding reperitore of HLA-DQA1*01:02-DQB1*06:02, we transduced murine fibroblast cells with HLA-DQA1*01:02-DQB1*06:02 (suscceptible), DQA1*01:03-DQB1*06:01 (resistant), DQA1*01:03-DQB1*06:03 (resistant), and DQA1*01:02-DQB1*06:04 (neutral) alleles by retrovirus-vectors and confirmed stable DQ proteins expression. Using these cell lysates we analyzed binding affinity of synthetic peptides designed for hypocretin-A, -B, and other proteins expressed in hypocretin producing cells.

Efficacy of search for the unrelated compatible transplant donors depends on a number of factors. Of most importance are the standards of primary HLA typing, and the immunogenetic diversity of the donor pool. Timely donor selection guarantees the optimal timing for stem cell transplantation. This factor exerts positive influence upon the transplantation outcomes. In 2019, The Bone Marrow Donors Registry at the Russian Research Institute of Haematology and Transfusiology has implemented HLA-typing for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 genes as a standard for primary immunogenetic examination, in order to reduce the donor search period. The aim of our study was to evaluate the HLA typing results for potential stem cell donors at our Registry as compared with immunogenetic profile of donors at the Registries arranged in two Russian megapolises. All currently known groups of HLA-C, HLA-DRB1, HLA-DQB1 gene alleles, 19 of 21 open groups of HLA-A gene alleles, 34 of 36 known groups of HLA-B gene alleles were screened in the donors from our Registry. The most common HLA alleles groups were as follows: A*02 (0.2957), A*03 (0.1432), A*01 (0.1155), A*24 (0.1128); B*07 (0.1282), B*35 (0.1084), B*44 (0.0921), B*18 (0.0745); C*07 (0.2738), C*04 (0.1361), C*12 (0.1202), C*03 (0.1134), C*06 (0.1127); DRB1*15 (0.1445), DRB1*07 (0.1420), DRB1*13 (0.1271), DRB1*01 (0.1269), DRB1*11 (0.1216); DQB1*03 (0.3517), DQB1*06 (0.2269). A total of 1702 HLA-A*-B*-C*-DRB1*-DQB1*-haplotypes were revealed in our donor pool. The frequency of nine HLA-haplotypes exceeded 0.01: A*01-B*08-C*07-DRB1*03-DQB1*02 (0.0366), A*03-B*07-C*07-DRB1*15-DQB1*06 (0.0269), A*03-B*35-C*04-DRB1*01-DQB1*05 (0.0238), A*02-B*13-C*06-DRB1*07-DQB1*02 (0.0204), A*02-B*07-C*07-DRB1*15-DQB1*06 (0.0184), A*25-B*18-C*12-DRB1*15-DQB1*06 (0.0127), A*02-B*18-C*07-DRB1*11-DQB1*03 (0.0126), A*02-B*15-C*03-DRB1*04-DQB1*03 (0.0123), A*02-B*41-C*17-DRB1*13-DQB1*03 (0.0109). We carried out a comparative analysis of the HLA-haplotypes distribution for the donors of three Russian registers: Russian Research Institute of Haematology and Transfusiology (St. Petersburg); First St. Petersburg State I. Pavlov Medical University (St. Petersburg); National Medical Research Center for Hematology (Moscow). The six most common HLA-haplotypes among the donors from three Russian registers had the same rank positions and frequencies. The differences of some less common HLA-haplotypes distribution were determined. The results of our study indicate the immunogenetic diversity of the donor pool the Registry of Russian Research Institute of Haematology and Transfusiology. This fact, along with usage of international standards for primary immunogenetic examination is a prerequisite for effective donor search for the patients requiring stem cell transplantation.

Conducted high-resolution HLA-typing loci HLA-A, -B, -C, -DRB1 and -DQB1 by massively parallel sequencing of 150 potential donors of hematopoietic stem cells from the Republic of Kalmykia. In the studied population, four new alleles identified that not previously registered by the International Committee on the Nomenclature of Factors of the HLA-system of WHO. During the HLA-typing identified: 29 alleles at the HLA-A locus, 44 - at the HLA-B locus, 26 - at the HLA-C locus, 15 - at the DQB1 locus, 37 - at the HLA-DRB1 locus. The following alleles have a frequency of more than 10%: HLA-A*02:01 (11,7%), HLA-A*01:01 (11%), HLA-B*51:01 (10,3%), HLA-B*58:01 (10,3%), HLA-C*06:02 (17,7%), HLA-C*03:04 (10,3%), HLA-C*03:02 (10%), HLA-DQB1*03:01 (26,7%), HLA-DQB1*02:02 (10%), HLA-DRB1*07:01 (11,7%). The most common HLA-A-B-C-DQB1-DRB1 haplotype is A*02:05-B*50:01-C*06:02-DQB1*02:02-DRB1*07:01 (3,7%). Deviations from the Hardy - Weinberg equilibrium not identified.

The aim of this study was to assess the correlations of clinical features of patients with moderate and severe courses of COVID-19, comorbidity (endocrine, autoimmune, cardiovascular, oncological, and pulmonary diseases), and alleles of the HLA class II system genes. One hundred COVID-19 patients hospitalized in the Endocrinology Research Centre, Moscow, Russia, were analyzed for age, gender, smoking, comorbidity, and invasive mechanical ventilation. Computer tomography was used to assess the severity of the disease. HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles were identified in samples from 100 patients and samples from 327 randomly selected individuals collected in the prepandemic period (control group). There was no association of gender, age, weight, body mass index, smoking, and comorbidity with the severity of COVID-19. Allele DQB1*06:02-8 was more common in patients (p < 0.00005), and DQB1*06:01 and DQB1*05:03 were more common in the control group (p < 0.00005, and p = 0.0011, respectively). DQB1*06:02-8 can probably be considered as predisposing to moderate and severe COVID-19, and DQB1*06:01 can be considered as protective. No association of these alleles with comorbidity was found. Our results suggest that carriers of predisposing alleles, with cardiovascular and non-autoimmune endocrine diseases, should take more stringent preventive measures, and if infected, a more aggressive COVID-19 treatment strategy should be used.

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.