Comparative analysis of immunogenetic characteristics of potential hematopoietic stem cell donors from the registries of two Russian megapolises

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

16(th) IHIW: population global distribution of killer immunoglobulin-like receptor (KIR) and ligands.

In the last fifteen years, published reports have described KIR gene-content frequency distributions in more than 120 populations worldwide. However, there have been limited studies examining these data in aggregate to detect overall patterns of variation at regional and global levels. Here, we present a summary of the collection of KIR gene-content data for 105 worldwide populations collected as part of the 15th and 16th International Histocompatibility and Immunogenetics Workshops, and preliminary results for data analysis

INFLUENCE OF HLA-DRB1* ALLELIC SETS ON THE DEVELOPMENT OF TUBERCULOSIS IN CHILDREN

According to the WHO data, tuberculosis still represents a serious public health problem worldwide. Deterioration of socio-economic conditions in the population complicates epidemic situation for tuberculosis inRussia, thus leading to increase in acute progressive and complicated forms of tuberculosis in children and, consequently, to worsening structure of its clinical forms. Objectives: to determine associations between certain HLA-DRB1 alleles and risk of tuberculosis development in children. We examined 188 children aged from 3 to 14 years with various manifestations of tuberculous infection. Along with thorough examination of the patients, including multi-spiral CT scans of chest, we undertook genotyping of HLA-DRB1 alleles. Activity of tuberculous infection was determined by a set of immunological tests, i.e., tuberculin skin test, DIASKINTEST® (recombinant allergen of tuberculosis DIASKINTEST®). X ray diagnostics was performed with multi-spiral «Aquilion-32» computed tomograph (Toshiba), according to standard procedures. Molecular genetic typing of HLA-DRB1 alleles was performed by polymerase chain reaction (PCR-SSP), using standard commercial kits PROTRANS Ceclerplate System Protrans HLA-DRB1*. The children were divided into two groups: I group, 90 healthy children, II group, 98 children with tuberculosis. A comparisons group consisted of healthy donors (n = 346). Statistical processing of genetic material included evauation and analysis of the following parameters: frequency distribution of the antigen (F), χ2 criterion for significance (chi-square), the relative risk ratio (RR), etiologic fraction (EF), preventive fraction (PF). Children of the II group had significantly higher *04 allele HLADRB1*, as compared with control group (36.7% vs. 21.1%, χ2 = 10.08; р < 0.01). This finding may suppose a predisposal of these allele carriers to development of tuberculosis. At the same time, the rates of *07 (14.3% vs. 27.5%, χ2 = 7.15, р < 0.01) and *15 (18.4% vs. 28.3%, χ2 = 3.92; р < 0.01) HLA-DRB1* alleles were significantly lower, thus suggesting a protective effect of this allele. *04 allele seems to be a predisposing factor, whereas *07 and *15 alleles are protective for development of tuberculosis in children

CLIPPERS. Обзор литературы и собственные наблюдения

CLIPPERS (Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a rare inflammatory disease of the central nervous system, during which the pons of the brain is damaged. This disease was described for the first time in 2010 by S.J. Pittock et.al. At present, there have been around 50 described cases of the disease. Up to the present moment, there are difficulties diagnosing this disease. In the article, a literature review and three clinical cases are presented. Furthermore, the necessity of further research is shown for improving the accuracy and specificity of the diagnostic criteria, as well as for defining biomarkers and developing algorithms of effective therapy.CLIPPERS (Chronic lymphocytic inflammation with pontine perivascular enhancement responsive tosteroids) – хроническое лимфоцитарное воспаление с поражением моста, контрастным усилениемпериваскулярных пространств, отвечающее на терапию глюкокортикостероидными препаратами,представляет собой редкое воспалительное заболевание центральной нервной системы, вовлекающеепреимущественно мост головного мозга. Впервые заболевание было описано в 2010 г. S.J. Pittock исоавт. В настоящее время в литературе описано около 50 случаев. Заболевание до настоящего временивызывает диагностические проблемы. В статье приведен краткий обзор литературы и собственныенаблюдения трех клинических случаев. Показана необходимость дальнейших исследований дляповышения точности и специфичности диагностических критериев, определения биомаркеров иразработки алгоритмов эффективной терапии

Six-minute walk test in cardiac rehabilitation

Six-minute walk test (6MWT) is a simple and safe tool for assessing exercise tolerance in  various  categories  of  patients.  Currently,  6MWT  is  used to assess the functional status of a patient and determine the strategy of increasing physical activity, primarily in patients with reduced exercise tolerance and contraindications for cardiopulmonary exercise  test. The basic requirements for the 6MWT are presented, taking into account the factors affecting its  informativeness  and  accuracy,  as  well  as the interpretation of results. The diagnostic and prognostic value of 6MWT in different categories of patients are discussed. The prospects for 6MWT use in cardiac rehabilitation for planning rehabilitation program, prescribing exercises,  determining  the  risk   of   complications,   and   evaluating the effectiveness  are  considered.  The  limitations  of  6MWT  and  ways to overcome it, as well as directions for further research are presented

SIGNIFICANCE OF IMMUNOGENETIC PREDISPOSAL FOR CLINICAL COURSE OF MYASTHENIA

Abstract. The aim of this work was to reveal novel criteria for prediction of clinical course in myasthenia, based on immunogenetic characteristics of the patients. Sixty-five patients with different clinical forms, various clinical course and severity of myasthenia were involved into the study. All the patients were subject to complete clinical and neurological examination, and all of them have undergone thymectomy, a histology of thymus has been performed. Immunogenetic studies included HLA class I typing (A and B loci), like as HLA class II typing (DRB* locus). A positive association was found between development of disorder and presence of HLAB8 antigen, HLA-DRB1*03, and their combination, thus allowing for suggesting these specificities as probable markers of genetic predisposition for myasthenia development. An HLA-B7 specificity may have a protective role in evolution of this disease. It was shown that clinical severity in myasthenia and degree of neuromuscular conductive disturbances were more expressed in the patients carrying HLA-B8 antigen and HLA-DRB1*03 allele. Evaluation of immunogenetic state at earlier stages of disorder allows of timely differential diagnostics and individual prediction of clinical variability in myasthenia patients