Key Achievements in the Field of Fundamental Researches
Study of the condition of the immune system in practically healthy population of Uzbekistan was conducted at the Institute from 1987 within the State Program.
As a result of performed scientific expeditions, there was designed a map of normative indicators of the immune system of adult and children population in Uzbekistan.
In 1990-1991, the Institute together with the Institute of Immunology in Russia (Moscow) participated in the research of the study of the immune status of the liquidators of the accident in the 30-km zone of the Chernobyl NPP. As a result of many years of observations, there was gathered the data, objectively reflecting the dynamics and the true state of health of liquidators of the accident- the data, which is of great importance for practical public health. These studies made a certain contribution to the development of clinical and radiation immunology.
The collaborative researches of scientists of the Institute of Immunology of the Academy of Sciences of Uzbekistan and Karakalpakstan, showed that the epidemiological situation in the Aral Sea region is characterized as intense. In fact, it reflects the uniqueness of the complex of ecological, climatic, social and hygienic factors of life and activities of the population in the region, where the widespread diseases belong to the respiratory, nervous system, organs of the digestive system, and the reproductive function, which implies the presence of secondary immunodeficiency in the population.
The Institute carried out large-scale studies with patients having malignant tumors and living in the Uzbek population of the South Aral Sea and Khorezm regions. There was detected the genotype HLA-A28, which indicates a dominating role of this antigen in the formation of gastric cancer and colorectal cancer.
Within the framework of the international project of large-scale studies on the ISAAC program in all regions of Uzbekistan there were examined over 3,000 children aged 7 -15 on the predisposition to the development of bronchial asthma.
The Institute of Immunology of the Academy of Sciences of the Republic of Uzbekistan became one of the centers of origin of the new independent branch of immunology – ecological immunology.
The result of population studies showed that the Uzbek population has in the genome all currently typeable loci antigens HLA-A, B, C, DR, and DQ. With high frequency there were identified antigens A1, A2, A9, A19, B5, B13, B21, and B35.The analysis of genetic distances between Uzbeks and other populations and races showed the presence of the similarities and differences between the frequencies of HLA genes between Uzbeks, geographically close peoples of Central Asia (Turkmens, Kazakhs, Kyrgyzs, and Tajiks) and European populations. The Uzbeks are distinct by a great variety of HLA genes; they possess almost all the peculiarities of HLA haplotypes and their combinations, which probably reflects the formation of the Uzbek population as ‘mixed’ – European and Mongoloid with a significant predominance of the European component.
The perspectives of these studies were related to the transition of studying HLA genes to the molecular level. Under the guidance of Professor R.M. Ruzybakiev, Institute of Immunology of Academy of Sciences of Uzbekistan in cooperation with Stanford University (R.S. Wells, USA) and the Oxford Institute of Molecular Medicine (W.J.Bodmer, Great Britain), in 1998 – 2000, organized international expeditions in Transcaucasia, Iran and Central Asia. The result of these studies was a unique collection of DNA (more than 3000 samples) from 18 ethnic groups. Using PCR – method was conducted the molecular typing of HLA genes and Y- chromosomes that allowed to include HLA-A2 gene of Uzbek population into the International Register.
Central Asia is characterized by a unique genetic diversity in both male and female line of inheritance. It testifies, that the given region is the Eurasian crossroads not only ways, but also genes since ancient times.
For the first time there was created a map of the genetic diversity of populations of Central Asia.
In 1996-2001, first and large-scale medical and genetic researches in Central Asia started on the initiative and under the guidance of Professor R.M. Ruzybakiev, with the participation in the global project ‘Human Genome’ in the direction of ‘The variety of the human genome’.
International studies were conducted on the fundamental study of anthropogenesis of peoples of Central Asia and the Caucasus, which appeared the basis for three unique international expeditions to collect genetic material in individuals of over 20 nationalities and ethnic groups living in the vast territory from the Caucasus and the Middle East to the eastern borders of Central Asia.As a result of this work, there was presented the allelic distribution of the markers of HLA-system and genes like CCR5, MC1R, CD45 as well as p53 gene mutation. Particularly impressive there were the results of a study on the genetic diversity of the Y-chromosome and mitochondrial DNA.
Based on these results, the key role of the ancestors of modern inhabitants of the Central Asian region in the formation of early man (Homo Sapiens), not only in the European, Oriental and Asian parts of Eurasia, but also on the American continent 10-50 thousand years ago was confirmed.
The ancient expansion of Homo Sapiens in Eurasia and multigene terrain of Central Asia. As a result of subsequent 22 expeditions from the Pamir to the Tien-Shan, for the first time in the world, there was obtained incontrovertible evidence that Central Asia is a vital source of genetic diversity in the world and the origin of most of the European population during the Paleolithic and Neolithic periods.
Central Asia takes an intermediate position between the gene pools of Europe and Asia: there were identified two major components – so-called West-Eurasian (dominant) and East Eurasian, where the first component is more ancient.
There were established migration routes of the ancient ancestors of modern humans in Eurasia – the expansion ofHomo Sapiens came from the East to the West during the Paleolithic and Neolithic periods.
The complex analysis of ethnographic, linguistic researches and data of genetic diversity of Y-chromosome and mitochondrial DNA among the peoples of Central Asia showed that the Turkic nomadic groups in contrast to the settled farmers were expressed more by the patrilineal organization. The leading factor in the formation of genetic diversity in Central Asia is a linguistic identity.
For the first time in Uzbekistan, there were conducted fundamental molecular immunogenic studies, which are actual to Uzbekistan, namely, viral infections: hepatitis B virus (HBV, HCV, HEV, and VSD) and HIV.
As a result of large-scale epidemiological studies for the presence of viral hepatitis in healthy individuals (donors) and groups in the territory of Uzbekistan, in addition to the existing genotypes A, D, C of viral hepatitis B, there was identified new, not studied previously genotype G.
HCV genotypes were presented by genotypes 1, 2, 3, 4. Moreover, genotype 1b, one of the most terrible and unfavorable in terms of prognosis and outcome, was identified in 70% of cases.
For the first time there were identified the genotypes and serotypes of HIV-1, circulating in Uzbekistan among various risk groups. It was found that among heterosexuals there are genotypes circulating in Africa, Southeast Asia and Russia. The genotype B HIV-1 is circulating among homosexuals, which is common around the world. Among drug addicts, the genotype A HIV-1 is found circulating, which is common in Ukraine, Belarus and Russia.For the first time there was assessed the prevalence of resistance to infection by HIV-1 among the indigenous population and among the HIV-infected. It was detected that mutation of CCR5 del35 in the homozygous state is found in 1.8% of the indigenous population and in the heterozygous form – in 10.5% of the population. Homozygosis provides resistance to infection by HIV-1, and heterozygosity prolongs the HIV / AIDS disease.
The recent studies showed that a particular impact on the outcome of treatment and the possibility of self-recovery from infection with hepatitis C virus is made by genetic factors, especially the polymorphisms of the IL-28B gene. IL-28B is a representative of three types of interferons, which has a strong antiviral effect. Under certain genotypes, getting a sustained viral response is achieved in 2 times more often.
The bank of DNA of patients with the coronary artery disease was created, and a method of DNA sequence analysis (qualitative, quantitative) of genes involved in the lipid metabolism in real time, based on pyrosequencing technology was adjusted. The data for progressive steno cardia showed that the genotype GA of gene ABCAI (rs2230806) was diagnostically important with respect to the predisposition to atherosclerosis in the Uzbek population.
Molecular genetic studies to determine the DNA sequence of the genes involved in the folate cycle rs1801133 MTHER in real time, based on pyrosequencing technology were conducted in women of Uzbek nationality with the precancerous cervical disease.
Due to the study of the frequency of detection in the Uzbek population of the antigenic human major histocompatibility complex (Human Leukocyte Antigens), there was accumulated a considerable material on the two main sections of Immune Genetics – population-based (or anthropological) and medical.
The developed approach of the automatic calculation of the risk of metabolic syndrome, based on MICROSOFT OFFICE EXCEL 2007 and considering the examined anthropometric, clinical, biochemical and molecular immunogenic research data, reliably forecasts MS.
For the first time in Uzbekistan, an open cross-sectional study of the association of mutational load of the human mitochondrial genome with the carotid atherosclerosis was held. In this connection, analytical and technological platforms for the examination of individuals with atherosclerosis were developed, coordinated and implemented.
For the first time, ethnic and clinical examination forms for families with pre-eclampsia were developed, coordinated and implemented. The bank of biological samples (mother, child, and father) with complete clinical data of individuals with pre-eclampsia living in different regions of Uzbekistan was created.
Key Achievements in the Field of Applied Researches
For the first time in Uzbekistan, there was developed the domestic anti-allergic drug ‘Allergodaf’, derived from the flavonoid fraction of the extract of Bidens, produced from local materials. The package of documents with the preclinical studies was presented to the Pharmacological Committee of Uzbekistan to obtain a permit on its use in applied medicine.
Patients with the initial kidney disease, coupled with anti phospholipid syndrome (APS) and without APS were examined. Researches of the cytokine status in patients with the initial kidney disease, coupled with and without APS were conducted. The mentioned individuals were examined for the concentration of IFN-γ, IL-1β, IL-4 and levels of serological markers (BA and aβ2 GP-I) in the blood serum. For the initial nephropathy with APS is quite common to have anti phospholipid antibodies, such as lupus anticoagulant and anti-β2 – glycoprotein – at least 2 times with an interval of at least 12 weeks. Higher rates are observed in patients with the high disease activity.
Algorithms of immunogenetic diagnosis, immune correction, and immunization were optimized.
The creation of highly effective immune modulating medicines is conducted. The influence of various immunomodulating agents (of plant and animal origin, final dosage forms) on the immune system in the experiment is studied.
The quality control of immune biological medications of domestic and foreign production is improved. Medical and genetic technologies and innovations are widely used.
Training of highly qualified scientific personnel in the field of allergology, immunology and medical genetics is conducted.
Paid health services in the field of immunodiagnostics, gene diagnostics, immunotherapy of immune diseases and diagnostics of infectious diseases, are provided to the population and health care institutions.