Вестник Санкт-Петербургского университета. Медицина https://medicine-journal.spbu.ru/ <p>«Вестник Санкт-Петербургского университета. Медицина» — рецензируемый междисциплинарный научный журнал, публикующий работы российских ученых из различных медицинских организаций, университетов, научных институтов, а также результаты исследований авторов из зарубежных медицинских организаций и университетов стран ближнего и дальнего зарубежья, которые охватывают основные области фундаментальной и прикладной медицины.</p> Санкт-Петербургский государственный университет ru-RU Вестник Санкт-Петербургского университета. Медицина 1818-2909 <p>Статьи журнала «Вестник Санкт-Петербургского университета. Медицина» находятся в открытом доступе и распространяются в соответствии с условиями <a title="Лицензионный Договор" href="/about/submissions#LicenseAgreement" target="_blank">Лицензионного Договора</a> с Санкт-Петербургским государственным университетом, который бесплатно предоставляет авторам неограниченное распространение и самостоятельное архивирование.</p> EDITORIAL https://medicine-journal.spbu.ru/article/view/9003 <p>The 4th Academy of Autoimmunity 11–13 October 2019 in Saint Petersburg State<br>University was the biggest among all the previous ones and attended by hundreds of participants from 10 countries and from many cities of Russia. It brought all the novelties in<br>autoimmunity in the last 2 years [1].<br>The development of autoimmune diseases is multifactorial and subordinated to laws<br>of the additive polygenetic inheritance with the threshold effect from the side of a whole<br>series of natural and sociocultural anthropogenic epigenetic factors, sometimes even including iatrogenic ones [2].<br>Since the autoimmune diseases of different organs and systems have much in common considering their pathophysiology, clinical manifestations, as well as their prevention and treatment approaches, a new interdisciplinary branch of Medicine — Autoimmunology — has formed recently in front of our eyes [3].<br>About 90 autoimmune diseases have been described, which implicate all organs and<br>systems. Autoimmunity related morbidity and mortality steadily grow in all developed<br>countries. There are strong evidences for existence of autoimmune/autoinflammatory<br>links in pathogenesis of severe COVID-19 cases of current global pandemic [4].<br>In spite of the successes in the study of aetiology, pathogenesis and models of many<br>autoimmune illnesses, the nature of the general disturbances, which underlie various particular forms of autoimmune disorders, remains the urgent object of scientific discussions.<br>At the same time practical health care worldwide experiences the utmost need for<br>their target prophylaxis and effective modalities of the treatment, whose adverse effects<br>would be minimized.<br>The evolution of nature and development of civilization set many new challenges for<br>biomedical science and for health care system, and there is great possibility that the 21st<br>century will turn into an Aeon of Autoimmunity. <br>266 Вестник СПбГУ. Медицина. 2019. Т. 14. Вып. 4<br>This trend may in future change the whole philosophy of Clinical Medicine.<br>The current believe how autoimmune diseases are induced entails the combination of<br>Genetics and environmental factors. Basically the genotype determines individuals who<br>may have inherited characteristics making them to have a hyperactive immune system<br>(i.e. HLA DRb1). The environmental factors include first of all those compounds that have<br>an adjuvant effects (from the Latin word: adjuvare — “to help or aid”). It means that such a<br>factor may enhance immune responses modifying the immune interactions [5].<br>In the presence of primary individual hereditary predisposition the pathological autoimmunity can manifest itself differently under the influence of various exogenous adjuvants or, vice versa — immunosuppressive factors — interplaying at different life periods<br>of a concrete person, while autoimmune disorders in her/his body seem to flow from one<br>nosological entity to another, keeping similar background which principle is known as the<br>“kaleidoscope of autoimmunity” [6].<br>That is the main subject of recent important scientific and educational event: 4th<br>Academy of Autoimmunity at Saint Petersburg State University [1].<br>The lessons, given by this Academy include update on the ASIA syndrome (autoimmune syndrome induced by adjuvants) and better understanding how these adjuvants<br>may affect B- and T-lymphocytes. Moreover, updates on diseases like diabetes mellitus<br>type I, systemis lupus erythematosus, myopathies, spondyloarthritis, systemic sclerosis<br>and autoimmune thyroid diseases were delivered by world experts in the fields. In poster<br>sessions we observed the descriptions of rare unusual cases of autoimmune diseases and<br>new methods of their diagnosis.<br>Yet new autoimmune entities and suspected autoimmune facets of various diseases<br>were discussed like HPV vaccines autoimmunity, cancer in autoimmune diseases, arrhythmogenic autoantibodies that may cause death (“lethal autoantibodies”).<br>Novel interrelations like those between endometriosis and autoimmunity were raised<br>and how the life style can positively affect the autoimmune tendency including a new body<br>manipulation of the myofacial syndrome.<br>The Academy discussed how to handle the new aspects of health into the hospital<br>and dealing with BIG DATA in order to better understand autoimmune phenomena. The<br>impact of autoimmunity into several actual problems of current Medicine, like infertility,<br>antiphospholipid syndrome, enigma of sarcoidosis or the adverse effects of checkpoint<br>inhibitor treatment in oncological patients and phenomenon of polyneuropathy involving<br>small neural fibers — all these matters were in scope of attention during 4th Academy of<br>Autoimmunity. The experts in immunodiagnostics, clinical and experimental Pathophysiology brought to this Academy new ideas and data concerning the application of new<br>clinical and experimental techniques, like multiplex autoantibody screening, advanced<br>ultrasound visualization of lymphoid organs or transgenic animal models — for the purposes of applied and fundamental Autoimmunology.<br>The pathways of interaction between the immune, nervous and endocrine systems,<br>integrating human organism, were also among the topics discussed. Autoimmunology<br>stands “on the shoulders of the giants” — the outstanding scholars of the past, like Paul<br>Ehrlich (1854–1915) and Ilya I.Mechnikov (1845–1916).<br>We see a special sign that this event took place within the walls of the St. Petersburg<br>University, where Ilya I.Mechnikov worked, in the year of the 150th anniversary of the<br>birth of his pupil, another pioneer of Immunology — Efim S.London (1869–1939), who <br>also worked at this university and was the first who demonstrated the presence of autoantibodies in healthy individuals and existence of antiantibodes, much lated re-discovered<br>and named antiidiotypes [7; 8].<br>Many young researchers and medical doctors, as well as students took part in 4th<br>Academy to continue this great tradition of autoimmunity studies which rooted here<br>long ago.<br>We wish them success and hope to see all of the participants also in the 12th Congress<br>on Autoimmunity in Athens, Greece, 28 May — 1 June 2021 [9].</p> Angela Tincani Леонид Чурилов Copyright (c) 2019 Angela Tincani , Леонид Чурилов 2020-06-15 2020-06-15 14 4 265–267 265–267 Pathways of information exchange between immune and nervous systems* https://medicine-journal.spbu.ru/article/view/7284 <p>An exchange of information between the immune and nervous systems, via main sympathetic and parasympathetic afferent and efferent ways of signal transmission providing the possibility of the constant dialogue between these systems. This article addresses new information about immune system innervation and its connections with the central nervous system. Vagal nerve appears to play a key role in this interaction. The antigen challenge induces cytokines production (IL-1, TNFα, IL-6, and IFNγ etc), which receptors are present on the peripheral neurons and terminals of n. vagus, which innervate many internal organs. These signals are transmitted to the neurons of central nervous system. Recent data are used to develop methods for correcting the functions of the immune system in allergic and autoimmune diseases, affecting the mechanisms of their regulation. For example, activation of parasympathetic system leads to suppression of the development of inflammation</p> Елена Корнева Copyright (c) 2019 Елен Корнева 2020-06-15 2020-06-15 14 4 268–272 268–272 10.21638/spbu11.2019.402 Immune system as a part of regulatory and integrating apparatus of the body: A biomedical philosopheme* https://medicine-journal.spbu.ru/article/view/7240 <p>This conceptual article addresses different underrecognized aspects of the immune system physiological activities. These ones include: the role of the immune system and physiologic autoimmunity in maintaining normal body’s own cell populations; its involvement in placentation and mother-to-fetus interactions; its embedding into immune-neuroendocrine communicative and integrating apparatus designated first of all for support of unique multicellularity of the organism and for regulation of its somatic cells’ growth and life. Besides cytokines, a powerful instrument of somatic regulation is agonistic (functional) autoantibodies, able to act on their receptors in hormone-like manner. The regulatory potential of antiidiotypic immunity is underappreciated. There is evidence, that anti-idiotypic antibodies can create internal immunological images and copy the ligand properties of different bioregulators and even drugs. What makes the regulatory interactions even more complex is the fact that antibodies are capable of penetrating living cell membrane, permeating the nucleus and produce a wide spectrum of regulatory effects on transcription, translation and post-transcription modifications.</p> Андрей Васильев Леонид Чурилов Тамара Федоткина Александр Трашков Алия Станова Владимир Утехин Copyright (c) 2019 Тамара Федоткина 2020-06-15 2020-06-15 14 4 273–276 273–276 10.21638/spbu11.2019.403 Transgenic animal models in translational biomedicine https://medicine-journal.spbu.ru/article/view/7431 <p>Recent revolutionary transgenic approaches have significantly increased the power of translational biomedical research. For instance, genetic animal models of brain disorders such as schizophrenia, bipolar disorder, depression, Parkinson’s disease and attention deficit hyperactivity disorder have been created. Such animal models are the valuable tools for the study of aetiology and pathogenesis of human disorders, as well as for the early pre-clinical drug development in pharmacology. In this article the advantages of transgenic mouse and rat models for studying and modeling human disease are reviewed. At the Saint Petersburg University there is a library of the most relevant animal models of neuropsychiatric disorders, including mice lacking the dopamine transporter (DAT-KO mice) and rats without brain serotonin (tryptophan hydroxylase 2 knockout, TPH2-KO). This collection of psychopharmacologyrelevant mutant models is planned to be routinely used in future collaborative studies with Russian and international drug development institutions and companies.</p> <p>&nbsp;</p> Рауль Гайнетдинов Copyright (c) 2019 Raul Gainetdinov 2020-06-15 2020-06-15 14 4 277–279 277–279 10.21638/spbu11.2019.404 Small fiber neuropathy and autoimmune diseases https://medicine-journal.spbu.ru/article/view/7257 <p>Small fiber neuropathy can be described as a dysfunction of the nerve fibers of the smallest diameter (A delta and C types), which are widely present in the skin, mucous membranes and internal organs. Among the causes of small fiber neuropathy various autoimmune and immune-mediated diseases have been recognized, including Sjogren’s syndrome, celiac disease, systemic lupus erythematosus, fibromyalgia, diabetes mellitus type I and sarcoidosis. This article addresses clinical features, diagnostic methods and treatment options of small fiber neuropathy. Sensory symptoms and autonomic dysfunction are the most common clinical manifestations. There are several validated questionnaires for the small fiber neuropathy, but the “gold standard” for the diagnosis is a skin biopsy followed by an immunofluorescence or immunohistochemical analysis to assess the density of small nerve fibers in the epidermis of the skin. Besides symptomatic treatment, pathogenetic therapy of autoimmune/inflammatory subtype of small fiber neuropathy should be considered.</p> <p>&nbsp;</p> Наталия Басанцова Юлия Зинченко Анна Старшинова Copyright (c) 2019 Наталия Басанцова, Юлия Зинченко, Анна Старшинова 2020-06-15 2020-06-15 14 4 280–283 280–283 10.21638/spbu11.2019.405 On the status of autoimmunity in the disorders of schizophrenic and depressive spectra* https://medicine-journal.spbu.ru/article/view/7253 <p>The immunopathological process is known to be a typical facet for many disorders of the nervous system. In this study, quantitative and functional parameters were used to assess the immune system status in patients with schizophrenia, affective disorders, organic brain diseases with psychotic disorders, and multiple sclerosis. The results confirm the possible role of autoimmune reactions in the structure of the pathogenesis of endogenous mental disorders. The immunological profiles in schizophrenia and affective disorders were very similar. Patients with later onset of schizophrenia have shown higher levels of C-reactive protein. It may<br>indicate its important role in the development of schizophrenia in this particular group of patients. Also, patients with schizophrenia having higher levels of neuron-specific enolase and C-reactive protein suffered from more severe thinking impairment.</p> Борис Бутома Наталья Петрова Маргарита Майорова Copyright (c) 2019 Борис Бутома, Наталья Петрова, Маргарита Майорова 2020-06-15 2020-06-15 14 4 284–287 284–287 10.21638/spbu11.2019.406 Anti-thyroid autoimmunity and psychic disorders* https://medicine-journal.spbu.ru/article/view/7223 <p>Thyroid hormones are essential for normal brain development and function, also regulatingsome processes in im mune system. The vicious effect of hypothyroidism for central nervous system displayed in myxoedema is known for many decades, but there is a CNS disorder related to autoimmune thyroid disease and not merely dependent on hypothyroidism. That is Hashimoto’s encephalopathy (steroid-responsive encephalopathy of autoimmune thyroiditis) — an enigmatic combination of cognitive, mood and motor disorders with psychotic symptoms, which pathogenesis is still unclear. The article describes natural history of this entity, its epidemiology, clinical and laboratory manifestation, and compares several existing theories of its pathogenesis with appropriate pros and contras. Vascular, dyshormonal and non-vascular autoimmune links of Hashimoto’s encephalopathy pathogenesis are discussed in intermingled discourse. The attempt to construct a synthetic concept of Hashimoto’s encephalopathy pathogenesis is given. The experience of authors based on investigation of clinical, endocrine and immunological parameters of 17 cases of autoimmune thyroiditis with schizophrenia-like manifestations is described, correlations are explored between immunoendocrine and psychic manifestations of disease</p> Полина Соболевская Тамара Федоткина Антон Гвоздетский Евгения Ефимова Юрий Строев Владимир Утехин Леонид Чурилов Copyright (c) 2019 Polina Sobolevskaya 2020-06-15 2020-06-15 14 4 288–291 288–291 10.21638/spbu11.2019.407 Laboratory diagnosis of peripheral autonomic failure of various origins https://medicine-journal.spbu.ru/article/view/7461 <p>Primary forms of peripheral vegetative insufficiency are relatively rare. This group includes peripheral vegetative insufficiency associated with damage to segmental vegetative structures: sympathetic and parasympathetic nuclei, nodes, peripheral pre- and postganglionic fibers. In the clinical picture of the disease, there are signs of a decrease in the function of the autonomic nervous system, which manifests as cardiovascular, respiratory, genitourinary, gastrointestinal and some other disorders. Since the symptoms are non-specific, autoimmune forms of peripheral vegetative insufficiency are difficult to diagnose. The equipment and methods used in clinical laboratories do not provide reliable diagnostics. Therefore, the identification of new significant diagnostic markers of the diseases, including autoantibodies to acetylcholinesterase, α3-nicotinic acetylcholine receptor and β2-adrenergic receptors, the development on their basis of modern test systems and the introduction of these systems in the practice of neurological medical centers is an important task.</p> Вера Ланцова Елена Сепп Игорь Строков Copyright (c) 2019 Вера Ланцова, Елена Сепп, Игорь Строков 2020-06-15 2020-06-15 14 4 292–294 292–294 10.21638/spbu11.2019.408 Apoptosis and autophagy, as inherent components of autoimmunity in the acute period of ischemic stroke https://medicine-journal.spbu.ru/article/view/7288 <p>Acute ischemic stroke is accompanied by aseptic inflammation, which alters the brain tissue and exposes the co-stimulatory molecules of the immune system and the neuronal antigens. It is known that apoptosis, autophagy, and necrosis are the main mechanisms of neuronal death after acute ischemic stroke. Modulation of apoptosis and autophagy in the acute period of the disease, as components of increased immunological reactivity, can contribute to the survival of neurons, preventing their delayed death. A comparative assessment of the dynamics of apoptosis and autophagy markers was performed for better understanding of the crossinteractions between these processes. The results indicate that several markers of apoptosis and autophagy are involved at various stages of the acute period of ischemic stroke and that<br>enhanced spontaneous apoptosis of peripheral blood mononuclear cells acts as one of immunosuppression factors in acute period of the disease. The obtained data confirm the active participation of autophagy, pro- and antiapoptotic processes in the autoimmune response and the formation of delayed neuronal death after acute ischemic stroke.</p> Анна Луговая Наталия Калинина Евгений Баранцевич Анастасия Артемова Copyright (c) 2019 Анна Луговая, Наталия Калинина, Евгений Баранцевич, Анастасия Артемова 2020-06-15 2020-06-15 14 4 295–298 295–298 10.21638/spbu11.2019.409 Reactions of mice brain to intracerebroventricular injection of thyroid peroxidase antibodies* https://medicine-journal.spbu.ru/article/view/7237 <p>Hashimoto’s encephalopathy is a rare disease of a presumable autoimmune aetiology. It has been shown that patients with this disease have high levels of anti-thyroperoxidase autoantibodies both in blood and cerebrospinal fluid. Specific astrocyte binding of anti-thyroperoxidase autoantibodies suggests a role of these autoantibodies in the Hashimoto’s encephalopathy pathogenesis. In this study the binding of anti thyroperoxidase with various regions of mice brain after intracerebroventricular stereotaxic injection was assessed. The results revealed no specific immunopositive labels in various brain structures of the mice which were subjected to the intracerebroventricular stereotaxic anti-thyroperoxidase injection. Direct application of human polyclonal IgG with high anti-thyroperoxidase titer on brain sections of intact mice demonstrated the same results. Apparently, absence of immunopositive staining in brain structures in the experiment can be explained by single administration of polyclonal IgG which may not contain enough of antibodies with this specificity. Further investigation of anti-thyroperoxidase binding with brain tissue in conditions of repeated intracerebroventricular administration is required.</p> Наталия Новикова Кристина Деревцова Анастасия Дятлова Елена Корнева Тамара Федоткина Леонид Чурилов Евгения Ефимова Полина Соболевская Copyright (c) 2019 Наталия Новикова, Кристина Деревцова, Анастасия Дятлова, Елена Корнева, Тамара Федоткина, Леонид Чурилов, Евгения Ефимова, Полина Соболевская 2020-06-15 2020-06-15 14 4 299–301 299–301 10.21638/spbu11.2019.410 The effect of orexin-A on the morphofunctional characteristics of LPS-stimulated microglial cells https://medicine-journal.spbu.ru/article/view/7474 <p>Microglial cells have a protective function and are essentially immunocytes present in the central nervous system. Activation of microglia results in the production of cytokines and trophic factors that can have a damaging or protective effect on brain cells. Orexin-A has anti-inflammatory and neuroprotective properties. Subcutaneous administration of orexin-A enhances the survival of mice with lipopolysaccharide-induced endotoxin shock, reducing the level of pro-inflammatory cytokines and chemokines. The aim of this study was to determine the effect of orexin-A administered intraventricularly on the morphological characteristics of microglial cells activated by intraperitoneal injection of lipopolysaccharide (LPS). With the introduction of lLPS, there is a change in the number of microglial cells in the somatosensory cortex, as well as in their morphology. When these indicators were analyzed after administration of orexin-A to animals against the background of LPS stimulation, no changes were detected.</p> Анна Рунде Copyright (c) 2019 Анна Рунде 2020-06-15 2020-06-15 14 4 302– 306 302– 306 10.21638/spbu11.2019.411 Evaluation of Toll-like receptors expression in rat brain under alcoholization and ethanol withdrawal https://medicine-journal.spbu.ru/article/view/7246 <p>In experiments on rodents and in the study of postmortem brain samples of people suffering from alcoholism, it was shown that ethanol increases the expression of Toll-like receptors in the brain, which persists for a long time. Toll-like receptors are known to be also involved in the development of autoimmune reactions. In the present study the expression of Toll-like receptors in hippocampus, amygdala, and medial entorhinal cortex of rats during prolonged alcoholization and alcohol withdrawal was assessed. In the group of prolonged alcoholization with 20% ethanol for 1 month there was no change in Toll-like receptors mRNA levels in the studied rat brain structures, except for a slight decrease in Toll-like receptor 3 mRNA levels in the hippocampus of alcoholized rats and its slight increase in medial entorhinal cortex. However, Toll-like receptors gene expression undergoes changes in all rat brain structures studied during alcohol withdrawal.</p> Сергей Ереско Мария Спешилова Кирилл Леонченко Татьяна Черных Марат Айрапетов Copyright (c) 2019 Сергей Ереско, Мария Спешилова , Кирилл Леонченко, Татьяна Черных , Марат Айрапетов 2020-06-15 2020-06-15 14 4 307–309 307–309 10.21638/spbu11.2019.412 Lethal autoantibodies: Do they exist?* https://medicine-journal.spbu.ru/article/view/7440 <p>Heart rhythm disturbances belong to the most complex and pressing problems of cardiology. Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 hour of acute manifestations’ onset). Tanatogenesis in this case is linked to ventricular arrhythmias. Patients with cardiomyopathies, myocarditis, ischemic heart disease and inherited cardiac channelopathies are at risk of SCD. However,a certain percentage of autopsy-negative cases of SCD in children and young adults remain unexplained even after a post-mortem genetic testing. Autoantibodies against cardiac proteins may be potentially involved in the pathogenesis of different heart diseases and in the occurrence of cardiac arrhythmias, including those, which can lead to SCD. In this review the prevalence of some antimyocardial autoantibodies in patients with different heart diseases and their mechanistical relevance are addressed. A classification of these autoantibodies is proposed, and their molecular and cellular effects are discussed.</p> Варвара Рябкова Copyright (c) 2019 Варвара Рябкова 2020-06-15 2020-06-15 14 4 310–313 310–313 10.21638/spbu11.2019.413 Multiplex immunoassay of the cytokine profile in systemic lupus erythematosus: Relationship with disease activity and level of antinuclear antibodies https://medicine-journal.spbu.ru/article/view/7244 <p>Systemic lupus erythematosus is an autoimmune disease characterized by pathological activation of B- and T-cells, the formation of antinuclear antibodies, and dysregulation of cytokine production. The aim of the work was to study the cytokine profiles in patients with this disease in comparison with the disease activity and levels of antinuclear antibodies when using multiplex immunoassay technology, which has a high analytical sensitivity and provide the possibility of simultaneous determination of a large number of biomarkers. Hyperproduction of chemokines IP-10 and MCP-1, regulated by IFN, was associated with high activity of the disease and increased production of antinuclear antibodies. Various immunological subtypes of systemic lupus erythematosus were identified according to the cytokine profile, which reflects the heterogeneity of this multifactorial disease.</p> Елена Александрова Александр Новиков Жанна Верижникова Татьяна Панафидина Галина Лукина Copyright (c) 2019 Елена Александрова, Александр Новиков, Жанна Верижникова, Татьяна Панафидина, Галина Лукина 2020-06-15 2020-06-15 14 4 314–317 314–317 10.21638/spbu11.2019.414 Family cases of primary Sjogren’s syndrome in monozygous twins* https://medicine-journal.spbu.ru/article/view/7258 <p>Primary Sjogren’s disease is a systemic disorder of unknown origin with chronic autoimmune inflammation of the exocrine glands and the obligatory involvement of the salivary and lacrimal glands. We present the cases of primary Sjogren’s disease in monozygous twins. These concordant cases suggest the genetic determination of the disease. Early diagnosis of the disease and initiation of immunosuppressive therapy in patient A.prevented the serious complications. The effect of treatment was clearly visible with patient’s cancellation of the basic therapy for almost 6 years, after which the general condition worsened, and a joint pain developed. Long-term therapy with small doses of alkylating cytostatics and glucocorticosteroids positively affects systemic manifestations of the disease, and significantly improves the survival of patients. The presence of complications caused by glucocorticosteroid therapy should be taken into account.</p> Александр Шишкин Наталия Басанцова Михаил Эрман Людмила Слепых Copyright (c) 2019 Александр Шишкин, Наталия Басанцова, Михаил Эрман, Людмила Слепых 2020-06-15 2020-06-15 14 4 318–321 318–321 10.21638/spbu11.2019.415 Analysis of the level of B-cell populations in patients with pulmonary sarcoidosis* https://medicine-journal.spbu.ru/article/view/7234 <p>Sarcoidosis is a granulomatous disease of unknown etiology. The role of B-cells in pathogenesis of sarcoidosis was shown in several studies. The importance of B-lymphocytes activation in sarcoidosis can be confirmed by the efficacy of anti-CD20 treatment. However, there is no data about alteration of certain B-cells subsets. In this study changes in subsets of B-lymphocytes in patients with sarcoidosis (n=37) and a control group (n=30) are analyzed. In patients with sarcoidosis misbalance of B-naïve and B-memory cells was found, the level of B-naïve cells proved to be more than 70.00% and B memory cells less than 30.00% (sensitivity 76%, specificity 70%). Among regulatory B cells there was detected an elevation of CD24+++CD38+++ B cells more than 6.5% (sensitivity 91%, specificity 88%) and CD5+CD27-B cells than 12.45% (sensitivity 76%,specificity 80%). These results show, that in sarcoidosis pathogenesis are involved B-naïve and B-memory cells, that is characteristic for granulomatous diseases, and also regulatory B cells, that produce anti-inflammatory cytokines.</p> Анна Малкова Игорь Кудрявцев Наталия Басанцева Юлия Зинченко Анна Старшинова Леонид Чурилов Петр Яблонский Copyright (c) 2019 Анна Малкова, Игорь Кудрявцев, Наталия Басанцева, Юлия Зинченко, Анна Старшинова, Леонид Чюрилов, Петр Яблонский 2020-06-15 2020-06-15 14 4 322–324 322–324 10.21638/spbu11.2019.416 Personalized prognosis of sarcoidosis based on the complex analysis of possible aetiological agents and mechanisms of immunopathogenesis https://medicine-journal.spbu.ru/article/view/7286 <p>The current concept of immunopathogenesis of sarcoidosis is based on an exaggerated immune response to a specific unidentified antigen. In recent years, the high Th17-cell plasticity has been shown to play an important role in the pathogenesis of sarcoidosis, along with contribution of Th1. In this study an analysis of Tfh subpopulation composition in peripheral blood of patients with chronic sarcoidosis debut was performed. Electron microscopic analysis of the microbiological component of bronchoalveolar lavage fluid was conducted to identify infectious agents, in order to determine their aetiological significance in patients in the early stages of sarcoidosis. The data obtained indicate a shift in the balance of Tfh cells towards cells with proinflammatory phenotype, which may indicate their active participation in the immunopathogenesis of sarcoidosis. Commensal bacteria representatives of the normal microbiota were observed in bronchoalveolar lavage fluid. Morphological properties of macrophages witnessed for the active manifestation of their phagocytic function.</p> Оксана Рыбальченко Ольга Орлова Татьяна Сесь Наталия Лазарева Андрей Бажанов Ольга Баранова Валентина Капустина Copyright (c) 2019 Оксана Рыбальченко , Ольга Орлова, Татьяна Сесь, Наталия Лазарева, Андрей Бажанов , Ольга Баранова, Валентина Капустина 2020-06-15 2020-06-15 14 4 325–328 325–328 10.21638/spbu11.2019.417 Features of vimentin autoantibodies formation in patients with pulmonary sarcoidosis* https://medicine-journal.spbu.ru/article/view/7235 <p>Sarcoidosis is suggested to be a granulomatous disease with unknown etiology and highly variable clinical manifestation.In recent years, vimentin has been considered the most possible autoantigen in sarcoidosis, as well as in the number of various “classic” autoimmune connective tissue disorders. The aim of the study is to determine the severity of the immune response to various modifications of vimentin in patients with sarcoidosis. In a prospective comparative study was were included patients with pulmonary sarcoidosis stage II (n=93), with nonspecific lung diseases (n=55), in which were studied patinets with chronic obstructive pulmonary disease (COPD) (n=25), granulomatosis with polyangiitis (n=15), alveolitis (n=15), and healthy individuals (n=40). Serum levels of antibodies to modified citrullinated vimentin (anti-MCV) were determined in all participants included in the study, serum of patients with elevated levels of anti-MCV was tested for antibodies to cyclic citrullinated peptide (anti-CCP) and to Sa-antigen (anti-Sa). Anti-MCV and anti-CCP were determined with ELISA. An increased level of anti-MCV was determined in 40.9% (38/93) cases of patients<br>with pulmonary sarcoidosis, which was significantly more frequent than in comparison and control groups. Antibodies to cyclic citrullinated peptide did not show their significance in the pathogenesis of sarcoidosis and other studied lung diseases (COPD, granulomatosis with polyangiitis, alveolitis). The absence of anti-CCP and the positive correlation between antiMCV and anti-Sa suggest that citrullination and modification of vimentin is not a key factor in the formation of an autoimmune response to this peptide in sarcoidosis.</p> Юлия Зинченко Наталия Басанцева Анна Малкова Сергей Лапин Александра Мазинг Елена Суркова Анна Старшинова Петр Яблонский Copyright (c) 2019 Юлия Зинченко, Наталия Басанцева, Анна Малкова, Сергей Лапин, Александра Мазинг, Елена Суркова, Анна Старшинова, Петр Яблонский 2020-06-15 2020-06-15 14 4 329–332 329–332 10.21638/spbu11.2019.418 Autoimmune aspects of pulmonary sarcoidosis* https://medicine-journal.spbu.ru/article/view/7297 <p>Despite a plenty of pulmonologic studies, aetiology and pathogenesis of lung sarcoidosis are still insufficiently clear. Most researchers are inclined to speculate about the possible autoimmune/immune-mediated genesis of the disease, finding new evidence of such. The minireview attempted an integral analysis of currently available data suggesting autoimmune origin of sarcoidosis divided into four categories: The role of triggers in the development of sarcoidosis; the presence of immunogenetic susceptibility to the disease; analysis of cellular and humoral immunity in it and evaluation of clinical signs detected in sarcoidosis patients. New original definition of sarcoidosis is suggested. New data are reviewed on the possible autoinflammatory disorder of macrophageal polarization in sarcoidosis distinguishing it from tuberculosis. Author’s original hypothesis on possible therapeutic effectiveness of rapamycin in sarcoidosis is first coined.</p> Анна Старшинова Леонид Чурилов Геннадий Ершов Юлия Зинченко Петр Яблонский Copyright (c) 2019 Анна Старшинова, Леонид Чурилов, Геннадий Ершов, Юлия Зинченко, Петр Яблонский 2020-06-15 2020-06-15 14 4 333–336 333–336 10.21638/spbu11.2019.419 Case report of autoimmune polyglandular syndrome IIIa https://medicine-journal.spbu.ru/article/view/7275 <p>Autoimmune polyglandular syndrome type III (subtype IIIa) has polygenic inheritance and is most common among other polyendocrine autoimmune syndromes. As the main feature polyglandular syndrome-IIIa includes one of the autoimmune thyroid diseases combined with other autoimmune endocrine diseases that are not included in the polyendocrine (polyglandular) autoimmune syndromes types I and II.Because of the rarity of the reported cases of autoimmune polyglandular syndromes, we present the case of patient, diagnosed with type IIIa autoimmune polyglandular syndrome. In the described case the first recorded autoimmune disease was autoimmune diabetes mellitus type I, followed by autoimmune thyroiditis. Based on the occurrence of polyglandular syndrome-IIIa type, it is necessary to emphasize the need for registration and dynamic monitoring of the patients with identified autoimmune diabetes mellitus type I or autoimmune thyroid diseases in order to early diagnosis the combination of these organ-specific autoimmune diseases.</p> Александр Прилуцкий Ольга Прилуцкая Ксения Ткаченко Copyright (c) 2019 Александр Прилуцкий, Ольга Прилуцкая, Ксения Ткаченко 2020-06-15 2020-06-15 14 4 337– 339 337– 339 10.21638/spbu11.2019.420 Urbanization-related factors as triggers of the development of type 1 diabetes mellitus* https://medicine-journal.spbu.ru/article/view/7426 <p>The proportion of autoimmune pathology increases along with urbanization. A cohort retrospective prospective study was performed to analyze the prevalence of type I diabetes mellitus in 83 regions of the Russian Federation during the period from 2008 to 2017 and the influence of urbanization factors on type I diabetes mellitus incidence. The main urbanistic factor obtained during mathematical modeling contributing to the development and distribution of the incidence of type I diabetes mellitus is air pollution with solid dust particles, namely air emissions from the stationary sources, highways density and the number of buses. The urbanization factors are controlled and, therefore, many of the adverse effects on human health can be prevented by using organizational and methodological recommendations as well as new regulations on air pollutants.</p> Лидия Сопрун Игорь Акулин Владимир Утехин Антон Гвоздетский Леонид Чурилов Copyright (c) 2019 Лидия Сопрун, Игорь Акулин, Владимир Утехин, Антон Гвоздетский, Леонид Чурилов 2020-06-15 2020-06-15 14 4 340–342 340–342 10.21638/spbu11.2019.421 Clinical experience of dispensary observation for ten thousand patients with Hashimoto’s autoimmune thyroiditis: Some features of aetiology, manifestations, treatment and comorbidity* https://medicine-journal.spbu.ru/article/view/7252 <p>Chronic autoimmune thyroiditis is the most common autoimmune disease and the main cause of hypothyroidism in the world. From March 14, 2011 to present we have systematically monitored in our outpatient dispensary center over 10,000 persons aged 1 year to 87 years with a newly diagnosed autoimmune thyroiditis (having totally ≈19,500 of their dynamic observations). In this article we address some features of autoimmune thyroiditis, namely aetiology (possible genetic predisposition and the role of some triggers, including excessive iodine intake), early manifestations of hypothyroidism, comorbidity (such as stigmata of non-syndromal marfanoid phenotype, metabolic syndrome, pituitary prolactinomas, lymphomas and some other malignancies) and treatment strategy (the proper time to start therapy, adjustment of the doses of Levothyroxine, monitoring follow-up dinamics of the disease and possible<br>complications of the therapy). Hashimoto’s thyroiditis in our experience looks like important cause of hyperprolactinemia and female/male infertility and essential prerequisite of early adolescent metabolic syndrome, causing precaucious metabolic senescence in subsequent life.</p> Юрий Строев Copyright (c) 2019 Yuri I. Stroev 2020-06-15 2020-06-15 14 4 343–346 343–346 10.21638/spbu11.2019.422 Atypical presentation of IgG4-related disease https://medicine-journal.spbu.ru/article/view/7442 <p>IgG4-related disease is a clinical entity which is characterized by tumefaction and fibrosis of affected organs, elevated serum IgG4 level, and tissue infiltration by IgG4-positive plasma cells. Most often, it affects the pancreas, main salivary and lacrimal glands, retroperitoneum. In this article an atypical manifestation of IgG4-related disease. The first manifestation of the disease was erroneously diagnosed as cutaneous systemic sclerosis. Pancreatic manifestation of the disease occurs during the second and the third relapse of the disease 11 and 13 years later correspondingly and were combined in the latter case with the coffee ground emesis, hepatic artheriitis, thrombosis of splenic artery and vein and diffuse peritonitis. Thus, the manifestation of IgG4-related disease may imitate some other clinical conditions, and therefore physicians must be aware of such a rare but multifaceted disorder in daily clinical practice.</p> Илья Артемьев Copyright (c) 2019 Илья Артемьев 2020-06-15 2020-06-15 14 4 347–349 347–349 10.21638/spbu11.2019.423 Effect of collagen breakdown products on mast cell activity during reparative regeneration https://medicine-journal.spbu.ru/article/view/7232 <p>Immune system including its effector cells and their products (autocoids and autoantibodies) definetly plays an important part in regulation of tissue regeneration. Collagen-based preparations, whose action is due to peptides that have a stimulating effect on the formation of self collagen and bone restoration, as well as indirectly affecting hemostasis and phagocytosis, have gained considerable interest because of frequent bacterial complications of wound healing. The effect of mast cells on the healing process of the wound surface in rats under the influence of collagen dissolution products was assessed in the present study. According to the results, mast cells were found to be activated on the wound surface under the influence of drugs based on collagen breakdown products, which directly caused an acceleration of the reparative regeneration process.</p> Баира Санданова Цындыма Баясхаланова Евгения Кондратьева Валентина Обыденко Лариса Баранчугова Copyright (c) 2019 Баира Санданова, Цындыма Баясхаланова, Евгения Кондратьева, Валентина Обыденко, Лариса Баранчугова 2020-06-15 2020-06-15 14 4 350–352 350–352 10.21638/spbu11.2019.424 The clinical and immunological features of bronchial asthma in patients with autoimmune thyroiditis https://medicine-journal.spbu.ru/article/view/7238 <p>Bronchial asthma often can be combined with autoimmune thyroiditis, and both diseases are linked with the immune system dysfunction, although via different pathogenetic mechanisms, but intermingled. In this study the clinical course of bronchial asthma, respiratory function, immune and hormonal status in patients with bronchial asthma and autoimmune thyroiditis were compared to those in patients with pure bronchial asthma without thyroid disease. Along with the marked changes in cellular and humoral components of the immune system, clinical observations showed that the addition of autoimmune thyroiditis to bronchial asthma worsens asthma course: it leads to an increase in the frequency of exacerbations, shortening the duration of remission, a significant decrease in the flow rates of МEF50 and МEF75 compared with isolated bronchial asthma, probably, related to myxoedematous component of bronchial conductivity impairment.</p> Элла Чурюкина Наталия Колесникова Евгений Филиппов Copyright (c) 2019 Элла Чурюкина, Наталия Колесникова, Евгений Филиппов 2020-06-15 2020-06-15 14 4 353–356 353–356 10.21638/spbu11.2019.425 Analysis of the application of laboratory tests in the diagnosis of diseases of connective tissue https://medicine-journal.spbu.ru/article/view/7430 <p>The determination of antinuclear antibodies is included in the criteria for the diagnosis of connective tissue diseases, differential diagnosis and determines the prognosis and treatment tactics of the patient. The existing strategy for laboratory diagnosis of connective tissue diseases involves screening (ANA Hep-2 cell + ENA / ELISA), followed by the selection of refinement tests (ELISA, immunoblot). The assessment of the actually used algorithms, however, revealed that every third patient was assigned almost all available tests simultaneously to confirm a connective tissue disease. Rational screening was performed in 1/3 of the cases. Low frequency of application of ANA immunoblots significantly reduced the effectiveness of diagnosis. It is advisable to provide more information about the primary screening methods for connective tissue diseases of practicing doctors, namely therapists and general practitioners, who act as the primary diagnostic link for this category of patients.</p> Диана Бацаца Татьяна Булгакова Сергей Бардаков Copyright (c) 2019 Диана Бацаца, Татьяна Булгакова, Сергей Бардаков 2020-06-15 2020-06-15 14 4 357–360 357–360 10.21638/spbu11.2019.426 Development of an immunoassay test system for diagnostics and differential diagnosis of autoimmune motility disorders of the gastrointestinal tract https://medicine-journal.spbu.ru/article/view/7466 <p>Gastrointestinal motility disorders associated with impaired intestinal innervation have been little studied. Disruptions in the work of parasympathetic and metasympathetic structures can be caused by an autoimmune process both against the receptor apparatus and against peptides that perform mediator functions. In this regard, the development of methods for determining antibodies to the α3-acetylcholine receptor and the gonadoliberin releasing factor, which are involved in the regulation of gastrointestinal motility is relevant. As shown in this article, detection of these autoantibodies in patients with gastrointestinal motility disorders allows one to diagnose autoimmune damage to the peripheral parasympathetic and metasympathetic division of the autonomic nervous system, to conduct differential diagnosis of clinically similar pathological processes and to provide adequate timely treatment aimed at suppressing autoimmune lesions of the autoimmune nervous system and improving the quality of life of patients with peripheral autonomic insufficiency.</p> Вера Ланцова Елена Сепп Copyright (c) 2019 Вера Ланцова, Елена Сепп 2020-06-15 2020-06-15 14 4 361–363 361–363 10.21638/spbu11.2019.427 Titer of antiphospholipid autoantibodies. Is it connected with clinical manifestation? https://medicine-journal.spbu.ru/article/view/7557 <p>Antiphospholipid syndrome is a systemic autoimmune disease characterized by persistent antiphospholipid autoantibodies, the development of thrombophilic conditions and recurrent pregnancy loss. In this study the incidence of antiphospholipid antibodies of different titers among the women with one or more episodes of fetal loss in the anamnesis was determined.According the data obtained, autoantibodies in medium and high titers for cardiolipin and beta-2-glycoprotein-1 were more common among the women with two or more episodes of recurrent pregnancy loss compared with the women who have only one episode of pregnancy<br>loss. In a group of women with one episode of pregnancy loss, antibodies in high titers were not detected. Based on this, it can be assumed that autoantibodies in medium and high titers have the most significant pathogenetic effect on the outcome of pregnancy. In contrast, autoantibodies in low titers are considered to be dubious and clinically insignificant.</p> Кирилл Чудотворов Сергей Чепанов Екатерина Корнюшина Екатерина Орлова Сергей Селков Copyright (c) 2019 Кирилл Чудотворов, Сергей Чепанов, Екатерина Корнюшина, Екатерина Орлова, Сергей Селков 2020-06-15 2020-06-15 14 4 364–366 364–366 10.21638/spbu11.2019.428 NK-cells in placenta of female patients with type 1 diabetes mellitus https://medicine-journal.spbu.ru/article/view/7322 <p>Placenta is a temporary organ that performs multiple functions to provide a normal course of the intrauterine development of the child. However, immune interactions in placenta are not well understood. Since women with type 1 diabetes mellitus have a greater risk of adverse pregnancy outcomes due to aberrant immunological adaptation, the study of immunological interactions in placenta of these women is of particular interest. In this study a comparative analysis of the age-related expression parameters of marker of NK-cells (CD57) in placenta in patients with type 1 diabetes mellitus was performed. The current study revealed differences in the expression parameters of NK-cells marker between two age subgroups of the patients and compared to healthy controls. The results indicate the high significance of inflammatory type 1 diabetes mellitusmarkers in women with type 1 diabetes mellitus for assessing the course of pregnancy and the possible development of somatic pathology in newborns, especially from older women.</p> Анна Дробинцева Дмитрий Медведев Ирина Юшкова Виктория Полякова Copyright (c) 2019 Анна Дробинцева, Дмитрий Медведев, Ирина Юшкова, Виктория Полякова 2020-06-15 2020-06-15 14 4 367–371 367–371 10.21638/spbu11.2019.429 Comparison of the effectiveness of various methods of pregnancy loss prevention in women with antiphospholipid syndrome https://medicine-journal.spbu.ru/article/view/9002 <p>Around 10–15% women with recurrent pregnancy loss are diagnosed with antiphospholipid syndrome. In 20–30% women conventional therapy approaches do not lead to desirable outcomes. A possible approach to improve pregnancy outcomes in women with antiphospholipid syndrome is combined use of plasmapheresis and intravenous immunoglobulin in addition to a conventional therapy, which was assessed in this study in comparison with conventional therapy+plasmapheresis only; with conventional therapy+intravenous immunoglobulin only and with conventional therapy only. According to the results, combined use of plasmapheresis with immunomodulating intravenous immunoglobulin and conventional therpapy leads to the most significant antiphospholipid antibodies titer lowering, reduces prevalence of pregnancy complications, such as threatened abortion, mild preeclampsia, placental insufficiency, intrauterine growth restriction and increases prevalence of favourable pregnancy outcomes. It can be assumed that this approach can be considered as the most effective for the treatment of pregnant women with antiphospholipid syndrome for prevention gestational complications and pregnancy loss. antiphospholipid syndrome</p> Екатерина Орлова Сергей Чепалов Екатерина Корнюшина Юлиан Рыжов Марина Зайнулина Сергей Селков Copyright (c) 2019 Екатерина Орлова, Сергей Чепалов, Екатерина Корнюшина, Юлиан Рыжов, Марина Зайнулина, Сергей Селков 2020-06-15 2020-06-15 14 4 371–373 371–373 10.21638/spbu11.2019.430 IVF/ICSI efficiency in women with Hashimoto thyroiditis https://medicine-journal.spbu.ru/article/view/7233 <p>It is known that in women affected with thyroid autoimmunity, namely Hashimoto’s thyroiditis, the prevalence of infertility is very high and reaches 47%. The retrospective cohort study was performed to assess the effects of thyroid autoimmunity on IVF/ICSI outcomes in women with infertility due to tubal factor and verified autoimmune thyroiditis in status of euthyroidism. The present study confirms a negative impact of thyroid autoimmunity on the course of pregnancy achieved through IVF/ICSI. Thyroid autoimmunity does not appear to have an impact on IVF/ICSI outcome in terms of mean number of oocytes retrieved. However, fertilization, implantation and delivery rates were lower, and the risk of miscarriage was higher in the presence of anti-thyroperoxidase autoantibodies. Thus, thyroid autoanantibodies positivity even in euthyroid state should be considered an independent risk factor for pregnancy complications after IVF/ICSI treatment.</p> Галина Сафарян Александр Гзгзян Ляиля Джемлиханова Дарико Ниаури Copyright (c) 2019 Галина Сафарян, Александр Гзгзян, Ляиля Джемлиханова, Дарико Ниаури 2020-06-15 2020-06-15 14 4 374–376 374–376 10.21638/spbu11.2019.431 Ultrasound and morphological parallels in assessing the state of the immune system organs in children with immune deficiency https://medicine-journal.spbu.ru/article/view/7428 <p>The diagnosis of immune disorders is still a very difficult task. This study was performed to determine of the diagnostic ultrasound possibilities in identifying the signs of immune deficiency in children. According to the results, an increase in the spleen mass coefficient occurs with the growth in the number and size of lymphoid follicles. This is confirmed by both morphological and ultrasound data. An increase of the spleen mass coefficient in children with chronic immune-endocrine insufficiency is a reflection of system changes, which, for the most part, are manifested by hyperplastic (in few cases — involutive) processes in lymphoid organs and tissues. The technique of ultrasound examination of the spleen and neck and abdomen lymph nodes can be a non-invasive method for identifying children with immune deficiency and those risky for the development of fatal complications.</p> Ольга Возгомент Андрей Надточий Нина Зайцева Елена Палтусова Copyright (c) 2019 Ольга Возгомент, Андрей Надточий, Нина Зайцева, Елена Палтусова 2020-06-15 2020-06-15 14 4 377–381 377–381 10.21638/spbu11.2019.432 Power to dissolve the bone: Autoinflammation behind the curtain. An update on chronic recurrent multifocal osteomyelitis with clinical case presentation https://medicine-journal.spbu.ru/article/view/7296 <p>Multifaceted presentation of rheumatic diseases makes patients to consult physicians of various medical specialties, including surgeons. In this paper we present a case of pediatric patient with chronic recurrent multifocal osteomyelitis — an autoinflammatory bone disorder — who was misdiagnosed a lot and thus improperly treated before coming to the rheumatologist. An extensive review of scientific papers on chronic recurrent multifocal osteomyelitis was also conducted to show recent advances in the disease imaging and treatment. Our case illustrates that autoimmune and autoinflammatory disorders are not solely the matter of rheumatologist’s concern. Physicians of different specialties, including surgeons, should be aware of miscellaneous clinical signs of rheumatic conditions to propel their prompt, accurate diagnosis and efficient treatment.</p> Елена Жолобова Екатерина Попова Copyright (c) 2019 Елена Жолобова, Екатерина Попова 2020-06-15 2020-06-15 14 4 382–387 382–387 10.21638/spbu11.2019.433 Prolactin and autoimmunity in silicone mammoplasty* https://medicine-journal.spbu.ru/article/view/7472 <p>The article is devoted to the study of the effect of silicone as an adjuvant on the development of autoimmune complications of mammoplasty and the development of autoimmune syndrome induced by adjuvants “ASIA”. This controlled cohort prospective non-randomized research is based on analysis of clinical observations of 121 patients undergoing plastic surgery on the mammary glands for aesthetic purposes, as well for reconstructive and oncological indications, both with and without silicone implants. To obtain preliminary results and evaluate the study, 27 blood serum samples were randomly selected, in which the dynamics of prolactin levels and autoantibody profiles towards 7 common autoantigens were studied before and after 3 and 6 months post-surgery. It was found that 5 out of 27 patients after mammoplasty showed an increase in 2 types of autoantibodies (against modified citrullinated vimentin and annexin V). Patient in need for mammoplasty have increased serum levels of prolactin at the day of operation. After surgery on the mammary gland, the level of prolactin decreases to normal range within 3 months, even if it was significantly higher than normal before surgery. Both of these facts require additional research and analysis on a wider cohorts of patients.</p> Валерий Золотых Сергей Лапин Антон Гвоздецкий Анна Ким Тимур Джуматов София Шаабани Екатерина Старовойтова Лия Михайлова Маргарита Вишнепольская Леонид Чурилов Петр Яблонский Copyright (c) 2019 Валерий Золотых, Сергей Лапин, Антон Гвоздецкий, Анна Ким, Тимур Джуматов, София Шаабани , Екатерина Старовойтова, Лия Михайлова , Маргарита Вишнепольская, Леонид Чурилов, Петр Яблонский 2020-06-15 2020-06-15 14 4 388–393 388–393 10.21638/spbu11.2019.434 The The analysis of the secondary structure of the proteins in blood serum of patients with multiple myeloma* https://medicine-journal.spbu.ru/article/view/7241 <p>Multiple myeloma (MM) is one of the most common hematologic diseases in the world, which is characterized by the proliferation of clonal plasma cells in the bone marrow producing a monoclonal immunoglobulin. In this research, analysis of the secondary structure of proteins in blood serum of patients with MM and healthy donors was carried out by an infrared spectroscopy method. There were shown a decrease in the average content of α-helical sites and an increase in the number of β-layered structures in blood serum proteins of patients with MM compared to healthy donors.</p> Елена Чихиржина Андрей Гарифуллин Алексей Кувшинов Людмила Плотникова Александр Поляничко Елизавета Тельная Сергей Волошин Copyright (c) 2019 Елена Чихиржина, Андрей Гарифуллин , Алексей Кувшинов, Людмила Плотникова, Александр Поляничко, Елизавета Тельная, Сергей Волошин 2020-06-15 2020-06-15 14 4 394–398 394–398 10.21638/spbu11.2019.435