Content of certain cytokines and chemokines in blood ofpatients with chronic hepatitis B in the early stages of liver fibrosis

Hepatitis B is an infectious viral disease in which damage or destruction of liver tissue occurs, and which can turn into a chronic form. In chronic hepatitis B (CHB), hepatocytes are replaced by connective tissue as they die, resulting in fibrosis, and then cirrhosis of the liver. Early diagnosis of liver fibrosis is an urgent task in the development of CHB. Already at this stage of the disease, the immune system is activated, which plays a leading role in liver damage in CHB. The main regulators of immune processes are cytokines, which mediate intercellular interactions. A separate group of cytokines are chemokines — proteins of cell migration. In CHB, they are responsible for infiltration of liver tissue by activated white blood cells. Cytokines and chemokines are active participants in fibrogenesis, so they can serve as biomarkers for the development of liver fibrosis, including in the early stages. The purpose of this study was to analyze the content of certain cytokines/chemokines in the peripheral blood of patients with CHB in order to search for potential biomarkers of the initial stages of liver fibrosis. The study included 30 patients with a confirmed diagnosis of CHB with stages of liver fibrosis F0-F1 on the Metavir scale, 36 patients with a diagnosis of chronic hepatitis C (F0-F1) and 37 conditionally healthy individuals as a control group. Concentrations of the following cytokines/chemokines were determined: IFNγ, TNFα, CCL2/MCP-1, CCL8/MCP-2, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC by multiplex analysis using xMAP technology (Luminex, USA). As a result of the study, it was found that in patients with CHB, the plasma content of cytokine TNFα and chemokines CCL2/MCP-1, CXCL9/MIG and CXCL10/IP-10 was increased, and the chemokine CCL8/MCP-2 was reduced, which indicates the possibility of using these cytokines/chemokines as biomarkers of liver damage in CHB. In the examined group of patients with CHB, there was no dependence of the concentrations of cytokines and chemokines in the blood plasma on the viral load, which may be explained by its low level. For plasma cytokines in patients with CHB, correlations were found between TNFα and CCL2/MCP-1 and CCL8/MCP-2 chemokines , which was not observed in the control group. At the same time, in the control group, a correlation was found between the content of TNFα and the chemokine CXCL9/MIG, which was not detected in the group of patients. For both groups, a correlation was found between the content of CXCL9/MIG and CXCL10/IP-10 chemokines. Based on the study data, an algorithm has been developed that allows us to establish chronic hepatitis B or chronic hepatitis C as the cause of the initial form of fibrosis F0-F1 in terms of the content of cytokines IFNγ, CCL2/MCP-1 and CCL8/MCP-2 in blood plasma with a diagnostic efficiency of 89.4%

АЛГОРИТМЫ МРТ ГОЛОВНОГО МОЗГА У ПАЦИЕНТОВ С ЛОКАЛИЗАЦИОННО-ОБУСЛОВЛЕННОЙ ЭПИЛЕПСИЕЙ

The aim of the work was to develop diagnostic algorithms of the magnetic resonance imaging (MRI) in the diagnosis of localization-related epilepsies (LREs) by using of complex MRI protocols. MRI in 236 patients with the clinically defined diagnosis of LRE was performed. Investigation was based on routine MRI protocols supplemented by specialized high resolution sequences to visualize microstructural changes in the brain, single-voxel proton MR-spectroscopy of the hyppocampi, MR-tractography with the analysis of the fractional anisotropy and volumetry in the hippocampal formation and associated structures. MRI investigation algorithms for the patients with LRE according clinical and electrophysiological data are proposed.Целью работы явилась разработка алгоритмов диагностики локализационно-обусловленной эпилепсии (ЛОЭ) на основе комплексного МРТ-исследования. Работа основана на результатах МРТ головного мозга 236 пациентов с диагнозом ЛОЭ с применением специализированных последовательностей высокого разрешения с целью выявления микроструктурных изменений вещества головного мозга, одновоксельной протонной МР-спектроскопии гиппокампов, МР-трактографии с анализом фракционной анизотропии и волюметрии гиппокампов и ассоциированных с гиппокампальной формацией структурами. Разработан алгоритм МРТ-исследования головного мозга у пациентов с ЛОЭ в зависимости от клинико-электрофизиологических данных

Clinical and immunological characteristics of patients with chronic hepatitis C during antiviral therapy in interferon-free regimen

Aim. To study the biomarkers of liver inflammation that occur during antiviral therapy in the interferon-free regimen. Methods. 14 patients were examined during antiviral therapy of chronic viral hepatitis C genotype 1. Treatment with dasabuvir, ombitasvir, paritaprevir and ritonavir for 12 weeks was received by 8 patients. Daklatasvir and asunaprevir was administered to 6 patients for 24 weeks. 11 patients had the concentrations of cytokines/chemokines (TNFα, CCL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITAC) measured in the blood plasma by multiplex analysis. In six patients, the content of CXCR3+ and CCR6+ receptors in different subpopulations of lymphocytes was determined by flow cytofluorimetry. Patients were divided into 2 groups: without liver fibrosis and with severe fibrosis. Results. 100% demonstrated virologic response. In both groups, significant reduction of CXCL10/IP-10 concentration was found in the patients at the end of treatment compared to pre-therapy (p=0.025 and 0.00015, respectively). In the first group a tendency to increase of the relative content of T-lymphocytes (p=0.065) was observed, and in the second group, a significant increase of the relative content of TNKCCR6+ (p=0.02) was observed. Conclusion. Chemokine CXCL10/IP-10 is a biomarker characterizing the decrease of liver inflammation during therapy and not depending on the degree of liver fibrosis. The tendency to increase of the relative content of T lymphocytes in the first group and a significant increase in TNKCCR6+ cells during treatment in the second group may play an important role in eliminating hepatitis C virus

Determination of HIV Tropism in Patients with Antiretroviral Therapy Failure in Arkhangelsk Region

The aim of the study was to determine the tropism of the human immunodeficiency virus in patients with virological failure of antiretroviral therapy (ART) from the Arkhangelsk Region based on the analysis of the env gene V3 loop nucleotide sequence.Materials and methods. We used blood plasma samples obtained from 76 HIV-infected persons from the Arkhangelsk Region with virological failure of antiretroviral therapy. The nucleotide sequences of the HIV env gene C2-V3-C3 region were studied by PCR followed by sequencing. The genotype of the studied strains was determined based on the analysis of their phylogenetic relations with reference sequences from the international GenBank database, as well as using specialized programs. To predict viral tropism, the Garrido rule and the online bioinformatic tool Geno2Pheno[coreceptor] were used. The Geno2Pheno[coreceptor] algorithm, determines the false positive rate (FPR) based on the analysis of the env gene V3 loop nucleotide sequence. Results and discussion. Significantly lower representation of R5X4/X4-tropic HIV variants in long-term infected persons with subsubtype A6 virus compared to subtype B virus has been shown. For all FPR cut-off algorithms, a significant correlation between subtype and HIV tropism was observed (p=0.0014 and p=0.013 for FPR 10 % and FPR 20 %, respectively). While among subtype B strains, at least 57 % were identified as R5X4/X4-tropic variants (for an FPR of 10 %), including two strains classified as X4-tropic; among HIV subsubtype A6 even at an FPR of 20 %, the frequency of R5X4/X4-tropic samples only slightly exceeded 22 %. It can be assumed that the dynamics of changes in HIV tropism depends on the virus subtype. Significant differences in the distribution of amino acid residues of the V3 region sequences in the examined group between R5-tropic and R5X4/X4-tropic strains of subsubtype A6 for positions 18 (χ2=7.616, p=0.0058), 21 (χ2=7.281, p=0.007), 24 (χ2=5.587, p=0.0181), and 34 (χ2=5.144, p=0.0233) have been demonstrated. Among the R5X4/X4-tropic strains of the A6 subsubtype, amino acid substitutions were registered at positions 6, 19, 21, 26, 29, 30, which were not found in the R5-tropic A6 strains. The high occurrence frequency of a number of mutations previously described as presumably associated with resistance to maraviroc and similar drugs may indicate a natural polymorphism characteristic of the A6 subsubtype, which does not correlate with resistance to CCR5 co-receptor antagonists

Влияние сердечно-сосудистых заболеваний на течение рассеянного склероза (обзор литературы)

Comorbidity is one of the factors determining the course of multiple sclerosis. Cardiovascular pathology is one of the most common in the population as a whole, especially in age groups over 50. Several studies showed that arterial hypotension and dyslipidemia affected the course, progression rate, and neuroimaging characteristics of patients with multiple sclerosis. An important issue is the effect of disease modifying therapy on the course of concomitant diseases in patients with multiple sclerosis and the effect of concomitant diseases on the effectiveness and safety of disease modifying therapy. The question of the use of statins in multiple sclerosis remains controversial. This review presents data on vascular comorbidity in multiple sclerosis, including the prevalence of risk factors for cardiovascular pathology and concomitant vascular diseases in the population of patients with multiple sclerosis. Data on the effect of cardiovascular pathology on the course and treatment of multiple sclerosis were also analyzed.Коморбидность является одним из факторов, определяющих течение рассеянного склероза. Кардиоваскулярная патология является одной из самых распространенных в популяции в целом, особенно в возрастных группах старше 50 лет. В нескольких исследованиях показано, что артериальная гипертензия и дислипидемия оказывают влияние на течение, скорость прогрессирования и нейровизуализационные характеристики пациентов с рассеянным склерозом. Важным вопросом является влияние препаратов, изменяющих течение рассеянного склероза, на течение сопутствующих заболеваний у пациентов с рассеянным склерозом и влияние сопутствующих заболеваний на эффективность и безопасность препаратов, изменяющих течение рассеянного склероза. Противоречивым остается вопрос о применении статинов при рассеянном склерозе. В настоящем обзоре приведены данные о сосудистой коморбидности при рассеянном склерозе, включающие в себя распространенность факторов риска сердечно-сосудистой патологии и сопутствующих сосудистых заболеваний в популяции пациентов с рассеянным склерозом. Также проанализированы данные о влиянии сердечно-сосудистой патологии на течение и терапию рассеянного склероза

ОПТИКОНЕЙРОМИЕЛИТ: ПОДХОДЫ К РЕШЕНИЮ ЗАДАЧ МЕДИЦИНСКОЙ РЕАБИЛИТАЦИИ

The necessity of search of the effective individual programs for rehabilitation in patients with neuromyelitis optica spectrum disorders (NMOSDs) is recognized by majority of authors. Clinical and laboratory features of these patients which could impact on the rehabilitation prognosis were provided in this article. The possible methods for evaluation of the neurological deficit and disability because of NMOSDs were described. The literature data devoted to priority tasks of rehabilitation programs for this category of patients were given.Необходимость поиска эффективных индивидуальных программ реабилитации для пациентов с заболеваниями спектра оптиконейромиелита (СОНМ) признается многими авторами. Охарактеризованы клиниколабораторные особенности этой группы больных, которые могли бы повлиять на реабилитационный прогноз. Описаны возможные методы оценки функционального состояния пациентов с заболеваниями СОНМ. Приведены литературные данные приоритетных задач при реализации реабилитационных программ у этой категории больных

Высокодозная иммуносупрессивная терапия с аутологичной трансплантацией гемопоэтических стволовых клеток при рассеянном склерозе: современный взгляд на метод (обзор литературы)

There is an increase in the incidence of multiple sclerosis in the world. Only in half of the cases, standard therapy allows for a short time to achieve control over this disease. High-dose immunosuppressive therapy and autologous hematopoietic stem cells transplantation is a promising and effective method of treating autoimmune diseases, including multiple sclerovsis. Over the past 20 years, progress has been made in understanding the immune mechanisms of the method. At present, the frequency and severity of adverse events of therapy significantly decreased by reducing the intensity of conditioning regimens. The objective of this review was to analyze scientific publications on the effectiveness of the method, and the data on the optimal conditions and criteria for its use in multiple sclerosis.  В мире отмечается рост заболеваемости рассеянным склерозом. Лишь в половине случаев стандартная терапия позволяет на непродолжительное время добиваться контроля над этим заболеванием. Высокодозная иммуносупрессивная терапия с аутологичной трансплантацией гемопоэтических стволовых клеток является перспективным и эффективным методом лечения аутоиммунных заболеваний, в том числе рассеянного склероза. За последние 20 лет достигнут прогресс в понимании иммунных механизмов метода. Значимо уменьшена частота и выраженность нежелательных явлений терапии за счет снижения интенсивности режимов кондиционирования. Целью настоящего обзора является анализ научных публикаций, посвященных эффективности метода, данных по выбору оптимальных условий и критериев его применения при рассеянном склерозе

ПОРАЖЕНИЕ НЕРВНОЙ СИСТЕМЫ, АССОЦИИРОВАННОЕ С АНТИ-RO/SS-AИ АНТИ-LA/SS-B-АНТИТЕЛАМИ: КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ И ОБЗОР ЛИТЕРАТУРЫ

Over the recent years, a number of publications on the central nervous system (CNS) damages associated with anti-Ro/SS-A and anti-La/ SS-B antibodies has increased, which can signify an increase in the incidence of neuroimmunopathological conditions. Two cases with isolated central nervous system (CNS) impairment and anti-Ro/SS-A and anti-La/SS-B antinuclear antibodies are discussed in the article. In the first case, the CNS impairment with increased rates of anti-Ro/SS-A and anti-La/SS-B antibodies preceded the clinical manifestations and pathomorphological signs corresponding to the diagnostic criteria of Sjogren’s syndrome (SS). In the second case, the paraneoplastic CNS disorder was associated with an increase in the rate of such antibodies and was followed by the oncological process disseminaton. The described studies demonstrate possible heterogeneity of neurologic manifestations of immunopathologic processes. Further research is needed for the immunological targets of anti-Ro/SS-A and anti-La/SS-B antibodies, as well as for the pathophysiological mechanisms of associated neurological disorders.За последние годы увеличилось число публикаций о поражениях центральной нервной системы (ЦНС), ассоциированных с анти-Ro/SS-Aи анти-La/SS-B-антителами, что может отражать увеличение частоты нейроиммунопатологических состояний. В статье представлены два клинических наблюдения с изолированным поражением ЦНС у пациентов, при обследовании которых выявлены антинуклеарные антитела анти-Ro/SS-A и анти-La/SS-B. В первом случае поражение ЦНС с повышенными титрами анти-Ro/SS-Aи анти-La/SS-B-антител предшествовало развитию клинических и патоморфологических признаков, соответствующих критериям синдрома Шегрена (СШ). Во втором случае после периода флюктуирующего течения воспалительного процесса подтверждено отсроченное онкологическое поражение ЦНС, которое сопровождалось увеличением титров антител, что расценено как паранеопластическое аутоиммунное состояние. Описанные наблюдения демонстрируют возможную гетерогенность неврологических проявлений иммунопатологического процесса и актуальность изучения как иммунологических мишеней анти-Ro/SS-Aи анти-La/SS-B-антител, так и патофизиологических механизмов, ассоциированных с ними заболеваний

DIAGNOSTIC VALUE OF SEROLOGICAL MARKERS OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a classic autoimmune disease associated with the production of wide range of autoantibodies, and their detection has diagnostic and prognostic implication. The objective of this study was to estimate the diagnostic value of antibodies against modified citrullinated vimentin (AMCV) and nuclear antigen RA33 of the IgA rheumatoid factor (RF) versus the value of routinely used profile of autoantibodies in diagnostic work-up of RA. Material and methods. 253 patients with RA prehistory of varying duration were included into the study group. The control group was comprised of 92 patients, including patients with seronegative spondyloarthropathies and diffuse connective tissue diseases, as well as sex and age matched healthy controls. Serum levels of IgM and IgA RF, antibodies against cyclic citrullinated peptide (ACCP), ACMV, anti-keratin antibodies (AKA), antibodies against RA33 antigen (ARA33) and antinuclear factor (ANF) were measured in all patients and controls. Results and discussion. Diagnostic sensitivity of AMCV equaled 78%, ACCP — 77%, IgM RF — 71%, IgA RF — 43%, AKA — 43%, ARA33 — 31% and ANF — 31%. All anti-citrullinic antibodies (AKA, ACCP, ACMV) were significantly more commonly associated with IgM RF. Among RF and ACCP seronegative patients ACMV were found in 24% cases with 20 IU/Ml detection threshold, and in 21% — with 30 IU/Ml, allowing to increase diagnostic specificity of the test up to 91% with the increment of diagnostic threshold. Incidence of ARA33 was not significantly different among the RF and ACCP positive or negative subgroups, thus making ARA33 an independent RA marker. Specificity of this marker was 87,9%, thus making it inferior to RF and ACCP by a composite of diagnostic characteristics. Conclusions. Integrated measurement of ACMV and ARA33 is a rational approach at the second stage of serologic testing work-up in suspected cases of RA onset, when initial RF and ACCP tests were negative

МОНОМЕЛИЧЕСКАЯ АМИОТРОФИЯ (БОЛЕЗНЬ ХИРАЯМА): КЛИНИКО-ЛУЧЕВЫЕ СОПОСТАВЛЕНИЯ

Non-progressive juvenile spinal muscular atrophy, also known as Hirayama disease, is a rare form of non-progressive motor neuron disease caused by necrosis of the anterior horns of the lower cervical cord. Magnetic resonance study is able to show forward displacement of the posterior wall of the lower cervical dural canal in neck flexion, which is presumed to be pathognomonic sign of Hirayama disease. Flexion MRI of the cervical spine can help to diagnosis HD in the early stages. We report two cases of Hirayama disease with different disease duration and different clinical and radiological presentation.Мономелическая амиотрофия, или болезнь Хираяма, представляет собой редкую форму непрогрессирующего заболевания мотонейронов, обусловленную некротическим поражением передних рогов спинного мозга. Болезнь Хираяма может быть диагностирована при помощи МРТ-исследования уже на ранних стадиях на основании типичного вентрального смещения задней стенки дурального мешка на высоте переднего сгибания шеи. В настоящей статье представлены два клинических случая болезни Хираяма с различной длительностью заболевания и клиническо-радиологической картиной