Bulletin of RSMU

ISSN Print 2500–1094 ISSN Online 2542–1204

Bulletin of RSMU

BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)

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Nakonechnaya TO, Shagina IA, Myshkin MYu, Mutovina ZYu, Ryazantseva EV, Chudakov DM, Turchaninova MA, Britanova OV

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation of connective tissue and damage to various organs, including joints, skin, kidneys and heart. The disease has a significant gender predisposition and is more common in women. The pathogenesis of SLE is based on a violation of immunological tolerance, accompanied by activation of B lymphocytes and the production of autoantibodies. Recent advances in basic research have significantly deepened the understanding of the immunopathogenetic mechanisms of SLE, which justifies the use of new pharmacotherapeutic approaches. These approaches involve the use of biological drugs aimed at blocking the activity of type I interferon (IFN) or its receptors. The article discusses the molecular mechanisms of activation of the interferon response in SLE, modern methods for diagnosing the interferon signature, and new approaches to treatment aimed at blocking the interferon pathway. The possible role of the interferon signature in the stratification of SLE patients is also discussed. Such stratification will make it possible to more effective select treatment regimens taking into account the individual characteristics of the immune response of each patient. This may increase the effectiveness of treatment, reduce the likelihood of side effects and improve the prognosis for patients with SLE.

Received: 2024-06-24

Published online: 2024-06-30

DOI: 10.24075/brsmu.2024.027

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VIEWS 135

Razenkova VA, Kirik OV, Pavlova VS, Korzhevskii DE

The Iba-1 protein is traditionally considered a highly selective marker of microglia because of the specific expression of the gene in this particular population of the CNS cells. Alternative splicing creates several isoforms of the Iba-1 protein, which may cause discrepancies in the results of immunohistochomic reactions depending on which epitopes of the immunogen the antibodies selected for the study were developed. In this connection, and with the aim at identifying reliable variants of antibodies to Iba-1 available to researchers in the Russian Federation, we organized with study, seeking to evaluate the results of detecting microglia and macrophages using antibodies to different protein sequences produced by different manufacturers. As material, we used samples of the brain and testis of sexually mature (3–5 months) male Wistar rats (n = 8). Polyclonal and monoclonal (clone JM36-62) antibodies to Iba-1 were used as primary reagents. We found that monoclonal antibodies of the JM36-62 clone enable more selective antigen detection with a better signal/background ratio; they can be used as replacements for reagents that are currently not available commercially. Polyclonal antibodies enabled not only immunospecific imaging of microglia and macrophages, but also the identification of cells of the epithelial-spermatogenic layer of the testis. It is assumed that epithelial-spermatogenic layer contains the Iba-1 isoform devoid of an epitope that corresponds to the sequence of the immunogenic antibody clone JM36-62 fragment of the native protein. Functionally, various isoforms of Iba-1 should be investigated further.

Received: 2024-05-17

Published online: 2024-06-29

DOI: 10.24075/brsmu.2024.026

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VIEWS 143

Zinchenko RA, Tebieva IS, Gabisova YuV, Shukan EYu, Khokhova AV, Marakhonov AV, Kutsev SI

Currently, there are more than 8000–10000 rare disease (RDs), among which 75–80% are hereditary. In the Russian Federation (RF), patients are provided medical care in accordance with two lists: 17 chronic progressive and life-threatening diseases (RLTDs) and 14 high-cost nosologies (HCNs). The study was aimed to assess the range, prevalence, and genetic epidemiological characteristics of the RDs from the lists of RLTDs and HCNs in the Republic of North Ossetia–Alania and RF in general. We determined the number of patients from the RLTD (a total of 18,744 people in the RF, among them 8713 children; 129 and 42 people, respectively, in the Republic of North Ossetia–Alania) and HCN (28727 people/13454 children in the RF; 554 and 64 in the Republic of North Ossetia–Alania) lists and calculated the prevalence per 100,000 population. The global prevalence of RDs was estimated using the Orphanet database. The average prevalence of RLTDs in the whole population of the RF was 11.51 cases and that among children was 25.08. Similar data were obtained for the Republic of North Ossetia–Alania (19.38 and 29.44, respectively). It was found that idiopathic thrombocytopenic purpura, disorder of the complement system, maple syrup urine disease, porphyria were more common in the Republic of North Ossetia–Alania than in the RF in general, while galactosemia was less common. The analysis of disorders from the RLTD list has shown lower prevalence of hemophilia and pituitary dwarfism in the Republic of North Ossetia–Alania compared to the RF and Orphanet, along with the higher prevalence of type VI mucopolysaccharidosis, hemolytic uremic syndrome, and systemic juvenile rheumatoid arthritis. In the Republic of North Ossetia–Alania, the features of the range of genetic variation in the genes РАН (phenylketonuria) and CFTR (cystic fibrosis) have been identified. Thus, assessment of the RD prevalence in the regions is important and essential for raising awareness of medical personnel, as well as for expansion and improvement of medical care provision to patients with RLTDs and HCNs.

Received: 2024-05-08

Published online: 2024-06-26

DOI: 10.24075/brsmu.2024.025

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VIEWS 151

Konyukhova TV, Trukhina EV

Thiamine responsive megaloblastic anemia (TRMA), or Rogers syndrome, is a rare autosomal recessive disease characterized by the development of megaloblastic anemia, diabetes mellitus, and progressive sensorineural hearing loss. In some cases, the syndrome causes ophthalmological disorders (retinitis pigmentosa, optic nerve atrophy, maculopathy, nystagmus), heart diseases (paroxysmal atrial fibrillation, supraventricular tachycardia, congenital heart defects, intracardiac conduction disorders) and neurological disorders (epilepsy, cerebrovascular accidents). TRMA develops due to a mutation in the SLC19A2 gene, which encodes ThTr-1 (thiamine transporter protein) expressed in hematopoietic stem cells, pancreatic beta cells, and inner ear cells. The article presents a clinical case of TRMA in a three-year-old child, with the onset in the first year of life, manifesting as anemia and diabetes mellitus. Thiamine therapy ensured a pronounced positive dynamics: the patient's peripheral blood parameters normalized. The clinical description and the literature review herein aim to raise awareness of doctors of all specialties about this syndrome. An atypical clinical picture and lack of knowledge about TRMA often delay the diagnosis and start of therapy.

Received: 2024-05-16

Published online: 2024-06-24

DOI: 10.24075/brsmu.2024.024

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VIEWS 192

Pavlenko VB, Vlasenko SV, Chuyan EN, Pavlenko DV, Orekhova LS, Biryukova EA

Neurorehabilitation courses employing a non-invasive brain-computer-hand exoskeleton interface in combination with traditional balneotherapy have been shown to reduce spasticity of hand muscles and improve motor skills in children with cerebral palsy. However, the coherence of the electroencephalogram (EEG) parameters have never been analyzed during such sessions. This study aimed to analyze the coherence changes in the bands of θ, α and β rhythms recorded in the EEG as part of balneotherapy combined with a course of neurorehabilitation prescribed to children with cerebral palsy, and to investigate the relationship of these changes with the indicators of motor activity. The study involved 23 children aged 7 through 15 years, both genders, diagnosed with spastic diplegia; we established coherence coefficients for the intra- and interhemispheric connections of the frontal, central, and parietal regions of the large hemispheres in the context of actions provoking kinesthetic imagery. A significant (p < 0.05) growth of the intrahemispheric connections coherence was registered for α rhythms, decline thereof — for θ, β1 rhythms, the fluctuations accompanied by a significant (p < 0.001) improvement of the motor functions on the Barthel scale. We identified a relationship between — rhythm coherence in the pair of C4–CP4 leads and the value of the Barthel index (r = 0.52; p = 0.04). The specifics of changes in the coherence of intrahemispheric connections within the studied rhythms can be used as indicators of neuroplasticity in children with cerebral palsy during rehabilitation, and support development of the new versions of the neurointerfaces classifier programs.

Received: 2024-05-08

Published online: 2024-06-23

DOI: 10.24075/brsmu.2024.020

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VIEWS 165

Baranova NS, Gris MS, Baranov AA, Spirin NN, Artyuhov AS, Kiselev DV

The effects of the disease modifying drugs (DMDs) for multiple sclerosis (MS), interferon beta (IFNβ) and glatiramer acetate (GA), on the cytokine levels of individuals with MS are poorly understood. The effects of persistent herpesvirus infection (PHVI) on the cytokine production during treatment with DMDs for MS have not been identified. The role of cytokines and PHVI in the development of the treatment-related adverse events (AEs) has not been determined. The study was aimed to assess serum cytokine levels in patients with MS treated or not treated with DMDs for MS, and to determine the relationships between the cytokine levels, herpesvirus infection, and AEs. A total of 36 patients (12 males and 24 females, median age 38.50 (28.00; 48.50) years) with relapsing-remitting MS (criteria by McDonald, 2010) were examined. PHVI reactivation was observed in 18 individuals; in 10 of them it was associated with the history of the virus-associated exacerbation (VAE) of MS or VAE detected during assessment. A total of 30 patients were treated with DMDs for MS: 16 individuals with IFNβ, 14 individuals with GA. Systemic AEs were reported in 9 individuals. Serum levels of 15 cytokines were determined using the xMAP multiplex technique. Patients with MS showed a significant increase in the levels of IL10 (p < 0.01) and IL33 (p < 0.001) relative to donors when treated or not treated with DMDs for MS; the increase in IL31 levels was reported only in naïve patients (p < 0.05). At the same time, individuals with MS had low levels of IL1β, IL17F, IL22, IL25, IL23, and TNFα (p < 0.01). We revealed no differences in cytokine levels in the context of taking IFNβ or GA. Elevated IL10 levels were associated with PHVI reactivation (p < 0.01). We revealed significant correlations between high levels of IL31 and VAE (p < 0.01), IL33 and PHVI (p < 0.01). The IL1β levels were significantly higher in individuals with PHVI reactivation treated with DMDs for MS. There were no differences in cytokine levels associated with the presence or absence of systemic AEs. The latter predominated in individuals with PHVI reactivation and VAE. The cytokine levels of individuals with MS are affected by treatment with DMDs for MS and herpesvirus infections.

Received: 2024-04-23

Published online: 2024-06-19

DOI: 10.24075/brsmu.2024.021

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VIEWS 187

Shepelkova GS, Chernyh NA, Kosiakova VK, Sadovnikova SS, Ergeshov A, Yeremeev VV

Given the fact, that adaptive immune response is important for control and elimination of viral infections causing human diseases, estimation of adaptive response to SARS-CoV-2 is extremely important. The neutralizing antibodies and CD4+/CD8+ T cells contribute to the SARS-CoV-2 control. Tuberculosis remains the leading cause of mortality among bacterial infections all over the world. Currently, treatment of tuberculosis is complicated by the COVID-19 co-infection. The aim of the study was to investigate the formation of neutralizing antibodies against SARS-CoV-2 and CD4+ and CD8+ T cells specific for SARS-CoV-2 in patients with pulmonary TB. The levels of neutralizing antibodies against SARS-CoV-2 and the amount of T cells specific for SARS-CoV-2 were estimated at two time points (3 and 6 months after COVID-19) in patients diagnosed with pulmonary tuberculosis (69 individuals: 33 females and 36 males aged 18–70 years). Patients without tuberculosis (35 individuals: 25 females and 10 males aged 18–70 years) who had undergone COVID-19 served as the control group. The study showed equal levels of SARS-CoV-2 neutralizing antibodies in both groups 3 months after COVID-19. The levels of antibodies decreased 6 months after COVID-19 compared to the levels reported 3 months after the disease in both groups. The antibody levels were significantly lower in the group of patients with TB (p = 0.01). The amount of SARS-CoV-2 specific T cells was lower in TB patients 6 months after COVID-19 (p < 0.001) compared to the control group. Thus, TB co-infection reduces the specific immune response to SARS-CoV-2 6 months after COVID-19.

Received: 2024-04-03

Published online: 2024-06-17

DOI: 10.24075/brsmu.2024.023

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VIEWS 177

Dobronos MA, Osipova ZM, Myshkina NM

Production of biotherapeutic drugs in mammalian cells, recombinant proteins in particular, may be handicapped by the limitations imposed on the cultures by metabolic burden. An alternative solution is to produce proteins in cells of other animals (e.g., Sf9, S2 and High Five insect cell lines, Caenorhabditis elegans and Schistosoma mansoni cell line) or orthogonal cell systems, including plant-based. In our opinion, non-traditional cell cultures may become promising tool for production of affordable and effective biotherapeutic drugs.

Received: 2024-04-20

Published online: 2024-06-13

DOI: 10.24075/brsmu.2024.022

Comments 0

VIEWS 200