Screening for tuberculosis of patients with HIV-infection. New possibilities

Background. Tuberculosis associated with HIV infection is becoming almost a new disease, where not only new approaches to treatment are being formed, but there is also a need to improve the quality and search for new means of early diagnosis of tuberculosis infection.The aim. To evaluate the diagnostic performance of the T-SPOT.TB test for the detection of latent tuberculosis infection and clinical forms of tuberculosis in patients with HIV infection.Materials and methods. 396 patients registered at the AIDS Center for more than a year were examined. Everyone underwent standard examinations for pulmonary tuberculosis using sputum bacterioscopy techniques with Ziehl – Neelsen staining; a molecular genetic method based on hybridization technology – HAIN-GenoType MTBDRplus; crops on liquid media in the automated BACTEC MGIT 960 system and on Löwenstein–Jensen dense medium. T-SPOT.TB was conducted as a screening for everyone. With positive T-SPOT.TB results, negative results of the MBT search, absence of specific changes on the X-ray a conclusion was made about latent tuberculosis infection. Statistical data processing was carried out using the software package Statistica 10 (StatSoft Inc., USA).Results. According to the results of a comprehensive examination, tuberculosis was diagnosed in 174 patients, verified using various methods of searching for Mycobacterium tuberculosis in 116 patients (66.6 %). Infiltrative (63.8 %) and disseminated (24.7 %) tuberculosis were more often diagnosed. Latent tuberculosis infection was diagnosed in 52 patients, 170 HIV-infected patients have no data for tuberculosis at this stage.Conclusions. T-SPOT.TB can be used in the diagnostic complex of monitoring patients with HIV infections – as a screening method to detect latent tuberculosis, for preventive chemotherapy

ELISPOT assay of the SARS-CoV-2 specific T cells immune response

The COVID-19 pandemic has stimulated interest in the development of biotechnology, as well as in the search for new solutions in the diagnostics of immune processes. The response of immunoglobulins A, M and G had a significant role in the assessment of virus-specific immune responses. Later, it was understood that for a comprehensive assessment of adaptive immunity processes, it is reasonable to study its cellular component. One of the most affordable methods for assessing T cell immunity, which has proven itself in the diagnosis of other infectious diseases, such as latent tuberculosis infection, is IGRA ELISPOT.The aim of the study. To determine SARS-СoV-2 specific immune response of T lymphocytes in vitro in the peripheral blood of volunteers from various groups using IGRA ELISPOT method. We evaluated the applicability of the method to assess T cell immune response to infection and vaccination. In addition, we determined the duration of the maintenance period of the SARS-CoV-2 specific T cells immune response induced by vaccination.Materials and methods. The study was carried out on venous blood samples of volunteers from three groups: 1) hospital patients with COVID-19; 2) COVID-19 convalescents; 3) vaccinated against COVID-19. The T cell immune response was assessed using the TigraTest® SARS-CoV-2 test system, which determines in vitro the number of T cells secreting interferon-gamma in response to stimulation with SARS-СoV-2 peptides in two antigens panels: 1) peptides of the spike protein (S); 2) peptides of N, M, Orf3a and Orf7a proteins.Conclusion. The IGRA ELISPOT assay is a specific and sensitive tool in the assessment of T cell immunity to the SARS-CoV-2 virus. The method makes it possible to assess SARS-CoV-2 specific T cell responses induced both by natural encounter with the pathogen and by vaccination. It is advisable to use the method in routine practice for comprehensive assessment of immunity to SARS-CoV-2

Studying the pharmacokinetics of biotechnological medicinal products on the example of monoclonal antibodies

Therapeutic monoclonal antibodies (mAbs), which are developed to treat many pathologies, including cancer, autoimmune and infectious diseases, are one of the fastest growing classes of medicinal products. Given the large number of mAbs in the pipeline and continued interest from pharmaceutical companies, the mAb market is expected to continue to grow in the coming years. To maximise both the therapeutic benefit and the safety of medicinal products in this class, it is essential that their pharmacological properties be carefully characterised and understood.The aim of the study was to analyse literature data on approaches to studying the pharmacokinetics of mAbs. This review presents data on the main physicochemical and pharmacological properties of mAbs and compares them with small molecules. The article describes the influence of various factors on mAb pharmacokinetics.For example, such factors include the method of administration, hydrophilicity, and charge of the mAb, individual characteristics of the patient (body weight, plasma albumin levels, genetic characteristics, etc.), and concurrent administration of other medicinal products. The authors evaluated the role of intra- and inter-individual variability of pharmacokinetic parameters. The rapid development of this group of medicinal products and the emergence of new promising molecules are indicative of the need to study the pharmacokinetics and pharmacodynamics of mAbs in detail and to maximise both the therapeutic benefit and the safety of the medicinal products in this class

Analysis of the TREC and KREC Levels in the Dried Blood Spots of Healthy Newborns with Different Gestational Ages and Weights

Inborn errors of immunity can be detected by evaluating circular DNA (cDNA) fragments of T-and B-cell receptors (TREC and KREC) resulting from the receptor gene rearrangement in T and B cells. Maturation and activation of the fetal immune system is known to proceed gradually according to the gestational age, which highlights the importance of the immune status in premature infants at different gestational ages. In this article, we evaluated TREC and KREC levels in infants of various gestational ages by real-time PCR with taking into account the newborn’s weight and sex. The 95% confidence intervals for TREC and KREC levels (expressed in the number of cDNA copies per 105 cells) were established for different gestational groups. The importance of studying immune system development in newborns is informed by the discovered dependence of the level of naive markers on the gestational stage in the early neonatal period. © 2022 National Research University Higher School of Economics. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Возможности иммунологических тестов в диагностике латентной туберкулезной инфекции и туберкулеза

The article assesses existing immunological tests aimed to detect tuberculosis infection (tuberculin skin test, IGRA, skin test with a recombinant tuberculosis allergen). The latest inventions in the development of immunological tests that can differentiate latent tuberculosis infection and active tuberculosis have been analyzed. The difficulties encountered when developing such a test and conducting clinical trials have been demonstrated. The article presents the experience of the Moscow TB service in using the skin test with recombinant tuberculosis allergen as a screening method for tuberculosis infection, its ability to detect the infection at the stage of its development when preventive therapy is most effective since anti-tuberculosis drugs kill mycobacteria that are replicating but not dormant. Such tactics contributed to the incidence rate decrease both in high-risk groups and among the general population.Дана оценка существующих иммунологических тестов для выявления туберкулезной инфекции (ТКП, лабораторных тестов IGRA, кожного теста с аллергеном туберкулезным рекомбинантным). Проведен анализ последних разработок по созданию иммунологических тестов, способных дифференцировать латентную туберкулезную инфекцию и активный туберкулез. Показаны трудности создания такого теста и проведения клинических испытаний. Приведен опыт Московской противотуберкулезной службы по использованию кожного теста с аллергеном туберкулезным рекомбинантным в качестве скринингового метода выявления туберкулезной инфекции, его способности выявлять инфекцию в стадии ее развития, когда превентивная терапия оказывается наиболее эффективной, поскольку противотуберкулезные препараты действуют на микобактерии, находящиеся в стадии репликации, а не в дормантном (спящем) состоянии. Такая тактика способствовала снижению заболеваемости как в группах повышенного риска заболевания, так и в целом среди населения

Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins

Water and water-mediated interactions determine thermodynamic and kinetics of protein folding, protein aggregation and self-assembly in confined spaces. To obtain insights into the role of water in the context of folding problems, we describe computer simulations of a few related model systems. The dynamics of collapse of eicosane shows that upon expulsion of water the linear hydrocarbon chain adopts an ordered helical hairpin structure with 1.5 turns. The structure of dimer of eicosane molecules has two well ordered helical hairpins that are stacked perpendicular to each other. As a prelude to studying folding in confined spaces we used simulations to understand changes in hydrophobic and ionic interactions in nano droplets. Solvation of hydrophobic and charged species change drastically in nano water droplets. Hydrophobic species are localized at the boundary. The tendency of ions to be at the boundary where water density is low increases as the charge density decreases. Interaction between hydrophobic, polar, and charged residue are also profoundly altered in confined spaces. Using the results of computer simulations and accounting for loss of chain entropy upon confinement we argue and then demonstrate, using simulations in explicit water, that ordered states of generic amphiphilic peptide sequences should be stabilized in cylindrical nanopores