Dmitry Isakov

Adult-onset Still’s disease (AOSD) is a complex systemic inflammatory disorder, categorized as an ‘IL-1 driven’ inflammasomapathy. Despite this, the interaction between T and B cells remains poorly understood. We conducted a study, enrolling 7 patients with relapsing AOSD and 15 healthy control subjects, utilizing deep flow cytometry analysis to examine peripheral blood T- and B-cell subsets. T-cell and B-cell subsets were significantly altered in patients with AOSD. Within CD4+ T cells, Th2 cells were decreased. Additionally, Th17 cell and follicular Th cell subsets were altered within CD45RA–CD62L+ and CD45RA–CD62L– Th cells in patients with AOSD compared to healthy controls. We identified changes in CD8+ T cell maturation and ‘polarization’ in AOSD patients, with an elevated presence of the TEMRA CD8+ T cell subset. Furthermore, the percentage of Tc1 cells was decreased, while the frequency of CCR6–CXCR3– Tc2 cells was elevated. Finally, we determined that the frequency of CD5+CD27– B cells was dramatically decreased in patients with AOSD compared to healthy controls. Further investigations on a large group of patients with AOSD are required to evaluate these adaptive immunity cells in the disease pathogenesis.

Pathogenic microbes use arginine-metabolizing enzymes as an immune evasion strategy. In this study, the impact of streptococcal arginine deiminase (ADI) on the human peripheral blood T lymphocytes function in vitro was studied. The comparison of the effects of parental strain (Streptococcus pyogenes M49-16) with wild type of ArcA gene and its isogenic mutant with inactivated ArcA gene (Streptococcus pyogenes M49-16delArcA) was carried out. It was found that ADI in parental strain SDSC composition resulted in a fivefold decrease in the arginine concentration in human peripheral blood mononuclear cell (PBMC) supernatants. Only parental strain SDSCs suppressed anti-CD2/CD3/CD28-bead-stimulated mitochondrial dehydrogenase activity and caused a twofold decrease in IL-2 production in PBMC. Flow cytometry analysis revealed that ADI decreased the percentage of CM (central memory) and increased the proportion of TEMRA (terminally differentiated effector memory) of CD4+ and CD8+ T cells subsets. Enzyme activity inhibited the proliferation of all CD8+ T cell subsets as well as CM, EM (effector memory), and TEMRA CD4+ T cells. One of the prominent ADI effects was the inhibition of autophagy processes in CD8+ CM and EM as well as CD4+ CM, EM, and TEMRA T cell subsets. The data obtained confirm arginine’s crucial role in controlling immune reactions and suggest that streptococcal ADI may downregulate adaptive immunity and immunological memory.

More than a century has passed since arginine was discovered, but the metabolism of the amino acid never ceases to amaze researchers. Being a conditionally essential amino acid, arginine performs many important homeostatic functions in the body; it is involved in the regulation of the cardiovascular system and regeneration processes. In recent years, more and more facts have been accumulating that demonstrate a close relationship between arginine metabolic pathways and immune responses. This opens new opportunities for the development of original ways to treat diseases associated with suppressed or increased activity of the immune system. In this review, we analyze the literature describing the role of arginine metabolism in the immunopathogenesis of a wide range of diseases, and discuss arginine-dependent processes as a possible target for therapeutic approaches.

Post-COVID syndrome develops in 10–20% of people who have recovered from COVID-19 and it is characterized by impaired function of the nervous, cardiovascular, and immune systems. Previously, it was found that patients who recovered from infection with the SARS-CoV-2 virus had a decrease in the number and functional activity of NK cells. The aim of the study was to assess the effectiveness of recombinant human IL-2 (rhIL-2) administered to correct NK cell phenotype and functional activity in patients with post-COVID syndrome. Patients were examined after 3 months for acute COVID-19 of varying severity. The phenotype of the peripheral blood NK cells was studied by flow cytometry. It was found that disturbances in the cell subset composition in patients with post-COVID syndrome were characterized by low levels of mature (p = 0.001) and cytotoxic NK cells (p = 0.013), with increased release of immature NK cells (p = 0.023). Functional deficiency of NK cells in post-COVID syndrome was characterized by lowered cytotoxic activity due to the decreased count of CD57⁺ (p = 0.001) and CD8⁺ (p < 0.001) NK cells. In the treatment of patients with post-COVID syndrome with recombinant IL-2, peripheral blood NK cell count and functional potential were restored. In general, the effectiveness of using rhIL-2 in treatment of post-COVID syndrome has been proven in patients with low levels of NK cells.

Th cells may exhibit pathological activity depending on the regulatory and functional signals sensed under a wide range of immunopathological conditions, including ankylosing spondylitis (AS). The relationship between Th cells and cytokines is important for diagnoses and for determining treatment. Accordingly, the aim of this study was to investigate the relationship between Th-cell subset composition and serum cytokine profile for patients with activity-driven AS. In our study, patients were divided into two groups according to disease activity: low-activity AS (ASDAS-CRP < 2.1) and high-activity AS (ASDAS-CRP > 2.1). The peripheral blood Th cell subset composition was studied by flow cytometry. Using multiplex analysis, serum cytokine levels were quantified and investigated. It was found that only patients with high-activity AS had reduced central memory (CM) Th1 cells (p = 0.035) but elevated numbers of CM (p = 0.014) and effector memory (EM) Th2 cells (p < 0.001). However, no activity-driven change in the Th17 cell subset composition was observed in AS patients. Moreover, low-AS activity patients had increased numbers of Tfh17 EM cells (p < 0.001), whereas high-AS activity was associated with elevated Tfh2 EM level (p = 0.031). The serum cytokine profiles in AS patients demonstrated that cues stimulating cellular immunity were increased, but patients with high-AS activity reveled increased IL-5 level (p = 0.017). Analyzing the data obtained from AS patients allowed us to conclude that Th cell subset differentiation was mainly affected during the CM stage and characterized the IL-23/IL-17 regulatory axis, whereas increased humoral immunity was observed in the high-AS activity group.

Background. The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited. Methods.. Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry. Results. Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on ‘naïve’, CM, EM4, and pE1 2–3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients. Conclusions. We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on ‘naïve’ and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response.

Background. Humoral immunity requires interaction between B cell and T follicular helper cells (Tfh) to produce effective immune response, but the data regarding a role of B cells and Tfh in SARS-CoV-2 defense are still sparse. Methods. Blood samples from patients with acute COVID-19 (n = 64), convalescents patients who had specific IgG to SARS-CoV-2 N-protein (n = 55), and healthy donors with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 44) were analyses by multicolor flow cytometry. Results. Patients with acute COVID-19 showed decreased levels of memory B cells subsets and increased proportion plasma cell precursors compared to HC and COVID-19 convalescent patients, whereas for the latter the elevated numbers of virgin naïve, Bm2′ and “Bm3+Bm4” was found if compared with HC. During acute COVID-19 CXCR3+CCR6− Tfh1-like cells were decreased and the levels of CXCR3−CCR6+ Tfh17-like were increased then in HC and convalescent patients. Finally, COVID-19 convalescent patients had increased levels of Tfh2-, Tfh17- and DP Tfh-like cells while comparing their amount with HC. Conclusions. Our data indicate that COVID-19 can impact the humoral immunity in the long-term.

Геморроидальная болезнь является наиболее часто встречающимся проктологическим заболеванием, в связи с чем актуальным остается поиск новых путей лечения, а также углубленного понимания механизмов влияния уже известных методов на патогенез заболевания. Эффекты бактериальной культуральной суспензии (БКС) кишечной палочки (Escherichia coli) как лечебного агента (уменьшение экссудации при воспалении, ранозаживление, регенерация тканей и стимуляция иммунитета) известны давно. С учетом данных последних научных открытий в области активации врожденного и приобретенного иммунитета была поставлена цель представить заинтересованному медицинскому сообществу механизмы реализации эффектов бактерий комменсальной флоры, в частности БКС-инактивированной кишечной палочки, что представляется важным для понимания патогенетического действия препаратов «Постеризан» и «Постеризан форте», нашедших широкое применение в лечении геморроя. На основании проведенного анализа был сделан вывод о реализации вышеупомянутых эффектов через сложные многовариантные и взаимодополняющие взаимодействия рецепторов клеток аноректальной области с микробными компонентами: NOD-лигандами, метаболитами, ферментами, белками теплового шока и нуклеиновыми кислотами, что приводит к продукции провоспалительных цитокинов колоноцитами, клетками анодермы, врожденного и приобретенного иммунитета, нейронами подслизистого сплетения в области транзиторного эпителия, а также и эндотелием геморроидального сплетения. На основании современных концепций можно считать, что биологически активные компоненты БКС E.coli препарата «Постеризан» способны оказывать как положительные местные, так и системные эффекты, что углубляет понимание и обоснованность его применения при геморроидальной болезни. Эффективность терапии препаратами «Постеризан» и «Постеризан форте» подтверждается их применением в реальной клинической практике согласно показаниям как в качестве консервативной терапии, так и после оперативных вмешательств.