Olga Sergeevna Boeva

Multiple myeloma (MM) is a malignant plasma cell disorder and one of the most common tumors of lymphoid origin. In the process of oncogenesis, there is a significant change in the immune balance in the body, which leads to the suppression of the immune response to the tumor. This immune suppression is one of the reasons why the tumor can progress and cause serious health problems for the patient. One of the key factors that affect immune balance is innate lymphoid cells (ILCs). ILCs play an important role in regulating the immune response and can both promote and hinder the development of tumor processes, depending on their functional state and interaction with other cells of the immune system. Among ILCs, ILC1 mainly exert antitumour activity, but ILC2 and ILC3 are usually protumorigenic. One of the standard treatments for MM is autologous hematopoietic stem cell transplantation (auto-HSCT), and the aim of our study was to evaluate the effect of auto-HSCT on ILCs in MM. We assessed the number and subpopulation composition of ILCs in MM patients before and after auto-HSCT. In MM patients, an increase in the proportion of ILC2 and a decrease in ILC1 are observed before auto-HSCT compared to healthy controls. The subpopulation composition of ILCs changes in patients with multiple myeloma after auto-HSCT, with an increase in ILC1 and a decrease in ILC2 compared to pre-auto-HSCT values. No differences were observed in the relative number of different types of ILC in MM patients after auto-HSCT and in healthy controls. It has been shown that the number of immature CD5⁺ILC2s in the peripheral blood of patients with multiple myeloma is comparable to that of healthy individuals. However, in MM patients, HSCT leads to an increase in the relative number of CD5⁺ILC2s.

The aim of the study is to systematize current data on the role of innate lymphoid cells (ILC) in the pathogenesis of rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic sclerosis, and systemic lupus erythematosus. Material and methods. A systematic review of the literature was conducted using data from PubMed, Scopus, and eLIBRARY.RU databases. The following keywords were used: «innate lymphoid cells», «ILC», «rheumatoid arthritis», «psoriatic arthritis», «spondyloarthritis», «systemic sclerosis», «systemic lupus erythematosus». This review presents up-to-date information on the role of various ILC subpopulations in the pathogenesis of rheumatic diseases, the maintenance of chronic inflammation in joints and other target organs, the involvement of ILC in the regulation of pathological remodeling of bone and cartilage tissue, as well as the phenotypic and functional plasticity of ILC. The perspectives of therapeutic modulation of ILC using inhibitors of pro-inflammatory cytokines and Janus kinases (JAK inhibitors) are discussed. Conclusions . ILC play a crucial role in the pathogenesis of rheumatological diseases such as rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, systemic sclerosis, and systemic lupus erythematosus. ILC regulate inflammation and the immune response, affecting joint tissue destruction and osteoclastogenesis. Under certain conditions, ILC can adapt to changes in the microenvironment, offering opportunities for the development of targeted therapeutic approaches. The use of drugs targeting ILC, such as JAK-STAT and IL-17 inhibitors, has shown encouraging results, making it a promising avenue for therapeutic interventions aimed at this immune cell subpopulation. However, further research is needed to deepen the understanding of ILC mechanisms and refine therapeutic strategies.

Trogocytosis is the process of engulfment of a portion of a cell’s membrane by another cell. This process is characterized by the transfer of membrane fragments and proteins between adjacent cells without their complete fusion or phagocytosis, which distinguishes it from classical cellular uptake pathways. In the immune system, the initiating signal for trogocytosis is antigen presentation or the interaction of the Fc receptor with an antibody bound to the cell. During trogocytosis, T cells transfer not only the MHC molecule with the antigenic peptide, but also the costimulatory molecules CD80, CD86, OX-40 and others. As a result of trogocytosis, cells can transfer various surface molecules, acquire new immunological properties, and modulate each other’s activity. This review examines the basic mechanisms of trogocytosis, the involvement of T2-mediated immunity components in trogocytosis, and its possible role in allergies.

Background/Objectives: Multiple myeloma (MM) is characterized by complex interactions between tumor plasma cells and the tumor microenvironment, in which immune escape mechanisms play a key role. Non-classical major histocompatibility complex (MHC) molecules HLA-E and HLA-G are receptors capable of suppressing the activity of NK cells and T lymphocytes. However, their expression on immune cells in oncology, particularly in MM, remains poorly understood. Methods: Peripheral blood mononuclear cells from patients with MM and healthy controls were used as study material. HLA-E and HLA-G expression on T lymphocytes and monocytes was analyzed using flow cytometry. Results: MM was shown to be associated with increased expression of non-classical molecule HLA-E by T lymphocytes and monocytes, as well as an increased proportion of cells with phenotype HLA-E+HLA-DR+ among cells. Conclusions: Our study demonstrates that non-classical HLA-E molecule are actively expressed on immune cells in multiple myeloma, which may serve as a mechanism for tumor immune evasion. These data support further exploration of HLA-E as potential target for MM immunotherapy.

Trogocytosis is the process of engulfment of a portion of a cell's membrane by another cell. This process is characterized by the transfer of membrane fragments and proteins between adjacent cells without their complete fusion or phagocytosis, which distinguishes it from classical cellular uptake pathways. In the immune system, the initiating signal for trogocytosis is antigen presentation or the interaction of the Fc receptor with an antibody bound to the cell. During trogocytosis, T cells transfer not only the MHC molecule with the antigenic peptide, but also the costimulatory molecules CD80, CD86, OX-40 and others. As a result of trogocytosis, cells can transfer various surface molecules, acquire new immunological properties, and modulate each other's activity. This review examines the basic mechanisms of trogocytosis, the involvement of T2-mediated immunity components in trogocytosis, and its possible role in allergies.

CD80 and CD86 molecules are key costimulatory ligands expressed primarily on the surface of antigen-presenting cells (APCs). However, the presence of these molecules on T cells is currently uncommon and may be associated with various immunopathologies, such as allergic diseases. Literature data demonstrate that the presence of these molecules on T cells can polarize the immune response toward Th2, thereby enhancing inflammation. In our study, we found that all Type 2-dependent diseases we examined (atopic dermatitis, bronchial asthma) were associated with increased CD80 expression by immune cells. One of the modern and effective treatments for these diseases is genetically engineered biological therapy (GEBT). In this study, we found that in patients with severe allergy pathology, GEBT-associated cells exhibit changes in the percentage of cells expressing CD80 and CD86 on both monocytes and T cells.

Multiple myeloma is a malignant tumor disease that affects plasma cells and is one of the most common tumors of lymphoid origin. In the process of oncogenesis, that is, the formation of a tumor, there is a significant change in the immune balance in the body, which leads to the suppression of the immune response to the tumor. This suppression is one of the reasons why the tumor can progress and cause serious health problems for the patient. One of the key factors that affect immune balance is innate lymphoid cells (ILCs). ILCs play an important role in regulating the immune response and can both promote and hinder the development of tumor processes, depending on their functional state and interaction with other cells of the immune system. It has been shown that the number of immature CD5+ILC2s cells in the peripheral blood of patients with multiple myeloma is comparable to that of healthy individuals. However, autologous hematopoietic stem cell transplantation in MM patients leads to an increase in the relative number of CD5+ILC2s.

Globally, the prevalence of bronchial asthma (BA) alone reaches 19%, with the number of affected individuals showing an upward trend. Atopic dermatitis (AD) affects 25-30% of children and 7-10% of adults. Remission remains elusive even with advanced genetically engineered biological therapies. Consequently, research into immunopathogenic pathways and the development of novel therapeutic strategies remain critical. A typical representative of “non-classical” HLAs, the HLA-E molecule, is a perspective for study. These molecules are also expressed across various tissues, notably in the respiratory system (bronchial epithelium) and skin keratinocytes. As a cell surface protein, HLA-E participates in diverse immune response pathways. VL9 peptides stabilize HLA-E expression, enabling presentation to its primary receptors, NKG2, on natural killer (NK) cells. In adaptive immunity, HLA-E serves as a ligand for CD8+ cytotoxic T cell receptors (TCRs). This study aimed to evaluate HLA-E-bearing cells (CD4+, CD8+, CD14+) in patients with BA and AD, both before and 12 months after initiating genetically engineered biological therapy (GEBT). Peripheral blood mononuclear cells (PBMCs) were analyzed from healthy donors (n = 16), BA patients (n = 4), and AD patients (n = 5). AD patients received dupilumab (300 mg loading dose), while BA patients were treated with benralizumab (30 mg). Prior to therapy, both AD and BA patients exhibited lower proportions of HLA-E-positive CD4+ and CD8+T cells compared to healthy donors. No significant differences were observed in HLA-E expression on CD14+ monocytes. During treatment, HLA-E levels across all cell types in patients reached levels comparable to those in healthy donors. These findings suggest HLA-E’s involvement in disease pathogenesis and the modulating effects of GEBT on HLA-E-positive cell populations.

Innate lymphoid cells (ILCs) are the innate analogues of lymphocytes that do not express antigen-specific receptors and are primarily found in tissues and mucosa. ILCs are divided into three groups based on the transcription factors and cytokines they secrete. Group 1 ILCs produce interferon (IFN)-γ in response to IL-12 and are dependent on the transcription factor T-bet; group 2 ILCs (ILC2s) predominantly produce type 2 cytokines (IL-5, IL-4, IL-9, and IL-13) in response to IL-33, IL-25, and thymic stromal lymphopoietin (TSLP) and are dependent on GATA3. Group 3 ILCs include ILC3s and lymphoid tissue inducer cells (LTi). The latter group secretes IL-17 and IL-22 in response to IL-1β and IL-23 and functionally depends on RORγt. Recently, early ILC precursors were found in peripheral blood, which were defined by the CD5 marker and are likely to be of thymic origin. These cells can, on demand, enter the bloodstream (like monocytes), move with the blood flow into tissues for subsequent differentiation into a mature phenotype. In this work, we assessed the content of CD5+ILC2 in peripheral blood of patients with rheumatoid arthritis (RA), which is characterized by chronic inflammation in the joints and uncontrolled cell proliferation, thus maintaining the inflammatory events. In this work, we used peripheral blood from patients with RA (n = 7) and conditionally healthy donors (n = 13). The obtained peripheral blood mononuclear cells (PBMPs) were stained with the following panel of antibodies: anti-lineage (CD2/3/14/16/19/20/56/235a), antiCD11c and anti-FceR1 alpha-FITC, anti-CD294-PE, anti-CD127-PerCP/Cy5.5, antiCD117-APC, anti-CD5-BV-450. Innate lymphoid cells were defined as Lin-CD127+, CD294+ILCs were identified as ILC2. The proportion of CD5+ cells among ILC2 was also evaluated. The cell phenotype was analyzed by flow cytometry. We showed that the proportion of ILC2 among all PBMPs was significantly lower in patients with RA compared to the donor group, and the number of CD5+ILC2 among ILC2 was significantly higher than in the control group. The obtained results are unique and provide us with new data on the changing percentage of ILC2 among PC MNCs and CD5+ILC2 among ILC2.

Complex mechanisms of thymus functioning affect its structural matrix thus promoting gradual accumulation of genetic mutations, changes in gene expression and premature immunosenescence. The study of early thymic cell migrants (ETM) is necessary to identify possible diagnostic biomarkers and potential checkpoints of autoimmune diseases (AID). We have studied peripheral blood samples of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PS) and healthy donors. The aim of the study was to assess the ratio of recent cell migrants from the thymus and circulating naïve T regulatory cells in healthy persons and autoimmune diorders. The relative numbers of recent thymic migrants CD4+CD45RA+CD31+ (ETM), and the contents of FoxP3+T regulatory cells (Treg) in this population were determined by flow cytometry. The number of proliferating cells was determined by intracellular Ki-67 marker. The results show that the number of ETM was reduced in the group of patients with RA and patients with PsA compared with the healthy donor group (17.3%, 18.6% vs. 23.6%), and did not change significantly in patients with psoriasis. There were no significant differences between donors and patients with AIDs on the contents of proliferating ETM and Tregs. The proliferation rates of T regulatory cells in patients with psoriatic pathology were comparable to donor values, with a trend for its increase in RA patients. The numbers of proliferating naive FoxP3+Tregs in RA patients was significantly higher than the numbers of proliferating ETM (15.8% vs 3.1%, p 0.05, respectively). A decrease in relative number of ETM in AID may be associated with activation of T lymphocytes and higher proportion of central memory T cells. The number of Tregs among ETM, and their proliferation rates in patients with psoriatic disorder suggest the absence of disturbed Treg generation in thymus. The ambiguous results obtained in patients with RA are of potential significance for diagnostics and therapy. However, they require additional confirmation in a larger sample of patients.