Publications by authors named "Dobroslav Kyurkchiev"

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a number of immunological aberrations in the mechanisms of innate and adaptive immune responses. Spontaneous and induced mouse models of the disease have contributed significantly to the advancement in lupus treatments. The involvement of humanized models, engrafted with lupus patients' immune cells, represented the possibility to study the development of SLE.

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Autoimmune diseases represent a severe personal and healthcare problem that seeks novel therapeutic solutions. Mesenchymal stem cells (MSCs) are multipotent cells with interesting cell biology and promising therapeutic potential. The immunoregulatory effects of secretory factors produced by umbilical cord mesenchymal stem cells (UC-MSCs) were assessed on B lymphocytes from 17 patients with systemic lupus erythematosus (SLE), as defined by the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria for SLE, and 10 healthy volunteers (HVs).

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IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and a leading cause of chronic kidney disease and renal failure. However, the Bulgarian population has limited epidemiological data and biomarkers for IgAN. In this retrospective monocentric analysis, we investigated all the patients with biopsy-proven IgAN over 10 years in a tertiary Bulgarian institution.

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Takayasu arteritis (TA) is a chronic large-vessel vasculitis characterized by immune-mediated panarteritis, which predominantly affects the aorta and its main branches and is most prevalent in young women. TA is unusually associated with the presence of antiphospholipid antibodies. We present a case report of a 48-year-old Caucasian woman with acute aortic dissection as an initial feature of TA, where detailed clinical, imaging and laboratory studies were performed.

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The central hypothesis for the development of glioblastoma multiforme (GBM) postulates that the tumor begins its development by transforming neural stem cells into cancer stem cells (CSC). Recently, it has become clear that another kind of stem cell, the mesenchymal stem cell (MSC), plays a role in the tumor stroma. Mesenchymal stem cells, along with their typical markers, can express neural markers and are capable of neural transdifferentiation.

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Background: Systemic lupus erythematosus (SLE) is a disorder with a complex immunopathogenesis. It is well known that the disease begins with immunological alterations and autoantibody appearance in the serum years before clinical onset. As SLE has a strong tendency to familial aggregation, first-degree relatives (FDRs) constitute a group at elevated risk.

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Introduction: Data on the associations between capillaroscopic changes and diagnostic systemic-sclerosis (SSc)-related antibodies are scarce. Presence of such correlation would improve current knowledge about the disease’s pathogenesis by revealing the mechanisms of microangiopathy. The microvascular pathology of SSc is a hallmark of the disease, and immunological abnormalities probably contribute to its development.

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Objectives: Mesenchymal stem cells (MSCs) exist in almost all tissues. Their unique nature is completed by their immunomodulatory functions, holding promise for the treatment of many diseases. An inflammatory environment precedes the immunosuppressive abilities of MSCs and this study was intended to better understand how umbilical cord MSCs (UCMSCs) react to the process of inflammation, regarding their basic characteristics and behavior when primed with the key pro-inflammatory cytokine, Interferon-γ (IFNγ).

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The pathogenesis of COVID-19 involves both humoral and cellular immunological responses, with cell-mediated immunity being discussed as the primary and most effective immune response to viral infection. It is supposed that COVID-19 vaccines also elicited effective cell immune response, and specifically IFNγ secreted by SARS-CoV-2-specific T-helper 1 and Tcytotoxic cells. Using an interferon-gamma release assay (IGRA) test, we aimed to monitor cellular post-vaccination immunity in healthy subjects vaccinated with BNT162b2 mRNA COVID-19 vaccine (Comirnaty).

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Systemic lupus erythematosus (SLE) is a severe autoimmune disease characterized by dysfunction of immune regulation, overproduction of inflammatory cytokines and attack on normal tissues by self-reactive cells and antibodies. The main role in the pathogenesis plays the autoreactive tandem of B-T cells, responsible for lupus progression and acceleration. Both activated B and T cells express a phospholipid binding protein Annexin A1 and abnormal levels of the protein were found in murine and human autoimmune syndromes, potentiating its role as a therapeutic target.

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Background: Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. "Classical" antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA.

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Systemic lupus erythematosus is an autoimmune syndrome characterized by the development of autoantibodies to a wide range of antigens. Together with B cells, respective self-reactive T cells have an important contribution in disease progression as being responsible for inflammatory cytokines secretion, B cell activation and promoting amplification of the autoimmune response. Annexin A1 is expressed by many cell types and binds to phospholipids in a Ca -dependent manner.

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Probiotics possibly affect local and systemic immune reactions and maintain the intestinal immune homeostasis in healthy individuals and patients with diseases such as irritable bowel syndrome (IBS). In this single-center, blinded trial, we enrolled 40 individuals (20 patients with IBS and 20 healthy individuals) whose blood and fecal samples were collected before and after a 21-day administration of a product comprising spp., larch arabinogalactan, and colostrum.

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Mesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics-first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their immunosuppressive capacity. Our results display cells with morphology and phenotype, clonogenic ability, and osteogenic potential, typical for MSCs.

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We aimed to assess the immunoregulatory effects of secretory factors produced by adipose tissue-derived MSC (AT-MSC) on Th17 and Treg subsets from patients with rheumatoid arthritis (RA). 17 patients with active disease matching the ACR/EULAR 2010 criteria for RA were included. Patients' peripheral blood mononuclear cells (PBMC) were cultured in AT-MSC-conditioned medium (AT-MSCcm) and in control medium.

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The case report presented here describes the culturing and characterization of mesenchymal stem cells (MSCs) isolated from a primary indolent B-cell lymphoma, located in the CNS of an immunocompetent patient. The presence of such cells in the tumor mass can further elucidate the pathogenesis of the disease and reveal possible future approaches for its treatment. We present a case report of a 61-year-old immunocompetent woman who had an episode of confusion with numbness in the right leg and the right arm, slurred and dysarthric speech and urine incontinence.

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Aim: To investigate T-cell activation, the percentage of peripheral T regulatory cells (Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis (SSc).

Methods: We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc (dcSSc, = 13) or limited cutaneous SSc (lcSSc, = 11). We performed a further subdivision of the patients regarding the stage of the disease - early, intermediate or late.

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Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production.

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Inflammatory bowel disease (IBD) is assumed to be caused by genetic and environmental factors that interact together in promoting intestinal immune dysregulation where cytokines have validated role. However, the underlying intimate mechanisms in the human IBD involving cytokines still needs to be supplemented especially in the clinical context. The aim of this study was to investigate the expression of some inflammatory and regulatory cytokines (IL-17A, IL-23, IL-6, TGFβ1, and IL-10) as well as of the transcription factor FoxP3 in mucosal samples of IBD and non-IBD patients.

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According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells (MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion.

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Glioblastoma multiforme (GBM) is the most common and malignant tumor in the central nervous system. One of the contemporary hypotheses postulates that its pathogenesis is associated with the cancer stem cells (CSCs) which originate from mutations in the normal neural stem cells residing in their specific "niches." Simultaneously with its aggressive development the tumor suppresses the local immune system by different secreted and/or cell expressed factors.

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Mesenchymal stem cells (MSCs) are a new and promising tool for therapy of autoimmune disorders. In recent years their possibility to take part in the modulation of the immune response is discussed. The exact mechanisms for immunoregulation realized by MSCs are not clear yet, but interactions with other immunoregulatory cells may be involved in this process.

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Progesterone is considered to be a major reproductive steroid hormone which supports the successful development of pregnancy. One of the basic targets of progesterone are stromal cells in endometrium which are triggered to undergo decidualization in preparation to accept the embryo. However, the endometrial stroma consists of different subpopulations of cells with varying characteristics and functions as one of the subpopulations are the endometrial mesenchymal stem cells (MSCs) which seem to be located both in the basal layer and in the functional layer of the endometrium.

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It is well known that the reproductive steroid hormones, particularly progesterone, in addition to its widely recognized effects on endometrial epithelial and stromal cells and spiral arteries, affect the activities of T cells and natural killer cells in the deciduas, thus inducing active immune tolerance against the fetal antigens. The immunomodulatory effects of progesterone on T cells, B cells and natural killer cells have been discussed extensively in the literature. The aim of the present review is to sum up and discuss the results from this and other laboratories of investigations on the effects of progesterone on dendritic cells and adult stem cells, which are some of the other cell populations present at the fetal-maternal interface and possibly are related to the immunoregulation during pregnancy.

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