Publications by authors named "M Buc"

135 Publications

Autoinflammatory process in the pathogenesis of generalized pustular psoriasis and perspectives of its targeted therapy.

Epidemiol Mikrobiol Imunol 2021 ;70(3):199-207

The dysregulated inflammatory process not only plays an important role in the development of chronic plaque psoriasis but also is a major pathogenetic mechanism behind the generalized pustular psoriasis (GPP) and other rare pustular forms of the disease. The key players in this process are the cytokines interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF), IL-12/23, IL-17A and especially IL-36. Their excessive activity or production in some GPP patients is due to mutations in genes that encode molecules involved in inhibiting the action of IL-36 (IL-36Ra) or in intracellular inflammatory signaling (CARD14, AP1S3). Knowledge about the pathological role of inflammatory cytokines in the development of pustular forms of psoriasis has also found application in their biological therapy with monoclonal antibodies that neutralize the action of IL-12/23, IL-17A, TNF or IL-1β. Other promising agents are monoclonal antibodies against the interleukin 36 receptor, which have already successfully gone through the first phases of clinical trials and are currently being tested for their long-term efficacy, safety and tolerability.
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October 2021

MAIT cells, their biological and medical significance.

Authors:
M Buc

Epidemiol Mikrobiol Imunol 2020 ;69(4):189-193

MAIT cells are a separate cell population differentiating in the thymus. They are mostly present in the peripheral blood, liver, intestine, and lungs, less often in other tissues, and infrequently in the lymph nodes. The presentation molecules for MAIT cells are MR1 proteins. They are evolutionarily conserved and non-polymorphic, resemble class I HLA molecules, and are expressed by all cell types. They present bacterial and yeast vitamin metabolites which arise during the synthesis of vitamin B2. The effector functions of MAIT cells are promoted through cytokine synthesis. They also act cytotoxically, directly killing infected or tumour cells. MAIT cells may also play a role in pathological processes. Their involvement in the development of rheumatoid arthritis, systemic lupus erythematosus, autoimmune diabetes mellitus, Crohn's disease, and bronchial asthma has been demonstrated. In practical terms, MAIT cells are very sensitive to therapeutic doses of glucocorticoids. Treatment of patients with BA or chronic obstructive pulmonary disease with glucocorticoids increases their susceptibility to pneumonia, especially when caused by Streptococcus pneumoniae.
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February 2021

Mechanisms of action of regulatory lymphocytes and a possibility to use them in the treatment of autoimmune diseases and GvH reactions.

Authors:
M Buc

Bratisl Lek Listy 2020 ;121(1):3-7

Basic characteristic of the immune system is its ability to distinguish self-molecules, cells, tissues and organs from not self, to tolerate self and dispose of not self. Immunosuppressive mechanisms, especially those mediated by regulatory lymphocytes, play a paramount role in the tolerance mechanisms. When there is an abnormal quantity and/or quality of regulatory cells, various autoimmune diseases are induced, e.g. SLE, RA, T1D, IBD, MS, and others.In recent years, a great progress was achieved in the field how to profit from immunosuppressive properties of T regulatory cells (Treg) in the treatment of patients suffering from autoimmune disorders or transplantation rejections. Nowadays, there are possibilities to up-regulate the function of patient's Tregs or supplement their low numbers. We can up-regulate the function of Treg cells in an affected organism by treatment by low dosage of IL-2 or to treat patients by in vitro expanded Treg cells themselves. Induced Tregs are, however, polyspecific, therefore they have been preferentially used for the treatment graft versus host reactions and some autoimmune disorders only. For those autoimmune diseases, where specific autoantigens are known, Treg cells equipped by antigen-specific chimeric T cell receptor (CARs) were introduced for their treatment (Tab. 1, Fig. 2, Ref. 47). Keywords: AIRE, autoimmune diseases, CAR, cytokines, iNKT cells, regulatory B and T cells.
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http://dx.doi.org/10.4149/BLL_2020_001DOI Listing
February 2020

HMGB1 as a potential new marker of disease activity in patients with multiple sclerosis.

Neurol Sci 2020 Mar 14;41(3):599-604. Epub 2019 Nov 14.

Institute of Immunology, Faculty of Medicine, Comenius University, Spitalska 24, 813 72, Bratislava, Slovakia.

Objectives: Neuroinflammation represents one of the two major pathological components of multiple sclerosis (MS). The aim of our study was to find the role of the late pro-inflammatory cytokine HMGB1 (high mobility group box) in MS pathogenesis.

Subjects And Methods: A total of 165 patients from three MS centers in Slovakia were enrolled in the study. Patients underwent a complex clinical investigation and their plasma levels of HMGB1 were analyzed by a sandwich ELISA test.

Results: MS patients had 4.5 times higher plasma level of HMGB1 (median, 13.529 ng/mL; IQR = 2.330-113.45) than healthy controls (median, 2.999 ng/mL; IQR = 1.686-9.844; P < 0.0001). The concentrations of HMGB1 were significantly associated with increased number of affected areas diagnosed by MRI (P < 0.0001) (the median for one affected area, 4.205 ng/mL; median for five affected areas, 17.843 ng/mL; P < 0.05). Patients with at least one active lesion in any of the affected areas in the brain had significantly higher plasma levels of HMGB1 (median, 20.118 ng/mL; IQR, 3.693-100.12) than those without any active lesion (median, 16.695 ng/mL; IQR, 3.255-113.45; P < 0.0235). We found also a very highly significant association of HMGB1 plasma levels with clinical condition expressed as EDSS (expanded disability status scale) (P < 0.0001); patients with higher EDSS had higher levels of HMGB1 (EDSS ≤ 2.5, 11.648 ng/mL vs. EDSS ≥ 3, 17.549 ng/mL; P = 0.0115).

Conclusion: Our results suggest chronic low-grade inflammation in MS patients that correlates with clinical conditions of MS patients, and for HMGB1 as a possible target molecule in future therapy.
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http://dx.doi.org/10.1007/s10072-019-04136-3DOI Listing
March 2020

Association of HLA-G Polymorphisms in the 3'UTR Region and Soluble HLA-G with Kidney Graft Outcome.

Immunol Invest 2019 Aug 16;48(6):644-658. Epub 2019 May 16.

d Cancer Research Institute, Biomedical Research Center , Slovak Academy of Sciences , Bratislava , Slovakia.

: Human leukocyte antigen G (HLA-G) belongs to nonclassical HLA I molecule involving in the suppression of immune response. Besides its profound effect to induce fetal tolerance, HLA-G expression has been associated with allograft acceptance. For the regulation of HLA-G levels, polymorphic sites within the 3' untranslated region (3'UTR) are of crucial importance. The aim of the study was to analyze the association between several 3'UTR variants (+3003T/C, +3010C/G, +3027C/A, +3035C/T, +3142G/C, +3187A/G, and +3196C/G), soluble HLA-G (sHLA-G) level, and kidney graft outcome in the Slovak Caucasian population. : We investigated 69 kidney transplant recipients (45 males, 24 females) of age 27-65 years. Out of this group, 37 recipients developed acute rejection that was biopsy proven. Recipient's plasma was obtained at 1 day before transplantation and analyzed by ELISA. The 3'UTR polymorphisms were typed by direct sequencing. : In the recipients with stable allograft function, significantly higher values of sHLA-G were found in the homozygous +3010GG, +3142CC, +3187GG, and +3196CC carriers in comparison to the acute rejection recipients (P = 0.01-0.05). : The study demonstrated genetic association between 3'UTR variants and sHLA-G level in kidney recipients leading to graft acceptance. We suggest to monitor the pretransplantation sHLA-G level as additional marker to predict kidney graft outcome. AMR: Antibody-mediated rejection; APC: antigen-presenting cell; CD: cluster of designation; del: deletion; HLA: human leukocyte antigen; ILT: immunoglobulin-like transcript; ins: insertion; KIR: killer-cell immunoglobulin-like receptor; NK: natural killer; sHLA-G: soluble HLA-G; SNP: single nucleotide polymorphism; TCMR: T cell-mediated rejection; URR: upstream regulatory region; UTR: untranslated region.
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http://dx.doi.org/10.1080/08820139.2019.1610888DOI Listing
August 2019
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