Publications by authors named "Daniel Kuba"

8 Publications

  • Page 1 of 1

Seasonal changes of circulating 25-hydroxyvitamin D correlate with the lower gut microbiome composition in inflammatory bowel disease patients.

Sci Rep 2020 04 7;10(1):6024. Epub 2020 Apr 7.

Comenius University Science Park, Comenius University in Bratislava, Ilkovicova 8, 84104, Bratislava, Slovakia.

Higher probability of the development of Crohn's disease (CD) and ulcerative colitis (UC) as a possible consequence of the north-south gradient has been recently suggested. Living far north or south of the equator is manifested in fluctuation of vitamin D (vitD) levels depending on the season in both healthy and affected individuals. In the present study we investigate the possible link between the seasonal serum vitD level to the microbial composition of the lower gut of Inflammatory Bowel disease (IBD) patients using 16S rRNA sequencing. Decrease of serum vitD level in winter/spring season in a cohort of 35 UC patients and 39 CD patients was confirmed. Low gut microbiota composition of patients with IBD correlated with the serum level of 25(OH)D that directly coupled to seasonal variability of the sunshine in the central European countries. It is supposed to be related to increased abundance of Actinobacteria and Proteobacteria in UC and Actinobacteria, Fusobacteria, Firmicutes and Bacteroidetes in CD. In summer/autumn period, we observed a reduction in abundance of bacterial genera typical for inflammation like Eggerthella lenta, Fusobacterium spp., Bacteroides spp., Collinsella aerofaciens, Helicobacter spp., Rhodococcus spp., Faecalibacterium prausnitzii; and increased abundance of Pediococcus spp. and Clostridium spp. and of Escherichia/Shigella spp.
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http://dx.doi.org/10.1038/s41598-020-62811-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138827PMC
April 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

Should Enteroviruses Be Monitored in Natural Recreational Waters?

Cent Eur J Public Health 2016 12;24(4):333-336

Enterovirus Laboratory, Faculty of Medicine, Slovak Medical University, Bratislava, Slovak Republic.

Enteroviruses (EVs) infections occur worldwide. Although, infections by these viruses are often asymptomatic and go unnoticed, they can be shed in stool for several weeks. The EVs are associated with sporadic outbreaks and a wide range of clinical symptoms, occasionally accompanied with fatal consequences. Presently in the Slovak Republic (SR) recreational waters are tested only for bacterial indicators. Our aim was to monitor EVs in recreational waters. Water samples were collected during the years 2012-2014 from different recreational natural lakes in Central and West regions of SR. The samples were concentrated by centrifugation using the two-phase separation method recommended by the World Health Organization (WHO) used for EVs surveillance in the treated sewage waste water. Each of the two phases collected from the samples was analysed by polymerase chain reaction for detection of EVs and primary sequencing was done. Our study demonstrated presence of EVs in three localities consecutively for three years, indicating a probability of constant local source of faecal contamination. This is the first monitoring report on the occurrence of EVs in the natural recreational waters in SR.
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http://dx.doi.org/10.21101/cejph.a4368DOI Listing
December 2016

Expression of HLA-G transcripts in graft biopsy samples of renal transplant recipients.

Transpl Immunol 2015 Nov 9;33(3):159-65. Epub 2015 Oct 9.

Cancer Research Institute, SAS, Vlárska7, 83391 Bratislava, Slovak Republic.

Background: The HLA-G molecule has a high potential to modulate immune response towards the improvement of graft survival after transplantation. In this work, we have analyzed the total HLA-G mRNA expression in graft tissues of dysfunctional transplanted kidneys.

Material And Methods: We examined 84 kidney biopsy samples obtained from 65 renal transplant recipients with dysfunctional graft (50 males, 15 females; average age 46.8 ± 11.9 years). 52 specimens were with signs of acute rejection and 32 without any rejection characteristics (diagnosed as glomerulonephritis, ATN and IFTA). Patients with acute rejection were divided into three groups: antibody-mediated rejection (AMR; n = 23), T cell mediated rejection (TCMR; n = 16) and combined antibody and T cell-mediated rejection (AMR + TCMR; n=13). The biopsy samples were taken from a dysfunctional graft at different time periods after kidney transplantation. The relative expression of total HLA-G mRNA in biopsy specimens was determined by real time RT-PCR. The correlation between HLA-G mRNA expression and dysfunctional graft state was investigated. The impact of different factors (post-transplantation interval, gender,mismatch, induction therapy and cold ischemia time) on relative expression of total HLA-G mRNA was also studied.

Results: We have found that the levels of HLA-G transcripts in kidneys with rejection were higher than those in non-rejected but dysfunctional grafts (P = 0.0003). The highest levels of HLA-G mRNA were detected at combined AMR + TCMR rejection (P= 0.005). The time-course analysis of total HLA-G mRNA expression was also studied. In both dysfunctional graft groups (rejected and non-rejected) the lower levels of HLA-G transcripts were detected during early post-transplant period (1–3 months), however a substantial increase of HLA-G mRNA expression was observed after an extended period of time(N3 months). It was also revealed that antibody induction therapy may reduce HLA-G expression (P=0.0004) and in female samples were higher levels of HLAG transcripts than those in male recipients (P=0.003). It was found no significant impact of age, cold ischemic time, PRA (Panel Reactive Antibody) score, and a number of HLA-mismatches on HLA-G mRNA expression.

Conclusions: We have demonstrated that the expression of total HLA-GmRNA in renal grafts can be influenced by different factors such as clinical state of transplanted kidney, elapsed time after transplantation, gender and antibody induction therapy. We have proved that HLA-G mRNA expression was significantly higher in recipients with acute rejection in comparison to patients with dysfunctional but non-rejected grafts.
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http://dx.doi.org/10.1016/j.trim.2015.10.001DOI Listing
November 2015

Genetic determinants of quantitative traits associated with cardiovascular disease risk.

Mutat Res 2015 Aug 15;778:18-25. Epub 2015 May 15.

Department of Experimental and Applied Genetics, Slovak Medical University, 83303 Bratislava, Slovakia.

Established risk factors for cardiovascular diseases (CVD) may be moderated by genetic variants. In 2403 unrelated individuals from general practice (mean age 40.5 years), we evaluated the influence of 15 variants in 12 candidate genes on quantitative traits (QT) associated with CVD (body mass index, abdominal obesity, glucose, serum lipids, and blood pressure). Prior to multiple testing correction, univariate analysis associated APOE rs429358, rs7412 and ATG16L1 rs2241880 variants with serum lipid levels, while LEPR rs1137100 and ATG16L1 rs2241880 variants were linked to obesity related QTs. After taking into account confounding factors and correcting for multiple comparisons only APOE rs429358 and rs7412 variants remained significantly associated with risk of dyslipidemia. APOE rs429358 variant almost tripled the risk in homozygous subjects (OR = 2.97; 95% CI 1.09-8.10, p < 0.03) and had a lesser but still highly significant association also in heterozygous individuals (OR = 1.67; 95% CI 1.24-2.10; p < 0.001). Associations with hypertension, diabetes mellitus, and metabolic syndrome were not significant after Bonferroni correction. The influence of genetic variation is more evident in dyslipidemia than in other analyzed QTs. These results may contribute to strategic research aimed at including genetic variation in the set of data required to identify subjects at high risk of CVD.
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http://dx.doi.org/10.1016/j.mrfmmm.2015.05.005DOI Listing
August 2015

Donor non-specific MICA antibodies in renal transplant recipients.

Immunobiology 2014 Feb 23;219(2):109-12. Epub 2013 Aug 23.

Department of Immunology, Comenius University Faculty of Medicine, Odborárske nám. 14, 813 72 Bratislava, Slovakia.

Despite recent advances in solid organ transplantations, an antibody mediated rejection caused by donor specific antibodies is still a major problem in kidney graft survival. Besides HLA-induced humoral response, antibodies against MICA antigens have recently attracted attention because of their possible role in graft rejection. The aim of our study was to establish whether renal recipients produce antibodies against MICA molecules due to the transplantation and if they are specific for MICA antigens of the donors. MICA antibody screening was performed in 124 kidney recipient sera. 22 sera, that were found to be MICA antibody positive, were further examined for MICA antibody profiles and compared with donor MICA alleles. The analysis of MICA antibody positive sera showed mostly more complex reactivity patterns. A significant fraction of patient sera (59%) reacted not only with the donor MICA antigens, but also with other MICA patterns. A match between antibody specificities and MICA antigens was observed in 41% of renal recipients only. On the other hand, as much as in 36% of recipient sera were detected antibodies against their own MICA molecules. We did not prove a complete correlation between the recipient MICA antibody specificities and MICA antigens of the donor. We assume that MICA antibody induction occurs not only due to the allogeneic stimulation itself but also due to other factors that need to be elucidated.
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http://dx.doi.org/10.1016/j.imbio.2013.08.006DOI Listing
February 2014

The 4H84 monoclonal antibody detecting beta2m free nonclassical HLA-G molecules also binds to free heavy chains of classical HLA class I antigens present on activated lymphocytes.

Hum Immunol 2004 Feb;65(2):157-62

Cancer Research Institute, Slovak Academy of Sciences, Institute of Preventive and Clinical Medicine, Bratislava, Slovak Republic.

We have found that 4H84 monoclonal antibody (mAb) used for detection of beta2m free HLA-G molecules also binds to free heavy chains of classical HLA class I antigens generated on the cell surface by mild acid treatment. Here we demonstrate that beta2m free classical HLA class I molecules induced on the surface of activated lymphocytes not expressing HLA-G also bind 4H84 mAb. These results demonstrate that 4H84 mAb should be used for detection of HLA-G in cells and tissues with backing by other HLA-G specific mAbs.
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http://dx.doi.org/10.1016/j.humimm.2003.10.005DOI Listing
February 2004

Analysis of HLA-G expression in malignant hematopoetic cells from leukemia patients.

Leuk Res 2003 Jul;27(7):643-8

Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, 83391, Bratislava, Slovak Republic.

It has been suggested that HLA-G antigens may provide tumor cells with an effective immune escape mechanism. So far mostly solid tumors have been analyzed; HLA-G antigen was only exceptionally detected. To further examine HLA-G expression, patients were chosen with different forms of leukemia: AML (25), CML (4), ALL (9), CLL (8), HCL (2) and NHL (3). Using flow cytometry with three HLA-G specific mAbs (87G, 01G and MEM-G/9), western blotting with two specific mAbs (4H84 and MEM-G/1) and RT-PCR, neither HLA-G antigen nor mRNA for any HLA-G isoform was detected. These results strongly suggest that HLA-G antigen is not expressed in freshly isolated human leukemia cells and therefore is not involved in their escape from immune attack.
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http://dx.doi.org/10.1016/s0145-2126(02)00228-xDOI Listing
July 2003
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