Publications by authors named "Maria Bucova"

20 Publications

  • Page 1 of 1

The Role of CX3CL1 and ADAM17 in Pathogenesis of Diffuse Parenchymal Lung Diseases.

Diagnostics (Basel) 2021 Jun 11;11(6). Epub 2021 Jun 11.

Institute of Immunology, Faculty of Medicine Comenius University, 811 08 Bratislava, Slovakia.

Fractalkine (CX3CL1) is a unique chemokine that functions as a chemoattractant for effector cytotoxic lymphocytes and macrophages expressing fractalkine receptor CX3CR1. CX3CL1 exists in two forms-a soluble and a membrane-bound form. The soluble CX3CL1 is released from cell membranes by proteolysis by the TNF-α-converting enzyme/disintegrin-like metalloproteinase 17 (TACE/ADAM17) and ADAM10. In this study, we evaluated the diagnostic relevance and potential roles of CX3CL1 and ADAM17 in the pathogenesis of diffuse parenchymal lung diseases (DPLDs) in the human population. The concentration of CX3CL1 and ADAM17 was measured by the enzyme-linked immunosorbent assay (ELISA) test in bronchoalveolar lavage fluids of patients suffering from different DPLDs. The concentration of CX3CL1 was significantly higher in patients suffering from idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis patients compared to the control group. A significantly higher concentration of CX3CL1 was measured in fibrotic DPLDs compared to non-fibrotic DLPD patients. We found a positive correlation of CX3CL1 levels with the number of CD8+ T cells, and a negative correlation with CD4+ T cells in BALF and diffusion capacity for carbon monoxide. The concentration of ADAM17 was significantly lower in the IPF group compared to the other DPLD groups. We noticed a significantly higher CX3CL1/ADAM17 ratio in the IPF group compared to the other DPLD groups. We suggest that CX3CL1 has a distinctive role in the pathogenesis of DPLDs. The level of CX3CL1 strongly correlates with the severity of lung parenchyma impairment. The results suggest that high values of CX3CL1/ADAM17 could be diagnostic markers for IPF.
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http://dx.doi.org/10.3390/diagnostics11061074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230701PMC
June 2021

5'URR regulatory polymorphisms are associated with the risk of developing gliomas.

Int J Neurosci 2021 Sep 28:1-10. Epub 2021 Sep 28.

Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

Background: Human leukocyte antigen G (HLA-G) belongs to non-classical MHC class I molecules that is involved in the suppression of immune response. As HLA-G plays important role in the maintenance of fetal tolerance, its overexpression has been associated with tumor progression. For the regulation of HLA-G levels, genetic variants within the 5' upstream regulatory region (5'URR) are of crucial importance. Our study aimed to analyze the association between 16 5'URR variants, sHLA-G level and clinical variables in glioma patients.

Methods: We investigated 59 patients with gliomas (mean age 54.70 ± 15.10 years) and 131 healthy controls (mean age 41.45 ± 9.75 years). Patient's blood was obtained on the day of surgical treatment. The 5'URR polymorphisms were typed by direct sequencing and the plasma level of sHLA-G assessed by ELISA.

Results: Haploblock within 5'URR consisting of -762T, -716G, -689G, -666T, -633A, followed by -486C and -201A alleles were significantly more frequent in patients with gliomas than in the controls ( < 0.05). No correlation of 5'URR variants with sHLA-G plasma level was found. Analysis of 5'URR variants with main clinical variables in patients with grade IV gliomas revealed that haploblock carriers of -762CT, -716TG, -689AG, -666GT, -633GA, -486AC, -477GC, -201GA followed by -369AC carriers tend to have lower age at onset as compared to other genotype carriers ( = 0.04).

Conclusion: Our results suggest genetic association of 5'URR variants with risk of developing gliomas and possible contribution of HLA-G to disease pathology.
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http://dx.doi.org/10.1080/00207454.2021.1922401DOI Listing
September 2021

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

TNFRSF1A polymorphisms and their role in multiple sclerosis susceptibility and severity in the Slovak population.

Int J Immunogenet 2018 Jul 16. Epub 2018 Jul 16.

Institute of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

Tumour necrosis factor (TNF)-mediated signalling plays a key role in inflammatory and neurodegenerative processes leading to the development of multiple sclerosis (MS). Recent studies have highlighted the role of tumour necrosis factor receptor superfamily member 1A (TNFRSF1A) gene encoding the type 1 TNF receptor in the genetic predisposition to MS. This study aimed to validate the association of TNFRSF1A rs1800693 and rs4149584 polymorphisms with susceptibility to MS in the Slovak population and analyse their influence on age at disease onset, severity, and disability progression. Polymerase chain reaction-restriction fragment length polymorphism method was used to genotype both TNFRSF1A polymorphisms in 541 MS patients and 724 healthy controls. Logistic regression analysis revealed a significantly increased risk of developing MS for the carriers of rs1800693 C allele (TC + CC vs. TT: pcorr = 0.005; OR = 1.61; 95% CI = 1.23-2.12), irrespective of sex and carriage of the major MS risk allele HLA-DRB1*15:01. On the other hand, no association could be found between rs4149584 and MS risk (GA + AA vs. GG: pcorr = 1.00; OR = 1.25; 95% CI = 0.71-2.21). Moreover, neither polymorphism was significantly associated with age at disease onset, MS Severity Score (MSSS) or MS Progression Index (PI) in any of the inheritance models. In conclusion, our results provide support for a sex- and HLA-DRB1*15:01-independent association of TNFRSF1A rs1800693 SNP with MS susceptibility, but not with age at disease onset, severity or rate of disability accumulation.
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http://dx.doi.org/10.1111/iji.12388DOI Listing
July 2018

High mobility group box 1 protein in bronchoalveolar lavage fluid and correlation with other inflammatory markers in pulmonary diseases.

Sarcoidosis Vasc Diffuse Lung Dis 2018 28;35(3):268-275. Epub 2018 Apr 28.

Institute of Immunology, Comenius University Faculty of Medicine, Bratislava, Slovakia.

Analysis of new markers in bronchoalveolar lavage fluid (BALF) provides new insights into the immunopathogenesis and may be helpful in differential diagnosis of lung diseases. High mobility group box 1 protein (HMGB1) is a non-histone nuclear protein and its release into the extracellular environment may be associated with the inflammatory response. The aim of the study is the analysis of HMGB1 in BALF, correlations with other markers of inflammation and differences in extracellular HMGB1 levels in various lung diagnoses. The concentration of HMGB1 was tested by an Elisa test. We calculated correlations with other inflammatory markers (leukocytes, total protein, albumin, IgG, IgA, IgM, C3 complement component, alpha-2macroglobuline, CD3, CD4, CD8, TREM-1 and TREM-2) and specified HMGB1 level in various diagnoses. A positive correlation was found between the level of HMGB1 and total protein levels (p=0.0001), albumin (p=0.0058), IgA (p=0.011), IgM (0.0439) and TREM-2 (p=0.0188). Conversely, a negative correlation was revealed between HMGB1 and TREM-1 (p=0.0009). HMGB1 level varied in different diagnoses: the highest level was detected in QuantiFERON TB-positive subjects (median: 30.2) and hypersensitivity pneumonitis (median: 33.2), followed by pulmonary sarcoidosis (median: 16.8) and idiopathic pulmonary fibrosis (median: 8.8). HMGB1 correlates with other inflammatory markers tested in BALF. Its level varies in different lung diagnoses. .
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http://dx.doi.org/10.36141/svdld.v35i3.5726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170153PMC
April 2018

Improvement in asymmetric dimethylarginine and oxidative stress in patients with limb salvage after autologous mononuclear stem cell application for critical limb ischemia.

Stem Cell Res Ther 2017 07 12;8(1):165. Epub 2017 Jul 12.

National Institute of Cardiovascular Diseases, Slovak Medical University, Bratislava, Slovakia.

Background: Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, acts as an inhibitor of angiogenesis and is associated with an increased risk of cardiovascular mortality. Administration of stem cells may affect endogenous mechanisms that regulate ADMA production and metabolism. The aim of the present study was to analyze ADMA concentration and changes in oxidative stress in patients with advanced critical limb ischemia (CLI) after bone marrow-derived mononuclear cell (BM-MNC) therapy.

Methods: Fifty patients (age 64 ± 11 years, 44 males, 6 females) with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were treated by intramuscular (n = 25) or intra-arterial (n = 25) injection of 40 ml BM-MNC concentrate. Patients with limb salvage and improved wound healing after 6 months were considered responders to cell therapy. The concentrations of markers of oxidative stress and angiogenesis were analyzed before, and at 3 and 6 months after BM-MNC delivery.

Results: At 6-month follow-up, four patients died of reasons unrelated to stem cell therapy. Among the survivors, 80% (37/46) showed limb salvage and improved wound healing. At 6 months follow-up, ADMA concentration significantly decreased in patients with limb salvage (1.74 ± 0.66 to 0.90 ± 0.49 μmol/L, p < 0.001), in parallel with decreased tumor necrosis factor (TNF)-α (2.22 ± 0.16 to 1.94 ± 0.38 pg/ml, p < 0.001), and increased reduced glutathione (6.96 ± 3.1 to 8.67 ± 4.2 μmol/L, p = 0.02), superoxide dismutase activity (168 ± 50 to 218 ± 37 U/L, p = 0.002), and coenzyme Q10 concentration (468 ± 182 to 598 ± 283 μg/L, p = 0.02). The number of delivered BM-MNCs significantly correlated with the decrease in ADMA concentration at 3 months (p = 0.004, r = -0.48) and the decrease in TNF-α concentration at 6 months (p = 0.03, r = -0.44) after cell delivery. ADMA or TNF-α improvement did not correlate with the number of applied CD34 cells, C-reactive protein concentration, leukocyte count, or the dose of atorvastatin.

Conclusions: The therapeutic benefit of BM-MNC therapy is associated with reduced ADMA levels and oxidative stress. Regulation of the ADMA-nitric oxide axis and improved antioxidant status may be involved in the beneficial effects of stem cell therapy.

Trial Registration: The study was approved and retrospectively registered by ISRCTN registry, ISRCTN16096154 . Registered on 26 July 2016.
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http://dx.doi.org/10.1186/s13287-017-0622-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506609PMC
July 2017

Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients.

Folia Microbiol (Praha) 2017 Jul 27;62(4):287-293. Epub 2017 Jan 27.

Institute of Immunology, Faculty of Medicine, Comenius University, Odborarske nam. 14, 813 72, Bratislava, Slovakia.

Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2 years) and 208 age-matched controls (mean 35.6 years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P = 0.04), suggesting that GG carriers tend to induce MS at an earlier age.
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http://dx.doi.org/10.1007/s12223-017-0499-6DOI Listing
July 2017

Characteristics of responders to autologous bone marrow cell therapy for no-option critical limb ischemia.

Stem Cell Res Ther 2016 08 17;7(1):116. Epub 2016 Aug 17.

National Institute of Cardiovascular Diseases, Slovak Medical University, Pod Krasnou horkou 1, 833 48, Bratislava, Slovakia.

Background: The present study investigated factors associated with therapeutic benefits after autologous bone marrow cell (BMC) therapy in patients with "no-option" critical limb ischemia (CLI).

Methods And Results: Sixty-two patients with advanced CLI (Rutherford category 5 or 6) not eligible for revascularization were randomized to treatment with 40 ml of autologous BMCs (SmartPreP2) by local intramuscular (n = 32) or intra-arterial (n = 30) application. The primary endpoint was limb salvage and wound healing at 12 months. Seven patients (11 %) died during the follow-up from reasons unrelated to stem cell therapy. The BMC product of patients with limb salvage and wound healing (33/55) was characterized by a higher CD34(+) cell count (p = 0.001), as well as a higher number of total bone marrow mononuclear cells (BM-MNCs) (p = 0.032), than that of nonresponders (22/55). Patients with limb salvage and wound healing were younger (p = 0.028), had lower C-reactive protein levels (p = 0.038), and had higher transcutaneous oxygen pressure (tcpO2) (p = 0.003) before cell application than nonresponders. All patients with major tissue loss at baseline (Rutherford 6 stage of CLI, n = 5) showed progression of limb ischemia and required major limb amputation. In the multiple binary logistic regression model, the number of applied CD34(+) cells (p = 0.046) and baseline tcpO2 (p = 0.031) were independent predictors of limb salvage and wound healing. The number of administrated BM-MNCs strongly correlated with decreased peripheral leukocyte count after 6 months in surviving patients with limb salvage (p = 0.0008).

Conclusion: Patients who benefited from autologous BMC therapy for "no-option" CLI were treated with high doses of CD34(+) cells. The absolute number of applied BM-MNCs correlated with the improvement of inflammation. We hypothesize that the therapeutic benefit of cell therapy for peripheral artery disease is the result of synergistic effects mediated by a mixture of active cells with regenerative potential. Patients at the most advanced stage of CLI do not appear to be suitable candidates for cell therapy.

Trial Registration: The study was approved and registered by the ISRCTN registry.

Trial Registration: ISRCTN16096154 . Registered: 26 July 2016.
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http://dx.doi.org/10.1186/s13287-016-0379-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987968PMC
August 2016

TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

Mediators Inflamm 2015 16;2015:181986. Epub 2015 Jun 16.

1st Department of Otorhinolaryngology, Faculty of Medicine, Comenius University, 85107 Bratislava, Slovakia.

TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels.
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http://dx.doi.org/10.1155/2015/181986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488005PMC
June 2016

The +190 G/A (rs1799864) polymorphism in the C-C chemokine receptor 2 (CCR2) gene is associated with susceptibility to multiple sclerosis in HLA-DRB1*15:01-negative individuals.

J Neurol Sci 2015 Feb 9;349(1-2):138-42. Epub 2015 Jan 9.

Department of Immunology, Faculty of Medicine, Comenius University in Bratislava, Bratislava, Slovakia.

C-C chemokine receptor 2 (CCR2) is one of the key players involved in the transmigration of mononuclear cells into the central nervous system (CNS) and subsequent development of multiple sclerosis (MS). The aim of the current study was to analyse the association of CCR2 +190 G/A (rs1799864) polymorphism with susceptibility to MS and its influence on the age at onset, severity and neurological disability in MS. CCR2 genotyping was carried out by a polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) in 301 MS patients and 342 healthy controls. Logistic regression analysis suggested a marginally significant association between MS and rs1799864 A allele (AA+GA vs. GG, P=0.047, OR=1.50, 95% CI=1.00-2.25), however, after stratification of study groups for the presence of HLA-DRB1*15:01 risk allele, this association could be found in HLA-DRB1*15:01-negative individuals only (AA+GA vs. GG, P=0.014, OR=1.84, 95% CI=1.13-2.98). Furthermore, there was no association between CCR2 polymorphism and clinical features of MS. In conclusion, our results suggest that CCR2 +190 G/A polymorphism may increase the susceptibility to MS, but its action seems to be restricted to individuals who do not possess the major risk allele HLA-DRB1*15:01.
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http://dx.doi.org/10.1016/j.jns.2015.01.002DOI Listing
February 2015

Chemical sympathectomy increases neutrophil-to-lymphocyte ratio in tumor-bearing rats but does not influence cancer progression.

J Neuroimmunol 2015 Jan 20;278:255-61. Epub 2014 Nov 20.

Institute of Immunology, Faculty of Medicine, Comenius University, Odborarske namestie 14, 811 08 Bratislava, Slovakia.

The sympathetic nervous system regulates many immune functions and modulates the anti-tumor immune defense response, too. Therefore, we studied the effect of 6-hydroxydopamine induced sympathectomy on selected hematological parameters and inflammatory markers in rats with Yoshida AH130 ascites hepatoma. We found that chemically sympathectomized tumor-bearing rats had significantly increased neutrophil-to-lymphocyte ratio, leukocyte-to-lymphocyte ratio, and plasma levels of tumor necrosis factor alpha. Although our findings showed that sympathetic denervation in tumor-bearing rats led to increased neutrophil-to-lymphocyte ratio, that is an indicator of the disease progression, we found no significant changes in tumor growth and survival of sympathectomized tumor-bearing rats.
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http://dx.doi.org/10.1016/j.jneuroim.2014.11.014DOI Listing
January 2015

Association of interleukin-10 gene promoter polymorphisms with susceptibility to acute pyelonephritis in children.

Folia Microbiol (Praha) 2014 Jul 22;59(4):307-13. Epub 2014 Jan 22.

Department of Immunology, Faculty of Medicine, Comenius University in Bratislava, Odborárske nám. 14, 81108, Bratislava, Slovakia,

Interleukin-10 (IL-10) is a potent inhibitor of leukocyte chemotaxis, bacterial killing in phagocytes and synthesis of pro-inflammatory cytokines and chemokines, and recent studies have suggested an important role for this immunoregulatory cytokine in the pathogenesis of urinary tract infections (UTIs). Therefore, the gene encoding IL-10 (IL10) is an attractive candidate for association studies attempting to identify susceptibility genes conferring risk of UTIs. In this case-control study, we aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the promoter region of IL10 with acute pyelonephritis in the Slovak population. Polymerase chain reaction with sequence-specific primers was used to analyse IL10 -1082A/G (rs1800896), -819C/T (rs1800871) and -592C/A (rs1800872) SNPs in 147 children with acute pyelonephritis and 215 healthy controls. Comparison of patients with healthy controls using the logistic regression analysis revealed significantly increased risk of developing recurrent attacks of acute pyelonephritis for -1082 G allele in a dominant genetic model GG (GG + AG vs. AA, P = 0.019, odds ratio (OR) = 2.26). A similar tendency was also found when the recurrent acute pyelonephritis subgroup was compared to episodic pyelonephritis cases (GG + AG vs. AA, P = 0.009, OR = 3.38). In conclusion, our results suggest that IL10 -1082 A/G SNP is a susceptibility factor for development of recurrent attacks of acute pyelonephritis.
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http://dx.doi.org/10.1007/s12223-014-0303-9DOI Listing
July 2014

Triggering receptor expressed on myeloid cells-1 and 2 in bronchoalveolar lavage fluid in pulmonary sarcoidosis.

Respirology 2013 Apr;18(3):455-62

Institute of Immunology, Comenius University, Bratislava, Slovakia.

Background And Objective: Pulmonary sarcoidosis (PS) is characterized by the formation of granulomas in the lungs and has been associated with infection by microorganisms. Triggering receptor expressed on the surface of myeloid cells (TREM)-1 is overexpressed in response to infection while TREM-2 is involved in granuloma formation. We hypothesized that these receptors are overexpressed in PS and might be useful for diagnostic testing.

Methods: Cell surface TREM-1 and TREM-2 expression in cells obtained at bronchoalveolar lavage (BAL) was measured in individuals with sarcoidosis (n = 26) and compared with that seen in individuals with other interstitial lung diseases (ILD) (n = 27).

Results: TREM-1 and TREM-2 expression was significantly increased in sarcoidosis compared with other ILD: total number of TREM-1, P = 0.0039 (23.81 vs 13.50 cells/μl), TREM-2, P < 0.0001 (32.81 vs 7.76 cells/μl); percentage of TREM-1: P = 0.0002 (41.30% vs 15.70%), TREM-2: P < 0.0001 (34% vs 9.60%); and mean fluorescence of TREM-1: P = 0.0005 (5.43 vs 1.96), TREM-2: P = 0.0011 (6.85 vs 2.77). Increase in both of these receptors seems to be typical for PS. In discriminating sarcoidosis from other ILD, the specificity (96%) and sensitivity (72%) of the combination of TREM-1 and TREM-2 was high.

Conclusions: Increased TREM-1 and TREM-2 cell surface expression is observed in sarcoidosis. Evaluation of BAL cell expression of both of these receptors may serve as a diagnostic marker for sarcoidosis.
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http://dx.doi.org/10.1111/resp.12028DOI Listing
April 2013

Relationship of self-reported exercise tolerance with inflammatory markers in women with stable ischemic heart disease.

Neuro Endocrinol Lett 2012 ;33 Suppl 2:50-4

2nd Department of Internal Medicine, Comenius University, Bratislava, Slovakia.

Objective: Ischemic heart disease (IHD) is associated with decreased exercise tolerance and it is subjectively reported as angina pectoris or dyspnea. Inflammation and pro- inflammatory cytokines are related to progression of IHD, but their level is seldom analyzed in association with self reported exercise tolerance.

Methods: Women aged 35-75 years with stable IHD from Homocysteine Slovakia study (N=175) were analyzed for monocyte chemoatractant protein-1 (MCP-1), interleukin 6 (IL-6), transforming growth factor β1 (TGF β1), Mannan binding lectin (MBL), heat shock proteins 60 (HSP60), carbonyl protein (CP), high sensitivity C-reactive protein (hsCRP) and oxidized glutathione (GSSG) in relation to exercise induced dyspnea or angina pectoris (AP) (≤200 m).

Results: Patients with dyspnea had higher HSP60 (77.3±107.2 vs 43.7±48.9 ng/ml; p=0.014) and IL-6 (2.9±1.3 vs 1.9±0.6 pg/ml; p=0.04) levels. IL-6 and HSP60 demonstrated direct correlation with dyspnea (rho=0.39; p=0.02 resp. rho=0.22; p=0.01). AP≤200 m patients showed only decreased protein carbonyl a marker of protein oxidation and increased oxidative stress (CP 61.7±27.3 vs. 72.1±23.1 pg/ml; p=0.001). CP indirectly correlates with AP≤200 m (rho=-0.25; p=0.001).

Conclusions: We have found associations of pro-inflammatory cytokines and inflammation markers with dyspnea or angina pectoris, but the relationship was not consistent in our patients with stable ischemic heart disease.
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April 2013

Inflammatory marker sTREM-1 reflects the clinical stage and respiratory tract obstruction in allergic asthma bronchiale patients and correlates with number of neutrophils.

Mediators Inflamm 2012 5;2012:628754. Epub 2012 Jul 5.

Institute of Immunology, Comenius University, Bratislava, Slovakia.

The knowledge that asthma is an inflammatory disorder has prompted us to investigate the plasma levels of a new inflammatory marker sTREM-1 that is released from the surfaces of activated neutrophils and monocytes. The plasma levels of sTREM-1 were analysed by a sandwich ELISA test in the cohort of 76 patients with allergic asthma bronchiale and 39 healthy controls. Our results revealed more than 3.5 times higher levels of sTREM-1 in AB patients (92.3 pg/mL ± 125.6) compared with healthy subjects (25.7 pg/mL ± 9.2; P = 0.0001). Higher levels of sTREM-1 were found also in patients with exacerbated AB (170.5 pg/mL ± 78.2) compared with nonexacerbated AB patients (59.1 ± 78.2; P < 0.0001), patients with respiratory tract obstruction (176.4 pg/mL ± 177.8), than those without obstruction (51.99 pg/mL ± 64.0; P < 0.0001) and patients with anti-IgE therapy (P < 0.0001). Levels of sTREM-1 correlated with number of leucocytes (P = 0.002), and absolute number of neutrophils (P = 0.001). Elevated plasma levels of sTREM-1 reflect the severity, state of exacerbation, presence of respiratory tract obstruction in AB patients and together with increased number of neutrophils point to the role of neutrophils in inflammation accompanying AB.
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http://dx.doi.org/10.1155/2012/628754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3399449PMC
November 2012

Polymorphisms in the genes encoding TGF-beta1, TNF-alpha, and IL-6 show association with type 1 diabetes mellitus in the Slovak population.

Arch Immunol Ther Exp (Warsz) 2010 Oct 5;58(5):385-93. Epub 2010 Aug 5.

Department of Immunology, Faculty of Medicine, Comenius University, Odborarske nam. 14, 813 72 Bratislava 1, Slovakia.

Numerous cytokines have been shown to participate in the pathogenesis of type 1 diabetes (T1D). As gene polymorphisms can influence cytokine production or function, they may potentially contribute to genetic predisposition to the disease. The aim of this study was therefore to investigate the role of 22 single nucleotide polymorphisms (SNPs) in 13 cytokine and cytokine receptor genes in genetic susceptibility to T1D. Polymerase chain reaction with sequence-specific primers was used to genotype cytokine SNPs and HLA-DRB1 alleles in 151 diabetics and 140 healthy individuals of Slovak origin. Univariate analysis showed that transforming growth factor (TGF)-beta1 codon 10 TT homozygotes were significantly more susceptible to developing T1D than C allele carriers (P (c) = 0.0066, OR = 2.46). Furthermore, tumor necrosis factor (TNF)-alpha -308 A allele carriers were also significantly overrepresented among the diabetics (P (c) = 0.0031, OR = 2.62); however, the association of the -308 A allele with T1D might be due to its strong linkage disequilibrium with the susceptibility allele HLA-DRB1*0301. An association was also found with interleukin (IL)-6 -174 G/C and nt565 G/A SNPs; however, its significance was lost when statistical correction was applied. These data suggest that the TGF-beta1 codon 10 SNP is among numerous genetic variations with small individual effects on T1D development. Moreover, a possible role of TNF-alpha and IL-6 SNPs cannot be ruled out, although their association with T1D was due to strong LD with the HLA class II susceptibility allele or did not withstand statistical correction, respectively.
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http://dx.doi.org/10.1007/s00005-010-0092-zDOI Listing
October 2010

Immunopathogenesis of bronchial asthma.

Arch Immunol Ther Exp (Warsz) 2009 Sep-Oct;57(5):331-44. Epub 2009 Aug 18.

Department of Immunology, Comenius University School of Medicine, Bratislava, Slovakia.

Bronchial asthma is a common immune-mediated disorder characterized by reversible airway inflammation, mucus production, and variable airflow obstruction with airway hyperresponsiveness. Allergen exposure results in the activation of numerous cells of the immune system, of which dendritic cells (DCs) and Th2 lymphocytes are of paramount importance. Although the epithelium was initially considered to function solely as a physical barrier, it is now evident that it plays a central role in the Th2-cell sensitization process due to its ability to activate DCs. Cytokines are inevitable factors in driving immune responses. To the list of numerous cytokines already known to be involved in the regulation of allergic reactions, new cytokines were added, such as TSLP, IL-25, and IL-33. IgE is also a central player in the allergic response. The activity of IgE is associated with a network of proteins, especially with its high- and low-affinity Fc receptors. Understanding the cellular and molecular mechanisms of allergic reactions helps us not only to understand the mechanisms of current treatments, but is also important for the identification of new targets for biological intervention. An IgE-specific monoclonal antibody, omalizumab, has already reached the clinic and similar biological agents will surely follow.
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http://dx.doi.org/10.1007/s00005-009-0039-4DOI Listing
October 2009

Association of MCP-1 -2518 A/G single nucleotide polymorphism with the serum level of CRP in Slovak patients with ischemic heart disease, angina pectoris, and hypertension.

Mediators Inflamm 2009 22;2009:390951. Epub 2009 Jul 22.

Institute of Immunology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.

The aim of our work was to find if MCP-1 -2518 (A/G) single nucleotide polymorphism (SNP) influences somehow the serum concentrations of high-sensitive CRP (hsCRP) both in patients suffering from ischemic heart disease (IHD), myocardial infarction (MI), angina pectoris (AP), and hypertension (HT) and in control group of healthy subjects. Totally, 263 patients with the diagnosis of IHD, out of them 89 with MI, 145 with AP, 205 with HT, and also 67 healthy subjects were included in the study. First, we estimated the serum levels of hsCRP. We found that patients with AP had significantly higher serum level of hsCRP than both control group of healthy subjects (P = .043) and IHD patients without AP (P = .026). The presence of the mutant G allele statistically significantly correlated with the higher serum levels of hsCRP in patients with IHD (P = .016), AP (P = .004), and HT (P = .013). Higher correlations were found in men (AP: P = .019; HT: P = .047). In all cases the highest levels of hsCRP were found both in patients and healthy controls with homozygous GG genotype.
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http://dx.doi.org/10.1155/2009/390951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715824PMC
October 2009

MCP-1 -2518 A/G single nucleotide polymorphism in Slovak patients with systemic sclerosis.

Mediators Inflamm 2008 ;2008:204063

Laboratory of Immunogenomics, Department of Immunology, Faculty of Medicine, Palacky University, I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.

Recent study in a group of German patients with SSc has implicated the SNP in the MCP-1 gene (-2518 A to G) as a factor of susceptibility to SSc. Reflecting the need for replication of genetic association studies, we investigated if this SNP is associated with SSc in another Caucasian population. MCP-1 -2518 A/G genotypes were determined using PCR-SSP in 46 SSc patients and in 449 healthy subjects, all unrelated and of Slovak (Slavonic) origin. The distribution of MCP-1 -2518 A/G genotypes complied with the Hardy-Weinberg equilibrium both in patient and healthy control groups. There was no difference in MCP-1 -2518*G allele frequency between SSc patients and healthy subjects (patients: 0.23; controls: 0.24; P > .05). Furthermore, MCP-1 -2518 GG homozygotes were similarly represented among SSc patients and healthy subjects (P > .05). The association of MCP-1 -2518 A/G SNP with SSc observed originally in German population was not replicated in the Slovak population.
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http://dx.doi.org/10.1155/2008/204063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408933PMC
June 2008
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