Publications by authors named "Buc M"

135 Publications

Associations between HLA class II alleles and type 1 diabetes mellitus in the Slovak population.

Endocr Regul 2006 Mar;40(1):1-6

Department of Immunology, Comenius University School of Medicine, Czech Republic.

Objectives: Several associations between HLA complex and diabetes mellitus type IA were found in various groups of patients of Caucasoid population. This study was therefore prompted to be conducted in Slovak population, since any such has not yet been performed in Slovak population.

Methods: Patients suffering from DM-1A originated from all regions of Slovakia. Their age ranged from 1 to 42 years; but the criterion for including the subject to the study was the definition of diagnosis in older patients before their age of 15 (Table 1). The diagnosis was set up according to internationally accepted criteria. A total of 460 patients was typed for HLA-DQB1 alleles, among them 97 also for HLA-DQA1 and 146 for HLA-DRB1 alleles. HLA-typing was performed by a PCR-SSP method. Control group consisted of 196 (DQA), 143 (DQB1) and 130 (DRB1) unrelated blood donors aged 19-55 years old irrespective of their age or sex. The data obtained were expressed in a 2 x 2 contingency table and statistical significance was calculated by the Fisher exact test.

Results: Among 11 HLA-DQB1 alleles tested DOB1*0302 was the most frequent in DM-1A patients (30.33% vs. 5.59% in healthy subjects (HS), followed by DQB1*0201 (22.93% vs. 12.94%, respectively). In contrast, the frequency rate of DQB1*0301 (10.66% vs. 24.48%), DOB1*0602 (2.17% vs. 10.14%) and DQB1*0603 (2.5% vs. 8.39 %) were decreased in DM-1A patients. Out of 14 DQA1 alleles the highest occurrence rate showed DQA1*0301 (30.93% vs. 17.09) and DQA1*0501 (34.02% vs. 25.76%), while DQA1*0102 (8.76% vs. 16.58%) and DQA1*0201 (6.18 % vs. 13.51%7), respectively, were found to be the least frequent. Among 13 HLA-DRB1 alleles tested, the most common occurrence rates showed DRB1*03 (26.37% vs. 9.62%) and DRB1*04 (7.19% vs. 14.23%), while the least frequent alleles were DRB 1*15 (2.74% vs. 12.31%), DRB1*07 (7.19% vs. 14.23%), and DRB1*11 (2.74% vs. 20.38%). The alleles DQB1*0302 and DQA1*0301, respectively, were present in the same individual in all DRB1*04 positive patients, suggesting that they belong to the haplotype. Similar situation was observed with the alleles DQB1*0201, DQA1*0501, and DRB*0301, respectively, forming the second HLA haplotype so characteristic for DM1A.
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March 2006

HLA class II allele frequencies in type 1A diabetes mellitus Slovak patients.

Bratisl Lek Listy 2006 ;107(3):76-9

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

Background: Diabetes mellitus type 1A (DM-1A) is an autoimmune disease in which the immune response is directed to pancreatic islet cells. DM-1A occurs in genetically predisposed individuals. Among type 1A diabetes associated genes, those of the HLA region have the greatest effect.

Objectives: The aim of our study was to obtain a comprehensive survey of the HLA-DRB1 and HLA-DQB1 allele frequencies in Slovak patients suffering from DM-1A.

Methods: HLA class II genotyping was performed on genomic DNA by the PCR-SSP method according to the 12th Workshop protocol.

Results: Our report gives the first presentation of the distribution of HLA-DRB1 alleles (including complete DRB1*04 subtypes) and that of HLA-DQB1 alleles in the Slovak diabetic patients diagnosed at 0-18 years of age. Susceptibility is significantly associated with the alleles DQB1*0302 (OR = 7.8), DRB1*04 (OR = 4.9), DRB1*0301 (OR = 4.2) and DQB1*02 (OR = 2.2), whereas the alleles DQB*0602 (OR = 0.05), DRB1*11 (OR = 0.2), DRB1*15 (OR = 0.2) and DQB1*0301 (OR = 0.3) were found to be protective.

Conclusions: Our results, consistent with other studies, show increased frequencies of known positively associated HLA class II alleles in our type 1A diabetes mellitus patients compared to the general (nondiabetic) population. The protective effect of previously reported alleles was confirmed as well. Results of our population-based study serve in clinical practice for the identification of subjects at risk of developing DM-1A among the first-degree relatives (Tab. 2, Ref. 12).
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August 2006

Association of HLA-DPB1 alleles with type I diabetes mellitus in Slovak population.

Bratisl Lek Listy 2006 ;107(3):73-5

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

Background: Genes of HLA complex on chromosome 6p21 principally contribute to the genetic risk of insulin-dependent diabetes mellitus type I (T1 DM). Associations of HLA class II loci allelic variants with T1 DM are well established. Another prime candidate, particularly the polymorphic DPB1 gene, has been reported as probably contributing to the disorder, but its relative contribution to the predisposition to the disease is difficult to assess due to strong linkage disequilibrium of HLA alleles. DPB1*0301 and DPB1*0202 have been reported as positively and DPB1*0402 as negatively associated alleles in different Caucasoid populations (predisposing versus protective alleles, respectively).

Objectives: The aim of this study was to establish the occurrence rates of HLA-DPB1 alleles in patients suffering from T1 DM and to compare them with those in healthy subjects.

Methods: A PCR-SSP method was performed to identify HLA-DPB1 alleles in 61 patients and 160 healthy controls. The exact Fisher's test was used to determine the statistical significance of allele frequency differences between patients and control subjects.

Results: The analysis of obtained results has shown a significantly decreased frequency of DPB1*0402 and slightly increased occurrence rates of DPB1*0101 and DPB1*1301, respectively in the investigated group of patients. Neither DPB1*0301 nor DPB1*0202 were observed to be over-represented.

Conclusions: The expected significant decrease in the frequency of DPB1*0402 was confirmed, whereas positive associations with DPB1*0301 and DPB1*0202, did not prove to be true, respectively (Tab. 1, Ref: 19).
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August 2006

Genetic susceptibility to type 1 diabetes mellitus in humans.

Authors:
D Kantárová M Buc

Physiol Res 2007 22;56(3):255-266. Epub 2006 Jun 22.

Internal Clinic, Comenius University, Jesenius School of Medicine, Martin, Slovakia.

Type 1 diabetes mellitus (DM 1A) is an autoimmune disease belonging to the most frequent chronic diseases of the childhood and young adults. DM 1A results from immune-mediated destruction of the insulin-producing beta cells of the pancreas. It is a genetically determined disease and many genes or genetic regions were found to be associated with its induction. In addition to the insulin-dependent diabetes mellitus 1 (IDDM1) gene, which marks the HLA region, and IDDM2 which marks the insulin gene, significant associations of DM 1A to other IDMM genes or genetic regions we reported. We shortly review recent achievements in the field, and the state of current knowledge.
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http://dx.doi.org/10.33549/physiolres.930956DOI Listing
November 2007

Toll-like receptors. III. Biological significance and impact for human medicine.

Authors:
F Sandor M Buc

Folia Biol (Praha) 2005 ;51(6):198-203

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

The ability of the innate immune system to recognize and respond to microbial components has been largely attributed to the family of TLRs. They are able to discriminate among distinct molecular patterns associated with microbial components. Recognition of microbial products by TLRs results in induction of innate immunity mechanisms as well in development of antigen-specific adaptive immune responses. Some of TLR ligands start to be used to enhance immune defence mechanisms in fighting infections or malignancies. On the contrary, others were shown to be involved in immunopathogenesis of autoimmune disorders such as SLE.
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May 2006

Toll-like receptors. II. Distribution and pathways involved in TLR signalling.

Authors:
F Sandor M Buc

Folia Biol (Praha) 2005 ;51(6):188-97

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

The innate immune system senses invading microorganisms by a phylogenetically conserved family of proteins--TLRs. They are expressed in several types of cells that represent a route of entry of pathogens into the host organism and that can contribute to protection against infection. Except for cells of the immune system, TLRs are present in epithelial cells of the skin, respiratory, intestinal, and genitourinary tracts that form the first protective barrier to invading pathogens. Polarized regulation of TLR expression in epithelial cells explains why pathogenic but not commensal bacteria elicit inflammatory responses. TLR-induced intracellular signalling pathways show remarkable complexity: apart from a common signalling pathway, additional signalling pathways specific for each of the TLRs are responsible for a fine tuning of the immune response, thus securing effective pathogen-directed biological responses.
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May 2006

Toll-like receptors. I. Structure, function and their ligands.

Authors:
F Sandor M Buc

Folia Biol (Praha) 2005 ;51(5):148-57

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

The innate immune system senses invading microorganisms by a phylogenetically conserved family of proteins PRRs of which TLRs are ones of the most important. There are at least 10 different TLRs in humans and 11 in mice. They have in the course of evolution specialized for the recognition of conserved structures among microorganisms called PAMPs. Activation of TLRs results in induction of innate immunity mechanisms as well in development of antigen-specific adaptive immune responses, thus bridging innate and adaptive immunity.
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January 2006

[Latent autoimmune (type I) diabetes mellitus in adults. Part. II. Association of HLA antigens, status of cellular immunity and occurrence of other autoimmune diseases].

Vnitr Lek 1999 Feb;45(2):103-9

I. interná klinika, JLF UK a MFN, Martin.

Aim Of Study: To assess some immunological and immunogenetic aspects in patients with latent autoimmune (Type-1) diabetes mellitus (DM) of adults (LADA).

Subjects: 24 patients with LADA, 11 patients with Type-2 DM and 20 healthy volunteers (Pilot study). PARAMETERS TESTED: HLA-DRB1* and HLA-DQB1* alleles, parameters of cellular immunity (CD4+, CD8+, CD3/HLA-DR+, CD8/HLA-DR+, CD45RA+[CD4], CD16+CD56), CD19+, IL-4, INF-gamma and organ specific (OSA) autoantibodies (against thyroid gland, gastric parietal cells, tubuli, basal membranes of glomerulus, AMA and ABBA).

Results And Discussion: Type-1 DM HLA-DRB1* and HLA-DQB1* risk alleles have been found in a majority of patients with LADA. The most frequent were HLA-DRB1*0301 and DQB1*0201. Assessement of parameters of cellular immunity and cytokine profiles (IL-4 a INF-gamma) in peripheral blood did not reveal any contribution to a differentiation between Type-1 and Type-2 DM). We confirmed increased occurence of OSA in patients with LADA, what stress importance of routine screening for OSA in patients with LADA.
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February 1999

HLA-G1-transfected K562 cells do not inhibit NK-cell-mediated lysis in europium release cytotoxicity assay.

Authors:
M Sapak M Buc

Bratisl Lek Listy 2003 ;104(10):300-4

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

The class Ia of HLA molecules are recognised by NK-cells either by inhibitory or stimulatory NK-receptors. When inhibitory signals prevail over stimulatoryones, the target cells expressing the class Ia of HLA molecules are not lysed by NK-cells. Similarly, class Ib of HLA molecules have been reported to induce the inhibitory signal in NK-cells. The cell line K562 is deprived of both class Ia and class Ib of HLA molecules, respectively, the fact of which enhances the lysis of K562 cells when they are co-cultivated with NK-cells. To study the role of HLA-G molecules in NK-cell cytotoxic activity, HLA-G tranfected K562 cells were used as target cells. NK-cells were isolated from the peripheral blood of 4 unrelated persons using Miltenyi's Biotec isolation system. The purity of directly isolated NK cells (CD56 Multisort kit) was 74.1%, and that of indirectly isolated NK-cells (NK-cell isolation kit) 69.4%. The europium release cytotoxicity assay was used in all experiments. The percentage of cytotoxicity ranged from 19% to 24% when K562 target cells were used. Similar results were obtained with the HLA-G1-transfected target cells: the percentage of cytotoxicity ranged from 17% to 29%. Our preliminary results indicate that NK-cells are able to lyse both, K562 cells and the HLA-G1-transfected K562 cells. (Tab. 1, Fig. 8, Ref. 21.).
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April 2004

Modulation of human lymphocyte proliferation by salivary gland extracts of ixodid ticks (Acari: Ixodidae): effect of feeding stage and sex.

Folia Parasitol (Praha) 2003 Dec;50(4):305-12

Institute of Zoology, Slovak Academy of Sciences, Dúbravská cesta 9, SK-84506 Bratislava, Slovakia.

Ixodid ticks remain attached to their hosts for several days to weeks. During this extended feeding process new proteins involved in the modulation of host immune responses are expressed in tick salivary glands. In our study a stimulatory or inhibitory effect of salivary gland extracts (SGE) of unfed and partially fed female Ixodes ricinus (Linnaeus, 1758), female and male Amblyomma variegatum (Fabricius, 1794) and Rhipicephalus appendiculatus Neumann, 1901 ticks on human lymphocyte proliferation induced by Concanavalin A (ConA) and phytohaemagglutinin (PHA), respectively, was investigated. SGE of all female ticks examined suppressed proliferation of ConA-induced lymphocytes; highly significant suppression was observed in the presence of unfed I. ricinus and 9-day fed A. variegatum SGE. SGE of partially fed A. variegatum and I. ricinus females suppressed PHA responses of lymphocytes. Lymphocytes showed reduced PHA and ConA responses in the presence of SGE of unfed and 2-day fed R. appendiculatus females, while SGE of 6-day fed females enhanced PHA responses, but reduced their ConA responses; generally SGE of 2-day fed females displayed the strongest inhibition. Amblyomma variegatum male SGE slightly enhanced PHA, but significantly reduced ConA responses of lymphocytes and their inhibitory effect increased during feeding. SGE of unfed and 2-day fed R. appendiculatus males enhanced PHA and ConA responses and those of 6-day fed males suppressed lymphocyte proliferation. The results suggest that (i) species- and sex-specific differences exist in the effects of tick salivary gland antigens on human lymphocyte proliferation and (ii) effect of SGE on human lymphocyte responses to mitogens varies depending on the tick feeding status.
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December 2003

Interleukin 1alpha single-nucleotide polymorphism associated with systemic sclerosis.

J Rheumatol 2004 Jan;31(1):81-4

Department of Immunology, Palacky University, Olomouc, Czech Republic.

Objective: In systemic sclerosis (SSc), constitutive expression of the proinflammatory and fibrogenic cytokine interleukin 1alpha (IL-1alpha) by dermal fibroblasts from the affected skin has been observed. We investigated the association of a single-nucleotide polymorphism at position -889 in the IL-1alpha gene in patients with SSc.

Methods: Genotyping of IL-1alpha-889 polymorphism was performed in 46 patients with SSc and in 150 healthy controls by polymerase chain reaction with sequence-specific primers. All subjects were unrelated Slovak Caucasians.

Results: In SSc patients, carriers of the IL-1alpha-889 T allele were significantly overrepresented in comparison with controls (63.0% vs 42.0%; p = 0.01, OR 2.3, 95% CI 1.2-4.6). The frequency of the IL-1alpha-889 T allele was increased in SSc patients (38.0%) in comparison with controls (25.7%; p = 0.02).

Conclusion: The IL-1alpha-889 polymorphism, previously shown to predispose to increased IL-1 protein expression, may be involved in susceptibility to SSc.
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January 2004

HLA alleles and susceptibility to dermatological disorders associated with Helicobacter pylori infection: a significant association to HLA-Cw*06.

Folia Biol (Praha) 2001 ;47(2):62-5

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

The occurrence rate of HLA class I and class II alleles was established in 24 patients suffering from dermatological disorders associated with the Helicobacter pylori infection. The increased frequency of HLA-C*0602, 4 was found to be 0.1875 compared to 0.0733 in the control group (odds ratio: 2.913; two-sided P value: P = 0.0251). Our data suggest that the HLA-Cw6 molecule play a role in the susceptibility to the Helicobacter pylori infection.
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August 2001

[Immunologic and immunogenetic aspects of autoimmune diseases].

Authors:
M Buc

Bratisl Lek Listy 2000 ;101(9):526-7

Imunologický ústav LFUK v Bratislave.

The primary property of the immune system is its ability to distinguish the organism's own substances from foreign bodies, to tolerate the former and to eliminate the latter. However, the immune reactions, in some cases, turn against own structures and when exceeding a particular threshold and duration, they begin to damage the tissues and organs causing autoimmune diseases.
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February 2001

[Chemokines].

Authors:
M Buc M Bucova

Bratisl Lek Listy 2000 ;101(9):507-11

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

Chemokines are a group of approximately 50 small peptides that are potent activators and chemoattractants of leucocytes. Except of their role in inflammation they are involved also in other biological activities as angiogenesis, hematopoesis, and enhancing the host response to tumors. The chemokine family is divided according to their different biochemical structure and biological activities into 4 subfamilies--C, CC, CXC, and CX3C. Activities of chemokines are mediated by a family of 7-transmembrane G-protein-coupled receptors. Chemokine receptors have been implicated in several disease states, esp. in allergy and malaria. However, the most fascinating was discovery that some of them serve as coreceptors for human immunodeficiency virus type 1. (Tab. 2, Fig. 1, Ref. 38.)
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February 2001

HLA-A, HLA-B and HLA-C polymorphism in the Slovak population.

Folia Biol (Praha) 2000 ;46(4):153-6

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

The occurrence rates of class I HLA alleles were investigated in a sample of the Slovak population by a PCR-SSP method. The frequencies of HLA-A alleles ranged from 0.00 for A*4301 to 0.2798 for A*0201-22; the frequencies of HLA-B alleles ranged from 0.00 for B 4601,B* 4801-3, B*5901,B* 7301, and B* 8101 to 0.1101 for B* 4402-10, and those of HLA-C alleles from 0.00 for Cw*1301 and Cw* 1402-3 to 0.2661 for Cw 0701-10. The occurrence rates of class I HLA alleles established in our study were compared with those in the Czech population. No significant differences were found.
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November 2000

[Effect of trypsinization on functional recovery of blast transformation of lymphocytes in adults and the aged].

Cas Lek Cesk 2000 Apr;139(7):213-5

Výskumný ústav reumatických chorôb, Piest'any Imunologický ústav LF UK, Bratislava.

Background: During the physiological ageing, function of individual factors of the immune system tend to decline. The aim of our study was to compare the ability of lymphocytes to respond to polyclonal mitogens and to the stimulation by antibodies anti-CD2/CD2R after an previous trypsinization.

Methods: 17 adult (28 to 54-year-old) and 32 aged persons (63 to 90-year-old) were investigated. Lymphocytes were isolated from the peripheral blood, trypsinizated and subsequently incubated with polyklonic mitogens--phytohemaglutinin (PHA), concavalin (Con A), and a monoklonic antibody MoPr) anti-CD2/CD2R. The speed of recovery of the blastic transformation of trypsinizated lymphocytes was compared among the adult and aged persons.

Results: The stimulation values were in all studied time intervals significantly lower in aged persons then in adult ones (p < 0.001). In the group of aged persons, when the trypsinizated lymphocytes were stimulated by MoPr anti-CD2/CD2R, their ability of blastic transformation has not recovered to previous values.

Conclusions: Our results indicate that function of T-lymphocytes diminishes in advanced age, however, lymphocytes still keep the ability to respond to specific stimulus. We found that the recovery of the blastic transformation of lymphocytes after a trypsinization requires in aged persons more than 20 hours. It probably corresponds with widespread decline of biological activities during ageing.
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April 2000

[Selection of donor-recipient pairs in families for allogenic bone marrow transplantation].

Bratisl Lek Listy 2000 ;101(3):173-5

Imunologický ústav Lekárskej fakulty Univerzity Komenského v Bratislave a Klinika hematológie a transfúziológie Fakultnej nemocnice v Bratislave.

In the years 1985-1999 452 were families investigated with the aim to find up an HLA-identical sibling for a patient suffering from a disease, the treatment of which requires bone marrow transplantation. Total number of investigated siblings (including patients) was 1334. HLA typing was done by serological methods, mixed lymphocyte culture test (MLC), and in the last three years also by DNA-typing (PCR-SSP). 188 HLA identical donor-recipient sib-pairs were found. At the same time the number shows that a potential donor could be found in 41.5% of investigated families.
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July 2000

[Comparison of the results of HLA typing using serologic and molecular genetics methods].

Bratisl Lek Listy 2000 ;101(3):134-7

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

A comparison of the HLA class I typing in 50 unrelated individuals by means of serological and molecular genetic (PCR-SSP) methods was carried out. DNA-typing is more fast and reliable method in comparison with serology. It is necessary to introduce molecular genetic methods for the detection of HLA class I alleles. On the other hand there are alleles, which are not expressed on cell surface. In our laboratory both methods are established and the results of both were compared. It may be useful for determining the selection strategy of HLA-identical donor-recipient pair suitable for bone marrow transplantation. The results demonstrated 9% misassignments of HLA-A antigens by serology, 11% of HLA-B and 39% of HLA-C. The serological discrepancies found were of three categories: false negatives, false positives, and an incomplete typing. The vast majority of the discrepancies were due to a combination of relatively low expression of HLA antigens, lack of serological reagents and misclassification of antigens within cross-reactive groups. These results indicate that nowadays the serological typing is insufficient for clinical histocompatibility testing. (Tab. 3, Ref. 16.)
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July 2000

[Latent autoimmune (type 1) diabetes mellitus in patients originally classified as type 2. Divergence of etiologic markers].

Cas Lek Cesk 2000 Mar;139(4):120-3

I. interná klinika Jesseniovej lekárskej fakulty Univerzity Komenského, Martinská Fakultná nemocnica, Martin.

Background: To assess the prevalence of markers of autoimmune insulitis (AII) in patients classified originally as having Type-2 diabetes mellitus (Type-2 DM). 386 patients subdivided according to the BMI, C-peptide and type of treatment.

Methods And Results: Age, BMI, C-peptide, Glutamic acid decarboxylase autoantibodies (GADA), HLA-DR/,-DQ alleles. Prevalence of GADA varied from < 5% in obese patients with normal/increased C-peptide to > 30% in non-obese patients with low C-peptide. In majority of GADA positive patients, the Type-1 DM high-risk HLA-DRB1*, HLA-DQB1* alleles have been found. Among them HLA-DRB1*0302 and HLA-DRB1*0201 were more frequent than HLA-DRB1*040x and HL:A-DQB1*0302.

Conclusions: Significant fraction of patients classified initially as Type-2 DM may have in fact Type-1 DM. Such patients can be recognized on the basis of assessment of serological (GADA) and immuno-genetical (HLA-DR/,-DQ alleles) markers. In some patients clinical, metabolic, immune, and immunogenetic markers may disagree. This divergence stresses multifactorial genesis of diabetes. Moreover, it can also suggest that both autoimmune insulitis and insulin resistance may coexist in parallel.
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March 2000

[Frequency of HLA-A, HLA-B and HLA-Cw antigens in the Slovak population].

Bratisl Lek Listy 2000 ;101(1):24-7

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

Results on HLA-A, -B and -Cw antigen frequencies in the Slovak population are presented. HLA-A, -B, -Cw antigens were determined in 654 healthy unrelated individuals. The highest frequency was observed for the antigens HLA-A2, -A1; HLA-B12, -B35, and HLA-Cw8. The least frequent antigens were HLA-A34, -A36, HLA-B58, -B67, -B70, -B77, and HLA-Cw8. The results were compared with those of the previous study and with those of Czech, Austrian and Hungarian populations. No statistically significant differences were observed. (Tab. 5, Fig. 2, Ref. 9.)
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June 2000

[Changes in the capacity of T-lymphocytes for spontaneous recovery of selected differentiation antigens in relation to age].

Cas Lek Cesk 1999 Nov;138(22):696-8

Výskumný ústav reumatických chorôb, Piest'any.

Background: During physiological ageing changes of the immune system take place at several levels. The objective of the submitted work was to compare the ability of spontaneous restoration of selected differentiation antigens on lymphocytes in the peripheral blood stream after previous trypsin treatment in a group of healthy elderly and adult subjects.

Methods And Results: Twenty-four adults were examined (19-59 years) and 36 elderly subjects (60-90 years). Isolated lymphocytes from the peripheral blood stream were treated with trypsin and then incubated in a cultivation medium. The authors investigated the capacity of restoration of differentiation antigens CD2, CD4, CD8 and CD45RA. Antigen CD2 was not restored in any of the investigated groups to original levels. However the difference between its expression on lymphocytes before trypsin treatment and on lymphocytes after 16-hour incubation was higher in the elderly subjects 16% (p < 0.001) than in the group of adults 7% (p < 0.01). Restoration of antigen CD4 was in both investigated groups almost equal. The number of CD8+ T-lymphocytes was in elderly people lower (p < 0.05), spontaneous restoration of antigen CD8 did not differ among the investigated groups and reached in both instances the baseline value. Antigen CD45RA was restored more slowly in elderly subjects, the difference between groups was at borderline of statistical significance (p < 0.0595).

Conclusion: From the results ensues that during physiological ageing the ability of spontaneous restoration of antigens CD2 and CD45RA declines but not of antigens CD4 and CD8. So far there is no unequivocal explanation why this change occurs, it is probably conditioned by several factors. Investigation of these changes and an attempt to influence them can help to understand age-conditioned immunological dysregulation, its consequences and the possibility to influence them by treatment.
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November 1999

[Frequency of loci of HLA-DRB1* and -DQB1* alleles in the Slovak population].

Bratisl Lek Listy 1998 Nov;99(11):601-4

Imunologický ústav LFUK, Bratislava, Slovakia.

Results on HLA-DRB1* and HLA-DQB1* allele frequencies in the Slovak population by PCR-SSP method are presented. HLA-DRB1* alleles were determined in 130 and HLA-DQB1* alleles in 143 healthy unrelated individuals. The highest frequency was observed for the alleles HLA-DRB1*1101-13 (0.203), HLA-DRB1*0701 (0.142), HLA-DQB1*0301 (0.244), and HLA-DQB1*0201 (0.209). The least frequent alleles were HLA-DRB1*1402-6-9, HLA-DRB1*0901 (both 0.0038), HLA-DQB1*0401 (0.007), and HLA-DQB1*0601 (0.0035). The results obtained by DNA-typing were compared with those calculated from the serological study. No statistically significant differencies were found. The allele frequencies obtained in our study were also compared with those of the Czech and Austrian populations. No statistically significant differencies were observed. (Fig. 2, Tab. 3, Ref. 13.)
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November 1998

Allogeneic BMT for haematological disorders: single centre experience of University Hospital Bratislava.

Bone Marrow Transplant 1998 Dec;22 Suppl 4:S67-70

Clinic of Haematology, University Hospital, Bratislava, Slovak Republic.

Data on 65 sibling bone marrow transplantations (BMT) for various hematological disorders are reported. 51 patients had leukemia, 8 severe aplastic anemia, 4 myelodysplastic syndrome, one suffered from non-Hodgkin lymphoma and one from myeloid metaplasia. All but two patients have engrafted. Overall, 43 (66%) of 65 patients were alive 0,03-7,2 years (median not reached) as of June 23, 1997. Median time of observation was 13 months. Outcome of standard risk patients was significantly better than that of high risk patients (p=0,006). Our data confirm, that sibling BMT is an effective treatment modality with acceptable toxicity for younger patients with an early stage of serious hematological disorders.
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December 1998

[Genes, polymorphism and function of the HLA gene region].

Authors:
M Buc

Bratisl Lek Listy 1998 Aug-Sep;99(8-9):447-53

Imunologický ústav Lekárskej fakulty Univerzity Komenského v Bratislave.

Great biological significance of the HLA complex and its impact on practical medicine impels researchers to study it, the result of which is an annual expansion of our knowledge on the system. The polymorphism of the HLA complex has increased--altogether 664 alleles are officially recognised. The genetic defect leading to the bare lymphocyte syndrome was elucidated, too--the mutations in genes coding transcription factors RFX5 and CIITA are responsible for. Also the role of HLA-DM antigens in the exogenous pathway of antigen presentation was elucidated. They are principle molecules which dislodge CLIP from the groove of HLA class II molecules leaving it free to accommodate more suitable immunogenic peptide. It was also discovered that HLA class I antigens are target structures for NK-cells. NK-cell receptors recognising them transduce negative signals switching their cytotoxic activity off. (Fig. 8, Tab. 1, Ref. 34.)
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December 1998

HLA-DRB1, -DQB1 and -DPB1 polymorphism in the Slovak population.

Tissue Antigens 1998 May;51(5):574-6

Department of Immunology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.

HLA-DRB1, -DQB1 and -DPB1 allele frequencies were investigated in a sample of the Slovak population by PCR-SSP and PCR-RFLP methods. The most frequent DRB1 alleles were DRB1*1101-5 (0.2038), DRB1*0701-2 (0.1423), and DRB1*1501-2 (0.1231). The most rare alleles found were DRB1*0901 (0.0038), and DRB1*1201 (0.015). The most common DQB1 alleles were DQB1*0301 (0.2448), DQB1*0201 (0.2098), and DQB1*0501 (0.1119), respectively. The alleles with the least occurrence rate were DQB1*0601 (0.0035) and DQB1*0401 (0.007). The most common DPB1 alleles found were DPB1*0401 (0.4329), DPB1*0402 (0.2089), and DPB1*0201 (0.1438), respectively. The least frequent alleles were DPB1*0601, *1101, and *1501 (0.0034). Allele frequencies found in our study were compared to those in Czech, Austrian, and German populations. No statistically significant differences were observed.
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http://dx.doi.org/10.1111/j.1399-0039.1998.tb02996.xDOI Listing
May 1998

Occurrence rates of HLA-DRB1, HLA-DQB1, and HLA-DPB1 alleles in patients suffering from vitiligo.

Eur J Dermatol 1998 Jan-Feb;8(1):13-5

Department of Immunology, Faculty of Medicine, Comenius University, 81108 Bratislava, Slovakia.

By investigating a group of 39 unrelated adults suffering from vitiligo it was found that alleles HLA-DRB1*0701, -DQB1*0201, and -DPB1*1601 differed in their frequencies in comparison to those observed in the healthy population. The allele HLA-DRB1*0701 was found in 26.5% of patients compared to 14.2% in the healthy group (p < 0,01, RR = 2.17). The allele HLA-DQB1*0201 was present in 33.8% of patients compared to 21.2% (p < 0,025, RR = 1.89). The allele HLA-DPB1*1601 was found in 6.41% of patients compared to 2.05% in the healthy group (p < 0.05, RR = 3.3). No other significant deviations in the frequencies of investigated alleles were observed.
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January 1999

[Frequency of the HLA-DPB1 allele in the Slovak population].

Bratisl Lek Listy 1998 Jan;99(1):54-7

Imunologický ústav Lekárskej fakulty Univerzity Komenského v Bratislave.

The polymorphism at the HLA-DPB1 locus was established in 146 unrelated persons. The polymerase chain reaction (PCR) in combination with restriction fragment length polymorphism (RFLP) technique was used. After PCR amplification of the second exon of the HLA-DPB1 locus, the PCR products were digested with seven allele specific endonucleases. The alleles DPB1*0401 (43.29%), DPB1*0402 (20.89%), DPB1*0201 (14.39%) and DPB1*0301 (9.25%) were the most common among 15 DPB1 alleles detected in the tested group. The least frequent alleles were DPB1 *0202, *0601, *1101 and *1501 (0.34%). The comparison with allele frequencies in Austrian and German populations showed no statistically significant differences. (Tab. 2, Ref. 18.)
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January 1998

[Cerebral infarct and the immune response].

Bratisl Lek Listy 1997 Jun;98(6):321-9

I. neurologická klinika Fakultnej nemocnice a Lekárskej fakulty Univerzity Komenského v Bratislave.

There are only few data available regarding the immunological mechanisms for cerebral infarction. The aim of this study was to find out the humoral and cell-mediated immunity under the conditions of focal brain ischemia (CI). As a method for humoral immunity, the complement consumption test against a panel of 8 antigens, quantitative analysis of immunoglobins and fractionized sedimentation of erythrocytes were used in the group of pts with CI, and the group of atherosclerotics (AS) and hypertonics (VH), potential victims of focal brain ischemia. It was found that the occurrence of antibodies against the whole panel of antigens in the group of CI is significantly higher as compared with the healthy controls, but it is lower than that in the group of AS and VH. The occurrence of antibodies exclusively against only brain antigens and that in CSF is similar. No correlation to the location of ischemic lesion and the degree of neurological deficit score was found. These findings didn't change in 2 and 4 weeks as well as in 1 year after the onset of CI. The quantitative analysis of immunoglobins revealed statistically higher levels of IgA and lower levels of IgM in comparison with the controls. IgG were higher, but without statistical significance. Statistically significant higher levels of all immunoglobins in CSF were found. As similar trend of changes found also in the group of AS and VH. These results of humoral immunity confirmed by the results of fractionized sedimentation of erythrocytes with EP. The results can be interpreted as a possible change or disorder of central regulation of immunizing processes due to the latent (in AS and VH) of manifest (in CI) lesions of the brain. But the quality and quantity of this response might have been affected by the entire case history of the patients who survived cerebral infarction. The changes in immunity response of the organism in CI was shown also in cell-mediated immunity. The results a statistically significant increase in stimulatory (SI) as well as in immunoregulatory (IRI) indices in stroke patients under the age of 40. These findings didn't change 2 and 4 weeks after the onset of CL. An increase in IRI was due to the increase in Th lymphocytes. In the immune response of the organism in CI, the antiphospholipid antibodies (aPLs = anticardiolipin antibodies (aCL) and lupus anticoagulant--LA) play an important role. aCLs were present in 9.8% of the first stroke pts when compared to 4.3% in controls. The most common isotype of the antibodies we IgG. Of all first-stroke pts who were aCL positive only 8% had no other stroke risk factors (atrial fibrillation, diabetes, hypertension and other). aCLs are an important risk factor for the first stroke, mainly in the young, but also in the elderly. The presence of aCLs increases the risk for recurrent strokes. aPLs are not necessarily associated with the specific location of clinical stroke syndrome but they are in significant correlation to the occurrence of multiple strokes on CT (30:18%). None of the initially aCL-negative patients became aCL-positive during the time course of CI. These data support the idea that aCLs play a causal role in stroke (PROPTER HOC changes) rather than vice versa (POST HOC changes). From the therapeutic point of view, currently there do not exist any good treatment guidelines for preventing the second stroke. The analysis of HLA. antigen showed an increase in some HLA (A2, A28 etc.) and a decrease in others (A3, A9 etc.) in comparison with the controls. This might refer to the participation of genetic factors in the onset of CI.
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June 1997

Screening of immunological properties of vermiculine in selected model situations.

Ann N Y Acad Sci 1997 Apr;815:369-71

Research Institute of Rheumatic Diseases, Piest'any, Slovakia.

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http://dx.doi.org/10.1111/j.1749-6632.1997.tb52087.xDOI Listing
April 1997

[Overview of the latest findings on nonclassical MHC antigens and activation pathways of T-lymphocytes].

Authors:
M Buc

Bratisl Lek Listy 1997 Feb;98(2):111-7

Immunologický ústav Lekárakej fakulty Univerzity Komenského v Bratislave.

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February 1997
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