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Vojvodic S.I.,Institute for Blood Transfusion of Vojvodina | Ademovic-Sazdanic D.S.,Institute for Blood Transfusion of Vojvodina | Popovic S.L.,Institute for Internal Medicine | Konstantinidis N.V.,Oncology Institute of Vojvodina
Annals of Human Biology | Year: 2015

Background: Killer cell immunoglobulin-like receptors (KIRs) are glycoproteins regulating the response of natural killer (NK) cells and a few sub-sets of T-cells. The KIR gene frequencies and genotype content vary considerably among different ethnic groups.Aim: The aim of this study was to analyse KIR gene polymorphism in the population of Vojvodina and to compare it with selected worldwide populations.Subjects and methods: The studied sample consists of 134 healthy unrelated individuals, residents of different geographical regions of Vojvodina. DNA samples isolated from peripheral blood leukocytes by the silica-based extraction method were used in reverse PCR-SSO and PCR-SSP technique to detect the presence and absence of KIR genes.Results: All 16 KIR genes, a total of 37 different KIR genotypes, were observed in the Vojvodina population with the presence of framework and pseudogenes in all individuals. The neighbour-joining phylogenetic tree shows that the Vojvodina population is in the same cluster with Croatians, Turkish, Russians, Czechs, Irish, Italians, French, Macedonians and Polish. The Vojvodina population shows polymorphism of the KIR gene family present in other European and European-derived populations studied previously.Conclusion: The present study may serve as a reference for comparisons in further anthropological and disease association studies and also provide more informative data valuable for donor search strategy in haematopoietic stem cell transplantation. © 2014 © 2014 Informa UK Ltd.


PubMed | Institute for Internal Medicine, Oncology Institute of Vojvodina and Institute for Blood Transfusion of Vojvodina
Type: Journal Article | Journal: Annals of human biology | Year: 2015

Killer cell immunoglobulin-like receptors (KIRs) are glycoproteins regulating the response of natural killer (NK) cells and a few sub-sets of T-cells. The KIR gene frequencies and genotype content vary considerably among different ethnic groups.The aim of this study was to analyse KIR gene polymorphism in the population of Vojvodina and to compare it with selected worldwide populations.The studied sample consists of 134 healthy unrelated individuals, residents of different geographical regions of Vojvodina. DNA samples isolated from peripheral blood leukocytes by the silica-based extraction method were used in reverse PCR-SSO and PCR-SSP technique to detect the presence and absence of KIR genes.All 16 KIR genes, a total of 37 different KIR genotypes, were observed in the Vojvodina population with the presence of framework and pseudogenes in all individuals. The neighbour-joining phylogenetic tree shows that the Vojvodina population is in the same cluster with Croatians, Turkish, Russians, Czechs, Irish, Italians, French, Macedonians and Polish. The Vojvodina population shows polymorphism of the KIR gene family present in other European and European-derived populations studied previously.The present study may serve as a reference for comparisons in further anthropological and disease association studies and also provide more informative data valuable for donor search strategy in haematopoietic stem cell transplantation.


Vojvodic S.,Institute for Blood Transfusion of Vojvodina | Ademovic-Sazdanic D.,Institute for Blood Transfusion of Vojvodina
Central European Journal of Medicine | Year: 2013

Background: The reactivity between donor's Human Leukocyte Antigen (HLA) and recipient's anti-HLA antibody in pretransplantation assessment is one of the critical factors to determining successful outcome of renal transplantation. Objective: The aim of present study was to compare different techniques of HLA antibody detection in patients waiting for a kidney transplant. Methods: Two techniques of HLA antibody screening were compared: the complement-dependent citotoxicity (CDC) test and enzyme-linked immunosorbent assay (ELISA). The study included 606 sera samples of 236 patients waiting for a first kidney transplantation. Results: Of 606 tested sera, 469 (77.39%) were negative by both methods. Of the 137 (22.6%) positive sera, 73 (12.04%) were positive only by ELISA method, 48 (7.92%) by both CDC and ELISA methods and 16 (2.64%) only by CDC method. There was a significant (p<0.05) correlation between optical densities obtained by ELISA and the PRA determined by cytotoxicity testing. Conclusion: Fast and precise characterisation of antibodies in patients before transplantation can be performed by both methods, CDC and ELISA, as complementary techniques. ELISA method is more sensitive and effective than CDC, enabling significant reduction of the CDC workload of the laboratory, but can be used only as adjunct to serum screening by citotoxic testing. © 2013 Versita Warsaw and Springer-Verlag Berlin Heidelberg.


Vojvodic S.,Institute for Blood Transfusion of Vojvodina | Ademovic-Sazdanic D.,Institute for Blood Transfusion of Vojvodina | Busarcevic I.,University of Novi Sad
Genetika | Year: 2013

Major histocompatibility complex (MHC) genes are involved in various mechanisms of pathogenesis and immunoediting of hematological diseases. This study aimed to investigate the association between HLA -A, -B and -DRB1 alleles with hematological diseases. In this study, we performed DNA-based HLA typing by polymerase chain reaction analysis with sequence-specific primers (PCR-SSP) to distinguish HLA-A, -B, and -DRB1 alleles. Eighty-two patients with hematological diseases (29 with acute lymphoblastic leukemia (ALL), 19 with acute nonlymphoblastic leukemia (ANLL), 5 with chronic myelogenous leukemia (CML), 2 with chronic lymphocytic leukemia (CLL), 9 with myelodysplastic syndrome (MDS), 9 with lymphomas (M.Hodgkin (HL) and non-Hodgkin (NHL)), 7 with aplastic anemia (AA) and 2 with multiple myeloma (MM)), were included in the study and compared with 111 healthy blood donors, residents from Vojvodina, evaluating the strength of the observed associations by measuring the aetiologic and preventive fractions. Among the alleles significantly associated with hematological diseases, HLA-A*24 showed an aetiologic fraction higher than those of HLA-A*26 and A*25 (RR=1.027, EF=1.233, RR=1.047, EF=1.141 and RR=1.213, EF=0.910).Negative association with significant preventive fraction was observed with HLA-B*18 and HLA-DRB1*11 alleles, with RR=0.400, PF=0.179 and RR=0.587, PF=0.176. Our results suggest that HLA-A*24, A*26 and A*25 as associated more frequently than other specificities with a hypothetical disease predisposing genes, may play a role in the pathogenesis of hematological diseases.


Vojvodic S.,Institute for Blood Transfusion of Vojvodina | Ademovic-Sazdanic D.,Institute for Blood Transfusion of Vojvodina
Genetika | Year: 2011

Genetical and environmental factors play an interactive role in the development of acute and chronic leukemias.HLA antigens have been considered as possible genetic risk factors.The aim of this work was to investigate a possible association between HLA class II polymorphisms and leukemias and myelodysplastic syndrome.In the present study we investigated HLA class II antigens, DR/DQ and DR51/DR52/DR53 haplotypes in 100 patients:7 suffering from myelodysplastic syndrome (MDS),37 from acute lymphoblastic leukemia(ALL),32 from acute myeloid leukemia (AML) and 24 from chronic myeloid leukemia(CML).A panel of 210 healthy unrelated individuals of the same origin, from Vojvodina, served as controls.HLA phenotyping was performed by two color fluorescence method. In patients suffering from MDS was found a positive association with DR7(RR=2.598, EF=0.175) and DQ7(3)(RR=4.419, EF=0.632), while negative association was found for DR15(2)(RR=0.405, PF=0.172) and DQ6(1) (RR=0.889, PF=0,936).Positive association was found in the group of patients with ALL for DR7(RR=2.391, EF=0.688) and DQ2(RR=1.62, EF=0.15),while negative association was found with DQ5(1)(RR=0.075, PF=0.324).In the group of patients with AML,there were positive associations with DR11(5)(RR=1.732, EF=0.211), DQ2(RR= 1.594, EF=0.151) and DQ7(3) (RR=2.547, EF=0.266),while possible protective antigen was DQ5(1) (RR=0.107, RF=0.701).Higher RR than 1 and EF>0.15, in patients suffering from CML was found for DQ6(1)(RR=1.661, EF=0.232), while negative association was found for DR4 (RR=0.182, PF=0.155).Possible protective haplotype in this study was DR3DQ8(3) for patients suffering from AML(RR=0.007, PF=0.501).The distribution of DR53-DR53 haplotypes showed significant difference in male patients with ALL(6% vs 0.09%), while DR52-DR52 haplotype was significantly less frequent in male patients with CML (4% vs 20.47%) and female patients with MDS (1% vs 18.57%), respectively, in comparison to controls. We deduced that DR7 antigen in male patients with ALL has the greatest impact to the higher frequency of DR53-DR53 haplotype in this type of leukemia.The role of HLA antigens as risk factors for development of leukemias in our population was shown and furthermore it could be useful in clinical practice.


Vojvodic S.,Institute for Blood Transfusion of Vojvodina | Ademovic-Sazdanic D.,Institute for Blood Transfusion of Vojvodina
Genetika | Year: 2011

Coeliac disease (CD) is a systemic autoimmune, complex and multifactorial disorder, which is caused by interactions between genetic and environmental factors. The only established genetic risk factors so far are the human leucocyte antigens. The aim of this study was to assess the distribution of II class human leukocyte antigens (HLA) in patients with coeliac disease and to investigate the susceptibility to coeliac disease in family members. We typed HLA DR and DQ antigens in 37 patients from Vojvodina with coeliac disease, 23 first-degree relatives, and 210 controls, serologically using standard lymphocytotoxicity technique. HLA DQ5(1), DQ6(1), DR11(5), DQ7(3), DQ2 and DR15(2) were the most common antigens in the control group. Frequency of HLA DQ2, DR3 and DR7 was higher in CD patients than in the control group. The relative risks for HLA DQ2, DR3 and DR7 were 4.846, 6.986 and 2.106, respectively, while positive association was found between HLA DQ2 and DR3 and CD. Frequency of HLA DQ2, DR3 and DR16(2) was higher in first-degree relatives than in the control group while a positive association was found between HLA DQ2 and DR3. A negative association was found between HLA DQ5(1) and DQ6(1) in coeliac patients from Vojvodina and their relatives, in addition to HLA DR11(5) in the group of relatives (RR=0.363,PF=0.232). These findings indicate the impact of the HLA testing for CD in clinical practice in order to rule out the possibility to CD in doubtful cases or in at-risk subjects.


Vojvodic S.,Institute for Blood Transfusion of Vojvodina | Ademovic-Sazdanic D.,Institute for Blood Transfusion of Vojvodina
International Journal of Immunogenetics | Year: 2012

Major histocompatibility complex encoding human leucocyte antigens (HLA) is a highly polymorphic gene cluster that makes it a valuable tool in the population genetic studies. The aim of our study was to compare HLA class II gene frequencies with other populations from Europe and to determine the relationship between the investigated populations. In this study, one hundred and twenty healthy individuals from Vojvodina, northern Serbia, were studied for 18 of the HLA-DRB1 and HLA-DQB1 loci. The HLA families of alleles were analysed by using sequence-specific primers for polymerase chain reaction (PCR-SSP). The results showed the increased frequency of HLA-DRB1*11(0.333), -DRB1*04(0.300), -DRB1*07(0.250), -DQB1*03(0.730) and -DQB1* 05(0.391), among the tested families of alleles. The two-locus haplotype analysis revealed significant positive linkage disequilibrium for DRB1*11DQB1*03 (Δ= 0.0788, χ2=12.61) and DRB1*04DQB1*03 (Δ= 0.0583, χ2=8.04). A phylogenetic tree constructed on the basis of the DRB1* gene frequencies derived from other populations revealed the clustering among the Vojvodina population together with other populations in Europe (Croats, Austrians and Hungarians). Close relationship of the Vojvodina population with the populations of Hungarians and Austrians can be the result of their historical influence on the region of Vojvodina. © 2012 Blackwell Publishing Ltd.


Vojvodic S.,Institute for Blood Transfusion of Vojvodina | Ademovic-Sazdanic D.,Institute for Blood Transfusion of Vojvodina
Russian Journal of Genetics | Year: 2011

The polymorphism at the HLA DRB1 and DQB1 loci in the population of Vojvodina was studied by PCR-SSP method. A total of 13 DRB1 and 5 DQB1 specificities displaying population-specific frequency distribution pattern were described. The most frequent HLA Class II alleles in Vojvodina population were: HLA-DRB1*11 (af = 0.30), -DRB1*04 (af = 0.28), -DRB1*07 (af = 0.21), -DRB1*13 and -DRB1*16 (af = 0.18), -DQB1*03 (af = 0.64), -DQB1*05 (af = 0.39) and -DQB1*02 (af = 0.35). The haplotypes with high frequencies (≥0.02) included HLA DRB1*11 DQB1*03 (0.0825), DRB1*04DQB1*03 (0.0725), DRB1*07DQB1*02 (0.0475). The allele DRB1*07 showed the strongest association with DQB1*02 (Δ = 0.0261, gC 2 = 4.437) and DRB1*13 allele with DQB1*06 (Δ = 0.0222, gC 2 = 4.247). The allelic frequencies and populations distance dendrogram revealed the closest relationship of Vojvodina population with Hungarians, Croat, and Greeks which can be the result of turbulent migration within this region and admixture with neighbour populations during the history. © 2011 Pleiades Publishing, Ltd.


Vojvodic S.,Institute for Blood Transfusion of Vojvodina
Genetika | Year: 2011

The polymorphism at the HLA DRB1 and DQB1 loci in the population of Vojvodina was studied by PCR-SSP method. A total of 13 DRB1 and 5 DQB1 specificities displaying population-specific frequency distribution pattern were described. The most frequent HLA Class II alleles in Vojvodina population were: HLA-DRB1*11 (af = 0.30), -DRB1*04 (af = 0.28), -DRB1*07(af = 0.21), -DRB1*13 and -DRB1*16 (af = 0.18), -DQB1*03 (af = 0.64), -DQB1*05 (af = 0.39) and -DQB1*02 (af = 0.35). The haplotypes with high frequencies (> or = 0.02) included HLA DRB1*11 DQB1*03 (0.0825), DRB1*04DQB1*03 (0.0725), DRB1*07DQB1*02 (0.0475). The allele DRB1*07 showed the strongest association with DQB1*02 (delta = 0.0261, chi2 = 4.437) and DRB1*13 allele with DQB1*06 (delta = 0.0222, chi2 = 4.247). The allelic frequencies and populations distance dendrogram revealed the closest relationship of Vojvodina population with Hungarians, Croat, and Greeks which can be the result of turbulent migration within this region and admixture with neighbour populations during the history.


PubMed | Institute for Blood Transfusion of Vojvodina
Type: Journal Article | Journal: Balkan journal of medical genetics : BJMG | Year: 2013

There are numerous studies showing the role of human leukocyte antigens (HLAs) related with susceptibility or resistance to certain diseases. The aim of this study was to determine the association of HLA-B27 with ankylosing spondylitis (AS), polyarthralgia, lumboishialgia, acute anterior uveitis (AAU), psoriatic arthritis (PA), synovitis coxae and rheumatoid arthritis (RA) in patients from Vojvodina, Serbia. An HLA I class typing was performed by the serological immunomagnetic two-color fluorescence method using peripheral blood T lymphocytes in 97 patients and 224 healthy controls from the population of Vojvodina, Serbia. We calculated HLA-B27 frequencies, relative risk (RR), ethiologic fraction (EF), e.g., population attributive risk, when RR was greater than 1, while, preventive fraction (PF) was calculated when RR was lower than 1. This study revealed the strongest association of AS with HLAB27 antigen: RR = 25.0, while the EF was greater than 0.15, respectively. The (2) test showed the significant difference (p <0.05) in HLA-B27 in patients with AS in comparison to controls ((2) = 52.5). It was concluded that there is a positive association of HLA-B27 with AS and that HLA-B27 can serve as a marker for predisposition to diseases.

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