TY  - JOUR
AU  - Đurić, Olivera
AU  - Anđelković, Marina
AU  - Vreca, Misa
AU  - Skakić, Anita
AU  - Pavlović, Sonja
AU  - Novaković, Ivana
AU  - Jovanović, Bojan
AU  - Skodrić-Trifunović, Vesna
AU  - Marković-Denić, Ljiljana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1426
AB  - Introduction: Single nucleotide variants (SNVs) represent important genetic risk factors for susceptibility to posttraumatic sepsis and a potential target for immunotherapy. We aimed to evaluate the association between 8 different SNVs within tumor necrosis factor alpha (TNFA), lymphotoxin alpha (LTA) and Tolllike receptor (TLR2 and TLR4) genes and the risk of posttraumatic sepsis. Methods: Nested case-control study was conducted in the emergency department of the Clinical Centre of Serbia including 228 traumatized patients (44 with sepsis and 184 without sepsis). To compare the results of trauma subjects with the data from the general population, a control group of 101 healthy persons was included in the study. Genotyping of TNFA (rs1800629 and rs361525), LTA (rs909253), TLR2 (rs3804099, rs4696480 and rs3804100), and TLR4 (rs4986790 and rs4986791) was performed for all patients within all three groups using the real-time PCR method. MutationTaster database and in silico software SIFT were used to predict the variant pathogenic effect. Results: Carriage of the G allele of the TNFA rs1800629 gene variant (OR 2.1, 95%CI 1.06-4.16) and T allele-carriage of the TLR4 rs4986791 genetic variant (OR 3.02, 95%CI 1.31-6.57) were associated with significantly higher risk of sepsis in trauma patients when compared to the general population prone to sepsis and traumatized patients without developing a sepsis, respectively. Of these two variants, only variant in TLR4 gene (rs4986791) has been labeled as disease causing by both the MutationTaster database and the in-silico software SIFT, which further supports the role of this variant in various pathologies including sepsis. For the remaining six variants no significant association with the susceptibility to sepsis was detected. Conclusions: Carriage of the G allele of the TNFA rs1800629 gene variant and T allele-carriage of the TLR4 rs4986791 genetic variant confer significant risk of posttraumatic sepsis. TLR4 gene variants (rs4986790 and rs4986791) has been labelled as disease causing.
PB  - Elsevier Sci Ltd, Oxford
T2  - Injury-International Journal of the Care of the Injured
T1  - Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA
EP  - 425
IS  - 3
SP  - 419
VL  - 52
DO  - 10.1016/j.injury.2020.12.039
ER  - 

@article{
author = "Đurić, Olivera and Anđelković, Marina and Vreca, Misa and Skakić, Anita and Pavlović, Sonja and Novaković, Ivana and Jovanović, Bojan and Skodrić-Trifunović, Vesna and Marković-Denić, Ljiljana",
year = "2021",
abstract = "Introduction: Single nucleotide variants (SNVs) represent important genetic risk factors for susceptibility to posttraumatic sepsis and a potential target for immunotherapy. We aimed to evaluate the association between 8 different SNVs within tumor necrosis factor alpha (TNFA), lymphotoxin alpha (LTA) and Tolllike receptor (TLR2 and TLR4) genes and the risk of posttraumatic sepsis. Methods: Nested case-control study was conducted in the emergency department of the Clinical Centre of Serbia including 228 traumatized patients (44 with sepsis and 184 without sepsis). To compare the results of trauma subjects with the data from the general population, a control group of 101 healthy persons was included in the study. Genotyping of TNFA (rs1800629 and rs361525), LTA (rs909253), TLR2 (rs3804099, rs4696480 and rs3804100), and TLR4 (rs4986790 and rs4986791) was performed for all patients within all three groups using the real-time PCR method. MutationTaster database and in silico software SIFT were used to predict the variant pathogenic effect. Results: Carriage of the G allele of the TNFA rs1800629 gene variant (OR 2.1, 95%CI 1.06-4.16) and T allele-carriage of the TLR4 rs4986791 genetic variant (OR 3.02, 95%CI 1.31-6.57) were associated with significantly higher risk of sepsis in trauma patients when compared to the general population prone to sepsis and traumatized patients without developing a sepsis, respectively. Of these two variants, only variant in TLR4 gene (rs4986791) has been labeled as disease causing by both the MutationTaster database and the in-silico software SIFT, which further supports the role of this variant in various pathologies including sepsis. For the remaining six variants no significant association with the susceptibility to sepsis was detected. Conclusions: Carriage of the G allele of the TNFA rs1800629 gene variant and T allele-carriage of the TLR4 rs4986791 genetic variant confer significant risk of posttraumatic sepsis. TLR4 gene variants (rs4986790 and rs4986791) has been labelled as disease causing.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Injury-International Journal of the Care of the Injured",
title = "Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA",
pages = "425-419",
number = "3",
volume = "52",
doi = "10.1016/j.injury.2020.12.039"
}

Đurić, O., Anđelković, M., Vreca, M., Skakić, A., Pavlović, S., Novaković, I., Jovanović, B., Skodrić-Trifunović, V.,& Marković-Denić, L.. (2021). Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA. in Injury-International Journal of the Care of the Injured
Elsevier Sci Ltd, Oxford., 52(3), 419-425.
https://doi.org/10.1016/j.injury.2020.12.039

Đurić O, Anđelković M, Vreca M, Skakić A, Pavlović S, Novaković I, Jovanović B, Skodrić-Trifunović V, Marković-Denić L. Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA. in Injury-International Journal of the Care of the Injured. 2021;52(3):419-425.
doi:10.1016/j.injury.2020.12.039 .

Đurić, Olivera, Anđelković, Marina, Vreca, Misa, Skakić, Anita, Pavlović, Sonja, Novaković, Ivana, Jovanović, Bojan, Skodrić-Trifunović, Vesna, Marković-Denić, Ljiljana, "Genetic variants in TNFA, LTA, TLR2 and TLR4 genes and risk of sepsis in patients with severe trauma: nested case-control study in a level-1 trauma centre in SERBIA" in Injury-International Journal of the Care of the Injured, 52, no. 3 (2021):419-425,
https://doi.org/10.1016/j.injury.2020.12.039 . .

TY  - JOUR
AU  - Loncarić, Darija
AU  - Stanković, Biljana
AU  - Ghousein, Amani
AU  - Vreca, Misa
AU  - Spasovski, Vesna
AU  - Villacreces, Arnaud
AU  - Debeissat, Christelle
AU  - Grosset, Christophe F.
AU  - Ivanović, Zoran
AU  - Pavlović, Sonja
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1263
AB  - A major limitation in the development of efficient clinical protocols for mesenchymal stromal cell (MStroC)-based tissue regeneration therapy is the low retention and survival of MStroC in injured tissue after therapeutic administration. Low oxygen concentration preconditioning (LOP) during ex vivo cultivation of MStroC, as a method for mimicking oxygenation in their physiological microenvironment, has been shown to be beneficial in clinical trials using MStroC. Introducing hypoxia-mimicking molecules into MStroC during cultivation could be an advantageous LOP strategy. MicroRNA (miRNA) drugs are good candidates for this approach. Analysis of the expression of miRNA-210 in human bone marrow-derived MStroC in conditions of acute and extended hypoxia (24 to 72 h) was performed using RT-qPCR methodology. HIF-1 alpha and HIF-2 alpha gene knockdown cell lines were generated using lentiviral transduction of short hairpin RNA (shRNA) in order to examine whether miRNA-210 expression is regulated by transcription factor HIF-1 and/or HIF-2. We detected a significant increase in miRNA-210 expression in hypoxic conditions at time points of 24, 48 and 72 h (p lt 0.05). Knocking down of HIF-1 alpha and HIF-2 alpha genes indicated involvement of both transcription factors in the elevation of miRNA-210 expression. These results point to miRNA-210 as a good candidate for a hypoxia-mimicking molecule in LOP strategy.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation
EP  - 208
IS  - 2
SP  - 201
VL  - 71
DO  - 10.2298/ABS181117001L
ER  - 

@article{
author = "Loncarić, Darija and Stanković, Biljana and Ghousein, Amani and Vreca, Misa and Spasovski, Vesna and Villacreces, Arnaud and Debeissat, Christelle and Grosset, Christophe F. and Ivanović, Zoran and Pavlović, Sonja",
year = "2019",
abstract = "A major limitation in the development of efficient clinical protocols for mesenchymal stromal cell (MStroC)-based tissue regeneration therapy is the low retention and survival of MStroC in injured tissue after therapeutic administration. Low oxygen concentration preconditioning (LOP) during ex vivo cultivation of MStroC, as a method for mimicking oxygenation in their physiological microenvironment, has been shown to be beneficial in clinical trials using MStroC. Introducing hypoxia-mimicking molecules into MStroC during cultivation could be an advantageous LOP strategy. MicroRNA (miRNA) drugs are good candidates for this approach. Analysis of the expression of miRNA-210 in human bone marrow-derived MStroC in conditions of acute and extended hypoxia (24 to 72 h) was performed using RT-qPCR methodology. HIF-1 alpha and HIF-2 alpha gene knockdown cell lines were generated using lentiviral transduction of short hairpin RNA (shRNA) in order to examine whether miRNA-210 expression is regulated by transcription factor HIF-1 and/or HIF-2. We detected a significant increase in miRNA-210 expression in hypoxic conditions at time points of 24, 48 and 72 h (p lt 0.05). Knocking down of HIF-1 alpha and HIF-2 alpha genes indicated involvement of both transcription factors in the elevation of miRNA-210 expression. These results point to miRNA-210 as a good candidate for a hypoxia-mimicking molecule in LOP strategy.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation",
pages = "208-201",
number = "2",
volume = "71",
doi = "10.2298/ABS181117001L"
}

Loncarić, D., Stanković, B., Ghousein, A., Vreca, M., Spasovski, V., Villacreces, A., Debeissat, C., Grosset, C. F., Ivanović, Z.,& Pavlović, S.. (2019). Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 71(2), 201-208.
https://doi.org/10.2298/ABS181117001L

Loncarić D, Stanković B, Ghousein A, Vreca M, Spasovski V, Villacreces A, Debeissat C, Grosset CF, Ivanović Z, Pavlović S. Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation. in Archives of Biological Sciences. 2019;71(2):201-208.
doi:10.2298/ABS181117001L .

Loncarić, Darija, Stanković, Biljana, Ghousein, Amani, Vreca, Misa, Spasovski, Vesna, Villacreces, Arnaud, Debeissat, Christelle, Grosset, Christophe F., Ivanović, Zoran, Pavlović, Sonja, "Expression of miRNA-210 in human bone marrow-derived mesenchymal stromal cells under oxygen deprivation" in Archives of Biological Sciences, 71, no. 2 (2019):201-208,
https://doi.org/10.2298/ABS181117001L . .

TY  - JOUR
AU  - Buha, Ivana
AU  - Skodrić-Trifunović, Vesna
AU  - Adžić-Vukicević, Tatjana
AU  - Ilić, Aleksandra
AU  - Protić, Ana Blanka
AU  - Stjepanović, Mihailo
AU  - Anđelković, Marina
AU  - Vreca, Misa
AU  - Milin-Lazović, Jelena
AU  - Spasovski, Vesna
AU  - Pavlović, Sonja
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1265
AB  - Introduction: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. Methodology: We investigated expression of TNF-alpha, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. Results: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-alpha and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-alpha and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-alpha mRNA were detected in patients with a longer duration of therapy ( gt 2 months) compared to those with a shorter therapy duration ( lt 2 months), and in patients without anemia. Conclusions: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-alpha gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy.
PB  - J Infection Developing Countries, Tramaniglio
T2  - Journal of Infection in Developing Countries
T1  - Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients
EP  - 425
IS  - 5
SP  - 419
VL  - 13
DO  - 10.3855/jidc.10949
ER  - 

@article{
author = "Buha, Ivana and Skodrić-Trifunović, Vesna and Adžić-Vukicević, Tatjana and Ilić, Aleksandra and Protić, Ana Blanka and Stjepanović, Mihailo and Anđelković, Marina and Vreca, Misa and Milin-Lazović, Jelena and Spasovski, Vesna and Pavlović, Sonja",
year = "2019",
abstract = "Introduction: Tuberculosis (TBC) is a contagious chronic respiratory disease which despite the known cause, Mycobacterium tuberculosis (Mtb), and many decades of successful therapy, remains one of the leading global health problems. Immune responses against Mtb infection involve both of types of immunity, but cellular immunity, in which certain cytokines and Th1 cells play a key role, is crucial. A better understanding of the functions of the cytokine network involved in the state and progression of TBC could identify specific molecular markers for monitoring of disease activity as well as therapy outcomes in TBC patients. Methodology: We investigated expression of TNF-alpha, IL-6 and IRAK1 genes using an RT-qPCR technique in peripheral blood mononuclear cells of 33 TBC patients and 10 healthy individuals. Results: Comparison between TBC patients and healthy individuals revealed statistically significant differences for all analyzed genes. The levels of expression of TNF-alpha and IL-6 mRNA were higher, while the level of IRAK1 mRNA was lower in the TBC group compared to controls. Moreover, a strong positive correlation was observed between TNF-alpha and IL-6 gene expression. When clinical parameters were analyzed, increased levels of TNF-alpha mRNA were detected in patients with a longer duration of therapy ( gt 2 months) compared to those with a shorter therapy duration ( lt 2 months), and in patients without anemia. Conclusions: Our results indicate that the inflammatory genes we examined play a crucial role in the pathogenesis of tuberculosis, and that the expression of the TNF-alpha gene could be a marker for monitoring the clinical effect of the ant-tuberculosis drugs during therapy.",
publisher = "J Infection Developing Countries, Tramaniglio",
journal = "Journal of Infection in Developing Countries",
title = "Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients",
pages = "425-419",
number = "5",
volume = "13",
doi = "10.3855/jidc.10949"
}

Buha, I., Skodrić-Trifunović, V., Adžić-Vukicević, T., Ilić, A., Protić, A. B., Stjepanović, M., Anđelković, M., Vreca, M., Milin-Lazović, J., Spasovski, V.,& Pavlović, S.. (2019). Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients. in Journal of Infection in Developing Countries
J Infection Developing Countries, Tramaniglio., 13(5), 419-425.
https://doi.org/10.3855/jidc.10949

Buha I, Skodrić-Trifunović V, Adžić-Vukicević T, Ilić A, Protić AB, Stjepanović M, Anđelković M, Vreca M, Milin-Lazović J, Spasovski V, Pavlović S. Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients. in Journal of Infection in Developing Countries. 2019;13(5):419-425.
doi:10.3855/jidc.10949 .

Buha, Ivana, Skodrić-Trifunović, Vesna, Adžić-Vukicević, Tatjana, Ilić, Aleksandra, Protić, Ana Blanka, Stjepanović, Mihailo, Anđelković, Marina, Vreca, Misa, Milin-Lazović, Jelena, Spasovski, Vesna, Pavlović, Sonja, "Relevance of TNF-alpha, IL-6 and IRAK1 gene expression for assessing disease severity and therapy effects in tuberculosis patients" in Journal of Infection in Developing Countries, 13, no. 5 (2019):419-425,
https://doi.org/10.3855/jidc.10949 . .

TY  - CONF
AU  - Zeković, Ana
AU  - Vreca, Misa
AU  - Spasovski, Vesna
AU  - Skodrić-Trifunović, Vesna
AU  - Marković-Denić, Ljiljana
AU  - Anđelković, Marina
AU  - Pavlović, Sonja
AU  - Damjanov, Nemanja
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1262
PB  - BMJ Publishing Group, London
C3  - Annals of the Rheumatic Diseases
T1  - Relationship between interleukin-23 and gastrointestinal involvement in patients with systemic sclerosis
EP  - 1229
SP  - 1228
VL  - 78
DO  - 10.1136/annrheumdis-2019-eular.2289
ER  - 

@conference{
author = "Zeković, Ana and Vreca, Misa and Spasovski, Vesna and Skodrić-Trifunović, Vesna and Marković-Denić, Ljiljana and Anđelković, Marina and Pavlović, Sonja and Damjanov, Nemanja",
year = "2019",
publisher = "BMJ Publishing Group, London",
journal = "Annals of the Rheumatic Diseases",
title = "Relationship between interleukin-23 and gastrointestinal involvement in patients with systemic sclerosis",
pages = "1229-1228",
volume = "78",
doi = "10.1136/annrheumdis-2019-eular.2289"
}

Zeković, A., Vreca, M., Spasovski, V., Skodrić-Trifunović, V., Marković-Denić, L., Anđelković, M., Pavlović, S.,& Damjanov, N.. (2019). Relationship between interleukin-23 and gastrointestinal involvement in patients with systemic sclerosis. in Annals of the Rheumatic Diseases
BMJ Publishing Group, London., 78, 1228-1229.
https://doi.org/10.1136/annrheumdis-2019-eular.2289

Zeković A, Vreca M, Spasovski V, Skodrić-Trifunović V, Marković-Denić L, Anđelković M, Pavlović S, Damjanov N. Relationship between interleukin-23 and gastrointestinal involvement in patients with systemic sclerosis. in Annals of the Rheumatic Diseases. 2019;78:1228-1229.
doi:10.1136/annrheumdis-2019-eular.2289 .

Zeković, Ana, Vreca, Misa, Spasovski, Vesna, Skodrić-Trifunović, Vesna, Marković-Denić, Ljiljana, Anđelković, Marina, Pavlović, Sonja, Damjanov, Nemanja, "Relationship between interleukin-23 and gastrointestinal involvement in patients with systemic sclerosis" in Annals of the Rheumatic Diseases, 78 (2019):1228-1229,
https://doi.org/10.1136/annrheumdis-2019-eular.2289 . .

TY  - JOUR
AU  - Vreca, Misa
AU  - Anđelković, Marina
AU  - Tošić, Nataša
AU  - Zeković, Ana
AU  - Damjanov, Nemanja
AU  - Pavlović, Sonja
AU  - Spasovski, Vesna
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1135
AB  - Systemic sclerosis (SSc) is a heterogeneous multisystem autoimmune disease with unknown etiology. Numerous studies have indicated that the disease heterogeneity implies various genetic abnormalities. Considering that SSc is characterized by a strong sex bias and that the position of IRAK1 gene is on the X chromosome, we assume that variations in IRAK1 gene could explain female predominance of SSc. It was previously described that miR-146a has a role in 'fine-tuning' regulation of the TLR/NF-kB signaling pathway through down-regulation of IRAK1 gene. The aim of the present study was to analyze both variants and expression level of IRAK1 and miR-146a genes in terms of susceptibility to SSc and clinical presentation of SSc patients. We analyzed variants IRAK1 rs3027898 C  gt  A and miR-146a rs2910164 C  gt  G in 102 SSc patients and 66 healthy subjects. Genotyping was performed by Sanger sequencing. Expression level of IRAK1 mRNA and miR-146a in PBMCs was performed in subset of 50 patients and 13 healthy controls by RT-qPCR. Our results showed that there was no association between IRAK1 rs3027898 and the risk of SSc in women. However, the analysis of genotype distribution of the mir-146a rs2910164 C  gt  G variant indicated that CC genotype shows strong association with lung fibrosis and active form of the disease. When expression level of IRAK1 gene was analyzed, we detected significant downregulation of IRAK1 mRNA in SSc patients compared to controls, as well as in male compared to female patients, in patients with ACAS autoantibodies and in patients with severe skin involvement. Regarding the expression level of miR-146a, we have found significantly reduced expression in SSc patients, in patients with skin involvement and in male SSc patients. The results from this study indicate that expression of IRAK1 gene could explain phenotypic heterogeneity of SSc and may be involved in the pathogenesis of SSc due to its differential expression in certain subgroups. Our results also suggested that miR-146a rs2910164 CC genotype may be predisposing factor for development lung fibrosis and more progressive form of SSc. Results from relative expression analysis of miR-146a demonstrated that changes in the level of this miRNA may have an impact on development and clinical course of SSc.
PB  - Elsevier Science Bv, Amsterdam
T2  - Immunology Letters
T1  - Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis
EP  - 8
SP  - 1
VL  - 204
DO  - 10.1016/j.imlet.2018.10.002
ER  - 

@article{
author = "Vreca, Misa and Anđelković, Marina and Tošić, Nataša and Zeković, Ana and Damjanov, Nemanja and Pavlović, Sonja and Spasovski, Vesna",
year = "2018",
abstract = "Systemic sclerosis (SSc) is a heterogeneous multisystem autoimmune disease with unknown etiology. Numerous studies have indicated that the disease heterogeneity implies various genetic abnormalities. Considering that SSc is characterized by a strong sex bias and that the position of IRAK1 gene is on the X chromosome, we assume that variations in IRAK1 gene could explain female predominance of SSc. It was previously described that miR-146a has a role in 'fine-tuning' regulation of the TLR/NF-kB signaling pathway through down-regulation of IRAK1 gene. The aim of the present study was to analyze both variants and expression level of IRAK1 and miR-146a genes in terms of susceptibility to SSc and clinical presentation of SSc patients. We analyzed variants IRAK1 rs3027898 C  gt  A and miR-146a rs2910164 C  gt  G in 102 SSc patients and 66 healthy subjects. Genotyping was performed by Sanger sequencing. Expression level of IRAK1 mRNA and miR-146a in PBMCs was performed in subset of 50 patients and 13 healthy controls by RT-qPCR. Our results showed that there was no association between IRAK1 rs3027898 and the risk of SSc in women. However, the analysis of genotype distribution of the mir-146a rs2910164 C  gt  G variant indicated that CC genotype shows strong association with lung fibrosis and active form of the disease. When expression level of IRAK1 gene was analyzed, we detected significant downregulation of IRAK1 mRNA in SSc patients compared to controls, as well as in male compared to female patients, in patients with ACAS autoantibodies and in patients with severe skin involvement. Regarding the expression level of miR-146a, we have found significantly reduced expression in SSc patients, in patients with skin involvement and in male SSc patients. The results from this study indicate that expression of IRAK1 gene could explain phenotypic heterogeneity of SSc and may be involved in the pathogenesis of SSc due to its differential expression in certain subgroups. Our results also suggested that miR-146a rs2910164 CC genotype may be predisposing factor for development lung fibrosis and more progressive form of SSc. Results from relative expression analysis of miR-146a demonstrated that changes in the level of this miRNA may have an impact on development and clinical course of SSc.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Immunology Letters",
title = "Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis",
pages = "8-1",
volume = "204",
doi = "10.1016/j.imlet.2018.10.002"
}

Vreca, M., Anđelković, M., Tošić, N., Zeković, A., Damjanov, N., Pavlović, S.,& Spasovski, V.. (2018). Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis. in Immunology Letters
Elsevier Science Bv, Amsterdam., 204, 1-8.
https://doi.org/10.1016/j.imlet.2018.10.002

Vreca M, Anđelković M, Tošić N, Zeković A, Damjanov N, Pavlović S, Spasovski V. Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis. in Immunology Letters. 2018;204:1-8.
doi:10.1016/j.imlet.2018.10.002 .

Vreca, Misa, Anđelković, Marina, Tošić, Nataša, Zeković, Ana, Damjanov, Nemanja, Pavlović, Sonja, Spasovski, Vesna, "Impact of alterations in X-linked IRAK1gene and miR-146a on susceptibility and clinical manifestations in patients with systemic sclerosis" in Immunology Letters, 204 (2018):1-8,
https://doi.org/10.1016/j.imlet.2018.10.002 . .

TY  - JOUR
AU  - Anđelković, Marina
AU  - Minić, Predrag
AU  - Vreca, Misa
AU  - Stojiljković, Maja
AU  - Skakić, Anita
AU  - Sovtić, Aleksandar
AU  - Rodić, Milan
AU  - Skodrić-Trifunović, Vesna
AU  - Marić, Nina
AU  - Visekruna, Jelena
AU  - Spasovski, Vesna
AU  - Pavlović, Sonja
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1146
AB  - Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X-linked disorder that mainly affects lungs. Dysfunction of respiratory cilia causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive hearing loss and recurrent lung infections with bronchiectasis. It is now well known that pathogenic genetic changes lead to ciliary dysfunction. Here we report usage of clinical-exome based NGS approach in order to reveal underlying genetic causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel) potentially pathogenic genetic variants, we established the genetic cause of 11 (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD patients so far, but were related to some symptoms of PCD. The most frequently mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in homozygous, compound heterozygous and trans-heterozygous state. For detailed characterization of one novel homozygous genetic variant in DNAI1 gene (c. 947_948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were performed. Molecular diagnostic approach applied in this study enables analysis of 29 PCD disease-causing and related genes. It resulted in mutation detection rate of 50% and enabled discovery of twelve novel mutations and pointed two possible novel PCD candidate genes.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants
IS  - 10
VL  - 13
DO  - 10.1371/journal.pone.0205422
ER  - 

@article{
author = "Anđelković, Marina and Minić, Predrag and Vreca, Misa and Stojiljković, Maja and Skakić, Anita and Sovtić, Aleksandar and Rodić, Milan and Skodrić-Trifunović, Vesna and Marić, Nina and Visekruna, Jelena and Spasovski, Vesna and Pavlović, Sonja",
year = "2018",
abstract = "Primary ciliary dyskinesia (PCD) is a rare inherited autosomal recessive or X-linked disorder that mainly affects lungs. Dysfunction of respiratory cilia causes symptoms such as chronic rhinosinusitis, coughing, rhinitis, conductive hearing loss and recurrent lung infections with bronchiectasis. It is now well known that pathogenic genetic changes lead to ciliary dysfunction. Here we report usage of clinical-exome based NGS approach in order to reveal underlying genetic causes in cohort of 21 patient with diagnosis of PCD. By detecting 18 (12 novel) potentially pathogenic genetic variants, we established the genetic cause of 11 (9 unrelated) patients. Genetic variants were detected in six PCD disease-causing genes, as well as in SPAG16 and SPAG17 genes, that were not detected in PCD patients so far, but were related to some symptoms of PCD. The most frequently mutated gene in our cohort was DNAH5 (27.77%). Identified variants were in homozygous, compound heterozygous and trans-heterozygous state. For detailed characterization of one novel homozygous genetic variant in DNAI1 gene (c. 947_948insG, p. Thr318TyrfsTer11), RT-qPCR and Western Blot analysis were performed. Molecular diagnostic approach applied in this study enables analysis of 29 PCD disease-causing and related genes. It resulted in mutation detection rate of 50% and enabled discovery of twelve novel mutations and pointed two possible novel PCD candidate genes.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants",
number = "10",
volume = "13",
doi = "10.1371/journal.pone.0205422"
}

Anđelković, M., Minić, P., Vreca, M., Stojiljković, M., Skakić, A., Sovtić, A., Rodić, M., Skodrić-Trifunović, V., Marić, N., Visekruna, J., Spasovski, V.,& Pavlović, S.. (2018). Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants. in PLoS One
Public Library Science, San Francisco., 13(10).
https://doi.org/10.1371/journal.pone.0205422

Anđelković M, Minić P, Vreca M, Stojiljković M, Skakić A, Sovtić A, Rodić M, Skodrić-Trifunović V, Marić N, Visekruna J, Spasovski V, Pavlović S. Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants. in PLoS One. 2018;13(10).
doi:10.1371/journal.pone.0205422 .

Anđelković, Marina, Minić, Predrag, Vreca, Misa, Stojiljković, Maja, Skakić, Anita, Sovtić, Aleksandar, Rodić, Milan, Skodrić-Trifunović, Vesna, Marić, Nina, Visekruna, Jelena, Spasovski, Vesna, Pavlović, Sonja, "Genomic profiling supports the diagnosis of primary ciliary dyskinesia and reveals novel candidate genes and genetic variants" in PLoS One, 13, no. 10 (2018),
https://doi.org/10.1371/journal.pone.0205422 . .

TY  - JOUR
AU  - Doknić, Mirjana
AU  - Savić, Dragan
AU  - Manojlović-Gacić, Emilija
AU  - Raicević, Savo
AU  - Bokun, Jelena
AU  - Milenković, Tatjana
AU  - Pavlović, Sonja
AU  - Vreca, Misa
AU  - Anđelković, Marina
AU  - Stojanović, Marko
AU  - Miljić, Dragana
AU  - Pekić, Sandra
AU  - Petakov, Milan
AU  - Grujicić, Danica
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1095
AB  - Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood.
PB  - Via Medica, Gdansk
T2  - Endokrynologia Polska
T1  - Clinical case seminar - familial intracranial germinoma
EP  - 618
IS  - 5
SP  - 612
VL  - 69
DO  - 10.5603/EP.2018.0060
ER  - 

@article{
author = "Doknić, Mirjana and Savić, Dragan and Manojlović-Gacić, Emilija and Raicević, Savo and Bokun, Jelena and Milenković, Tatjana and Pavlović, Sonja and Vreca, Misa and Anđelković, Marina and Stojanović, Marko and Miljić, Dragana and Pekić, Sandra and Petakov, Milan and Grujicić, Danica",
year = "2018",
abstract = "Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood.",
publisher = "Via Medica, Gdansk",
journal = "Endokrynologia Polska",
title = "Clinical case seminar - familial intracranial germinoma",
pages = "618-612",
number = "5",
volume = "69",
doi = "10.5603/EP.2018.0060"
}

Doknić, M., Savić, D., Manojlović-Gacić, E., Raicević, S., Bokun, J., Milenković, T., Pavlović, S., Vreca, M., Anđelković, M., Stojanović, M., Miljić, D., Pekić, S., Petakov, M.,& Grujicić, D.. (2018). Clinical case seminar - familial intracranial germinoma. in Endokrynologia Polska
Via Medica, Gdansk., 69(5), 612-618.
https://doi.org/10.5603/EP.2018.0060

Doknić M, Savić D, Manojlović-Gacić E, Raicević S, Bokun J, Milenković T, Pavlović S, Vreca M, Anđelković M, Stojanović M, Miljić D, Pekić S, Petakov M, Grujicić D. Clinical case seminar - familial intracranial germinoma. in Endokrynologia Polska. 2018;69(5):612-618.
doi:10.5603/EP.2018.0060 .

Doknić, Mirjana, Savić, Dragan, Manojlović-Gacić, Emilija, Raicević, Savo, Bokun, Jelena, Milenković, Tatjana, Pavlović, Sonja, Vreca, Misa, Anđelković, Marina, Stojanović, Marko, Miljić, Dragana, Pekić, Sandra, Petakov, Milan, Grujicić, Danica, "Clinical case seminar - familial intracranial germinoma" in Endokrynologia Polska, 69, no. 5 (2018):612-618,
https://doi.org/10.5603/EP.2018.0060 . .

TY  - JOUR
AU  - Zeković, Ana
AU  - Vreca, Misa
AU  - Spasovski, Vesna
AU  - Anđelković, Marina
AU  - Pavlović, Sonja
AU  - Damjanov, Nemanja
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1102
AB  - Genetic predisposition to systemic sclerosis (SSc) has still not been fully revealed. Interleukin-6 (IL-6) is a mediator of T cell proliferation and fibrotic events in SSc. Polymorphisms in the IL-6 are found to be important in susceptibility to development of SSc. We aimed to assess the frequency of -174 C/G of IL-6 gene polymorphism in SSc patients and healthy controls, as well as correlation with disease manifestations. In the case-control study, 102 patients with SSc and 93 controls were included. PCR-RFLP method was performed for genotyping promotor variants -174 C/G of IL-6 gene. The expression level of IL-6 was determined by qRT-PCR on subset of 50 patients and 13 healthy controls with different IL-6 genotypes. We used UCLA GIT 2.0 questionnaire to assess gastrointestinal involvement in SSc patients. The expression level of IL-6 gene was significantly higher in patients with SSc in comparison with healthy controls (p  lt  0.05). Carriers of C-allele of IL-6 gene compared to those with G allele, showed higher expression of IL-6 gene (95.8 vs. 41.2, p  lt  0.05), higher GIT total score (0.85 vs. 0.5, p  lt  0.05) and higher distension scale score (1.4 +/- 0.9 vs. 0.78 +/- 0.8, p = 0.05). No significant differences in genotype distribution and allele frequency were observed between patients and controls. The expression of IL6 gene varies significantly during the course of SSc. The IL-6 gene variant -174 C/G (presence of C-allele) is associated with higher IL-6 gene expression and greater GIT impairment in patients with SSc.
PB  - Springer London Ltd, London
T2  - Clinical Rheumatology
T1  - Association between the-174 C/G polymorphism in the interleukin-6 (IL-6) gene and gastrointestinal involvement in patients with systemic sclerosis
EP  - 2454
IS  - 9
SP  - 2447
VL  - 37
DO  - 10.1007/s10067-018-4163-6
ER  - 

@article{
author = "Zeković, Ana and Vreca, Misa and Spasovski, Vesna and Anđelković, Marina and Pavlović, Sonja and Damjanov, Nemanja",
year = "2018",
abstract = "Genetic predisposition to systemic sclerosis (SSc) has still not been fully revealed. Interleukin-6 (IL-6) is a mediator of T cell proliferation and fibrotic events in SSc. Polymorphisms in the IL-6 are found to be important in susceptibility to development of SSc. We aimed to assess the frequency of -174 C/G of IL-6 gene polymorphism in SSc patients and healthy controls, as well as correlation with disease manifestations. In the case-control study, 102 patients with SSc and 93 controls were included. PCR-RFLP method was performed for genotyping promotor variants -174 C/G of IL-6 gene. The expression level of IL-6 was determined by qRT-PCR on subset of 50 patients and 13 healthy controls with different IL-6 genotypes. We used UCLA GIT 2.0 questionnaire to assess gastrointestinal involvement in SSc patients. The expression level of IL-6 gene was significantly higher in patients with SSc in comparison with healthy controls (p  lt  0.05). Carriers of C-allele of IL-6 gene compared to those with G allele, showed higher expression of IL-6 gene (95.8 vs. 41.2, p  lt  0.05), higher GIT total score (0.85 vs. 0.5, p  lt  0.05) and higher distension scale score (1.4 +/- 0.9 vs. 0.78 +/- 0.8, p = 0.05). No significant differences in genotype distribution and allele frequency were observed between patients and controls. The expression of IL6 gene varies significantly during the course of SSc. The IL-6 gene variant -174 C/G (presence of C-allele) is associated with higher IL-6 gene expression and greater GIT impairment in patients with SSc.",
publisher = "Springer London Ltd, London",
journal = "Clinical Rheumatology",
title = "Association between the-174 C/G polymorphism in the interleukin-6 (IL-6) gene and gastrointestinal involvement in patients with systemic sclerosis",
pages = "2454-2447",
number = "9",
volume = "37",
doi = "10.1007/s10067-018-4163-6"
}

Zeković, A., Vreca, M., Spasovski, V., Anđelković, M., Pavlović, S.,& Damjanov, N.. (2018). Association between the-174 C/G polymorphism in the interleukin-6 (IL-6) gene and gastrointestinal involvement in patients with systemic sclerosis. in Clinical Rheumatology
Springer London Ltd, London., 37(9), 2447-2454.
https://doi.org/10.1007/s10067-018-4163-6

Zeković A, Vreca M, Spasovski V, Anđelković M, Pavlović S, Damjanov N. Association between the-174 C/G polymorphism in the interleukin-6 (IL-6) gene and gastrointestinal involvement in patients with systemic sclerosis. in Clinical Rheumatology. 2018;37(9):2447-2454.
doi:10.1007/s10067-018-4163-6 .

Zeković, Ana, Vreca, Misa, Spasovski, Vesna, Anđelković, Marina, Pavlović, Sonja, Damjanov, Nemanja, "Association between the-174 C/G polymorphism in the interleukin-6 (IL-6) gene and gastrointestinal involvement in patients with systemic sclerosis" in Clinical Rheumatology, 37, no. 9 (2018):2447-2454,
https://doi.org/10.1007/s10067-018-4163-6 . .