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  - Jeremić, Ivica
AU  - Đurić, Olivera
AU  - Nikolić, Milos
AU  - Vlajnić, Marina
AU  - Nikolić, Aleksandra
AU  - Radojković, Dragica
AU  - Bonaci-Nikolić, Branka
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1257
AB  - Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naive SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p  lt  0.001), BAFF and DNase I concentration (p  lt  0.01). Contrary, NETolytic activity was lower in SLE patients (p  lt  0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p  lt  0.001, p  lt  0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p  lt  0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p  lt  0.01), cfDNA and BAFF levels (p  lt  0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p  lt  0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naive SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression.
PB  - Springer Heidelberg, Heidelberg
T2  - Rheumatology International
T1  - Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus
EP  - 1857
IS  - 11
SP  - 1849
VL  - 39
DO  - 10.1007/s00296-019-04426-1
ER  - 

@article{
author = "Jeremić, Ivica and Đurić, Olivera and Nikolić, Milos and Vlajnić, Marina and Nikolić, Aleksandra and Radojković, Dragica and Bonaci-Nikolić, Branka",
year = "2019",
abstract = "Neutrophil extracellular traps (NETs) are the main source of autoantigens in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the clinical importance of NETs-associated markers in SLE. We compared NETs-associated markers in SLE patients (n = 111) with healthy controls (n = 50). Moreover, in 35 patients with drug-naive SLE (n = 35), we investigated correlation between NETs-associated markers [DNase I concentration, myeloperoxidase (MPO) activity, anti-MPO antibodies, cell-free DNA (cfDNA), NETolytic activity] with serological parameters [anti-dsDNA antibodies, C3, C4 and B-cell activating factor (BAFF) levels] and disease activity measured by modified SLE Disease Activity Index (M-SLEDAI-2K). In comparison with healthy controls, SLE patients had higher cfDNA, MPO activity, anti-MPO antibodies (p  lt  0.001), BAFF and DNase I concentration (p  lt  0.01). Contrary, NETolytic activity was lower in SLE patients (p  lt  0.05), despite higher concentration of DNase I. MPO activity and cfDNA levels showed correlation with DNase I concentration (p  lt  0.001, p  lt  0.01, respectively). BAFF levels correlated with cfDNA, DNase I concentration and MPO activity (p  lt  0.05). Anti-dsDNA antibodies showed correlation with MPO activity (p  lt  0.01), cfDNA and BAFF levels (p  lt  0.001). Anti-dsDNA and C3 levels were independent predictors of M-SLEDAI-2K in multivariate analysis (p  lt  0.01). We demonstrated that sera of SLE patients have decreased NETolytic activity, leading to increased levels of various NETs-associated markers, which correlate with anti-dsDNA antibodies in drug-naive SLE. We showed that BAFF participates in a complex relationship between NETosis and anti-dsDNA antibodies production. These findings have important implications for a better understanding of SLE pathogenesis and development of therapy that inhibits NETs persistence and disease progression.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Rheumatology International",
title = "Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus",
pages = "1857-1849",
number = "11",
volume = "39",
doi = "10.1007/s00296-019-04426-1"
}

Jeremić, I., Đurić, O., Nikolić, M., Vlajnić, M., Nikolić, A., Radojković, D.,& Bonaci-Nikolić, B.. (2019). Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus. in Rheumatology International
Springer Heidelberg, Heidelberg., 39(11), 1849-1857.
https://doi.org/10.1007/s00296-019-04426-1

Jeremić I, Đurić O, Nikolić M, Vlajnić M, Nikolić A, Radojković D, Bonaci-Nikolić B. Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus. in Rheumatology International. 2019;39(11):1849-1857.
doi:10.1007/s00296-019-04426-1 .

Jeremić, Ivica, Đurić, Olivera, Nikolić, Milos, Vlajnić, Marina, Nikolić, Aleksandra, Radojković, Dragica, Bonaci-Nikolić, Branka, "Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus" in Rheumatology International, 39, no. 11 (2019):1849-1857,
https://doi.org/10.1007/s00296-019-04426-1 . .