Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus
Само за регистроване кориснике
2019
Аутори
Jeremić, IvicaĐurić, Olivera
Nikolić, Milos
Vlajnić, Marina
Nikolić, Aleksandra
Radojković, Dragica
Bonaci-Nikolić, Branka
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
SLE / NET / DNase I / Cell-free DNA / BAFF / Anti-dsDNAИзвор:
Rheumatology International, 2019, 39, 11, 1849-1857Издавач:
- Springer Heidelberg, Heidelberg
Финансирање / пројекти:
- Клинички значај поремећаја урођене и стечене имуности код имуноинфламаторних и имунодефицитних обољења (RS-MESTD-Basic Research (BR or ON)-175065)
- Комплексне болести као модел систем за проучавање модулације фенотипа-структурна и функционална анализа молекуларних биомаркера (RS-MESTD-Basic Research (BR or ON)-173008)
DOI: 10.1007/s00296-019-04426-1
ISSN: 0172-8172
PubMed: 31444555
WoS: 000490008100002
Scopus: 2-s2.0-85070999809
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .