Neutrophil extracellular traps-associated markers are elevated in patients with systemic lupus erythematosus
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2019
Authors
Jeremić, IvicaĐurić, Olivera
Nikolić, Milos
Vlajnić, Marina
Nikolić, Aleksandra
Radojković, Dragica
Bonaci-Nikolić, Branka
Article (Published version)
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Show full item recordAbstract
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.
Keywords:
SLE / NET / DNase I / Cell-free DNA / BAFF / Anti-dsDNASource:
Rheumatology International, 2019, 39, 11, 1849-1857Publisher:
- Springer Heidelberg, Heidelberg
Funding / projects:
- Clinical significance of dysfunctions of innate and adaptive immunity in immunoinflammatory and immunodeficiency diseases (RS-MESTD-Basic Research (BR or ON)-175065)
- Complex diseases as a model system for phenotype modulation- structural and functional analysis of molecular biomarkers (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
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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 . .