scholarly journals The role of peripheral immunological tolerance in the pathogenesis of systemic lupus erythematosus

2016 ◽  
Author(s):  
Αικατερίνη-Κυριακή Βλάχου
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Reactive Oxygen ◽  
Immunological Tolerance ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Ifn Γ

Παρά την πολυπλοκότητα της αιτιοπαθογένειας των αυτοάνοσων νοσημάτων, της πλούσιας ποικιλίας των κλινικών συμπτωμάτων μεταξύ ασθενών και τη διαφορετική ανταπόκριση των ασθενών σε κοινές συμπτωματικές θεραπείες, υπάρχει μια κοινή αρχή: τα αυτοάνοσα νοσήματα αναπτύσσονται εξαιτίας της απώλειας της ανοσολογικής ανοχής στα αυτοαντιγόνα. Συνεπώς είναι αναγκαίο να διαλευκάνουμε τις γενεσιουργές αιτίες στις οποίες οφείλεται η αδυναμία ελέγχου και διατήρησης της ανοσολογικής ανοχής. Η κατανόηση των σχετικών υπεύθυνων μοριακών μηχανισμών θα προσφέρει την ευκαιρία ανάπτυξης στοχευμένων, έγκαιρων και αποτελεσματικότερων θεραπειών με κοινά οφέλη για ένα μεγάλο εύρος αυτοάνοσων νοσημάτων. Τα κατασταλτικά κύτταρα μυελικής προέλευσης (MDSCs) είναι ένα ετερογενής πληθυσμός μυελικών, ατελώς διαφοροποιημένων κυττάρων με ανοσορυθμιστικές ιδιότητες, τα οποία πρόσφατα έχουν συγκεντρώσει το ενδιαφέρον της επιστημονικής κοινότητας. Αποτελούνται από δύο υποπληθυσμούς κυττάρων, τα κοκκιοκυτταρικά (G-MDSCs) και τα μονοκυτταρικά (M-MDSCs). Το κύριο χαρακτηριστικό των MDSCs είναι ότι μπορούν να καταστείλουν τις ανοσολογικές αποκρίσεις των Τ λεμφοκυττάρων. Στην παρούσα ερευνητική εργασία, εστιάσαμε στο ρόλο των MDSCs στην παθογένεια του Συστηματικού Ερυθηματώδη Λύκου (ΣΕΛ). Ο ΣΕΛ είναι ένα συστεμικό αυτοάνοσο νόσημα, όπου η επιμένουσα απώλεια των ρυθμιστικών μηχανισμών διατήρησης της ανοσολογικής ανοχής συμβάλει στην παθογένεια της ασθένειας και την εγκαθίδρυση χρόνιας φλεγμονής. Για το λόγο αυτό, σχεδιάσαμε να εξετάσουμε το ρόλο των MDSC ρυθμιστικών κυττάρων στο ΣΕΛ, χρησιμοποιώντας το ζωικό μοντέλο NZB/W F1, ποντίκια τα οποία αυθόρμητα αναπτύσσουν ένα φαινότυπο παρόμοιο με του ΣΕΛ στον άνθρωπο. Με την εργασία αυτή δείχνουμε πως τα CD11bhighGr-1+ MDSCs ανιχνεύονται σε χαμηλά επίπεδα στα NZB/W F1 ποντίκια, τόσο στο υποκλινικό όσο και στο κλινικό στάδιο της νόσου. Αυτό κυρίως οφείλεται στη μειωμένη συχνότητα εμφάνισης των CD11bhighLy6G+ G-MDSCs στο μυελό των οστών και στα περιφερικά λεμφικά όργανα των ποντικιών με τη νόσο. Ο μειωμένος αριθμός των CD11bhighLy6G+ G-MDSC συνοδεύονται και από την ελαττωματική λειτουργία τους όσον αφορά στην in vitro καταστολή των CD4+ T λεμφοκυττάρων. Ενδιαφέρον προκαλεί ότι τα G-MDSC του λύκου όχι μόνο δεν μπορούν να καταστείλουν τα CD4+ T λεμφοκύτταρα, αλλά αντίθετα προκαλούν τον πολλαπλασιασμό κα την ενεργοποίηση τους. Σημαντικό είναι το εύρημα μας ότι τα CD11bhighLy6G+ G-MDSCs είναι μειωμένα στο λύκο εξαιτίας της αυξημένης απελευθέρωσης εξωκυττάριων παγίδων (Extracellular Traps, ETs) που προκαλείται από το φλεγμονώδες περιβάλλον του λύκου. Η αυξημένη απελευθέρωση των ETs (ΕTωση) εξαρτάται από την παραγωγή αντιδραστικών ριζών οξυγόνου (Reactive Oxygen Speces, ROS), η οποία επίσης προάγεται από τις φλεγμονώδεις ιδιότητες του περιβάλλοντος του λύκου. Τέλος, δείχνουμε ότι τρεις από τις εμπλουτισμένες κυτταροκίνες στο περιβάλλον του λύκου, οι IFN-α, IFN-γ και IL-6 έχουν την ικανότητα να επάγουν την ETωση στα κοκκιοκυτταρικά κύτταρα. Συμπερασματικά, τα δεδομένα μας αποδεικνύουν τη μειωμένη έκπτυξη των G-MDSC κυττάρων στο μικροπεριβάλλον του λύκου εξαιτίας του σχηματισμού των ETs, μια διαδικασία που αποτελεί ένα καινοφανή τύπο κυτταρικού θανάτου. Επιπλέον, παρέχουμε στοιχεία που υποστηρίζουν τη μεσολάβηση των ROS στο φαινόμενο αυτό. Η εξάλειψη των G-MDSC ενδεχομένως να έχει ως αποτέλεσμα την ελαττωματική ρύθμιση των ανοσολογικών αποκρίσεων συμβάλλοντας έτσι στην εξέλιξη της ασθένειας. Τα ευρήματά μας παρέχουν νέα στοιχεία στην κατανόηση της παθογένειας του ΣΕΛ και θα μπορούσε να συνεισφέρει στην ανάπτυξη νέων θεραπευτικών μεθόδων.

scholarly journals THE ROLE OF PLATELETS IN FORMATION OF NEUTROPHIL EXTRACELLULAR TRAPS IN PATIENTS WITH IMMUNOCOMPLEX PATHOLOGY

2016 ◽  
pp. 66-70
Author(s):  
J. V. Zubkova ◽  
I. A. Novikova ◽  
V. V. Zhelezko
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Rheumatoid Factor ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
In Vitro Cultures ◽  
Systemic Lupus ◽  
Extracellular Traps

The article presents the results of the assessment of the role of platelets in formation of extracellular traps by neutrophils. We have detected the ability of platelets to oppress the formation of extracellular traps by neutrophils in vitro cultures in patients with rheumatoid arthritis (RA) (n = 42) and systemic lupus erythematosus (SLE) (n = 24), but not in patients with hemorrhagic vasculitis (GW) (n = 15). The study has revealed the interrelation of NETosis and rheumatoid factor in patients with RA and SLE, as well as NET formation and number of platelets in patients with GW.

scholarly journals Downregulated Serum Exosomal miR-451a Expression Correlates With Renal Damage and Its Intercellular Communication Role in Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Lina Tan ◽  
Ming Zhao ◽  
Haijing Wu ◽  
Yuezhong Zhang ◽  
Xiaoliang Tong ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Intercellular Communication ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Systemic Lupus ◽  
Immune Imbalance ◽  
Serum Exosomes

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterized by continuous inflammation and the production of autoantibodies. Exosomes, acting as a critical tool for communication between cells, are involved in the pathogenesis of SLE, particularly in inflammation and immune imbalance. In this study, we aimed to extract and confirm the pro-inflammatory effect of serum exosomes in SLE. Then, we attempted to find differentially expressed exosomal microRNAs in the serum of healthy subjects and SLE patients via miRNA microarray analysis and validated the target exosomal microRNA, exosomal miR-451a, which expression level decreased in serum of SLE patients by RT-qPCR. Furtherly, we analyzed the correlation between exosomal miR-451a and disease activity, kidney damage and typing, and traditional medicine therapy. Finally, we investigated the intercellular communication role of exosomal miR-451a in SLE by co-culture assay in vitro. Taken together, our study demonstrated that downregulated serum exosomal miR-451a expression correlated with SLE disease activity and renal damage as well as its intercellular communication role in SLE which provided potential therapeutic strategies.

scholarly journals SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus

2021 ◽  
Vol 22 (8) ◽  
pp. 4169
Author(s):  
Kyoko Kawahara ◽  
Tomoyuki Mukai ◽  
Masanori Iseki ◽  
Akiko Nagasu ◽  
Hajime Nagasu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Dendritic Cells ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Adaptor Protein ◽  
Systemic Lupus ◽  
Murine Systemic Lupus Erythematosus

Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells. It controls intracellular signaling pathways. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model. Methods: For the lupus model, we used Faslpr/lpr mice. Clinical and immunological phenotypes were compared between Faslpr/lpr and SH3BP2-deficient Faslpr/lpr mice. Splenomegaly and renal involvement were assessed. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody, and increased splenic B220+CD4−CD8− T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice. Conclusions: SH3BP2 deficiency ameliorated lupus-like manifestations. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases.

scholarly journals Netosis in the pathogenesis of antiphospholipid syndrome and systemic lupus erythematosus

2021 ◽  
Vol 15 (5) ◽  
pp. 96-102
Author(s):  
K. S. Nurbaeva ◽  
T. M. Reshetnyak ◽  
A. M. Lila
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Space Form ◽  
Clinical Manifestations ◽  
Immunosuppressive Drugs ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Activated Neutrophils

Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are autoimmune diseases. In recent years, APS has been considered as an autoimmune thrombo-inflammatory disease. It has been established that clinical manifestations of APS can persist, progress over time, or debut during an adequate anticoagulant therapy and, in some cases, require administration of immunosuppressive drugs, which indicates the role of autoimmune inflammation in their development. The formation of extracellular neutrophil traps (neutrophil extracellular traps, NETs) is one of the connecting links of inflammation and thrombosis. Netosis is the process by which activated neutrophils in the extracellular space form netlike structures (NETs). This review examines the role of neutrophils and netosis in the pathogenesis of APS and SLE.

scholarly journals Role of neutrophil dysfunction in the pathogenesis of systemic lupus erythematosus

2017 ◽  
Vol 89 (12) ◽  
pp. 110-113 ◽  
Author(s):  
E V Smirnova ◽  
T N Krasnova ◽  
E V Proskurnina ◽  
N A Mukhin
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Protective Function ◽  
Extracellular Traps ◽  
Novel Drugs ◽  
Subsequent Degradation ◽  
Extracellular Environment ◽  
Neutrophil Dysfunction

Neutrophil dysfunction plays a considerable role.in systemic lupus erythematosus (SLE) The protective function of neutrophils is carried out through various mechanisms: isolation of granular antimicrobial peptides (gAMP), microbial phagocytosis with subsequent degradation via reactive oxygen species inside the phagolysosomes; as well as bactericidal action due to the release of networks from chromatin and gAMP, also called neutrophil extracellular traps (NECTs). The development of neutropenia in SLE has multiple causes, including the formation of antibodies directly to leukocytes; that of neutralizing autoantibodies to the growth factors of neutrophils and cells - myeloid precursors; bone marrow suppression; involvement of neutrophils in the processes of apoptosis and NETosis. Neutrophils in SLE are characterized by reduced phagocytic ability and pathological oxidative activity. In SLE, there is a decrease in the ability to remove the products of neutrophil apoptosis, which is correlated with disease activity. SLE patients are noted to have a higher expression level of the genes specific for low-density granulocytes, an abnormal immature neutrophil population. The impaired processes of formation of NECTs and removal NETosis products play a substantial role in the pathogenesis of SLE. It is shown that the abnormal formation of NECTs also causes endothelial injury and increases the risk of thromboses. The design of novel drugs that act on the specific parts of the formation of NECTs or contribute to their removal from the extracellular environment can propel therapy for SLE and other autoimmune diseases to new heights. There is evidence for further investigations of neutrophil-mediated pathogenetic processes in SLE in order to identify potential therapeutic targets and to understand the mechanisms of action of drugs used in clinical practice.

scholarly journals Role of Neutrophil Extracellular Traps Regarding Patients at Risk of Increased Disease Activity and Cardiovascular Comorbidity in Systemic Lupus Erythematosus

2019 ◽  
Vol 47 (11) ◽  
pp. 1652-1660 ◽  
Author(s):  
Stanley Moore ◽  
Hsin-Hsuan Juo ◽  
Christoffer T. Nielsen ◽  
Helena Tyden ◽  
Anders A. Bengtsson ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
At Risk ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Severe Disease ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Patients At Risk

ObjectiveNeutrophil extracellular traps (NET) are essential in host defense, but are also linked to inflammation and autoimmunity, including in systemic lupus erythematosus (SLE). We recently described that immune complexes (IC) induce NET formation, promoting SLE-like disease in mice. In the current study, we investigated, for the first time to our knowledge, the role of NET in human SLE and their association with disease activity and severity.MethodsLevels of NET (myeloperoxidase-DNA complexes) were analyzed in plasma from 4 cross-sectional SLE cohorts (n = 44–142), 1 longitudinal SLE cohort (n = 47), and healthy individuals (n = 100) using ELISA. Type I interferon activity was determined using a cell reporter system.ResultsPatients with SLE had elevated levels of NET in circulation compared to healthy controls (p < 0.01). NET levels identified patients with a severe disease phenotype characterized by IC-driven nephritis (p < 0.05). Though not associated with current disease activity (p = 0.20), levels of NET were associated with future increase in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) within 3 months (OR 1.75, p = 0.01), as well as an overall heightened SLEDAI over 1 year (p < 0.01). Finally, levels of NET were associated with arterial events (OR 5.0, p = 0.02) and endothelial cell activation (p < 0.001).ConclusionNET levels are elevated in patients with SLE, associated with IC-driven disease. NET levels provide significant clinical value in identifying patients at risk of active disease and/or severe disease, including nephritis and cardiovascular disease, and may allow for early interventions.

scholarly journals Role of the Promoter Polymorphism IL-6 −174G/C in Dermatomyositis and Systemic Lupus Erythematosus

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Maria Hristova ◽  
Lyubomir Dourmishev ◽  
Zornitsa Kamenarska ◽  
Svetla Nikolova ◽  
Radka Kaneva ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Interleukin 6 ◽  
Promoter Polymorphism ◽  
Polymorphism Analysis ◽  
Systemic Lupus ◽  
Muscle Enzymes

The promoter polymorphism −174G/C within the interleukin-6 gene (IL-6) has been reported to have a functional importance through the modulation of IL-6 gene expression in vitro and in vivo. IL-6 is thought to play an important role in autoimmune diseases and the effect of its receptor inhibitor—tocilizumab—has been recently studied. The aim of this case-control study was to investigate the association between the interleukin-6 −174G/C single nucleotide polymorphism and the susceptibility to dermatomyositis (DM) and systemic lupus erythematosus (SLE) in Bulgarian patients. Altogether, 87 patients—52 with SLE and 35 with DM—as well as 80 unrelated healthy controls were included in this study. All of them were analyzed by restriction fragment length polymorphism analysis (RFLP). The GG genotype and the G allele appeared to be associated with SLE, especially in women. None of the genotypes showed an association with DM. However, the G allele appeared to be associated with muscle weakness and it is a risk factor for elevated muscle enzymes. Our results indicate that IL-6 −174G/C polymorphism might be associated with the susceptibility to SLE especially in women. Although it is not associated with DM, it seems that IL-6 −174G/C polymorphism could modulate some clinical features in the autoimmune myopathies.

scholarly journals SH3BP2 Deficiency Ameliorates Murine Systemic Lupus Erythematosus

2020 ◽  
Author(s):  
Kyoko Kawahara ◽  
Tomoyuki Mukai ◽  
Masanori Iseki ◽  
Akiko Nagasu ◽  
Hajime Nagasu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Dendritic Cells ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Systemic Lupus ◽  
Dsdna Antibody ◽  
Murine Systemic Lupus Erythematosus

Abstract Background: The adaptor protein Src homology 3 domain-binding protein 2 (SH3BP2) is widely expressed in immune cells, such as myeloid cells, B cells, and T cells. It controls intracellular signaling pathways, including Syk and Src. The present study was undertaken to investigate the role of SH3BP2 in a murine systemic lupus erythematosus model.Methods: For the lupus model, we used Faslpr/lpr mice (C57BL/6 background). Clinical and immunological phenotypes were compared between Faslpr/lpr and SH3BP2-deficient Faslpr/lpr mice. Splenomegaly and renal involvement were assessed in 35-week-old mice. Serum levels of anti-dsDNA antibody and rheumatoid factor were determined using ELISA. Lymphocyte subsets in the spleen were analyzed by flow cytometry. To examine the role of SH3BP2 in specific cells, B cell-specific SH3BP2-deficient lupus mice were generated and analyzed; T cells and bone marrow-derived dendritic cells and macrophages were analyzed in vitro. Results: SH3BP2 deficiency significantly reduced lupus-like phenotypes, presented as splenomegaly, renal involvement, elevated serum anti-dsDNA antibody and rheumatoid factor, and increased splenic B220+CD4-CD8- T cells. Notably, SH3BP2 deficiency in B cells did not rescue the lupus-like phenotypes. Furthermore, SH3BP2 deficiency did not substantially affect the characteristics of T cells and macrophages in vitro. Interestingly, SH3BP2 deficiency suppressed the differentiation of dendritic cells in vitro and reduced the number of dendritic cells in the spleen of the lupus-prone mice.Conclusions: SH3BP2 deficiency ameliorated clinical and immunological manifestations in lupus-prone mice, possibly via targeting dendritic cell differentiation. Modulating SH3BP2 expression could thus provide a novel therapeutic approach to autoimmune diseases.

scholarly journals Macrophage Polarization and Plasticity in Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariame Mohamed Ahamada ◽  
Yang Jia ◽  
Xiaochuan Wu
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Macrophage Polarization ◽  
Systemic Disease ◽  
Close Relation ◽  
Systemic Lupus ◽  
Macrophages Polarization

Systemic lupus erythematosus (SLE) is an autoimmune disease that attacks almost every organ. The condition mostly happens to adults but is also found in children, and the latter have the most severe manifestations. Among adults, females, especially non-Caucasian, are mostly affected. Even if the etiology of SLE remains unclear, studies show a close relation between this disease and both genetics and environment. Despite the large number of published articles about SLE, we still do not have a clear picture of its pathogenesis, and no specific drug has been found to treat this condition effectively. The implication of macrophages in SLE development is gaining ground, and studying it could answer these gaps. Indeed, both in vivo and in vitro studies increasingly report a strong link between this disease and macrophages. Hence, this review aims to explore the role of macrophages polarization and plasticity in SLE development. Understanding this role is of paramount importance because in-depth knowledge of the connection between macrophages and this systemic disease could clarify its pathogenesis and provide a foundation for macrophage-centered therapeutic approaches.

scholarly journals Effects of platelets on extracellular traps of neutrophils in patients with systemic lupus erythematosus

2021 ◽  
Vol 22 (6) ◽  
pp. 1173-1178
Author(s):  
I. A. Novikova ◽  
Z. V. Zubkova
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Functional Activity ◽  
Blood Platelets ◽  
White Blood Cells ◽  
Neutrophil Extracellular Traps ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Activated Platelets

Platelets are central participants in hemostasis, and also contribute to the host inflammatory and immune responses. Platelets are known to have a direct effect on the formation of neutrophil extracellular traps. Moreover, the patients with systemic lupus erythematosus exhibit multidirectional disturbances in the functional activity of platelets and neutrophils. Changes in inflammatory and thrombotic events can be considered predictors for adverse clinical course in systemic pathology. The aim of present study was to evaluate the possible role of platelets in maintaining increased netosis in patients with systemic lupus erythematosus. Blood platelets and white blood cells from 29 patients with systemic lupus erythematosus (SLE) were subject to the study. We have registered the in vitro effects of platelets upon formation of extracellular traps by autologous neutrophils under the conditions of co-cultivation for 30 minutes (vital NETosis) and 150 minutes (suicidal NETosis), as well as the relationships between the platelet counts, their activity and the number of NETs observed. It was found that the severity and direction of the platelets effect upon NETosis in vitro cultures depends on the degree of activity of disease: in the 1st degree of SLE, the effect of platelets did not differ from healthy individuals, i.e., intact platelets suppress NETosis (p = 0.002), whereas ADP-induced patelets did not exert any effect); at the 2nd degree of activity, both intact and activated platelets increase NETotic activity (p = 0.03 and p = 0.04 for intact and activated platelets, respectively). In the patients with 3rd degree of the disease activity, platelets did not affect formation of NETs. Hyperactivation of platelets was detected in SLE patients, mostly pronounced in the cases with 2nd degree of activity. However, we have not revealed any significant relationships between the count of platelets, their functional activity (according to results of ADP-test aggregation), and the indexes of NETosis. At the same time, the counts of neutrophil extracellular traps in bloodstream depended on the concentration of C-reactive protein (r = 0.58; p = 0.02), the titer of autoantibodies (anti-SS-A and anti-SS-B) (r = 0.66; p = 0.04 and r = 0.76; p = 0.02, respectively), rheumatoid factor (r = 0.73; p = 0.007) and circulating immune complexes (r = 0.68; p = 0.02). The obtained results indicate that the platelet/neutrophil interactions are not the leading cause for increased NETs numbers in SLE, compared to significantly higher effects of soluble autoagressive factors.

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