الفهرس 
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Abstract
Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. 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 (NETs).
Neutrophil extracellular traps (NETs) represent a form of cell death distinct from apoptosis or necrosis. The imbalance between the formation and degradation of NETs has long been considered to be closely associated with the activity of autoimmune diseases such as systemic lupus erythematous (SLE).
NETs are web-like structures composed of chromatin backbones and granular molecules. They are released by activated neutrophils through a process called ”NETosis”
Circulating neutrophils from SLE patients release more NETs than those from healthy donors; this was further stimulated by the antimicrobial autoantibodies, suggesting a mechanism for the chronic release of immunogenic complexes in SLE.
The defective clearance of apoptotic material, together with neutrophil extracellular traps (NETs), provides abundant chromatin or self-dsDNA to trigger the production of anti-dsDNA antibodies, although the mechanisms remain to be elucidated.
Most of the studies confirmed apoptosis as the major cfDNA release mechanism in various conditions, but formation of neutrophil extracellular traps may significantly contribute to the cfDNA generation in SLE patients.
Insults leading to endothelial damage in the setting of lupus include oxidized low density lipoprotein (oxLDL), autoantibodies against endothelial cells and phospholipids, type I interferons (IFN) and neutrophilextracellular traps (NETs) directly or through activation of type I IFN pathway.
Compared to NETs from healthy donors, the histones present in NETs formed by SLE-derived neutrophils contain increased amounts of acetylated and methylated residues, which we previously observed to be associated with apoptosis and SLE. NETs are also related to drug induced lupus which is a spectrum of drug-induced reactions often characterized by a clinical phenotype similar to that of idiopathic systemic lupus eruthematosus (SLE) but usually lacking major SLE complications.
In SLE patients, decreased NETs degradation was associated with manifestations of glomerulonephritis as well as low complement levels and elevated levels of antibodies directed against histones and DNA. Furthermore, the odds ratio for the patient to develop alopecia and fever after an episode of decreased NETs degradation was increased.
Study show that the interfering with immune complexes formation using a combination of rituximab (RTX) and belimumab (BLM) led to specific reductions in ANAs and regression of excessive NET formation.
Vitamin D could reduce endothelial damage by decreasing NETosis activity. This result may reveal the possibility of Vitamin D as supplementary therapy for SLE patients with hypovitamin D to prevent endothelial damage.