الفهرس 
Introduction
Causes of SLEOnly 14 pages are availabe for public view
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Abstract
The pathogenesis of SLE is highly complicated and multiple genes are responsible for disease susceptability, and defective immune regulation, such as clearance of apoptotic cells and immune complexes, modify this susceptibility.
The loss of immune tolerance, increased antigenic load, excess T cell help, defective B cell suppression, and shifting of Th1 to Th2 immune responses lead to cytokine imbalance, B cell hyperactivity, and the production of pathogenic autoantibodies are the main immune events that provoke the disease Finally, certain environmental factors are probably needed to precipitate the onset of the disease
Given the complex aetiopathogenesis, heterogeneous clinical manifestations and varying rates of disease progression among SLE patients, it is reasonable to predict that a particular SLE biomarker may be informative regarding only one specific aspect, rather than all aspects, of the disease process at any give time
Because the antibodies and accompanying inflammatory cells can affect tissues anywhere in the body, lupus has the potential to affect a variety of areas. Sometimes lupus can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous system
The diagnosis of SLE relies on revised ACR criteria published in 1982 and 1997, but this approach is problematic in routine clinical practice. For example, development of 4 of 11 criteria for a definite SLE diagnosis may take years to decades to evolve in some patients.
Laboratory tests or biomarkers that facilitate early and accurate diagnosis of SLE are essential. More sensitive and specific biomarkers for lupus diagnosis like The miRNAs which play crucial roles in diverse biologic processes, including the regulation of immunologic functions and autoimmunity Therefore, the dysregulation of miRNAs, and how this process may contribute to autoimmune disease, is an important area of research.
Recent studies have provided growing evidence that the dysregulation of miRNAs contributes to the pathogenesis of SLE. For instance, it was shown that underexpression of miR-146a in lupus patients contributed to abnormal activation of the type I interferon pathway would also improve efficiency and accuracy of clinical trials by assuring that patients presumed to have SLE actually have the disease
Lupus disease activity could be assessed by several biomarkers including reticulocyte bound c4d which proportionate to the extent of complement activation at that time, thereby reflecting lupus disease activity.
A causal relation between overproduction of BLyS and development of systemic lupus erythematosus (SLE) has been found. Studies have demonstrated elevated circulating levels of BLyS in 20–30% of human SLE patients tested at a single point in time
It was observed that the IFN signature predicts more severe disease, such as cerebritis, nephritis, and hematological involvement, in those patients.
The C1q receptors on the surface of phagocytes constitute an extremely important mechanism for the clearance of apoptotic cells. Patients with homozygous C1q deficiency develop autoantibodies and a lupus-like syndrome apparently because of the inability to eliminate apoptotic cells effectively, which leads to an increase in the exposure of antigens to the immune system. patients with a targeted deletion of C1q show glomerulonephritis with deposits of immune complexes and apoptotic cells in the glomeruli
CD4 is a co-receptor that assists the T cell receptor (TCR) in communicating with an antigen-presenting cell (APC).
CD4+ Th1 cells recognize their autoantigen and adhere to glomeruli. With production of interferon-γ which induces proinflammatory mediators.
The treatment of SLE involves preventing flares and reducing their severity and duration when they occur.
Treatment can include corticosteroids and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require bouts of cytotoxic drugs. These drugs include cyclophosphamide and mycophenolate.
Associations of rising serum and urinary NGAL levels (uNGAL) with acute renal injury have been shown in both adult and pediatric patients .In lupus nephritis, it was postulated that injured tubular cells, infiltrating neutrophils, or inflamed vasculature are the sources of uNGAL. Studies have demonstrated the promise of uNAGL as a biomarker of lupus nephritis in both pediatric and adult patients with SLE
A positive correlation between serum levels of antinucleosome antibodies and histological activity index in LN patients was observed. Moreover, there was a trend toward a positive correlation between the score of endocapillary proliferation and serum levels of antinucleosome antibodies.
This association seems to depend on a complex interaction between charges associated with the quaternary structure of the nucleosomes and epitope targets in renal tissue. That is, the histones that constitute part of the nucleosomes have a cationic charge, whereas the glomerular basement membrane has an anionic charge, which permits an interaction between them
The presence of anti-Rib-P antibodies in patients with SLE has been reported to be associated with younger age at disease onset, multiple organ involvement, and an overall severe disease course including presence of central nervous system involvement ,nephritis, photosensitivity, malar rash, and hepatic involvement and was associated with psychiatric features in patients with psychosis secondary to SLE
Recommendations
• MiRNAs are recommended to be more investigated to provide a rationale for the development of novel therapeutic strategies for SLE.
• NGAL is secreted in high levels into the blood and urine within 2 hours of injury. Because NGAL is protease resistant and small, the protein is easily excreted and detected in the urine
• Using NGAL as a biomarker can lower hospital costs because less patients will reach a critical stage in kidney injury.It is more precise and sensitive marker than serum creatinine Ultimately, diagnosis of AKI with NGAL can reduce the time a patient stays in a hospital., the early diagnosis of AKI with NGAL as a biomarker can help a patient avoid kidney dialysis.
• The determination of circulating anti-nucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.
• There is a real need for investigating markers to predict the degree of renal involvement. There are evidences that UMCP-1 is a biomarker for LN and may resolve problems of renal biobsy
• Adding the anti-C1q auto antibodies in clinical practice could be a useful noninvasive biomarker (versus the invasive renal biopsy) for the prognosis, diagnosis, and monitoring of LN. Which may lead to new therapeutic strategies for the disease.
• patients with high BLyS mRNA levels may be those patients whose disease is strongly driven by BLyS and may be especially helped by BLyS antagonist therapy. Future clinical trials should be able to establish whether the BLyS mRNA levels are good predictors of response to such agents
• Researches should investigate the relation between the expression levels of selected IFNα-inducible genes and the clinical disease activity , active renal disease, decreased C3 levels, and positive anti-dsDNA and anti-RNA-binding protein autoantibodies . So, providing a good indicator for early detection disease flares which is very useful for good treatment and preventing morbidity and mortality