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Abstract Conclusion This study highlights relation between autophagy related genes dysregulation and susceptibility to develop SLE and its relation to the disease activity. mTOR gene expression was downregulated in PBMCs of SLE patients while that of ATG10 and P62 genes were upregulated. Only mTOR was positively correlated with SLEDAI. The study approved that there was relation between IL-17 concentration, mTOR gene expression and SLEDAI, where its concentration was lower in patients than controls and there was positive correlation between IL17 conc., mTOR gene expression and SLEDAI. Recommendations It seem obvious that much more detailed understanding of the link between autophagy related genes abnormalities and susceptibility to develop autoimmune diseases including SLE is needed in the future researches. Also better understanding of the functional balance between pathogenic and protective autophagy processes in autoimmunity will be of great value. Great potential lies in expanding the toolbox of pharmacological interventions targeting autophagy to rebalance its cytoprotective effects against deleterious consequences of excessive or insufficient self-eating. Autophagy-targeted therapeutic approaches offer a great chance for good improvement and prognosis of autoimmune diseases including SLE. Combining conventional agents used in treatment of SLE with mTOR inhibitors as rapamycin could result in increasing efficacy, thereby allowing lower dosages and limited side effects. In addition, a reappraisal of routinely used drugs in SLE that have been recently recognized to modulate autophagy by distinct mechanisms appears to be mandatory. Summary Systemic lupus erythematosus (SLE) is a multisystem chronic autoimmune disease with a relapsing and remitting course. Its prevalence is higher in women of childbearing age, with a female predominance of 9:1. The exact etiology of this disease is not understood well. However, it has been demonstrated that environmental and genetic factors interact to trigger immune responses resulting in the excessive production of pathogenic autoantibodies by the B cells and cytokines dysregulation leading to tissue and organ damage. Autophagy is a catabolic process where cytosolic components are delivered to the lysosomes for degradation, aimed at recycling macromolecules in order to maintain cellular metabolic haemostasis and cell survival. Autophagy also plays an important role in inflammation and immunomodulation. Several immunological processes are dependent on cellular autophagy, including pathogen recognition, antigen presentation and lumphocyte survival. Autophagy can be classified into three main types: macroautophagy, microautophagy and chaperone-mediated autophagy. The role for autophagy in SLE pathogenesis has also been detected by two different mechanisms genetic by autophagy related genes (ATGs) and immunemediated processes relevant to disease pathogenesis, including the removal of dead cells by monocyte and the scavenging of intracellular DNA and RNA, regulation of type I interferon (IFN) responses and B- and T-cell survival. Autophagy related genes (ATGs) in human referred to the human genes involved in autophagy and 222 ATGs were collected in the human autophagy database to date. The role of ATGs in autophagy is formation of the autophagosome that requires approximately 20 ATGs which are called core ATGs. Many other genes playing an essential role in autophagy process. For example., LC3, Beclin1, mTOR and P62. IL-17 is an important cytokine that is involved in the pathogenesis of human autoimmune diseases, including SLE. It has been shown that high serum levels of IL17 predict poor histopathological outcomes after immunosuppressive therapy. The study aimed to determine the level of expression of mTOR, ATG10 and p62 genes in PBMCs of SLE patients and their relationship with SLEDAI and C3 and C4. It also aimed to determine serum level of IL17 and its relationship to mTOR, ATG10 and P62 gene expression and to SLEDAI. A total of 100 subjects were included in this study; 70 SLE patients and 30 healthy persons as controls. The basic characteristics of the 70 SLE patients of this study are summarized in table (5) Among these patients, 63 (90%) were females, the mean age was 33.5 years and the mean disease duration was 4 (3-6) years. The SLEDAI score was 0 in 1 patients (1.4%), 1-5 in 10 patients (14.3%), 6-12 in 20 patients (28.6%), 13-20 in 28 patients (40%), and above 20 in the remaining 11 patients (15.7%). The clinical manifestations of SLE patients were as follows: 46 patients (65.7%) with alopecia, 43 patients (61.4%) with arthritis, 40 patients (57.1%) with photosensitivity and 39 patients (55.7%) with oral ulcers. The mRNA relative expression level of mTOR in PBMCs of SLE patients was high in controls than cases (P=0.000), but The mRNA relative expression level of ATG10 and P62 was high in cases than controls (P=0.000), (P=0.002) respectively. Correlation between mTOR, ATG10 and P62 relative mRNA level, SLEDAI score, C3 and C4 levels revels that there was only significant correlation between expression of mTOR and SLEDAI with mild negative correlation between them. There was statistically significant difference of IL17 concentration between cases and controls. IL17 concentration was lower in the patients than controls. Also there was highly significant mild positive correlation between IL17 conc., mTOR gene expression and SLEDAI, but correlation between ATG10 and P62 expression with IL17 concentration was insignificant. |