الفهرس 
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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.