الفهرس 
Historical background of SLEOnly 14 pages are availabe for public view
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Abstract
SLE, a severe multisystem autoimmune disease, is characterized
by a loss of immune tolerance to self-antigens, which results in the
continuous production of pathogenic autoantibodies, activation of
lymphocyte and release of inflammatory mediators. SLE pathogenesis and
autoantibody production are dependent upon CD4+T cells. Upon antigen
stimulation, naïve CD4+ cells can be differentiated into several different T
cell subsets, including Th1, Th2, Th17, and Treg based on the patterns of
cytokine present in the local environment.
T- and B-lymphocytes are important in SLE pathogenesis; an
increased number of circulating plasma memory B cell subsets are linked
to disease activity, and B-cell-targeted therapies have showed some
clinical improvement. miRNAs are small (only 21–25 nucleotide long)
regulatory non-coding RNA molecules which are function as an
epigenetic regulator of gene expression and play vital roles in various
physiologic and pathologic processes. Tregs exhibit a distinguished
miRNA profile compared with conventional T cells. Individual miRNA or
miRNA clusters might contribute to the Treg biology through several
mechanisms. miRNAs guide the differentiation, suppressive function, and
stability of tTreg and Treg-induced in the pTreg or in vitro iTreg.
Thus, this work is designed to evaluate the changes in the
percentage of Treg cells in SLE in view of miRNAs expression that might
influence Tregs. The inter-relationship of miRNAs with different T cell
subsets and cytokine secretion profile in SLE patients was evaluated The frequency of Treg was assessed by flow cytometry. Expression
level of miR-10a, miR-17, miR-21, miR-24, miR-125a, miR133b, miR-
145, miR-146a, miR-148a and miR-155 were analyzed using qRT-PCR in
100 SLE patients versus 100 controls. Plasma levels of cytokines IL-10,
TGF-β, IL-6, IL-17, IL-23 and TNF-α were measured by ELISA.
A significant increase in Treg cells in SLE patients than controls
was observed with maximum elevation inactive SLE cases. A significant
upregulation in CD3+ (P<0.01), CD8+ (P<0.01) and Treg cells’ frequency
(P<0.001) with a significant downregulation in CD4+ cells (P<0.05) were
detected in SLE patients compared to controls.
SLE patients showed a significant increase in miR-21 (p<0.01),
miR-148a (p<0.001), miR-146a (p<0.05), miR-155 (p<0.001) and miR-
145 (p<0.01) and significant reduction in miR-24 (p<0.001) miR-10a
(p<0.001) and miR-133b (p<0.001). An insignificant decrease in miR-
125a and miR-17 was observed in lupus patients.
There was a significant elevation in IL-6 (P<0.001), IL-17
(P<0.001) and IL-10 (P<0.001) with a significant diminution in TNF-α
(P<0.001) and TGF-β (P<0.001) with no change in IL-23 was recorded in
in patient group versus control group.
In conclusion, this study approved a significant down regulation in
CD4+ cells with a substantial upregulation of Treg cells’ frequency in SLE
patients, especially those in the active state. It stressed on the idea that
these elevated cells might be malfunctioning based on the miRNAs and
cytokine secretion profile.