الفهرس 
Systemic Lupus Erythematosus SLE)Only 14 pages are availabe for public view
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Abstract
S
ystemic lupus erythematosus (SLE) is an autoimmune disease that may result from disturbed tolerance to self antigens and development of auto-antibodies leading to the formation of immune complexes. These immune deposits in the tissues initiate an immune response by activating the complement cascade and recruiting inflammatory cells. The defective clearance of apoptotic cells is believed to be one of the multiple causes of SLE.
In recent years, GAS6 and its receptors; the Tyro 3, Axl and Mer receptors (TAM receptors), have been extensively studied. The GAS6/TAM system regulates multiple biological processes, including cell survival and proliferation, cell adhesion and migration, and inflammatory cytokine release. Therefore, the role of this system has been found to be important in inflammation, autoimmune disease, nervous, reproductive, and vascular systems and cancer biology.
The TAM receptor signaling plays an especially important role in the engulfment and phagocytic clearance of apoptotic cells and membranes in adult tissues. In this process, a TAM ligand, GAS6 or protein S, serves as a bridging molecule that physically links a phosphatidyl serine which is displayed on the surface of the apoptotic cell that will be engulfed to TAM receptor, generally Mer or Axl, expressed on the surface of the phagocyte and in so doing activate its intracellular tyrosine kinase domain.
The TAM receptors, especially Axl, have been implicated in inhibiting proinflammatory Toll like Receptors responses. During inflammation, Axl is strongly induced via Type I IFNs which is triggered by TLR stimulation of dendritic cells and macrophages and when activated, it provides a feedback signal to shut down the immune response.
The present study aimed to assess serum concentrations of GAS6 and sAxl and their association to different laboratory findings in SLE patients, and whether it has a role as a biomarker for disease activity in SLE. The study included fifty patients diagnosed as having SLE, in addition to 40 age and sex matched healthy controls. SLE Patients were divided according to disease activity into two groups: inactive SLE group including 18 patients and active SLE group including 32 patients. Moreover, all SLE patients were grouped into two additional subgroups, the kidney sparing SLE subgroup (n=25) and SLE patients with nephritis (lupus nephritis) (n=25).
Patients under study were subjected to full history taking, full clinical examination and laboratory investigations including CBC, liver and kidney function tests (serum creatinine, BUN, ALT and AST), anti-dsDNA by indirect immunoflourescence, ESR, CRP, as well as SLEDAI score for evaluating the
disease activity. In addition, all patients and controls were
assessed for serum GAS6 and sAxl levels using a commercially available ELISA kit.
The study has demonstrated that active SLE group had a highly significant increase in serum GAS6 levels than the inactive patients or the control group. Active patients also demonstrated statistically significant positive association of serum GAS6 levels to SLEDAI score. A highly significant increase of serum GAS6 levels among lupus nephritis group has also been demonstrated in comparison to kidney sparing group. On the other hand, our data did not show a similar statistically significant increase in serum levels of sAxl between the above mentioned groups, though its levels still show a significant increase in all SLE patients when compared to controls.
Diagnostic performance study using ROC curve analysis and multiple cut-off level for prediction of disease activity showed highly self discriminated results for GAS6 between active and inactive patients with a cut off value lying between 28.5ng/dl and 33ng/dl. In contrast, the best cut off value available for sAxl was >32.5ng/ml with a low diagnostic sensitivity (46.9%) and specificity (77.8%). On the other hand, ROC curve analysis of GAS6 and sAxl levels to discriminate lupus nephritis patients from those without nephritis revealed that the optimum cut-off level of serum GAS6 was >28.5 ng/ml, with 92.6% sensitivity and 69.6% specificity. The optimum cut-off level of serum sAxl was >65mg/ml with diagnostic sensitivity and specificity of 40.7% and 78.3%, respectively.
In conclusion, the present study illustrated the role of both serum GAS6 and sAxl in pathogenesis of SLE. Both GAS6 and sAxl showed highly significant increase among SLE patients compared to controls. Serum GAS6 level was found to be a biomarker which is significantly associated with disease activity and renal involvement in SLE. On the other hand, sAxl failed to show a similar significant association with disease activity or renal involvement.