Clinical significance of serum concentration of Growth Arrest Specific Protein 6 (GAS6) and the Soluble Form of Its Tyrosine Kinase Receptor (sAxl) in Patientswith Systemic Lupus Erythematosus

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 engulfedto 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).