Plasma sMer, sAxl and GAS6 levels correlate with disease activity and severity in lupus nephritis

Abstract

Objective The purpose of this study is to determine whether TAM receptors and ligands associated with the activity and severity of lupus nephritis. Methods Clinical data were statistically analysed and studied in 122 SLE patients, diagnosed from 2013 to 2016 in First Hospital Affiliated to Harbin Medical University. Levels of TAM receptors and ligands in the plasma of 122 SLE patients were measured by ELISA. Renal biopsies were performed to confirm lupus nephritis (LN) by histopathology in 68 patients. The associations of TAM receptors and ligands with clinical and serological parameters were analysed in 68 LN patients. Results Amongst patients with SLE, those with LN had significantly higher plasma sMer, sAxl and GAS6 levels than those without renal involvement (P < 0.01 for all comparisons). Additional comparisons on the renal function‐associated clinical parameters confirmed an indicative role of the sMer, sAXL and GAS6 levels in the cohort of patients with more severe nephritis. Patients with higher sMer, sAXL and GAS6 levels of LN patients tended to suffer from proliferative glomerulonephritis. The sAXL and GAS6 levels had a strong positive correlation with activity index (AI) in LN patients. Furthermore, there was a significant drop of the sMer, sAXL and GAS6 concentrations from the time of the biopsy to month t6, but no further decrease from months t6 to t12. Conclusions These results suggest that plasma sMer, sAxl and GAS6 can be an additional clinical marker related to the disease activity and severity in LN.

Gas6/TAM Receptors in Systemic Lupus Erythematosus

“…Significantly elevated concentrations of plasma sAxl in SLE patients were repeatedly reported by different groups to correlate with disease activity and severity in lupus [48, 52, 54, 55] and lupus nephritis [52]. Plasma levels of sAxl followed the same trend as the plasma levels of sMer.…”

“…Several groups made further association analysis of sMer levels with clinical and serological parameters. A strong association of higher plasma levels of sMer with nephritis was reported by three groups [49, 52, 53]. Zhu et al studied 108 Chinese SLE patients and found that plasma levels of sMer were significantly elevated in patients with proteinuria compared to those without increased urinary protein [53].…”

“…Similarly, Wu et al found that sMer correlated with the presence of nephritis in a study of 96 Swedish SLE patients [49]. It was subsequently reported that SLE nephritis patients with higher sMer levels tended to suffer from proliferative glomerulonephritis (GN) [52]. Notably, there was a correlation between the concentration of sMer and the presence of autoantibodies [53].…”

Role of Gas6 and TAM Receptors in the Identification of Cardiopulmonary Involvement in Systemic Sclerosis and Scleroderma Spectrum Disorders

“…On these bases, Gas6 and its soluble receptors have been proposed as biomarkers in different human conditions [21,22], specifically in autoimmune diseases [23][24][25][26]. In the present study, we aim to evaluate Gas6 and sAxl and sMer as potential biomarkers for cardiopulmonary complications of SS and SSD.…”

Novel AXL-specific inhibitor ameliorates kidney dysfunction through the inhibition of epithelial-to-mesenchymal transition of renal tubular cells

“…The extracellular domain of AXL is reported to be shed from the cell surface by proteases and deposited in blood [13,14]. Serum concentrations of this soluble AXL and the Gas6 ligand increase in patients with class 3 or 4 lupus nephritis and are well correlated with the disease activity index [15][16][17][18][19]. Moreover, soluble AXL decreases in patients responding to conventional therapy, but remains stable in non-responders [20].…”