Plasma concentrations of Gas6 and sAxl correlate with disease activity in systemic lupus erythematosus

Abstract

Objectives: SLE is a systemic autoimmune disease with an annual incidence of 3.8 per 100,000. Several pathogenic mechanisms are believed to be operating in SLE, including an impaired clearance of apoptotic cells, activation of the type I IFN pathway and generation of autoimmune leucocytes. Growth arrest-specific protein 6 (Gas6) and its receptor Axl are known to regulate inflammation and may be implicated in lupus pathogenesis. We have recently developed immunological methods to quantify the vitamin-K-dependent protein Gas6 and its soluble receptor sAxl in human plasma, which we have used to investigate the role of Gas6 and soluble Axl in SLE.

Methods: We have investigated the relation between the plasma concentrations of Gas6 and sAxl and disease activity and specific symptoms in 96 SLE patients.

Results: Gas6 and sAxl concentrations correlated with SLEDAI (r = 0.48, P < 0.001 and r = 0.39, P < 0.001, respectively). Furthermore, concentrations of Gas6 and sAxl correlated with ESR and CRP and inversely with haemoglobin levels. Gas6 and sAxl concentrations were significantly higher in patients with anti-DNA antibodies, leucopenia and GN.

Conclusion: The plasma concentrations of Gas6 and sAxl vary with disease activity in SLE, in particular GN, and may have a role in lupus pathogenesis. Furthermore, Gas6 and sAxl may be of use as biomarkers of disease activity.

Fig. 1

Correlation of the SLEDAI with Gas6 and sAxl concentrations in plasma. Each symbol represents one person. (A) The correlation between SLEDAI and Gas6 (r = 0.48, P < 0.0001, n = 96). (B) The correlation between SLEDAI and sAxl (r = 0.39, P = 0.0001, n = 94). The correlations were evaluated with Spearman’s non-parametric test.

Fig. 2

Concentrations of Gas6 (A) and sAxl (B) in the same patient at high and low SLEDAI scores. Each patient is represented by one dot in each column, the dots between columns being interconnected by a line. The level of significance is P = 0.0003 for Gas6 and P = 0.0271 for sAxl.

Fig. 3

Distribution of Gas6 (A) and sAxl (B) concentrations in patients without and with GN (70 and 24, respectively). Both are significant using the Mann–Whitney U-test, P < 0.001 as indicated by the triple asterisks.