Increased plasma levels of the soluble Mer tyrosine kinase receptor in systemic lupus erythematosus relate to disease activity and nephritis

ELISA kits were used to test plasma concentrations in controls and in patients with SLE, RA or CLI.Increased levels of, in particular, sMer and, to some extent, sTyro3, were found in patients with SLE or RA, but not in patients with CLI. Patients with SLE demonstrated the highest sMer levels and there was a strong correlation to higher SLE disease activity score (SLEDAI). In contrast, in patients with RA, the sMer levels did not correlate with the disease activity score (DAS). In SLE, sMer levels were particularly high in those with lupus nephritis, patients who also had decreased C1q levels and increased titers of anti-DNA antibodies. After therapy, the plasma concentrations of sMer decreased in parallel to the decrease in SLEDAI score.The plasma concentrations of sMer and sTyro3 were significantly increased in patients with active SLE and RA, suggesting the TAM receptor shedding was affected by these autoimmune diseases. In particular, sMer was increased in SLE, the plasma levels of sMer reflecting disease activity.Mer is a cell membrane-bound receptor tyrosine kinase (RTK), which together with Axl and Tyro3 constitutes the TAM receptor family [1,2]. The vitamin K-dependent proteins Gas6 (a 'product of growth arrest-specific gene 6') and protein S are important biological ligands for the TAM receptors [3]. Axl is ubiquitously expressed, whereas Tyro3 is predominantly found in the central nervous system and the reproductive system. Mer is named after its expression in monocytes, epithelium and reproductive tissue. Activation of the TAM receptors has been shown to affect a diversity of cellular functions, including survival, proliferation, migration and phagocytosis [4]. Mer is an important mediator of apoptotic cell phagocytosis [5]. It is also important for phagocytosis of photoreceptor outer segments (POS) by retinal pigment epithelial (RPE) cells and genetic defects of the Mer gene Mertk are associated with retinitis pigmentosa, which results in the development