ArticleArthritis research & therapy2010
TAM receptor ligands in lupus: protein S but not Gas6 levels reflect disease activity in systemic lupus erythematosus.
Article in Arthritis research & therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 92 citations in OpenAlex.
- Extracellular Vesicles in Drug Delivery: From Quality Assurance to Therapeutic Application.International journal of nanomedicine · 2026Review
- Impaired Macrophage Efferocytosis: Shared Mechanisms and Therapeutic Implications in Immune-Mediated Inflammatory Diseases.Journal of inflammation research · 2026Review
- Review
- Clinical significance of TAM receptor in the minor salivary glands of patients with Sjögren's disease.Scientific reports · 2025Article
- Tuberculosis and Autoimmunity.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022Review
- Modulation of protein S and growth arrest specific 6 protein signaling inhibits pancreatic cancer cell survival and proliferation.Oncology reports · 2020Article
- How macrophages deal with death.Nature reviews. Immunology · 2019Review
- The Pros1/Tyro3 axis protects against periodontitis by modulating STAT/SOCS signalling.Journal of cellular and molecular medicine · 2019Article
- Gas6/TAM Receptors in Systemic Lupus Erythematosus.Disease markers · 2019Review
- Sjogren's Syndrome and TAM Receptors: A Possible Contribution to Disease Onset.Journal of immunology research · 2019Review
- Article
- Coagulopathies and inflammatory diseases: '…glimpse of a Snark'.Current opinion in immunology · 2018Review
- Review
- The many ways tissue phagocytes respond to dying cells.Immunological reviews · 2017Review
- The clearance of dying cells: table for two.Cell death and differentiation · 2016Review
- Gas6/Axl is the sensor of arginine-auxotrophic response in targeted chemotherapy with arginine-depleting agents.Oncogene · 2016Article
- Article
- TAM receptor signaling in immune homeostasis.Annual review of immunology · 2015Review
- Plasma growth arrest-specific protein 6 levels in premenopausal and postmenopausal women: the role of endogenous estrogen.Endocrine · 2014Article
- Receptor tyrosine kinases, TYRO3, AXL, and MER, demonstrate distinct patterns and complex regulation of ligand-induced activation.The Journal of biological chemistry · 2014Article
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5 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionThe TAM (tyro 3, axl, mer) kinases are key regulators of innate immunity and are important in the phagocytosis of apoptotic cells. Gas6 and protein S are ligands for these TAM kinases and bind to phosphatidyl serine residues exposed during apoptosis. In animal models, absence of TAM kinases is associated with lupus-like disease. To test whether human systemic lupus erythematosus (SLE) patients might have deficient levels of TAM ligands, we measured Gas 6 and protein S levels in SLE.
methods107 SLE patients were recruited. Of these, 45 SLE patients were matched age, gender and ethnicity with normal controls (NC). Gas6 and free protein S were measured with sandwich enzyme linked immunosorbent assays (ELISAs).
resultsOverall, the plasma concentrations of Gas6 and free protein S were not different between 45 SLE patients and 45 NC. In SLE patients, the levels of free protein S were positively correlated with age (r = 0.2405, P = 0.0126), however those of Gas6 were not. There was no correlation between the concentrations of Gas6 and free protein S in individuals. Levels of free protein S were significantly lower in SLE patients with a history of serositis, neurologic disorder, hematologic disorder and immunologic disorder. Gas6 levels were elevated in patients with a history of neurologic disorder. The SLE patients with anti-Sm or anti-cardiolipin IgG showed lower free protein S levels. Circulating free protein S was positively correlated with complement component 3 (C3) (r = 0.3858, P < 0.0001) and complement component 4 (C4) (r = 0.4275, P < 0.0001). In the patients with active BILAG hematologic involvement, the levels of free protein S were lower and those of Gas6 were higher.
conclusionsIn SLE, free protein S was decreased in patients with certain types of clinical history and disease activity. Levels of free protein S were strongly correlated with C3 and C4 levels. Gas6 levels in SLE patients differed little from levels in NC, but they were elevated in the small numbers of patients with a history of neurological disease. The correlation of decreased protein S levels with lupus disease activity is consistent with a role for the TAM receptors in scavenging apoptotic cells and controlling inflammation. Protein S appears more important functionally in SLE patients than Gas6 in this regard.
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