Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Kim, Hyoun‐Ah; Nam, Jin-Young; Jeon, Jun Young; An, Jie; Jung, Ju‐Yang; Bae, Chang-Bum; Suh, Chang‐Hee

doi:10.1007/s10875-012-9765-1

Cited by 22 publications

(16 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous results found a negative correlation between disease and free ProS, but no significant decrease [18]. GAS6 was found to be increased and correlated with SLEDAI in two studies [22,32], but not in a smaller sample [18]. Most likely, the differences among studies are due to the intrinsic heterogeneity of the populations in each case.…”

Section: Discussionmentioning

confidence: 86%

Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

et al. 2013

View full text Add to dashboard Cite

IntroductionGrowth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population.MethodsFifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples.ResultsPlasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients.ConclusionsThe present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE.

show abstract

Section: Discussionmentioning

confidence: 86%

Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Kim et al found that human serum Gas6 levels were significantly associated with disease activity in systemic lupus erythematosus which is resulted from disorder of immunity (Kim et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Exogenous Gas6 attenuates silica-induced inflammation on differentiated THP-1 macrophages

Shen

Cui

Rong

et al. 2016

Environmental Toxicology and Pharmacology

View full text Add to dashboard Cite

“…An association between decreased protein S levels and SLE has been described, 80 whereas elevated Gas6 levels are associated with disease activity in SLE. 81 Mutations in the murine and human genes coding for Mer lead to impaired phagocytosis by retinal pigment epithelial cells. This leads to cumulation of photoreceptor outer Figure 2.…”

mentioning

confidence: 99%

TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis

Meer

Poll

Veer

2014

Blood

283

228

View full text Add to dashboard Cite

TAM receptors (Tyro3, Axl, and Mer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K–dependent proteins Gas6 and protein S. Protein S is more commonly known as an important cofactor for protein C as well as a direct inhibitor of multiple coagulation factors. To our knowledge, the functions of Gas6 are limited to TAM receptor activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation and display an anti-inflammatory or a proinflammatory effect, depending on cell type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, we compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S+/−, Gas6−/−, TAM−/−, and variations of these). In this manner, we aim to display which features are attributable to the different ligands. Because of the effects TAM receptors have on hemostasis, inflammation, and cancer growth, their modulation could make interesting therapeutic targets in thromboembolic disease, atherosclerosis, sepsis, autoimmune disease, and cancer.

show abstract

Serum Growth Arrest-Specific Protein 6 Levels are a Reliable Biomarker of Disease Activity in Systemic Lupus Erythematosus

Cited by 22 publications

References 32 publications

Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity

Exogenous Gas6 attenuates silica-induced inflammation on differentiated THP-1 macrophages

TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis

Contact Info

Product

Resources

About