title: 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.
abstract: BACKGROUND
  Growth 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.
  
  
  METHODS
  Fifty 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.
  
  
  RESULTS
  Plasma 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.
  
  
  CONCLUSIONS
  The 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.
authors.forename: Pedro
authors.initials: P
authors.lastname: Recarte-Pelz
authors.forename: Dolors
authors.initials: D
authors.lastname: Tàssies
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Begoña
authors.initials: B
authors.lastname: Hurtado
authors.forename: Núria
authors.initials: N
authors.lastname: Sala
authors.forename: Ricard
authors.initials: R
authors.lastname: Cervera
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Reverter
authors.forename: Pablo García
authors.initials: PG
authors.lastname: de Frutos
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D017293:Protein S; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood*; D014812:Vitamin K / Q000378:metabolism; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D017293:Protein S; D020794:Receptor Protein-Tyrosine Kinases; D014812:Vitamin K; D000099255:Growth Arrest-Specific Protein 6; C504026:protein S (159-245), human