The association of Tyro3/Axl/Mer signaling with inflammatory response, disease activity in patients with primary Sjögren's syndrome

Joint Bone Spine. 2015 Jul;82(4):258-63. doi: 10.1016/j.jbspin.2015.01.008. Epub 2015 Apr 13.

Abstract

Objectives: Defects in Tyro3/Axl/Mer signaling may lead to impaired phagocytosis of apoptotic cells, eventually contributing to the development of autoimmune disease. The association of TAM signaling with several autoimmune disease has been investigated, but it remains unclear in primary Sjögren's syndrome. Therefore, the aim of this study was to evaluate the level of TAM signaling in primary Sjögren's syndrome with its clinical significance.

Methods: Real-Time Polymerase Chain Reaction was used to determine the mRNA expression of Mer, Tyro-3, Axl, Gas6, and Protein S in Peripheral Blood Mononuclear Cell from 43 pSS and 46 control. The Enzyme-Linked Immunosorbent Assay method was used to test plasma levels of soluble TAM signaling from those individuals, and the relationship of their levels with clinical characteristic was evaluated.

Results: The mRNA expression levels of Tyro-3, Axl were decreased in pSS patients. When considering the plasma level, increased levels of soluble Mer was observed with statistically significant difference. Soluble Mer levels were positively correlated with IgG levels (r=0.53, P<0.01), Erythrocyte Sedimentation Rate levels (r=0.44, P<0.01) and Sjögren's Syndrome Disease Activity Index (r=0.48, P<0.01). And the levels of soluble Mer in patients with the presence of SSA/SSB were higher than those without SSA/SSB.

Conclusions: The plasma levels of sMer were increased in pSS patients, which was associated with inflammatory response and disease activity.

Keywords: Peripheral blood mononuclear cell; Plasma; Primary Sjögren's syndrome; TAM receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axl Receptor Tyrosine Kinase
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Signal Transduction / genetics
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / metabolism
  • c-Mer Tyrosine Kinase

Substances

  • Proto-Oncogene Proteins
  • RNA, Messenger
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • TYRO3 protein, human
  • c-Mer Tyrosine Kinase
  • Axl Receptor Tyrosine Kinase
  • AXL protein, human