Stem Cell Growth Factor Expression in Rheumatoid Arthritis

Youn Jung Woo¹, Young Ae Baik¹, Yong-Beom Park², Soo-Kon Lee³, William H. Robinson⁴ and Jason Jungsik Song³, ¹Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, ²Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, ³Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, ⁴Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: inflammation and rheumatoid arthritis, pathogenesis

Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Stem cell growth factor (SCGF) is a member of the C-type lectin superfamily, encoded by gene CLEC11A. SCGF is not related to stem cell factor (a ligand for the receptor-type protein-tyrosine kinase KIT) although the two proteins can be confused due to similarity in name. SCGF has been recently discovered as a growth factor of hematopoietic precursor cells in the bone marrow. However, the role of SCGF in inflammation has not been investigated. Because various growth factors such as M-CSF (macrophage colony stimulating factor) have been shown to be involved in RA pathogenesis by promoting the survival and activity of inflammatory cells, we investigated SCGF expression using samples derived from RA patients and controls.

Methods: SCGF level is measured using sandwich ELISA methods with synovial fluid and serum derived from RA patients and controls. SCGF expression in synovial tissue is evaluated by immunohistochemistry using anti-SCGF antibody. SCGF localization in synovial tissue is evaluated with confocal microscopy using anti-SCGF antibody and anti-von Willebrand Factor (vWF) antibody (a marker for endothelial cells). SCGF expression in endothelial cells is evaluated using HUVEC cell and EAhy.926 cells by quantitative PCR and immunocytostaining.

Results: SCGF levels in RA synovial fluid (n=25) were significantly elevated compared to SCGF levels in osteoarthritis synovial fluid (n=25) (RA 9.4±1.6 vs OA 4.6±0.9 ng/ml, p<0.01). However there was no difference in SCGF levels in serum from RA patients and healthy controls. Immunohistochemical analyses demonstrated that SCGF is highly expressed in the endothelium of synovial tissues derived from RA patients. Confocal microscopy demonstrated SCGF positive cells are colocalized with vWF positive cells. Immunocytostaining with anti-SCGF antibody detected SCGF from various types of endothelial cells, such as HUVECs and EA.hy926 cells. LPS increased CLEC11A mRNA in EA.hy926 cells.

Conclusion: These results suggest that SCGF expression is associated with rheumatoid arthritis. SCGF is locally produced by endothelial cells in RA synovial tissue. Inflammation promotes SCGF expression in endothelial cells. SCGF might be involved in immune cell survival and differentiation in peripheral inflammatory tissue. Studies are underway to investigate the pro-inflammatory role of SCGF in RA.

Disclosure:

Y. J. Woo,
None;

Y. A. Baik,
None;

Y. B. Park,
None;

S. K. Lee,
None;

W. H. Robinson,
None;

J. J. Song,
None.

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