The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations

Author(s): David M. Kofler, Aron Farkas, Michael von Bergwelt-Baildon, David A. Hafler.

Journal Name: Current Drug Targets

Volume 17 , Issue 6 , 2016

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Abstract:

The cell surface glycoprotein CD6 is expressed on leukocytes and mediates T cell trafficking across endothelial cell barriers. There is evidence suggesting that CD6 is implicated in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and rheumatoid arthritis (RA). CD166, the physiological ligand of CD6, is expressed on endothelial cells in the central nervous system and in the collagen tissue of joints as well as on the cell surface of synovial fibroblasts. Animal models and in vitro experiments have shown that CD166 facilitates leukocyte trafficking into the central nervous system and mediates interactions of synovial cells with T lymphocytes, thereby representing a possible common mechanism of pathogenesis in MS and RA. In recent years, genome-wide association studies (GWAS) have established a genetic link between CD6 and MS. The single nucleotide polymorphism (SNP) rs17824933 in the CD6 gene has been identified and validated as a genetic risk factor for the development of MS. The SNP is associated with altered CD4+ T cell functions and with the expression of alternative CD6 splice variants in T cells. Several other independent CD6 gene polymorphisms have been associated with disease susceptibility or with clinical features such as worse attack recovery in MS. In addition to the genetic associations found in MS, an allelic variant of the CD6 gene correlates with clinical response to tumor necrosis factor- (TNF-) inhibitors in patients with RA. Preliminary data indicate that anti-CD6 blockade may be a promising tool for the treatment of RA and psoriasis. Taken together, genetic associations and clinical observations provide new evidence for a role of CD6 in autoimmunity.

Keywords: CD6, genetic association, multiple sclerosis, T cells, CD166, rheumatoid arthritis, TNF-α inhibitors, autoimmunity.

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Article Details

VOLUME: 17
ISSUE: 6
Year: 2016
Page: [651 - 665]
Pages: 15
DOI: 10.2174/1389450117666160201105934
Price: $58

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