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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