Kofler, David M., Farkas, Aron, von Bergwelt-Baildon, Michael and Hafler, David A. (2016). The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations. Curr. Drug Targets, 17 (6). S. 651 - 666. SHARJAH: BENTHAM SCIENCE PUBL LTD. ISSN 1873-5592

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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-alpha (TNF-alpha) 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kofler, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Farkas, AronUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Bergwelt-Baildon, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hafler, David A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-290362
DOI: 10.2174/1389450117666160201105934
Journal or Publication Title: Curr. Drug Targets
Volume: 17
Number: 6
Page Range: S. 651 - 666
Date: 2016
Publisher: BENTHAM SCIENCE PUBL LTD
Place of Publication: SHARJAH
ISSN: 1873-5592
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ANTI-CD6 MONOCLONAL-ANTIBODY; LYMPHOCYTE DIFFERENTIATION ANTIGEN; PROGRESSIVE MULTIPLE-SCLEROSIS; TNF-ALPHA-308 G/A POLYMORPHISM; INTRACELLULAR IONIZED CALCIUM; CHRONIC PLAQUE PSORIASIS; COLLEGE-OF-RHEUMATOLOGY; CYSTEINE-RICH DOMAIN; AUTOREACTIVE T-CELLS; TNF-ALPHA-BLOCKERSMultiple languages
Pharmacology & PharmacyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/29036

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