Sunday, 27 January 2013

Research: MCAM a marker of inflammation

EpubDuan et al. Soluble CD146 in cerebrospinal fluid of active multiple sclerosis.Neuroscience. 2013 Jan  doi:pii: S0306-4522(13)00050-X. 10.1016/j.neuroscience.2013.01.020. 

Background: The soluble form of CD146 has been reported to be present in various inflammatory diseases and displays pro-inflammatory properties. However, little is known about sCD146 in multiple sclerosis. 

Findings: Here we show that sCD146 is significantly elevated in the cerebrospinal fluid of patients with active MS compared with that of inactive MS or patients with non-demyelinating diseases. Moreover, abnormally increased sCD146 in the CSF of active MS patients correlated with albumin quotient, MBP antibody and MOG antibody from both CSF and sera. Importantly, the level of CSF sCD146 is correlated with levels of inflammatory factors, such as TNFα, IFNγ, IL-2, and IL-17A in the CSF. We also found that CSF sCD146 might originate from membrane-bound CD146 on inflamed BBB endothelial cells. 

InterpretationIn addition, sCD146 promotes leukocyte transmigration in vitro, at least in part by stimulating the expression of ICAM-1 and VCAM-1 on endothelial cells. Our findings suggest that CSF levels of sCD146 may provide a potential marker for monitoring disease activity in MS patients.

CD146 (cluster of differentiation 146) also known as the melanoma cell adhesion molecule (MCAM) or cell surface glycoprotein MUC18, which present on brain blood vessles. Many adhesion molecules have a soluble form that is shed from the cells. This study suggests that it is involved in white cell migration into the brain. This was also recently shown, where MCAM could be targeted to block migration into the brain.

As we reported recently (Multiple Sclerosis Research: Research: Another Tysabri-like drug for ...) it was shown that MCAM could serve as a potential biomarker for multiple sclerosis and represents a valuable target for the treatment of neuroinflammatory conditions. In nother study it was found that MCAM influences T cell migtraton into the brain

Where will this lead? I don't know maybe an alternative to Tysabri for the future. 

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