Research Topic #2

Researchers Show How Immune Attack May Directly Damage Nerve Fibers in MS

Researchers report on a protein that may engage the immune attack to target nerve fibers in MS; studies suggest that damage to nerve fibers may be the root cause of long-term disability in MS. Edgar Meinl, MD (Max Planck Institute of Neurobiology, Martinsried, Germany) and colleagues reported their findings in Proceedings of the National Academy of Sciences USA, (2009 May 19;106(20):8302-7). This study was funded by the MS Society of Great Britain and Northern Ireland, among others.

Background: Multiple sclerosis occurs when the immune system attacks and damages the brain and spinal cord, with a major target being the myelin that ensheathes nerve fibers. Recent research indicates that damage to nerve fibers themselves may occur early and contributes to long-term disability in people with MS. But it is not clear how nerve fibers are damaged in the course of the immune attack, or whether they are directly targeted by the immune system.

The Study: First, Dr. Meinl’s team used proteomics – technology that scans thousands of proteins at once – to identify antibodies (immune proteins that target specific molecules) in brain tissue from people with MS that react to nerve fiber components. This process highlighted a protein called “contactin-2/TAG-1” (transiently expressed axonal glycoprotein 1). Contactin-2/TAG-1 is active on nerve cells, in the region where myelin connects with the nerve fibers.

They then compared the reactivity of immune T cells from individuals with MS and other disorders by exposing their T cells to Contactin-2/TAG-1. They found that T cells from people with MS showed signs of “recognizing” and mounting immune responses to this molecule, and also found evidence of antibodies in MS spinal fluid that reacted to this molecule.