The Etiology of Multiple Sclerosis

Lauren B. Krupp, MD: The underlying biology of MS [multiple sclerosis] is both fascinating and complex. It’s a real interaction between genetic factors and environmental factors. This is an immune-mediated condition where, probably, the events that lead to the development of MS biologically occur within the first decade of life. What happens is, presumably, an immune response to some viral infection or other external factors goes a bit awry or makes a wrong turn. The result is that the immune system turns against itself, and in this case, the covering of nerves or myelin. Factors that seem to promote this include certain genetic predisposition, exposure to certain viruses early on, such as EBV [Epstein-Barr virus], low vitamin D levels, or exposure to certain pollutants, toxic factors, or smoke.

There are things that make it more likely than not. Obesity among girls is a risk factor. The end result is that the immune system goes against this covering of the nerves through immune cells going from the blood into the central nervous system, causing demyelination, which is an unraveling of the myelin and sometimes damage to the underlying nerves. The result is a variety of different symptoms of the central nervous system. So the targets of this immune attack are within the brain and spinal cord.

Some people are under the impression that there’s a specific virus that causes MS. That’s not the case. What seems to be clear is that Epstein-Barr viral exposure early on is a factor, as is the fact that people who get infectious mononucleosis, which is caused by Epstein-Barr virus, have an increased risk of developing MS. That doesn’t mean that it’s causal, because there are all these people who have had infectious mono who don’t develop MS. What likely happens is, in the process of fighting off that viral exposure or that viral infection, a misdirect occurs. Immune cells, probably T cells aided by B cells, become refocused on what they think is Epstein-Barr virus, but is really the person’s own bits of myelin basic protein or other fragments of myelin that are floating around in the bloodstream. The immune cells see these little protein fragments of self and act as if they were a foreign entity and mount an immune attack that then leads to the symptoms of the condition.