Identifying Secondary Progressive Multiple Sclerosis - Episode 2
Peter L. Salgo, MD: Can we come back for a second because, as you point out, it’s autoimmune, it’s an inflammatory disease.
Patricia K. Coyle, MD, FAAN, FANA: I don’t like to call it autoimmune because we’ve never identified an autoantigen target. Immune mediated, I have no problem with. But I don’t like calling it autoimmune. It’s not documented that way.
Peter L. Salgo, MD: You jumped right on it. I was going to go there, and you did it for me. How do we know it’s autoimmune? Because I’m wondering, and I’ve wondered throughout my career, why for so many of these diseases, we call them autoimmune as a wastebasket because we don’t know what causes them. Are we sure it’s autoimmune or is there an inciting factor?
Patricia K. Coyle, MD, FAAN, FANA: No, I really think if you haven’t identified an autoantigen target you shouldn’t be calling it autoimmune. It’s not myasthenia gravis, it’s not NMO [neuromyelitis optica] spectrum disorder. There, you have autoantigen targets.
Peter L. Salgo, MD: OK, let me ask this again. Since we don’t identify an autoimmune target, what’s causing it?
Patricia K. Coyle, MD, FAAN, FANA: There’s no doubt that the host immune system is attacking and causing damage within the CNS [central nervous system]. It’s an immune mediated disease, that’s a definite component. All of our DMTs [disease-modifying therapies] manipulate the immune system, and they are successful.
Peter L. Salgo, MD: But what is the trigger?
Patricia K. Coyle, MD, FAAN, FANA: That’s very interesting.
Peter L. Salgo, MD: I know, that’s why I asked.
Patricia K. Coyle, MD, FAAN, FANA: OK, you have genetics and you have environmental factors, very interesting environmental factors. For example, there is no adult onset MS [multiple sclerosis] case that’s not Epstein-Barr virus [EBV] antibody positive. There’s not a single case in the literature of adult onset MS that’s EBV seronegative. Why is that?
Peter L. Salgo, MD: That’s a tricky way to phrase that because a lot of people are Epstein-Barr positive who don’t have MS.
Thomas P. Leist, MD, PhD: It’s a confluence. It’s a confluence of the genetic makeup of an individual plus what has happened to this individual immunologically. Keep in mind that Epstein-Barr virus after you acquire it, it is within your body. Where does it survive? Among other things, it survives in B cells and T cells. What does a virus do in B cells and T cells? It gives this T cell and the B cell an ever so slight survival advantage.
If you were to use this, and I don’t want to overstress this, but in a pro-oncogenic kind of model, it puts the cell up so it no longer responds in an equal way to the surrounding controlling mechanisms. So it is now a cell that can do things when it should no longer do things.
Peter L. Salgo, MD: It tips a little bit.
Thomas P. Leist, MD, PhD: It’s tipping.
Peter L. Salgo, MD: So these inflammatory cells start doing things you wished they hadn’t done, like chewing up myelin and gray matter, for example.
Thomas P. Leist, MD, PhD: Or no longer being there when they shouldn’t be there. Think of it.
Peter L. Salgo, MD: They don’t defend against something that is attacking.
Thomas P. Leist, MD, PhD: Well, think about what happens to old T cells that you have in your body when you get the flu. At the end when you clear the flu, the great majority do the decent thing: they apoptose, they die. If you have an ever so slight survival advantage because of Epstein-Barr virus, you may not go away when you should go away, which then leads to an ongoing autoimmune disease, or immune activation depending on our terminology.