Current Series: Multiple Sclerosis: A Disease of an Immune System Gone Awry

Fred D. Lublin, MD: We’ve been studying the underlying biology of multiple sclerosis [MS] for several decades. Surprisingly, given how far we’ve gotten with our therapies, we don’t know the cause. We have a very good understanding of some of the immunologic events that lead up to multiple sclerosis. It’s a dis-immune state. We treat it like an autoimmune state, but we haven’t proven autoimmunity. There are clearly abnormalities of the immune system occurring. In a sense, this is a hyperactive immune system that, like in other autoimmune diseases, is attacking an organ or a system. In this case, it’s the nervous system: the brain, the spinal cord, and the optic nerves. We have a pretty good understanding of the cellular components that are involved in that, the T cells and B cells. We’re looking at the role of humoral immunity and, rather importantly, the role of innate immune system within the central nervous system [CNS]. But we haven’t put all the pieces of the puzzle together just yet.

Patricia K. Coyle, MD: We don’t know what causes MS, but we do know there are 3 factors. There are genetic factors, there are environmental factors, and there are host immune factors. We don’t know how these exactly fit together yet, but we’ve known each plays a role in MS for many, many years. MS is not an inherited disease. There’s no gene that passes it on, but there are genes that increase risk for development of MS, several hundred risk susceptibility genes—probably protection and disease severity genes—that have been identified.

Secondly, there are important environmental factors that may actually trump genes, things like smoking, adolescent obesity, vitamin D deficiency, or Epstein–Barr virus infection. Somehow, they promote the development of MS. And then, the person’s own immune system is attacking their own organs, the central nervous system. All of the MS disease-modifying therapies manipulate the immune system, and they are effective therapies for MS. I believe if we can ever figure out how genes, environmental factors, and the immune system fit together, that will allow us to ultimately cure MS.

The gut microbiota is a fascinating, fascinating topic. We do not know yet whether it plays a critical role in MS or not, but it may play a very important role. We know that the gut is the major part of the mucosal immune system. It is colonized by flora that are, to a certain extent, unique for every individual. There’s a special gut/CNS access: strong connections and interplay between the central nervous system and the gut microbiota. We know that flora of the gut control the systemic immune system and inflammation within the body. It appears in MS, regarding very preliminary data—and MS is not the only disease being studied—that there may be a gut flora that promotes development of MS, and it may be that we can manipulate or change the gut flora as a treatment for MS. That possibility is very exciting, and it’s being studied.

Fred D. Lublin, MD: Most autoimmune diseases affect women more than men. MS is a good example of that. The ratio is about 3-to-1, women to men. Interestingly, that ratio has gone up over the past 20 or 30 years; it used to be 2-to-1. The majority of new MS cases we’re seeing are occurring in women. It’s not entirely clear why that is, but because it has occurred over such a short period of time—just several decades—it can’t be genetic. It suggests something environmental that is impacting women more than men. There are hormonal explanations as well as to why women may be more susceptible to autoimmune disease, and we see that in animal models as well. But hormonal therapies and manipulations haven’t been particularly successful as a therapeutic endeavor.

(Transcript edited for clarity)