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What Causes NMO?

Sean Pittock, MD:

For NMO, the age of onset of the disease can vary from, I think the youngest we’ve had is two years of age up until the oldest that I’ve seen I think is in the mid nineties. So the onset of the disease can vary dramatically. Why one person develops it at postpartum period or another person develops it after a vaccination or another person develops it in the setting of a cancer. These are just unknowns. We don’t know the answer to those questions and those are important questions that need to be answered because I think once we can try and answer those questions, we can really get a handle on what’s happening in this disease.

Dean Wingerchuk, MD:

So the question about triggers is a very long standing one because again, there’s not very much that’s known about the mechanism or the causes of why attacks happen, whether it’s the first attack or later attacks. In multiple sclerosis we know viruses can do it. We think that vaccines uncommonly can do it and there’s no reason to believe that those things couldn’t be important in NMO. The challenge really is to sort out is there any systematic pattern.

Brian Weinshenker, MD:

As far as the triggers that cause the disease in the first place and might vaccines be important, I don’t think we have any conclusive evidence in MS where this has been studied a great deal more and it’s been suspected as a trigger for many years all of the carefully done studies do not document that vaccines are a problem. And at this point I reassure patients that they may have vaccines and I don’t think we have any evidence that they are. But you know, it’s very hard in individual patients to prove or disprove anything.

Claudia Lucchinetti, MD:

You know the reality is that NMO IGG is kind of like having that bio marker in your blood. I see it as a ticking time bomb and trying to understand what takes it from having this thing in your blood, which I don’t know how many actually have it because we don’t routinely test it to figuring out what the next hit is, whether that’s an infection or a parasite or who knows what. But we need to really begin to understand that because that’s going to really unlock, I think, the mystery of where we need to go next with the disease because it can’t just be the antibody.

Sean Pittock, MD:

How does Autoimmunity start? Is it possible that somebody is primed immunologically to develop NMO, but that something must happen before the full blown disease can occur? And there was recently a case from Japan that was published where a patient that had NMO, and it just so happened that they had a serum stored on that patient from 10 years prior to the onset of their disease and when they looked at that serum, they found that that serum actually contained the antibodies that target the water channel. So the question would be why did that patient have the antibody 10 years prior to the development of their disease? And so ultimately something must happen. There is not just having the antibody, you have the disease. You develop the antibody, and then there are steps that are involved. Is it possible that a vaccination or a viral infection or the presence of a malignancy or stress or whatever could be one of those steps? I think it’s absolutely possible.

Dean Wingerchuk, MD:

A person with a susceptibility to NMO may need something that’s just a very nonspecific trigger for inflammation and just happening at the right time, either the right time of the year or the right time of that phase of their life, may be enough to just trigger the disease in one individual but not in another.

Claudia Lucchinetti, MD:

So it’s complicated. The important thing is to keep an open mind about that. So before we dismiss a vaccine, before we say, “Oh, it has nothing to do with hormones, forget it.” We have to be paying attention to it. And Victoria reminds us about all those different things to think about and the importance to now test them in the laboratory and hopefully bring them back to the patient and see how that explains some of the mystery.

Dean Wingerchuk, MD:

So there may be a clue there either something genetic or environmental that determines this person who is susceptible to autoimmune disease is going to express it in a specific way. And if that’s true and that fact or those factors were discovered, that would be a major advance because that would lead to something that could be potentially tested for and intervened even on a population level. So that’s sort of big picture thinking about prevention of the disease.

 

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