International genetic research into MS susceptibility
My little ladybug antenna have been wiggling furiously. I am starting a new thread as I don’t want to intrude on Myra’s thread Melbourne Treating Doctor for Cpn.
I have become something of a patient activist on this side of the world. Think of me as an antipodean aphidcatcher, in which the aphids are little pinholes of opportunity to pass on to Very Important People some of that secret, weighty Cpn knowledge...
I have not yet had a response from Professor Stewart, leader of the Australian and New Zealand contribution to the recently published International Multiple Sclerosis Genetics Consortium research Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. I have transcribed the relevant section of the Margaret Throsby interview below and would be really grateful if some of you MS people could give me some feedback before I pursue the matter further with Professor Stewart.
I should explain that Margaret Throsby has a radio show in Australia called The Morning Show in which she interviews interesting people and plays their choice of music. I love listening to it as she is a fabulous interviewer and her guests are interesting and insightful people. Professor Stewart is no exception; he comes across as a very decent and compassionate man with a deep interest in improving the lot of his fellow humans. He is a doctor and researcher for all the right reasons. I think that there is scope for expansion of his research into the area of infection, Cpn infection in particular, and I am putting together a compelling case for this, which I intend to forward to him.
I know nothing about the validity of the connection between sunlight exposure and multiple sclerosis and your ideas on this would be invaluable in preparing my case.
I have added citations to indicate which articles I think Professor Stewart is referring to. I am assuming that the “Australian data” he refers to is . I have not been able to obtain a copy of that research report as it is not available online. I have got a copy of  and it is a freetext article available from brain dot oxford journals dot org. I have got a copy of Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis, The International Multiple Sclerosis Genetics Consortium & The Wellcome Trust Case Control Consortium 2, Nature 476, 214-219, published online 10 August 2011. It was the publication of this latter article that caused a flurry of interest in multiple sclerosis in Australia, hence Professor Stewart’s presence on Margaret Throsby’s show on 15 August 2011.
Hey Mackintosh, bet you’re glad you didn’t hang around for the gene therapy.
Here you are, people – please post your thoughts on the transcript which follows.
Partial transcript by Ladybug of the Australian Broadcasting Commission (ABC) Morning Interview on 15 August 2011
Interviewer: Margaret Throsby
Interviewee: Professor Graeme Stewart, consultant physician and immunological pathologist, founding director of the Institute for Immunology and Allergy Research (IIAR), one of the four founding research groups of the Westmead Millennium Institute.
The full interview is available here:
<Start of partial transcript>
Graeme Stewart We’ve reported in Nature last week 57 genes. That’s a lot and we haven’t yet found them all. It’s certainly not so, that every patient will have the disease-associated variant for all 57 genes. They won’t. It’ll be a selection of those out of that number of 57 or more, and that will probably vary with the particular environmental trigger.
Margaret Throsby Do you get them because your mother or father had them? Is it passed down in families?
GS It’s not passed down in families in the way that people think of genetic diseases, like say cystic fibrosis or Huntington’s, where there’s a single gene, and if you get that gene, you get the disease. Sometimes you need a double copy of it, like cystic fibrosis. These are diseases of complex genetics, where you need a whole number of genes to come together, and then be triggered by the environment: almost all of the major unsolved diseases of humankind actually fall into that category.
MS What in the environment triggers these genes in MS patients?
GS Hm. Again, despite decades of research I still can’t give you a clear answer on that but I can tell you some hard facts. We know that the further you live from the equator, the higher your risk of MS. The best data for that worldwide is the Australian data  that shows that if you grew up in Tasmania, you’re about 7 times more likely to develop MS than if you grew up in northern Queensland.
MS I’ve seen that and I’ve seen the extrapolation from that that therefore, it must be something to do with sunlight. Is that the only “therefore” that exists in that?
GS The study’s now been done so well that I think we can say, it’s, we can act as if it’s conclusive, that it is sunlight.
MT It’s not some other factor that exists in the northern, near the equator compared with further away?
GS Within Australia, and within countries where we’ve looked at the same genetic populations, no, I think it is sunlight, I think that, that took me a while I think you know I wrote an editorial on this  a couple of years ago so I, in the journal Brain, I had to really look very hard at the, at the data . And I think as I said that, the world can now act as if it is sunlight because the, the evidence is very, very conclusive. In France, for example, it’s odd, and the French are always odd although I love them, their sunlight exposure doesn’t just increase as you get closer to the equator, it also increases from east to west, and the same gradient of MS prevalence goes from east to west...
MT Is that so?
GS ...along with the sunlight.
MT You said - have you identified these 57 genes, are they all identified now?
GS What we’ve actually found is genetic variations in 57 spots along the chromosomes. For some of those spots we actually don’t know exactly the gene and we’re looking now at doing what’s called fine mapping, to actually work out exactly which gene...
MT And are they – those 57 – solely concerned with MS, or could, do they have, do they have an association with other diseases?
GS I’m glad you asked that, because these discoveries tell us a lot about MS, but they help us, they help to tell us a lot about some other diseases, some of which I’ve mentioned, the autoimmune diseases, such as lupus, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, psoriasis have genes in common with the, gene risk factors in common with the genetic risk factors for MS. When you have a list of 57 you can go looking. Ah, remember, only 4 years ago we only had 2...
GS ...MS genes.
MT It’s as quick as that. So, do I understand you to say that if you’ve got that, those 57 genes, if they’re in your make-up, then that predisposes you perhaps to autoimmune diseases per se, of a variety?
GS In fact some of them do. Probably no more than a handful. Some of them predispose humans to autoimmunity in general. And then there are others which are quite specific to the individual disease.
MT Is this a pie in the sky question? Is it possible for you guys to manipulate genes so that they don’t have this... problem?
GS We can do it well in experimental animals, particularly, particularly mice, and I know this isn’t exactly your question but it’s, I think there’s a good point here, we, the gene discoveries we’ve got at the moment ... we can go back to a mouse model of multiple sclerosis – it has the awkward name of experimental encephalitis – autoimmune encephalitis – and we can knock out or increase the function of these genes in that mouse model, and we’re, my lab’s already going down that pathway and many labs around the world will now have 57 new genes to, or 50 odd new genes to work on. And you can see whether that protects or worsens the animal model. When it comes to humans, gene therapy still has quite a long way to go.
MT Ethically, or literally?
GS No not ethically. Scientifically. It’s been applied to some single gene diseases with benefit but the technology’s, getting a safe technology has been difficult.
MT In theory then, would it be easier to manipulate the environment, so that the trigger doesn’t happen?
GS Absolutely, the best example of that is vaccination, isn’t it? If we’d found a virus for MS we would have vaccinated for it and you and I wouldn’t be talking about MS – it would be a prevented disease.
MT This brings us to this: when you say “If we’d found a virus for MS then we could vaccinate against it.” When we look at human disease as a whole – when I was thinking about this, I was thinking well, it can be caused by a virus, it can be caused by – am I right here? – it can be caused by bacteria, disease can, or it can be caused by a malfunction of the immune system. Is that correct?
GS Or a combination of all of those things. But the world has looked very hard for a virus that causes MS, and it hasn’t found it.
MT Do you suspect it exists?
GS Ah, there’s good evidence that the glandular fever virus – Epstein-Barr virus is its correct name – is a factor in increasing the risk of MS.
MT So you have an episode of glandular fever...
GS Yes, but you see most people do. Just about everybody with MS has had glandular fever – about 90% of the population has had glandular fever by the time they reach adult life.
MT And not realised it?
GS And often not realised it.
MT You can have glandular fever – you can have a mild dose of it and not...
GS Absolutely. Absolutely, it’s just like chicken pox. Most of us have chicken pox antibodies in our blood don’t remember ever having it.
MS Is that so? Really?
GS Yes. Absolutely.
MT You’re telling me stuff I have no idea about. So most of them, people who have glandular fever and you can have it during childhood or adolescence and not know it, then they have a greater potential for having... so, if you’re tracking patients who’ve got MS and you take, go backwards in their story, you ask them whether they’ve ever had glandular fever and if they say well no, not that I’m aware of, you still don’t know that they haven’t, do you?
GS Well you can do a blood test to show that they’ve got antibodies.
GS A footprint remains even after the virus has gone.
MT And most MS patients have had glandular fever.
GS Yep, yep. In fact there’s an Australian study called Ausimmune that’s funded by Multiple Sclerosis Research Australia which is doing exactly that – tracking back.
MT So most or all? Most or all?
GS Almost all.
MT Well then why...
GS There’s occasional people.
MT Well then why wouldn’t you say that MS is caused by a virus that started off as glandular fever and then developed into MS?
GS There’s just no evidence for that. There’s a, it’s not a unique, or a variant of the glandular fever virus, it’s just... Glandular fever virus stimulates your immune system quite, in quite an extraordinary way, and in almost everybody you control that and you’re just left with, perfectly healthy, but along the way it stimulates some of the cells of your immune system that could encourage later development of autoimmunity.
MT Hah. All right.
<End of partial transcript>
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