There is convincing evidence that environmental factors are contributing to the rise in autoimmune diseases like Multiple Sclerosis, Crohn’s disease and Type 1 diabetes around the world. A study coordinated at ANU is set to discover what some of these factors might be.
Teams of medical scientists worldwide are searching for cures for autoimmune diseases like Type 1 diabetes, Multiple Sclerosis and Crohn’s disease. While this worthy activity progresses, there is a quiet anticipation elsewhere that we may be close to discovering some of the risk factors that cause these devastating conditions.
Australia provides a particularly enticing setting for this research because of the unexplained, but quite strong, latitude-related gradient in the occurrence of several of these autoimmune diseases.
“It’s very exciting,” Dr Robyn Lucas, a Research Fellow at the National Centre for Epidemiology and Population Health, says. “We have all of this data coming in but at this stage can only anticipate what answers might be hidden within it.”
The information is trickling in as the study nears the end of three years of fieldwork gathering data on environmental influences on immune disorders, and there are tantalising hints about what it will reveal.
As part of a team of researchers, doctors and nurses around the country, Lucas is studying what is known as a ‘first demyelinating episode’ (FDE) in people in four locations on the eastern seaboard of Australia.
An FDE is an inflammatory condition in which the fatty coating around nerve fibres, known as myelin, is disrupted. About 85 per cent of people who have an FDE will develop multiple sclerosis, one of the most devastating diseases to attack the body’s central nervous system.
After the FDE, it’s difficult to pinpoint how long MS will take to develop or indeed whether it will ever develop at all. Symptoms, which include sensory changes like pins and needles or numbness, speech and cognitive impairment, temporary blindness or paralysis, can range from mild to severe. According to the MS Society of Australia, the number of Australians who suffer from MS is around 15,000. This figure has increased sharply since 1960.
“Our study is focused on the precursors of multiple sclerosis, which is why we are looking at people right after they’ve been diagnosed with an FDE, rather than those who already have MS,” Lucas says. “One of the many reasons for this is that we hope studying FDEs will help us understand why most people who have had an FDE go on to develop MS, when 15 per cent or so do not.”
Environmental factors are thought to play a large part in the onset of an FDE, but exactly what those factors are is not yet well-known.
This study, coordinated by Lucas at ANU and known as the Ausimmune Study, is quantifying for the first time the impact of different environmental forces on the immune system.
Study with latitude
It was once thought that Tasmanians had a high incidence of MS compared to the rest of Australia because Scotland had a high MS rate – and many Scots emigrated to Tasmania.
“But research has shown that a latitudinal gradient in MS in Australia, with lower prevalence in Queensland and higher in Tasmania, persists even if you restrict the analysis only to people with origins in the UK and Ireland,” Lucas says. It is now thought that MS rates may be higher in locations like Scotland and Tasmania, compared to more tropical countries – along with other countries on latitudes closer to the South and North poles – because they have fewer daylight hours and are colder. Ultraviolet radiation (UVR) from the sun may play a significant protective role against the development of an FDE or MS.
“The latitudinal gradient of MS is now well known. MS becomes more common as you move further north or south of the equator. So based on this effect the difference between Hawaii, which is closer to the equator, and Scotland, which is closer to the North Pole, would be marked.”
But is it really down to just sun exposure? The variation between Scotland and Hawaii could be due to differences in the healthcare systems of Scotland and Hawaii that result in more people being diagnosed with MS in the former, compared to the latter. Or it could even be because Scots and people living in Hawaii are relatively genetically different.
The Ausimmune Study was born when it was recognised that a multi-centred, environmental study of the factors contributing to MS was needed to understand the environmental antecedents to the disease. It was also clear that Australia would be the ideal location for a study of this type.
“It is the best location because of the wide variation in latitude, our standardised healthcare system and relative genetic homogeneity,” Lucas says.
The Ausimmune Study is studying a range of environmental factors in participants, including infection history, climate and exposure to sun, diet, exposure to synthetic chemicals and materials, past history of head injury and history of recent stressful life events.
There are currently 598 people participating in the Ausimmune Study of which 232 people have been diagnosed with a FDE, known as ‘cases’. The other 366 participants are ‘controls’, individually matched to a case on age, sex and region of residence in four locations along the eastern seaboard: Brisbane, Newcastle, Geelong and Western Victoria, and Tasmania. By comparing data on environmental exposures between cases and controls, the Ausimmune Study hopes to identify likely causative factors.
There have been few studies that have measured the incidence or prevalence of MS in Australia.
A project undertaken in 1981 found that the number of people who had MS in Brisbane was 11.9 per 100,000. In Tasmania it was 75 per 100,000. Another study, published in 1996, measured the growth in MS incidence in Newcastle and found the number of people affected in the 35 years to 1996 doubled to 2.4 per cent per 100,000 people.
“The marked increase in immune disorders is thought to reflect modern environmental and lifestyle factors rather than diagnosis changes,” Lucas says.
Lucas coordinates the work in each of the study centres, where there is a network of neurologists and radiologists who refer people who’ve had an FDE to the study and nurses who gather data.
Latitudanl variation in MS case notifications 2003-2006 (Soure: Ausimmune Study).
Participants are asked to provide a copy of their MRI scan, a blood sample, and undergo physical measurements on the skin, as well as completing an extensive questionnaire covering a wide range of topics, including ancestry, birth order, life sun exposure, places of residence, pet ownership, diet, immunisation and infection history, family history and exposure to chemicals. “This is a lot of information so the data analysis will be lengthy,” Lucas says. “It’ll be a very, very rich data set.”
The final data collection for the study is expected to be completed by May 2007. “There’s a real element of excitement and anticipation about what we might find,” Lucas says.
Covering every angle
The Ausimmune Study will also be first to measure, on a large population-based sample, viral loads of Epstein Barr virus (the cause of glandular fever) in participants’ blood samples.
“I stress that most people who get glandular fever do not go on to get MS, but it has been well established that people who have MS have a history of these infections more commonly than the rest of the population,” Lucas says. “The early indications in our study are that this is certainly looking like it will be the case in this study population.”
Past studies have looked at antibodies of these viruses in the blood, but the Ausimmune Study is examining both antibodies and blood viral load – how much virus is still left in the blood – and will compare this to the control group.
“We are probably the first to look at antibodies in people who don’t actually have MS, but have experienced this first demyelinating episode, so we feel we may just be on the cusp of something very exciting.”
Other data being collected includes the measurement of cumulative skin damage caused by the sun. This is registered by taking a silicone cast of the back of participants’ hands and rating it out of six for the ‘coarseness’ of the skin cell lines.
“When you’re a baby, your hands are lovely and soft, and have lots of little fine lines in the skin. As you get older and are exposed to more and more sun, you lose the fine lines and they become a lot coarser,” Lucas says. “The silicone casts between a person who has had a lot of sun skin damage and those who haven’t should show up that contrast between fine and coarse lines.”
A spectrophotometer is also used to take a reading of sun exposure on four body sites: the back of the hand and the shoulder for recent sun exposure readings, and the buttock and the inside of the arm to gauge natural pigmentation. “The biological effect of sun exposure is determined by how much pigmentation you’ve got,” she says. “We need to adjust our measures of how much sun people have had for what their skin type is.”
The Ausimmune Study is funded by the National Multiple Sclerosis Society of the US, the MS Society of Australia, and the National Health and Medical Research Council. Lucas has also received a Macquarie Bank MSRA Fellowship to work on the study.
“The study would not be possible without the fantastic support of clinicians, radiologists and study nurses in each region, the participants themselves, Multiple Sclerosis Australia and Multiple Sclerosis Research Australia,” Lucas says.
For more information on the Ausimmune Study and its partners go to: http://nceph.anu.edu.au/Ausimmune/