The Australian Multi-centre Study of Environment and Immune Function (the AusImmune Study) is a multi-centre, case-control study investigating the role of environmental factors in the development of first demyelinating events (FDEs), a frequent precursor to multiple sclerosis. The environmental factors include past and recent sun exposure (and vitamin D levels), viral infections, chemical exposures, diet, and genetic factors.
The AusImmune Study is the first observational epidemiological study to be able to provide population-based incidence data for early demyelinating disease across a broad latitudinal gradient (from more northern to southern parts of Australia) encompassing considerable environmental diversity, within a uniform health care system. As such, Australia provides a unique opportunity to do this work.
AusImmune received initial funding support from the US National MS Society, with top-up funding from MS Research Australia. The team have since been awarded a number of grants from the Australian National Health and Medical Research Council (NHMRC), most recently to complete long-term follow-up studies (10 and 15 years) on the original group of participants – known as the ‘AusLong’ and ‘AusLong 3’ studies.
In a meeting convened by the National Multiple Sclerosis Study of the US, the AusImmune Study was recognised by several speakers from the US and UK as a gold standard study to understand the causes of MS.
The AusImmune study has demonstrated that there is indeed a latitudinal gradient in the onset (incidence) of FDEs in Australia. This mirrors a previously described gradient in the prevalence of MS (total number of existing cases). The team are continuing to explore the causes of that gradient, and have contributed to the growing body of evidence that among several possible factors, ultra-violet light and vitamin D levels may underly this gradient (see more below).
An intriguing variation in the sex ratio and type of demyelinating disease presentations, such as optic neuritis, and latitude has also been found.
A detailed history of sun exposure over the life course (for every year of age) has been gathered for each case and an objective measure of cumulative sun exposure has also been used – silicone rubber casts of the skin on the back of the hand to measure sun damage to the skin.
The results indicate that healthy control individuals tend to have higher levels of skin damage on the back of the hand (reflecting higher sun exposure) than those with a first clinical diagnosis of demyelination. This suggests that higher levels of past sun exposure may reduce the risk of developing FDEs.
Most participants in the AusImmune Study also had blood taken for a vitamin D level and this showed that individuals with a first clinical diagnosis of CNS demyelination tended to have lower levels of vitamin D, than age and sex-matched healthy control individuals.
Virology experts at Westmead Hospital and at the Queensland Institute of Medical Research have also analysed blood from a subset of 446 participants (cases and matched controls) to investigate infection with two herpes viruses, Epstein Barr virus (EBV) and Human Herpes virus 6. This work has revealed that a past history of infection with EBV is a strong risk factor for the onset of FDE.
Further work from the team has shown links between smoking and FDE onset and levels of fats in the blood and disease risk.
There is considerable work ongoing by the large multidisciplinary team. In particular, they have analysed DNA from the participants to examine genetic risk factors for disease, and investigate how the interplay between genetic and environmental factors may contribute to the onset and progression of demyelinating diseases.
The ongoing extension of AusImmune, (AusLong), is continuing to follow and analyse data from participating individuals with annual telephone reviews and face-to-face reviews and MRI scans every 5 years, out to 15 years. This will allow further determination of any environmental and genetic factors important in the progression from FDE to MS or progression of disability in MS – or indeed why some people with an FDE never go on to have another event.
The Ausimmune Study and its follow-up studies have been uniquely powerful in shedding light on environmental risk factors for this potentially debilitating and disabling neurological disease.
Click here for a full list of research publications arising from the AusImmune and AusLong studies.