Ausimmune: Australian Multi-centre Study of Environment and Immune Function

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The Australian Multi-centre Study of Environment and Immune Function (the Ausimmune Study) is a multi-centre incident case-control study investigating the role of environmental factors, including past and recent sun exposure (and vitamin D), viral infections, chemical exposures and diet, and genetic factors, in the development of first demyelinating events (FDEs), a frequent precursor to multiple sclerosis.

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 encompassing considerable environmental diversity – within a relatively homogeneous population and a uniform health care system. Australia provides a unique opportunity to this work, as evidenced by funding support for this work from the US National MS Society.

In a recent 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.

1. Variation in immune disorders by latitude

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 prevalence (existing cases) gradient. We are now exploring the causes of that gradient.

Many factors vary with latitude – ambient UVR decreases with increasing latitude and it may follow that sunshine-induced vitamin D levels are lower at higher latitude, although this remains to be proven.

An intriguing variation in the sex ratio and type of demyelinating disease presentations, such as optic neuritis, and latitude has also been found.

2. Environmental factors that influence immune disorders

A detailed history of sun exposure over the life course (for every year of age) and also use an objective measure of cumulative sun exposure – silicone rubber casts of the skin on the back of the hand – to measure past sun exposure is taken for each case.

Early results indicate that healthy controls 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. Preliminary results indicate that higher levels of past sun exposure may reduce the risk of developing FDEs.

Most participants in the Ausimmune Study had blood taken for a vitamin D level. In preliminary analyses of these results, individuals with a first clinical diagnosis of CNS demyelination tended to have lower levels of vitamin D, than their age and sex matched healthy controls.

3. Ongoing work

There is considerable work ongoing by the large multidisciplinary team. In addition to more complete analyses of sun exposure and vitamin D, DNA from all participants is currently being analysed to examine genetic risk factors for disease, and particularly the interplay between genetic and environmental factors.

Virology experts at Westmead Hospital and at the Queensland Institute of Medical Research are currently analysing blood from a subset of 446 participants (cases and matched controls) to examine infection with two herpes viruses, Epstein Barr virus and Human Herpes virus 6. These analyses will determine if cases are more likely to have had past infection with these viruses or some type of aberrant response to infection with them.

All cases in the Ausimmune Study had a MRI of the brain and/or spinal cord.  Neuroradiology experts at Royal Brisbane and Women’s Hospital have catalogued all of these scans. It has become evident that, in Australia, different radiology services use a wide range of protocols for undertaking scans for “possible demyelination” – this work has driven calls for standardisation of MRI protocols so that scans from different locations are comparable.

The new AusLong study will continue to follow participating cases with annual telephone reviews and with a 5 year face-to-face review and MRI scan. 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 has been a unique study in a unique setting globally to shed light on environmental risk factors for this debilitating and disabling neurological disease.