The war inside: living with inflammatory disease

Around the world, millions of people suffer from inflammatory diseases, which has a number of classifications. In industrialised nations around five per cent of the population suffers inflammatory disease resulting from autoimmune conditions — where the body’s own tissues are directly attacked by its immune responses.

Although symptoms can vary greatly within the classification, the similarity between inflammatory disease caused by autoimmune failure and those resulting from other causes is that in both cases, white blood cells (T cells) that typically work to fight infection are not functioning correctly.  In short, the body’s natural immune system attacks its own tissue instead of a foreign bacteria or invading infection, resulting in damage to the body’s tissues and the development of an autoimmune disease. 

Autoimmune diseases can affect one or several organs and parts of the body and depending on this, the severity of symptoms range immensely from mild to life-threatening. There is no cure, but symptoms can be managed. 

The causes are not completely known but there is a link to gender – around two thirds of people with the condition are women and typically the condition surfaces during child-bearing years.

Inflammatory bowel diseases (IBDs) as distinct from irritable bowel syndrome (IBS), which is much less severe, are the result of destructive inflammation in the gut.  Chronic IBD, which includes Crohn’s disease and ulcerative colitis, are common conditions in most Western populations. In Australia over 61,000 people have IBD and about 1600 new cases are diagnosed each year.

Diagnosed last year at the age of 32, ‘Gwen’ has Crohn’s disease. She first saw a specialist at the age of 20 after having symptoms such as constant tiredness and diarrhoea. For years she was told her symptoms were more than likely to be irritable bowel syndrome. But it wasn’t until her mother told her she couldn’t go on living the way she was that Gwen finally saw a GP who identified the symptoms.

“After so many years, I had a scope and on seeing how ulcerated my intestine was, the doctors confirmed it was Crohn’s,” she says.

Receiving the diagnosis was confronting and life-changing. 

“To be told you had an incurable autoimmune disease when you’re young and want to travel and do things with your life was very hard to hear,” she says.

Complications of living with Crohn’s disease include cancer, gastrointestinal perforations and haemorrhages, stomas, malnutrition, complications with pregnancies and osteoporosis caused by prolonged steroid treatment.

To assist in reducing the symptoms, Gwen’s diet eliminates all insoluble fibre. Nothing can be wholegrain, no skins from vegetables, no seeds of any sort, anything that is hard for the body to digest.

“I can’t cheat on what I eat because I have strictures in my bowel and if I have fibre which my system can’t digest, I get blockages and end up vomiting my food up. I was recently hospitalised for a week due to a blockage.

“The really hard part is other people just don’t get it. I went into a café the other day and when I was checking the menu and told the waitress I couldn’t eat fibre, she rolled her eyes. People just assume you’re on some fad diet.”

Her current treatment regime is also confronting, as she says it increases the risk of cancer and infection due to the suppression of her immune system.

Professor Ian van Driel from the Department of Biochemistry and Molecular Biology at the Bio21 Institute at the University of Melbourne leads research into inflammatory disease in the gut.

“People with severe IBD cannot avoid living with a strict diet but we are looking at ways to improve prediction, prevention and overall treatment of inflammatory diseases in the gut, which will affect a person’s overall lifestyle,” he says.

Researchers in his team are trying to do determine the mechanisms that lead to the initiation of inflammatory disease, to better understand how the immune system normally “tolerates” our own tissues and to ultimately develop treatment strategies.

“The discovery of genes and pathways that control inflammatory disease could lead us to predict who may develop these diseases, and ensure that all is done to either prevent disease or to manage conditions before they become too severe,” he says.

The team has concentrated on some of the most common autoimmune diseases of the gut including pernicious anaemia and autoimmune gastritis. These are the also the commonest cause of vitamin B12 deficiency which can lead to serious illness.

“In terms of treatment, our group has demonstrated that a recently defined type of cell called a regulatory T cell can reverse very advanced autoimmune disease in animal models. We hope these cells can be developed into specific therapies for autoimmune disease that don’t cripple the entire immune system, like many conventional therapies do,” he says.

Another inflammatory disease of focus for University of Melbourne researchers and their collaborators is Multiple Sclerosis. MS affects the ability of nerve cells in the brain and spinal cord to communicate with each other effectively. The disease includes a range of neurologial symptoms and often progresses to physical and cognitive disability. There is no cure for the disease and no one test to diagnose it.

Nerve cells communicate by sending electrical signals down long fibres called axons, which are contained within an insulating substance called myelin. In MS, the body’s immune system attacks and damages the myelin. When myelin is lost, the axons can no longer effectively conduct signals.

There are an estimated 23,000 people with Multiple Sclerosis in Australia.

For decades diet has been considered as potentially playing a role in the disease but there is no conclusive evidence. According to MS Australia researchers Dr Laurence Harbige and Dr Lorna Layward, since infections can trigger relapses in some people with MS, it makes sense to maintain good nutrition to support a healthy immune response.

Professor Trevor Kilpatrick who is Director of the Melbourne Neuroscience Institute at the University of Melbourne and leads the MS Division at the Florey Institute of Neuroscience and Mental Health, says there is great interest in the potential link between the gut and many autoimmune diseases including MS.

“Very significantly, a trend for increased prevalence of both MS and inflammatory bowel disease (IBD) has been observed in Japan compared with other developed countries in recent years. It has been hypothesised that westernisation of the Japanese lifestyle, and in particular of the diet – with more fatty foods and sugar intake – could be driving this phenomenon,” he says.

He said that alterations in gut flora have already been linked to both IBD and the severity of some animal models of MS. 

“It’s of great interest to speculate that changes in diet could drive a change in the composition of friendly bacteria in the gut, thereby altering the susceptibility to autoimmune diseases, including MS,” he says.

Work reported last year in the scientific journal Nature led by the University of Melbourne and Monash University provided important insights into how the gut-autoimmunity link could happen. Immune cells within the gut known as mucosal associated invariant T (MAIT) cells could potentially influence the development of autoimmune disease. The MAIT cells are, in turn, greatly influenced by gut flora, especially given that receptors on these cells are stimulated by vitamin metabolites processed by bacteria.

Dr Lars Kjer-Nielsen from the University of Melbourne led the five-year study.

“Humans are unable to make vitamin B and obtain it mostly from diet. Because bacteria can synthesise vitamin B, our immune system uses this as a point of difference to recognise infection,” he says.

“Given the relative abundance of the MAIT cells lining mucosal and other surfaces, such as the intestine, the mouth and lungs, it is quite probable they play a protective role in many infections, from thrush to tuberculosis.

Deputy Vice-Chancellor (Research) at the University and Professor of Microbiology and Immunology James McCluskey says the discovery opens opportunities for vaccine development and other potential therapeutics.

“This is a major breakthrough in which Australian researchers have beaten many strong research teams around the world, becoming the first to unlock the mystery of what drives a key component of our immune system and the connection to the gut,” he says.

The next step is to explore whether MAIT cells might also be involved in intestinal or mucosal disorders such as inflammatory bowel disease and irritable bowel syndrome. 

For advancing research and treatments for MS however, Professor Kilpatrick says the holy grail depends on who you are. 

“For a family member of a person with MS the holy grail may be knowing your risk, and if this is significant, being able to block its conversion into clinical disease.  But for someone with recent onset MS, it is either being able to reverse the immune attack on the central nervous system or preventing further. For someone with significant disability, it’s about being able to repair the damaged nervous system.”

Professor Kilpatrick has research teams that focus on all three of these areas. 

One of these teams has identified several ‘risk’ genes that increase susceptibility to MS. Most intriguing is the finding that a variant in one of these genes is inherited by a small but significant subset of people with MS. If confirmed further, this will have profound significance for prevention-focused treatments.

Crohn’s disease sufferer Gwen says more could be done to improve awareness of autoimmune diseases like Inflammatory Bowel Disease.

“The world isn’t equipped to deal with people with IBD. Everyone knows about breast cancer because of the awareness campaigns — but it’s not the case for IBD. It’s not as marketable. When it’s about your bowel, it’s not the kind of thing people want to know about or that you necessarily want to share with everyone.”

www.mdhs.unimelb.edu.au/

www.melbournebraincentre.edu.au/

www.bio21.com.au

Free Public Lecture: Monday 29 April, 5.30-8.00 pm

To celebrate World Day of Immunology listen to four of Melbourne’s best scientists talk about what happens “when immune cells go bad”, for example in coeliac disease, allergy, cancer and multiple sclerosis. Melbourne Brain Centre, University of Melbourne.  More: www.dayofimmunology.org.au/