Lupus Research at Australian National University

I think I've mentioned before, probably a number of times, that my super-heroes don't wear tights and capes. They wear lab coats.  They're working on saving my life, and the life of other lupies around the world.

We haven't got a cure yet, but we haven't been forgotten, either.  There's lots of people working on trying to piece this problem together.

The Centre for Personalised Immunology at the Australian National University has given me this explanation of the amazing work that they're doing at the moment, to share with you all.

I know everyone and their dog is always after you for money, but if you have some to spare, you can donate to the Centre's work here.

Lupus research at the Centre for Personalised Immunology

Background

The global prevalence of lupus is about 10 per 100,000. Lupus is much more common in women (by about 9: 1). Many patients present between 20 and 45 years of age, but lupus can affect men and women of any age. Sometimes, even children are affected.

Lupus can affect the body in many different ways. Most typically, patients present with a butterfly rash across their cheeks, joint aches and pains, mouth ulcers and chest pains. Other significant problems include inflammation in the kidneys (lupus nephritis), inflammation in the nervous system (cerebral lupus), and problems with the blood count (haemolytic anaemia and immune-mediated thrombotyopenic purpura (or ITP). At the moment, lupus is a chronic condition because there is no cure. Lupus disease activity often fluctuates over time, with patients experiencing flare-ups and then periods of disease remission. 

We know that lupus is an autoimmune disease. This means that in patients with lupus, the immune system goes awry and recognises elements of the body as if they were microbes. In other words, the immune system treats otherwise healthy parts of the body as if there were a serious infection present, and this leads to chronic inflammation and tissue damage.

There are other autoimmune diseases besides lupus. These include autoimmune thyroid disease (Hashimoto’s thyroiditis and Graves’ disease), pernicious anaemia, Sjogren’s syndrome, rheumatoid arthritis). Sometimes, these other conditions also occur in patient with lupus, or in their close relatives. Clustering of autoimmune diseases within families provides evidence that lupus, and indeed all autoimmune diseases, have a significant genetic component.

All current treatments for lupus are aimed at reducing inflammation and suppressing the immune response. Most of these treatments, however, are quite non-specific and suppress the immune responses that contribute to lupus, but at the cost of suppressing the immune responses necessary for fighting infections. Ultimately, we need to find more specific treatments, which depends on a better understanding of the mechanisms of lupus.

Our research strategy

The immune system is extremely complicated and therefore even once we have narrowed the cause of lupus down to a problem with immunity, it remains an enormous challenge to understand the precise nature of the abnormality. We are taking several different approaches to this problem.

In general, we are seeking to understand the genetic specification of abnormalities in immunity that lead to lupus. The technical challenges for performing this sort of research are substantial. We have been working on these questions for quite some time and have established significant research infrastructure to perform state-of-the-art genomics analysis, which enables us to identify single genetic variants anywhere within the 3 billion bases that make up the human genome. Analysis of genomes from patients with lupus or other immune disorders provides the first step in the discovery pathway. Each individual harbors thousands of genetic variants and the difficult task is to understand how these might alter normal immune function. This is where our efforts are concentrated. In order to accelerate this process, we also stratify our discovery based on the knowledge that:

1. Severe cases of immune-mediated disease sometimes yield answers more readily than milder cases. For lupus, severity can be assessed by early age of onset, unusually severe or refractory manifestations. Detailed analysis of patients with severe cases can then provide signatures of genetic and immune abnormalities that are more obvious. Once we have identified these signatures, we can then proceed to look for the same abnormalities in patients with milder disease.
2. Genetic predisposition would predict an increased incidence in relatives with lupus. We are investigating families in which more than one person is affected by lupus or autoimmune disease.

How is this work funded?

Our progress in the area was recently recognized by the award of a Centre of Research Excellence grant from the National Health and Medical Research Council of Australia. This is a highly prestigious grant and recognition of consistently high quality work. It also represents acknowledgement of the potential for our approach to make important progress in understanding diseases, including sarcoidosis. More information about the centre can be found here: http://jcsmr.anu.edu.au/research/cpi.

How do I get involved?

Patients provide written informed consent to participate. After this, we proceed to extensive gene sequencing (whole exome or whole genome sequencing). Once candidate genes are identified, then detailed laboratory analysis is performed to try and identify which genetic abnormalities are instrumental in causing disease. Some of this work is performed on patient lymphocytes obtained from a blood test.