Does epigenetics have a part to play in scleroderma?

As many of you may have seen in the latest edition of our magazine, a core theme of SRUK's 5-year strategy is the identification of causes behind the development of Raynaud's and scleroderma. Achieving this will mean that we are one step closer to finding a cure and understanding if there are preventative measures that can be taken to slow the diseases' progression. This is closely linked to another pillar of the strategy, early detection; this is based on the possibility of recognizing biomarkers that may indicate if someone is likely to develop Raynaud's or scleroderma in the future.

Biomarkers represent an exciting and promising line of investigation; they are characteristics that can be measured and analysed to provide an overview of whether normal biological processes, pathogenic processes or pharmacological responses to therapy are taking place. This means that if there are known biomarkers for scleroderma, the diagnostic waiting period could be dramatically reduced. It is thought that on average, it takes a person 5 years to be diagnosed with scleroderma, the first 3 of which being the period with the most extensive and damaging changes.

Biomarkers can be thought of as the functional product of a person's genes. Genes are made of DNA, and when expressed, they act as instructions to make molecules that travel around a person's body. It is not necessary that these genes will always be expressed however – sometimes there will be chemical modifications to the genes. This is a natural process referred to as epigenetics and can be influenced by a range of factors such as age, lifestyle and health state. There are no changes to the underlying DNA sequence but the way the cell reads the gene is changed. A gene can go from being expressed to 'silenced', generally by a process called DNA methylation. This is where a small chemical group is added to the DNA sequence – this can therefore change the activity of the gene within the according DNA sequence, without changing the sequence itself. The chemical group can also be removed from the DNA by natural processes, thus expressing the gene once again. Although this is a regular process, at times epigenetic changes can have detrimental effects that can result in diseases like cancer.

It is thought that epigenetic changes may contribute to the presentation of scleroderma and has been suggested in the study 'Integrative analysis of DNA methylation in discordant twins unveils distinct architectures of systemic sclerosis subsets', published in the journal Clinical Epigenetics. The investigators of the study focused on this area to progress from 'compelling evidence that DNA methylation plays a role in the development of auto-immune diseases' such as lupus, rheumatoid arthritis and psoriasis. They looked solely at twins, where one had either diffuse cutaneous systemic sclerosis or limited cutaneous systemic sclerosis, and the other had neither. This was to minimise the impact of potentially differing factors such as age, genetic backgrounds and early-life environments.

The results displayed that affected siblings did have different DNA methylation patterns to those of their siblings, meaning that different genes were silenced for them. This implies that there is perhaps the existence of specific DNA methylation sites in those living with scleroderma. Furthermore, some of these sites were the same as those found in people who had lupus, suggesting that these modifications are linked to auto-immune conditions as a whole.

Although research in this area is limited and so no conclusive statements can be made as of yet, this evidence acts as a strong foundation to continue this line of questioning. By understanding changes that may be happening at a genetic level, the likelihood of being able to develop therapies that target these changes and rectify them increases, contributing to our ultimate aim of helping people who live with scleroderma. We hope that by funding research like this, that specifically looks at causes and precision medicine (as well as quality of life and early detection), we will be closer to achieving this goal.

If you are interested in helping SRUK to fund more work like this, then please visit our donations page here. We rely on the generosity of our community to continue to support groundbreaking research in both scleroderma and Raynaud's.

If you would like information on managing scleroderma, please visit: Managing scleroderma

A recent news article covering tips for self-management in scleroderma can be found here: 6 tips for self-management